Abstracts

Akt1 and ERB2 Activity Is Associated with Tumor Growth Inhibition.  Camille Alfonso, Department of Human Science, Adriana Stoica, Ph.D., Department of Human Science, School of Nursing and Health Studies and Department of Oncology, Georgetown University.  
MCF-7 has been used for many years as a model cell line in order to investigate hormonally-responsive breast cancer.  Estrogen-dependent breast tumors have shown the tendency to regress following the withdrawal of estrogen. (1)  We inoculated MCF-7 cells into ovariectomized female athymic nude mice, allowing the formation of tumors after estradiol supplementation. The mice tissue samples were then analyzed for tumor growth and Akt, ER-α, PR expression/ activity through western blots and immunohistochemistry and the following conclusions were discovered. Inoculation of parental MCF-7 cells into ovariectomized female athymic nude mice led to tumor appearance 4 weeks after estradiol supplementation and the selective ErbB2 inhibitor, AG825 blocked this effect.  Tumor volumes were ~80% smaller upon inoculation of MCF- 7/DN-Akt1 cells: K179M-Akt1 or R25C-Akt1.  AG825 inhibited the growth of established tumors by ~60% for MCF-7 or MCF-7/myr-Akt1 cells.  In tumors from MCF-7/myr-Akt1 xenografts, decreased ER- α expression and increased PR was observed, effects that were blocked by the ErbB2 inhibitor.  In contrast, in tumors from MCF-7/ K179M-Akt1 or MCF-7/ R25C-Akt1 xenografts, ER- α expression and activity were inhibited.  Tumor extracts from animals inoculated with MCF-7 cells with an estradiol pellet or myr-Akt1 cells without estradiol, showed high p-Akt, that was blocked by AG825, suggesting that loss of Akt1 activity was associated with tumor growth inhibition).  These results suggest that loss of Akt1 activity and inhibition of ErbB2 was associated with tumor growth inhibition.

 The Role of C-Reactive Proteins in Inflammatory Bowel Disease. Daliha Aqbal, Assya Abdallah, Estefani Belloso., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
C-reactive protein (CRP), a prominent acute-phase protein present in inflammatory responses, performs a major role in inflammatory bowel disease (IBD). Characterized by chronic gastrointestinal irritation, IBD results in the stimulation of three specific cytokines: interleukin-1β, interleukin-6, and tumor-necrosis factor-α. These cytokines trigger the elevated production of CRP in the hepatocytes, increasing its plasma concentration from 0.8mg/L to approximately 45mg/L, almost a 500 fold increase. As a result of its palpable prevalence and proliferation in IBD, this review explores the role of CRP as a marker, pro-inflammator, and anti-inflammator. As a clinical aid, CRP levels serve as a marker for detecting IBD, differentiating it from functional bowel disorders, categorizing the disease severity and risk, and monitoring the effective treatments based on disease activity. CRP, as a pro-inflammator, operates by associating itself with the main cytokinal release of interleukin-6 and engaging in pseudo-antibody reactions with extrinsic or autologous ligands, which initiate the complement system. Finally, as an inhibitor of inflammation, CRP prevents neutrophil-endothelial adhesion through the shedding of L-selectin molecule expression in neutrophil cells possibly by binding to CD-32. While CRP functions as a pro and anti inflammator in inflammatory responses, its net effect in IBD patients requires further investigation.

 C-reactive protein (CRP) as a Biochemical Marker in Hodgkin's Lymphoma. Erin Bailey, Allison Boyd, Katherine Albutt, and Allan Angerio, Ph.D., Department of Human Science (A.B. and A.A.), Department of International Health (E.B. and K.A.), School of Nursing and Health Studies, Georgetown University.
Hodgkin’s lymphoma (HL) is a malignant cancer of lymphatic tissue in which neoplastic B-lymphocytes demonstrate a profound aberration in their cell cycle. The disturbance of lymphatic tissue initiates an inappropriate inflammatory response, resulting in an increased incidence of infection and systemic toxicity. This article reviews current literature surrounding the biology of HL and C-reactive protein (CRP), a non-specific marker of inflammation. Elevated CRP levels have been reported in patients with HL. Our review concludes that CRP is a better prognostic indicator for HL than an indicator of HL incidence. Prognostically, CRP plays a role as a staging tool, is correlated to disease progression, and is indicative of treatment success. A more thorough understanding of the cellular origins of HL and the role of CRP in the inflammatory process is necessary. Future studies to identify this relationship may contribute to innovative treatment strategies in the future.

