Standardization of Protein Nomenclature for Complexes. Anna Bank and Darren Natale, Department of Biochemistry and Molecular Biology, Georgetown College, Georgetown University.
In 2003, the Human Genome Project determined the base-pair sequence of human DNA. But simply knowing the genome is not enough. Genes produce proteins, which participate in almost every biological function in the human body. Proteomics is the study of the structure and function of these proteins in humans and other organisms. The Protein Information Resource in the Department of Biochemistry and Molecular Biology operates a large-scale protein database which is a crucial resource for biomedical researchers and scientists around the world.
The purpose of my research, which I authored with assistance from Darren Natale, was to facilitate faster and more precise database searches. Protein families were computationally assigned to complexes based on the functions of their members; the complexes themselves were labeled according to the cellular component system of gene ontology (GO), a controlled vocabulary for describing gene products. I standardized the names of protein families within the same complex, reassigned families that were incorrectly placed, and added missing families to their correct complexes by comparing information within PIR along with published literature. In order to increase accessibility and accuracy, I adopted the most common nomenclature in the literature.
Of the 1,338 families considered, 678 were successfully standardized. Of the 275 complexes containing these families, 171 underwent changes, 37 were already correct, and 67 contained complications which require further research.
In conclusion, I successfully standardized a large number of protein families belonging to GO cellular component complexes. In the process, I also identified a number of as-yet-uncreated families that will complete complexes once they are in place. Both changes should increase the effectiveness of database searches. Additionally, the standardization technique has implications for future research because it can be applied to other areas of classification, starting with the other two GO systems: molecular function and pathway complexes.
Synthesis of Nitric Oxide Containing Complexes Using N-nitrosamines and Copper Metalloenzyme Model Complexes. Ashley Bartell and Timothy H. Warren, Department of Chemistry, Georgetown College, Georgetown University.
Nitric oxide (NO) is a small molecule involved in vital processes such as vasodilation, anti-coagulation, broncodialation, and neurotransmission. NO activates guanylate cyclase, a heme iron containing metalloenzyme that regulates the protein phosphorylization responsible for arterial relaxation and functions with glutamate in neurotransmission. By inducing the release of nitric oxide from these molecules, possibly through metalloenzyme facilitated cleavage, the physiological benefits of NO may be realized and the mutagenic properties of N-nitrosamines may be circumvented.
Preparative measures included the synthesis of a biomimetic copper species and organic derivatives with R2NNO (nitrosamine) groups. Ligand choice proved important in effectively mimicking a copper-based metalloenzyme. An organic ligand and copper model complex approximating a dual cis-histidine structure, the beta-diketiminate, was originally proposed and synthesized. A phenyl group was added in a successive generation to improve prospects for future crystallization by x-ray crystallography. During the process of ligand refinement, a library of nitrosamines, varying by associated alkyl and phenyl substituents, was created by reacting amines with tert-butyl nitrite.
Studies are being performed to ascertain the bonding mode between copper active site mimics and nitrosamines. Reactivities with NO gas are also being explored. NMR spectroscopy revealed a pronounced upfield chemical shift in the methyl region from the dimethylnitrosamine to the dimethylnitrosamine-copper-ligand complex, possibly signifying an NO-copper bond with implications in the degradation of alkylating nitrosamine carcinogens. In addition, change in the NMR spectra was observed when this species when reacted with NO gas. Further work expanding on the type of nitrosamine, ligand environment, and reactivity is in progress with a focus on characterization of novel species that may further elucidate Cu-NO chemistry with biomedical applications.
Role of the renal prostaglandins in health and disease. Laura Boitano, Miguel De Leon, Kaileen Rohr, Kristina Durikas, Elizabeth Mongan, and Allan Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Multiple studies have been done on a variety of subjects ranging from mice to human subjects, to discover the role of prostaglandins, in health and disease. The focus of these studies revolved around pathologies involving renal prostaglandins. Specifically, these pathologies included chronic renal failure, ischemic acute renal failure, and disease processes resulting from the inhibition of renal prostaglandins. By taking note of the symptoms associated with varying levels of prostaglandins during these processes, the roles of prostaglandins were seen. The research shows that prostaglandins were key players in vasodilatation, glomerular filtration rate during pathological processes, and the healthy maturation of the kidney. Having understood these roles, it offers insight on how to prevent and treat diseases, due to the role prostaglandins play in the pathologies themselves. For example, to combat ischemic acute renal failure, giving a patient prostaglandins can help prevent the typical symptoms of the disease, the symptoms are due to low prostaglandin count. Through careful analysis of different disease processes, important information such as this can be discovered.
Poor maternal mental health as a risk factor for a shortened inter-pregnancy interval among adolescent mothers. Dominique Caruso and Robin Gaines Lanzi, Ph.D., MPH, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Background: Young mothers commonly express depressive symptoms that often go untreated or undiagnosed (1). Samples of several hundred indigent mothers from primary-care clinics or community-based programs consistently report a prevalence of depressive symptomology from 40% to 50% (1). Maternal depressive symptoms have demonstrated detrimental effects for both mothers and their children. Parental attitudes and capabilities decline, and children encounter challenges with growth and development, performance, and peer and family relationships (1,2). Maternal depression has also been hypothesized to reduce the inter-pregnancy interval and lead to subsequent, frequently unplanned, pregnancies. This association is worrisome, as short intervals between pregnancies have been related to adverse perinatal outcomes (3).
Objective: To examine the prevalence and influence of poor maternal mental health on maternal developmental factors during the inter-pregnancy interval among adolescent mothers via focus groups and a systematic qualitative review of client records.
Methodology: This qualitative study builds upon an established unintended subsequent pregnancy prevention program, Teen Alliance for Prepared Parenting (TAPP) at Washington Hospital Center (WHC), Washington, DC (DC). This program offers extremely promising, focused interventions designed to prevent unintended subsequent pregnancy. The proposed study presents the methodology for conducting focus groups about depression with adolescent mothers and for developing a system for identifying indicators of depression in client records via tracking system based upon the Beck Depression Inventory, SCL-90-R, Postpartum Depression Scale, and the Trauma Screening Module. Participants are between 13 and 18 years of age and have each experienced a subsequent pregnancy (19 unintended, 2 intended) within two years.
Implications: This research is of paramount significance because there are alarming rates of depression among adolescent and high-risk mothers and limited understanding of the maternal developmental factors related to the onset, severity, and duration of depression.
Breast Cancer and Resistance to Hormonal Treatments. Whitney Cesari, Department of Human Science, School of Nursing and Health Studies, Georgetown University, Lombardi Cancer Center Department of Biotechnology
Presence of ER-α 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 I 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-estrogen’s power to inhibit growth is overcome by activating the ErbB2 /PI 3-K/Akt1 signaling pathway. I prepared 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 are compared in MCF-7 cells versus LCC cells.
Age Deficits in Probabilistic Category Learning. Natatlie Ciomek, Sunbin Song, James H. Howard, Jr., and Darlene V. Howard, Department of Psychology, Georgetown College, Georgetown University.
The weather prediction task has been used to characterize probabilistic category learning in several patient populations such as Parkinson’s (Sage et al. 2003), amnesiacs (Knowlton et al. 1994), and schizophrenics (Keri et al. 2005, Weickert et al. 2002) as compared to healthy older adults. To date, no aging studies have been conducted. In the present study, healthy older adults demonstrated deficits when compared to younger subjects.
Old (n=16) and young (n=29) participants were tested on the weather prediction task. Four different cards serve as neutral cues probabilistically associated with one of two outcomes, rain or sunshine. Subjects predicted an outcome upon seeing various combinations of stimuli and received feedback about the correctness of each response. Subjects then completed two recognition tests, including a forced choice recognition task in which they chose the outcome more highly associated with each of the 14 possible stimuli combinations. This more direct measure of declarative learning was not used in previous studies. The present results demonstrated that the age groups did not differ in classification accuracy on the earlier implicit stages of the task (trials 1-45). However, younger adults continued to learn after the first 45 trials (p <0.02), whereas older adults did not (p=0.99). There was also a trend for an age deficit (p=0.07) when classification accuracy for all trials was compared. Further analyses revealed that subjects mainly learned to associate responses with single cue conditions. Assessment of the questionnaires revealed that both groups exhibited some degree of explicit awareness. Younger adults displayed significant awareness for 7 out of the 14 cue combinations, whereas older adults demonstrated significant awareness for only 2 combinations. Declarative awareness, rather than implicit learning, may account for the observed age deficits.