 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 is a relatively small molecule involved in vital processes such as vasodilation, anti-coagulation, broncodialation, and neurotransmission as well as carcinogen degradation. NO activates guanylate cyclase, a heme iron containing metalloenzyme that regulates the protein phosphorylization responsible for arterial relaxation and functions with glutamate in neurotransmission. Certain NO-containing alkylating agents are capable of altering the structure of the amino acids composing DNA as well. By inducing the release of nitric oxide from these molecules, possibly through metalloenzyme facilitated cleavage, the mutagenic properties inherent in the alkylating N-nitrosamines can be circumvented.
I synthesized dimethylnitrosamine by reacting a dimethylamine-HCl salt with tert-butyl nitrite and by taking advantage of the amphoteric quality of the dimethylamine salt to react it with a base (potassium carbonate). In order to create an organic ligand and copper model complex to approximate the dual cis-histadine structure of a copper based metalloenzyme, I made a ligand copper complex in which the metal is partially exposed by allowing the ligand to react with copper t-butoxide. I mixed equal molar equivalents of the copper-ligand model complex and dimethylnitrosamine, stirred, and filtered the product. NMR spectroscopy revealed a pronounced up field chemical shift in the methyl region, possibly signifying an NO-copper bond with implications in the degradation of alkylating nitrosamine carcinogens.
            For future work, I intend to substitute various substituents on my N-nitrosamine and increase the number of nitrogens bonding in my ligand complex from two to three using trispyrazolylborate, perhaps inducing a new bonding mode in the Cu complex. I plan to test the reactivity of these molecules with NO gas, hoping to find a stable storage molecule for nitric oxide that can be stimulated to release NO in specific environments.

 C-Reactive Protein in Sickle Cell Crisis.  Mike Blainefield, Mary Kate DeLong, Laura DiLeo, Roland Dimaya, and Allan Angerio, Ph. D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Sickle cell disease is a hereditary blood disorder that results in sickle-shaped red blood cells. This abnormal shape prevents adequate oxygen transportation, a condition that leads to hypoxia and ultimately, crisis.  Inflammation is a primary symptom of sickle cell crisis.  As a response to inflammation, the liver releases a number of acute phase proteins, including C-reactive protein (CRP).  As a marker of inflammatory response, CRP levels tend to rise during sickle cell crisis.
We reviewed studies showing CRP levels in non-SCD patients, SCD patients in crisis, and SCD patients not in crisis were compared.  Results show very low levels of CRP in non-SCD patients, elevated levels of CRP in SCD patients not in crisis, and highly elevated levels of CRP in SCD patients in crisis.  We suggest CRP levels should be measured in carriers of the sickle cell trait, who experience no symptoms of SCD. Levels of CRP may be useful in the prediction of sickle cell crisis onset.

Key words: acute phase proteins, C-reactive proteins, cytokines, high sensitive C-reactive protein, inflammation, inflammatory response, sickle cell crisis, sickle cell disease

 Antiretroviral drug resistance among treatment-naïve HIV-1 infected individuals.  Allison Boyd, Brittany Braga, Emily Herzberg.  Departments of Human Science & Nursing, Georgetown University, Washington, D.C.
Drug resistance in anti-retroviral (ARV)-naïve individuals infected with HIV-1 is a growing concern among both scientists and clinicians.  An increasing number of reports appear in the literature documenting primary infection by HIV-1, containing mutations associated with drug resistance and/or a reduction in viral susceptibility in individuals unexposed to ARV therapy (HIV-1 naïve individuals).  Mutations conferring resistance to current ARV therapies occur mainly in the protease (PR) and reverse transcriptase (RT) genes of the viral genome. 
Fourteen articles listed in PubMed provide data on mutations in HIV-1 infected individuals within the U.S. prior to receiving ARV therapy.  Resistance to NNRTIs was shown in 2.3-30.8% of the study participants.  NRTI resistance was between 1.7-15% (as averaged from the reports of 8 studies).  Resistance to PR inhibitors was between 1.9-80.2% (as determined from data of 9 studies).  Mutations in the RT gene occur in 2.3-3.8% of HIV-naïve individuals receiving one drug class of RT-ARV and in 1.7-15% of individuals receiving another class of RT-ARV.  Mutations to PR inhibitors are between 1.9-80.2%. 
Many of the studies do not provide clarification of experimental terms, making interpretation of data difficult.  Studies often do not distinguish whether the data are percentages referring to the number of individuals with HIV-1 mutations within that specific gene, or if percentages refer to the number of individuals with mutations that cause actual drug resistance.  Furthermore, many studies lack standardized variables; the definitions of experimental terms (such as resistance and mutation) are applied inconsistently, making it difficult to compare results.  To reduce this lack of clarity, future studies should place an emphasis on establishing a standard set of criteria to be used in HIV-1/drug resistance research.  
In addition, although information concerning drug resistant HIV-1 has been collected from cohorts in the major metropolitan areas with considerable HIV-positive populations, there is currently no data available to indicate the rate of drug resistant HIV-1 in ARV-naïve patients receiving treatment in the Washington D.C. area.  For this reason, we have designed a study to determine the rate of HIV-1 drug resistance using baseline genotypes from 85-100 treatment-naïve individuals in a Washington, D.C cohort. This study will provide a foundation for the future research and analyses of drug resistant HIV-1 in individuals receiving ARV therapy in the Washington D.C., and greater metropolitan areas.   