Role of Gender in Health Opportunities. Noelle Diedrich, Department of International Health, School of Nursing and Health Studies, Georgetown University.
This paper examines the interplay between gender and health, particularly as concerns nutrition, among rural women in Ghana. Hypothesis: Gender dynamics compromise women’s opportunities to achieve optimal health, and thus play a directive role in food access and nutrition-related practices among rural woman in Dangme West, Ghana. Method: Individual interviews were conducted at community clinics to assess the nutritional practices, knowledge and status of 53 women in Dangme West District of Ghana. Demographic data was taken to identify access to life opportunities that are associated with achieving optimal health. Nutritional status was determined through body mass index (BMI) calculations. Respondents answered questions about nutritional beliefs and practices, including their personal experiences and own dietary intake. Findings: Early pregnancy and marriage (before age 18) was found to be a relatively common experience among interviewed women, and it was also common for girls to leave school by the equivalent to Middle School, or earlier. Although most respondents had a healthy BMI, over 30 percent were found to be overweight or obese. Most respondents reported eating three meals a day, but many dietary recalls listed two meals or less. Boys and girls (ages 1- 10) are given the same amount of food in this community, but the belief that male infants need to be breastfed longer than female infants was widely held. Conclusion: Gender plays a role in determining the health outcomes of rural women in Dangme West. During infancy, female infants are at higher risk for malnourishment than are males. Women are more vulnerable in food shortage, eating less so others have more. Finally, socialization of girls places the primary roles and responsibilities of mother and wife over other roles, truncating important life opportunities for development and attainment of optimal wellbeing.
A Systematic Methodology for Identifying Factors Associated with Program Participation Among Adolescent Mothers. Patricia A. Dougherty, Loral Patchen CNM, Robin Gaines Lanzi, Ph.D., MPH, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Adolescent mothers who have a second child within two years are more likely evidence greater social and economic challenges and to have children who are more likely to experience developmental delay and to be placed in foster care than those who have only one child before the age of 20 (1,2). There have been a number of adolescent pregnancy prevention programs designed to prevent subsequent adolescent pregnancies; however, the strategies considered to be most successful are unclear (2). One of the major impediments is difficulties with the recruitment and retention and issues with program fidelity. Often 50% are missed or not completed, and drop-out rates can be as high as 50% – 66% after 1 year (3, 4, 5, 6, 7, and 8). Reasons include: scheduling difficulties; lack of stability; domestic violence; sickness; and perception that the visit is intrusive (9). Increasing levels of parent engagement and program fidelity so that the fully intended treatment is delivered remains one of the most challenging issues. The Teen Alliance for Prepared Parenting at Washington Hospital Center has been extremely effective in reducing the prevalence of subsequent births among adolescent mothers and only has experienced about 10 % attrition. The proposed study seeks to develop a system for assessing which factors are associated with continued participation and with attrition. The methodology includes an intensive review of client records who dropped out of the program (n=19) and an equal number of randomly selected client records who continued to participate. Information includes intensity and duration of participation as well as maternal, child, and family factors that may affect participation. A systematic mechanism for documenting these factors will be presented. Findings from focus groups with clients about perceptions of why adolescent mothers chose not to participate in programs will be discussed. Identifying the most influential factors associated with attrition is essential to improve service delivery (7, 10, 11, and 12).
College Student Bereavement: Multidimensional Responses, Programs and Policies, and Future Directions. David Fajgenbaum, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
The purpose of this study is to conduct a comprehensive examination of bereavement among college students. It has a three-fold purpose: (1) to assess the science behind the body’s physiological and psychological response to bereavement; (2) to evaluate the current practices used by colleges and universities to support bereaved students; and (3) to develop a synthesis of current policies and practices and provide recommendations for future directions. This paper includes an extensive review of the literature, results from a bereavement survey of college and university administrators (N=54), and five in-depth interviews with expert informants. Administrators at four-year public, private and geographically diverse colleges and universities responded to the survey concerning the practices, programs, and policies they used to support bereaved college students. All colleges and universities surveyed offer psychological counseling services and most (71%) provide faith-based counseling. The data lead to three major findings: (1) university administrators (100% of respondents) underestimate the prevalence of bereaved students; (2) administrators reported believing that bereaved students need support from friends more than from counselors; however, only one institution has an established mechanism for peer support; and (3) administrators believe that programs that raise awareness and educate campus members about student bereavement are the most important new programs for universities to provide. New programs that they indicated as most important to implement include specialized educational workshops on grief for students, training for administrators that provides information about bereavement, and raising consciousness on campus about bereavement by disseminating information. According to these results, institutions of higher learning need to assess their practices, policies, and programs for their effectiveness in reaching and assisting bereaved students.
Factors contributing to low utilization of artesunate-amodiaquine for the treatment of malaria in rural populations of the Kassena-Nankana District of Northern Ghana. Anne Hoffa and Patricia Akweongo, Ph.D., Department of International Health, School of Nursing and Health Studies, Georgetown University, and Navrongo Health Research Centre, Ghana.
Background: Ghana has resistant malaria strains where some monotherapies (Chloroquine) may not always be effective as treatment regimens. In order to combat drug-resistant strains, Ghana introduced artemisinin-based combination therapies (ACTs) in 2005.
Objective: This study aims to establish the utilization rate of Chloroquine and Artesunate-amodiaquine combination therapy and determine if factors such as gender, drug cost, side-effects, or care-seeking behavior affect utilization rates of ACTs.
Methods: A random sample of 100 individuals completed a cross-sectional survey conducted in the Kassena-Nankana District of Northern Ghana between September and October 2005. Epidata and SPSS were used for data collection and analysis.
Results: Most individuals used ACTs at 48% followed by Chloroquine at 22% (p<.01). Prescription accounted for most of the ACTs used at 87.5% (p<.05) while known drug effectiveness was not significant in drug choice (p>.685). Gender and income did not play a significant role in ACT use. Most of those who used ACTs had district health insurance (p<.01). Individuals paid more for ACTs than Chloroquine (p<.01). Individuals who did not complete their ACT dose (34.5%) reported their reason as side-effects (p<.05).Those who visited hospitals used ACTs the most at 67.7% (p<.01). Those visiting clinics used chloroquine the most at 40% (p<.01).
Conclusion: ACTs provide an alternative to monotherapy, and many countries have endorsed ACTs for the treatment of malaria. Some factors, however, inhibit ACT utilization such as non-hospital care, no health insurance, side-effects, and higher costs. Governments have taken a positive step in adopting ACTs as first-line treatment; however, further studies and analyses are needed to formulate how to ensure higher drug coverage.
Identification of a functional nuclear export sequence in the apoptosis-modulating protein Aven. Helena M. Kuhn and Pablo M. Irusta, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Aven is a recently identified protein that interacts with Bcl-2 family members and affects cell fate by modulating apoptosis. Inside cells, Aven is predominantly found in the cytoplasm, although a small proportion of the protein localizes to the nucleus. The roles played by the nuclear versus cytoplasmic pools of Aven in the apoptosis-modulating functions displayed by the protein have not been elucidated. In search of protein regions governing the intracellular trafficking of Aven, we analyzed its amino acid sequence and identified two leucine-rich domains resembling canonical nuclear export signals (NES). These two putative NES sequences are located between residues 190-196 and residues 286-292, respectively. We generated mutant Aven proteins carrying leucine to alanine substitutions at positions predicted to disrupt the putative export signals and analyzed the effects of these mutations on the localization and apoptosis-modulating functions of Aven. Our results demonstrated that disruption of the second putative NES sequence of Aven (residues 286-292) leads to a significant accumulation of the protein in the nuclear compartment, indicating that this region functions as a bona fide nuclear export signal. Furthermore, Aven proteins with disrupted NES sequences displayed altered apoptosis-modulating functions.