  Characterization of the Drosophila melanogaster Ortholog of the Mammalian Anti-apoptotic Protein Aven.  Joy W. Chang*, Haruyoshi Yamaza#, Pablo Irusta*, Sige Zou#
*Department of Human Science, Georgetown University, Washington, District of Columbia 20057; # Functional Genomics Unit, Laboratory of Experimental Gerontology,
National Institute on Aging, National Institute on Aging, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, Maryland 21226
Throughout the process of aging, a fine balance between cellular survival and death must be maintained. In multicellular organisms, the processes of ageing and programmed cell death (PCD) or apoptosis appear to be linked, since several components of molecular pathways that modulate ageing are also members of apoptotic signaling networks. In adult animals, PCD is essential to proofread and eliminate cells with abnormal genetic content, destroy cells infected by microorganisms, and prevent uncontrollable proliferation. Apoptosis typically begins with the formation of a multiprotein complex called the apoptosome which triggers the activation of caspases, a family of proteases that mediate the cleavage of vital cellular components normally needed for cellular life. As a result of caspase activity, apoptotic cells endure severe morphological changes that lead to the disassembly of their structure and phagocytosis by neighboring cells.
            Aven is a recently described anti-apoptotic protein that associates with components of the apoptosome and inhibits caspase activation by interfering with the ability of Apaf-1, a caspase regulator, to self-associate. This current and available research has been preformed to explore the role of mammalian Aven. Here, we identify a putative ortholog Aven gene in Drosophila melanogaster and wish to determine whether the Drosophila Aven protein affects apoptosis and ageing in flies. Preliminary research has pointed towards the role of Aven in cells with reduced Aven expression. Sensitivity experiments preformed on Drosophila Schneider (S2) cells with Aven-specific dsRNA knock-down suggest that reduction of Aven gene expression may reduce cell viability under oxidative stress. Future direction of this research includes replicating Aven knock-down results as well as exploring the effects of Aven overexpression in S2 cells treated with oxidative stress, irradiation, and apoptosis-inducing drugs. In addition, the creation and expression of various Aven gene constructs will allow determination of protein regions vital to a possible anti-apoptotic function.

 Aspirin’s effect on C-reactive protein in inflammation and stroke.  Bridget Dowd, Robert Hagbom, Carter Hibbs, Kathryn King.  Allan Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University. 
The purpose of this article is to investigate aspirin as a preventative agent in stroke through its effect on CRP and inflammation.  Inflammation increases the risk of developing atherosclerotic plaque, creating a greater incidence of clotting.  If this clotting occurs in the cerebral vasculature the occluded vessel could result in a stroke.  Thus, detecting and preventing early inflammation will decrease the risk of stroke. CRP is not only an early indicator of an inflammatory disease process, but it could be a main player in the inception of stroke.
            Aspirin has a greater effect reducing the risk of stroke in patients with elevated levels of CRP.  The discrepancy between CRP levels in patients corresponds to the beneficial anti-inflammatory effects of aspirin that they receive.  Aspirin is effective in reducing the levels of CRP in the blood through its anti-inflammatory properties. Therefore, CRP could be the missing link in our understanding of stroke awareness and prevention.

 An Illusory Illusion? The Role of Spatial Attention in the McGurk Effect. Himabindu Ekanadham, Guinevere Eden, Ph.D., and Elizabeth Hoffman, Ph.D., Department of Biology, Georgetown College (H.E.), Center for the Study of Learning, GUMC (G.E. and E.H.), and Department of Pediatrics (G.E. and E.H.), Georgetown University.
A powerful demonstration of the bimodal nature of speech perception occurs in the McGurk Effect (MGE), an audiovisual illusion.  In classic MGE studies, a viewer perceives a novel phoneme when auditory and visual inputs are discrepant (e.g., s/he perceives |da| when an auditory |ba| is dubbed onto a visual |ga|).  For this reason, MGE is often described as hearing lips and seeing voices. MGE is robust and can be elicited under suboptimal conditions where variables such as the temporal delay between auditory and visual stimuli, and clarity of visual presentation are manipulated.
In this research we sought to determine whether manipulation of another variable, eye gaze direction, influences MGE.  Studies have shown that perception of another’s gaze directs one’s own attention to the same space. With this result in mind, we reasoned that looking at a face whose gaze is horizontally averted could reduce a viewer’s attention toward the center of the face and therefore interfere with lip-reading. Reduced attention to the lips could decrease the visual component of phonological perception and hence attenuate or abolish MGE.
            We measured MGE in twenty native English-speaking healthy adults (aged 19-22, 10 females) using MGE stimuli that we had validated in a pilot study. Eye gaze was varied across 270 stimuli and either shifted horizontally from the center (or vice versa), or preserved centrally. Participants responded as to what they heard. Reaction time and accuracy were recorded per each stimulus.
             Consistent with previous studies, we found a significant MGE effect.  Participants were less accurate and slower in the MGE condition compared to the concordant and discordant control conditions (Phoneme pair impact on accuracy: [F(4,2) = 311.04, P<0.0001] ; Phoneme: [F(4,2) = 29.10, p<0.0001]) .  Contrary to our predictions, eye gaze did not influence MGE (Gaze impact on accuracy: [F(4,2) = .01, n.s.] ; Gaze impact on reaction time: [F(4,2) = .05, n.s.]).  This result was surprising given that eye gaze shifts reliably redirected attention in line with the perceived gaze in a separate spatial cueing task completed by all of our participants.  It appears that MGE is robust and perhaps impervious to changes in allocation of spatial attention.

 C - reactive protein Monitors Renal Disease.   Laura Emmanuel, Princess Jones, Jaime Gloria, Allan Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
C-reactive protein (CRP) is an acute phase protein that increases in response to inflammation, infection, ischemia, and trauma.  Tumor Necrosis factors and Interleukin 6 regulate the synthesis of C-reactive protein with most of the synthesis occurring in the liver.  The kidney tubules reabsorb most of the C-reactive protein.  Recognizing foreign pathogens and activating complement are some of the major functions of the protein. Our review of the literature indicates CRP is an excellent marker of renal disease.  CRP is an active participant in the deterioration of kidney functions.  With C-reactive protein clinicians are able to detect the progression of renal failure.  Using drugs that reduce CRP plasma levels may prolong the life of renal patients.

  Students of AMF: A collaborative, student-led, university-based health promotion initiative.  David Fajgenbaum, Department of Human Science, School of Nursing and Health Studies, Georgetown University.
The Students of AMF (Ailing Mothers & Fathers) Support Network is a university-sponsored organization utilizing peer-support, service, mentoring, and community outreach to help college students to cope with the psychological, social, spiritual, and academic difficulties associated with having a sick or deceased loved one. The goal of this presentation at the 2005 American Association of Colleges & University’s  Civic Engagement Imperative: Student Learning and Public Good  in Providence, RI was to share about how Students of AMF was conceived, developed, reproduced, and sustained as well as how to apply this model to other initiatives.
         This initiative began after the founder experienced the loss of his mother, Anne Marie, in October 2004 and discovered the prevalence and universal pain of college student bereavement.  22-30% of all college students are within the first 12 months of coping with the death of a close friend or family member and 33-48% of all college students are within the first 24 months of mourning the death of a close friend or family member. These students often complain of feeling alone, helpless, and disconnected from their loved ones.  These issues often result in psychological pathology, social stress, spiritual decline, and decreased academic performance (the loss of a close friend or family member within the last year is the 8th greatest factor affecting academic performance).
            Students of AMF addresses these issues by providing a collaborative, university-based community approach to student bereavement through four inter-related components: Support group, Service group, Angels, and SAINTS. This presentation will use clinical research, experiential findings, and longitudinal studies to display how Students of AMF uses these components to provide support to the whole person and how this initiative can be reproduced in the same methodological, step-wise fashion.