The methodology of a student research team studying resistance to antiretroviral drugs within a Washington, DC group of HIV-1 treatment-naïve patients. Nicole A Lamparello, Mariah M. Marshall, Miguel A. de Leon, Emily M. Herzberg, Allison C. Boyd, and Allison Porter, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
It is standard care to use antiretroviral (ARV) drugs in treatment of patients infected with the HIV-1 virus. However, data show that the continual use of ARV drugs in patients may lead to ARV drug resistance. It has been reported that even treatment-naïve patients, patients who have not received ARV drugs, infected with HIV-1 may have resistance at time of infection. Studies have been done in many large U.S. Metropolitan areas that track resistance levels. Data in Washington DC however, remains undocumented, despite having the highest HIV prevalence in the US. The goal of this study is to identify rates of drug resistance among treatment naïve HIV-1 infected patients in the Washington, DC area. During 2005, 42 new patients infected with HIV-1 had genotypes and were included in this study. Baseline genotypes, along with demographics accounting for gender, sexual orientation, family history, and previous high-risk behaviors, of these patients were collected through chart review. It must be noted, that all the aforementioned data must be handled in a manner that is in accordance with the rules and regulations set by HIPPA, with a method that is approved by the Georgetown University Institutional Review Board. Likewise, to protect confidential information, a series of techniques such as random numbering, and file locking are utilized. Following this data collection, the data is entered into analysis software, such as SPSS to organize the information and ease analysis. The final culmination of all the information gathered comes in the form of a research article, which will hopefully be published in a research journal, and to communicate the data to a large population through various research conferences. All of this is part of the research process, and when executed well, clear and concise data can be found and reported to the scientific community.
Behavioral Assay and Histological Analysis of Retinal Layers in Hyperglycemic Zebrafish. Josh Levitz and Lynne Arneson, Department of Biology, American University.
The chronic presence of high blood sugar in vertebrates has been shown to be linked to vision loss. In diabetics this is known as diabetic retinopathy and it affects nearly half of all known individuals with diabetes for 20 years or more. Vision loss results from damage to capillaries that provide oxygen to retinal cells.
Layers of retinal cells capture light and relay information to the brain via the optic nerve. Photoreceptors, rods and cones, on the outer nuclear layer capture light and transduce a signal. This signal travels through nerves in the outer plexiform layer, inner nuclear layer, inner plexiform layer, and eventually to the ganglion cells. Ganglion cell axons then connect with the optic nerve to send an image to the brain.
Previous data have shown that zebrafish alternately placed in 2% glucose for 24 hours and 0% glucose for 24 hours develop hyperglycemia, excessive glucose in the blood plasma. Zebrafish were alternated between 2% glucose water and regular spring water for 42 days in this experiment. We performed a behavior test to determine if vision loss had occurred. This test was based on the perception of rotating black and white bands of light that control fish were known to either follow with eye motion, directed swimming, or both. Chronically hyperglycemic fish were found to have a significantly reduced ability to perceive bands of black and white.
To examine the morphological effects of chronic hyperglycemia, the histology of treated zebrafish eyes was examined. Preliminary results obtained by DAPI staining indicated that both the inner plexiform layer and inner nuclear layer of the retina were reduced in thickness in hyperglycemic fish. We are now examining the histology of the retinas by staining cross sections of fixed eyes with 1% methylene blue stain and Harris hematoxylin. Both of these stains are nuclear stains.
Renal Toxicity of Selective Inhibitors of COX-2 due to inhibition of renal prostaglandin production. A. Maher, J. Maximos, L. McGrath, J. Simpson, and Allan Angerio, Ph.D. Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Traditional non-steroid anti-inflammatory drugs [(t)NSAIDs] are well documented as a source of acute renal failure in patients with underlying renal pathology. These drugs inhibit the COX-1 and -2 enzymes, leading to a decrease in renal prostaglandins necessary for the maintenance of renal blood flow. A new class of drugs, the COX-2 selective inhibitors (coxibs), has been introduced in an attempt to reduce side effects associated with (t)NSAIDs. By inhibiting only the COX-2 enzyme, primarily associated with inflammation, and not the homeostatic COX-1 enzyme, the COX-2 inhibitors have been shown to lead to a decrease in gastrointestinal side effects common with the (t)NSAIDs. However, this decrease has not been mirrored by a decrease in renal toxicity; especially in cases of underlying renal pathology, the inhibition of prostaglandin E2 and prostaglandin I2 via inhibition of the COX-2 enzyme has been shown to have negative effects on both renal blood flow and glomerular filtration rate.
Angiogenesis’ Role in Collateral Growth as Potential Treatment for Coronary Artery Disease. Maria Martin, Sunaina Yarlagadda, Emily Lange, Sunny Hwang, Brigitte Granger, and Allan Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Coronary artery disease is a very prominent disease in America, putting many at risk for heart attacks. For those with heart disease, current treatments that clear the blocked arties that cause myocardial infarctions include thrombolysis to dissolve clots, bypass surgery to redirect blood vessels, angioplasty, to open up vessels through use of stents, and heart transplants. Although these have proved effective, a potential alternative therapeutic method would be angiogenesis, the growing of new blood vessels called collaterals, through VEGF (vascular endothelial growth factor), an angiogenic peptide. VEGF is a protein that increases the collateral growth by attaching to the ligand PLGF-1, which triggers this process. VEGF has been shown to increase in hypoxic conditions, which may be particularly damaging to those suffering from heart disease. Because it is a natural protein found in the body, there may be fewer risks if VEGF is injected into the body in order to increase blood flow, as opposed to current invasive treatments.
Factors Contributing to the Requirements for Blood Transfusions among Children with Malaria Infections. Lauren Moldawer, Department of International Health, School of Nursing and Health Studies, Georgetown University.
Malaria infections in sub-Saharan Africa are the primary cause for the requirement for blood transfusions in hospitalized pediatric patients. Because blood transfusions are expensive, and pose considerable long-term health risks to the patient, including the transmission of HIV or hepatitis B or C, understanding the variables that determine the requirement for blood transfusions can provide insights into ways to optimize their use. A prospective, noninterventional case-control study examined the biosocial factors in 69 pediatric patients admitted to the War Memorial Hospital with malarial infections in Navrongo, Ghana between October and November, 2006. Thirty-four of the subjects required transfusion while 35 did not. The only major factors that significantly discriminated subjects who required blood transfusions was the number of past hospitalizations and past blood transfusions. Socio-economic factors were not statistically different between subjects who required and did not require transfusions, although families with smaller numbers of children and higher family income were associated with a reduced risk for requiring transfusion. Although preliminary in nature, these studies suggest that efforts aimed at reducing prior hospitalization and malarial infections might be associated with a reduced requirement for transfusions. Socio-economic factors, such as family income, family size, and education level are not as strongly associated with the requirement for blood transfusions.
Antiestrogen Resistance and IRF-1. Jennifer E. Mulla, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Antiestrogens are a class of drugs commonly used in the treatment of breast cancers that express the estrogen receptor (ER). Data show that up to 75% of breast tumors expressing ER and another receptor, the progesterone receptor (PR), respond to tamoxifen initially. Unfortunately many of these cancers develop a resistance to antiestrogen treatment (Clarke, Leonessa et al. 2001).1 The Clarke Labs have used gene microarrays to detect genes that may be altered in antiestrogen resistant cell lines LCC9 and have found an inverse correlation between antiestrogen resistance and expression of the transcriptional factor interferon regulatory factor (IRF-1). Interferon regulatory factor 1 is an integral part of the antiviral response as well as apoptosis and cell cycle arrest. Decreased IRF-1 expression is associated with various cancers including leukemia and gastric carcinomas. Additionally, basal IRF-1 transcriptional activity is 18 fold lower in antiestrogen resistant breast cancer cell lines (Bouker, Skaar et al. 2004).2 This decrease in IRF-1 expression is associated with an increase in the expression of the prosurvival protein Bcl-2. Induction of IRF-1 in antiestrogen cell lines using interferons has shown to restore IRF-1 levels and consequently knock down Bcl-2 expression. It is therefore possible that IRF-1 plays a role in antiestrogen resistance and indicates induction of IRF-1 levels in antiestrogen resistant cell lines as a mechanism to restore antiestrogen sensitivity.
1 Clarke, R., F. Leonessa, et al. (2001). Cellular and molecular pharmacology of antiestrogen action and resistance. Pharmacol Rev 53(1): 25-71.
2 Bouker, K. B., T. C. Skaar, et al. (2004). Interferon regulatory factor-1 mediates the proapoptotic but not cell cycle arrest effects of the steroidal antiestrogen ICI 182,780 (faslodex, fulvestrant). Cancer Res. 64: 4030-9.
Comparing Chemical Reactions for Measuring Ground-Level Ozone. Khrysle C. Roberts, and Iliana M. Restrepo, Departments of Chemistry/Biochemistry, Trinity University, Washington DC, 20017; David N. Whiteman, NASA, Goddard Space Flight Center, Greenbelt, MD 20771; and Everette Joseph, Department of Physics, Howard University, Washington DC, 20059.
Current measurements of atmospheric ozone are carried out using sondes launched on meteorological balloons. Concentrations of ozone are determined using the iodometric method described by this chemical equation: O3 (g) + 3I- (aq) + 2H+ (aq) à I3 (aq) + O2 (g) + H2O (l).
The accuracy of the data obtained with this method is compromised by several factors such as the pH and the concentration of other species included in the preparation of the electrochemical cells used for the sounding.
An alternative method to measure ozone concentrations uses indigo. The indigo method is simpler and more specific to the detection of ozone than the iodometric method. We therefore desire to study the viability of this method both for ground level ozone monitoring as well as for ozone sounding on a balloon. Here we present the results of our ground-based testing performed in July-August, 2006 during the WAVES 2006 field campaign held at the Howard University Research Campus in Beltsville, MD.
Initially we compared measurements of ground-level ozone using the iodometric and the indigo methods side by side. Experimental ozone concentrations were determined measuring the concentrations of I3/ I2 and indigo using a portable UV-vis spectrophotometer. To compare their accuracy we used ozone measurements obtained directly with a 49C ozone analyzer (Thermo Environmental Instruments).
Good calibration curves were obtained with the indigo. Plots comparing trends from our experimental results with indigo showed good agreement with those from the ozone analyzer over the same time periods. However, we were unable to get good calibration curves to measure the concentrations of I3/I2.
In conclusion the indigo method seems to be a viable alternative in the measurement of atmospheric ozone, but further experiments should be carried out for comparison with the iodometric method. Currently we are working to obtain better calibration curves for the I3/I2 solutions as prepared for ECC sondes and compare both methods side by side.
Female protection from aldosterone-induced hypertension is not due to reduced NaCl intake in females as compared to males. V. Shalkey, M. Shi, D.M. Roesch, C. Maric, J.G. Verbalis, C.A. Ecelbarger, and K. Sandberg, Department of Biology, Georgetown College, and Department of Medicine, Georgetown University.
Approximately 10% of the cases of hypertension are due to hyperaldosteronism. Since the incidence of hypertension is higher in men than in age-matched pre-menopausal women, we are studying the effects of sex on responsiveness to aldosterone. When rats are fed without restriction, male rats become hypertensive after aldosterone infusion while females do not. Male rats tend to eat more than females, so the increased NaCl consumption may lead to hypertension in males. We tested the hypothesis that by clamping NaCl consumption, we would abolish the sex difference in aldosterone-induced hypertension.
Rats were infused with vehicle or aldosterone (200g/day) for four weeks. Four groups (n=3/group) were studied: male controls (MC), aldosterone-infused males (MA), female controls (FC), and aldosterone-infused females (FA). NaCl intake was monitored and clamped at ~70mg/day. Mean arterial pressure (MAP) was measured weekly via radiotelemetric monitoring devices.
There was a significant effect of sex on MAP in the aldosterone-infused rats (p=0.008) but not in the control rats. MA rats developed a significantly higher MAP compared with FA rats (p=0.008). After four weeks, MAP was 103.2±4.3mmHg in MC rats and MAP was significantly (p=0.016) increased to 122.4±4.3mmHg in MA rats. In contrast, MAP was 102.3±4.3mmHg in FC rats and MAP was not significantly different in FA rats (97.2±5.3mmHg).
When NaCl intake is clamped, females are protected from aldosterone-induced hypertension. This suggests that the sex difference in aldosterone-induced hypertension is not due to NaCl intake and that aldosterone lacks the same potency or efficacy in female rats. Further study is required to determine the mechanism by which female rats are protected.
In depth qualitative study of the health needs and perceptions of healthcare among Ghanaians. Martyna Skowron and Robin Gaines Lanzi, Ph.D., MPH, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Although Ghana has the potential to improve its health system, it currently lacks most of the basic necessities. In order for Ghana to prosper, a stable healthcare foundation must be established. To support this effort, this study sought to assess the health needs and perceptions of healthcare among Ghanaians.
With approval of Georgetown’s IRB, 200 Ghanaians from the Central Ghana region were surveyed about their health needs and perceptions of the Ghana healthcare system, including specific questions related to whether they have healthcare insurance, diseases that affect their family most, rates of immunizations, aspects of healthcare they would like to see addressed, as well as money spent on healthcare. Further inquiries investigated their water supply and involvement in humanitarian efforts including both Ghanaian government and international government involvement. Participants were recruited by the primary investigator at the Swedru Government Hospital over the course of 2 months. The study sample includes about half females (49.5 %) and males (50.5%), ranging between 18 and 60 years of age.
The findings indicate that: (1) the majority (69.5%) have no health insurance; (2) malaria affects about 4 out of 5 (79%) Ghanaians; (3) about a 1/3 of all participants (35.6% males; 37.4% females) have no immunizations; and (4) although many rate the healthcare system as poor to very poor, significantly more are female (63.6%) than male (48.5%). It is noteworthy that of those who do participate in the health insurance program, none feel that the program meets their needs. Interestingly, participants overwhelmingly indicated that the international response was very successful when provided.
Given these findings, it is clear that humanitarian efforts must focus on providing systemic support and address the healthcare needs, particularly for the delivery and receipt of effective healthcare but this must be done along with additional support from the Ghanaian government.
The Preventative Effect of Ibuprofen on Interluekin-1 Induced Neuroinflammation in Alzheimer’s Disease. Silpa Thiavalappil, Nereida Jaime, Stephanie Szary, and Allan Angerio, Ph.D., Departments of International Health, Human Science, and Nursing, School of Nursing and Health Studies, Georgetown University.
The interleukin-1 (IL-1) super family is made up of ten members, which are named upon their respective activities and responses. They all stimulate the production of different cytokines, nitric oxide, and prostanoids. The production of IL-1 can be a direct determinant or an intermediate step in disease processes, either promoting or inhibiting inflammation. Alzheimer’s disease contains a cascade of events that can be viewed as an example of such an inflammatory process, and this neuroinflammation, along with plaque formation and progression can be linked to the overexpression of interleukin-1 in the microglia of the brain. Data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may decrease the incidence of Alzheimer s disease, further supporting a role for inflammation and IL-1. While the exact mechanisms for the inhibition of IL-1 inflammation by NSAIDs are unknown, the levels of beta-site APP-cleaving enzyme-1 (BACE1), -1-antichymotrypsin (ACT), and Apolipoprotein E (apoE) were tested with high doses of ibuprofen to determine the effects on the production of beta-amyloid plaque formation and results showed increased levels of ACT and IL-1, implicating a pathway to inflammatory response. Further research is needed to determine the length and frequency of ibuprofen dosage that is most effective in long term Alzheimer s disease prevention.
C-Reactive Protein, Stroke and Statins. Bradley M. White, Matthew F. Bialko, Allan D. Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
CRP is an important indicator and player in inflammatory diseases such as stroke. CRP may be involved in the earliest stages of stroke. Monitoring the levels of CRP may help in the prevention and treatment of stroke. Statin drugs may be useful in lowering CRP and the incidence of stroke.