 Post Traumatic Stress Disorder (PTSD) and Anxiety effects of the Tsunami and Terrorist Attacks in Sri Lanka. Anoma Hapangama, Allison Abbe, Ph.D., Department of Psychology, Columbian School of Arts and Sciences, George Washington University
The purpose of this study is to better understand the effects of stressful events on Sri Lanka’s population. With the numerous terrorist attacks this country has faced by the LTTE (Liberation Tigers of Tamil Eelam) for the past decade and the recent Tsunami that hit the Southeast Asian shores, it is possible that the population has experienced symptoms of Post Traumatic Stress Disorder (PTSD) or Anxiety. Unfortunately, Sri Lanka has few practicing psychologists; therefore, little intervention has occurred, and little is known about the attitudes and behaviors of mental health amongst Sri Lankans. Because psychologists and psychiatrists came predominantly from the West in aid of the tsunami survivors, therapies and interventions that were conducted may not have been fully effective due to the cultural differences of Sri Lankans and Southeast Asians in general. Questions remain as to whether these victims truly need psychological help, and if so, how intervention can be better implemented by taking cultural values into consideration.
The study shows that many Sri Lankans who have survived terrorist attacks and the tsunami are experiencing PTSD, according to American scales. However, there are many differences in comparison to Westerners in the way these victims express their emotions. This study shows varying degrees of stress through cultural views and religious philosophies of the survivors. Perhaps by better understanding the culture, we can give better and improved intervention in the future, when dealing with survivors in the East of natural disasters, terrorist attacks, and other traumatic events. Now in the midst of an overwhelming occurrence of natural disasters in both the Eastern and Western regions, better PTSD intervention is needed more than ever, and perhaps these cross cultural considerations will give clinical psychologists more insight into enhancing therapy in other countries.

 C-Reactive Protein and Its Effect on Inflammatory Bowel Diseases.  Amanda Irene, Catherine Flaherty, Gabriel Gaviola, Alexander Formosa. School of Nursing and Health Studies, Georgetown University.
Our literature review of C-reactive protein and inflammatory bowel disease shows a role for C-reactive protein both in the diagnosis and treatment of Crohn’s and ulcerative colitis, inflammatory bowel diseases.
C-reactive protein (CRP) is classified as a plasma protein. CRP is the classical acute phase protein  that is often used clinically to diagnose disease processes. CRP is used as a biological marker for inflammatory bowel diseases. Multiple studies have produced concurring results finding that patients with Crohn’s disease have high levels of CRP than patients with ulcerative colitis. CRP levels have also been proven to correlate well with disease activity and with markers of inflammation in Crohn’s disease. Clinically, change in CRP concentration is more important than actual CRP levels for a given patient. In most patients, it has been found that CRP levels fall only when disease activity spontaneously decreases or with therapy. The levels of CRP rise when patients relapse. While both erythrocyte sedimentation rate (ESR) and CRP protein levels correlate well with disease activity, ESR responds with less consistency than CRP changes.
Although many tests have proven CRP to be a valuable marker for inflammatory bowel diseases, C-reactive protein is not to be relied on as an absolute indicator of treatment efficaciousness or relapse. Some patients show consistently high levels of the protein despite mild disease activity and a low CDAI, most likely due to genetic differences in the ability to produce C-reactive protein.  The reverse case is true as some patients have a high CDAI, yet maintain low levels of C-reactive protein.
In conclusion, while CRP can be useful in tracking disease activity, and helping with differential diagnoses for inflammatory bowel diseases, there is still not enough evidence that CRP can solely be relied on as the dominant criteria in observation of IBD.

 C-Reactive Protein Link to Adipose Tissue and its Effect on Stroke.   Natasha LaBeaud, Melissa Mohammad, Carolyn Plunkett, Endera Preval, Joanna Rodgers and Allan Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies.  Georgetown University.
Individuals who are genetically predisposed to obesity have an elevated C-reactive Protein (CRP) concentration, which is a major indicator of the probability of suffering an ischemic stroke. Adipose tissue releases certain cytokines, including Interleukin-6, that subsequently stimulate the augmentation of CRP levels. CRP plays a direct role in inflammation by increasing blood levels of cellular adhesion molecules and endothelin-1 and a decreasing nitric oxide concentration. Inflammation contributes to the development and evolution of atherosclerosis.  Atherosclerosis is a chronic inflammatory vascular condition that ultimately facilitates thrombotic complications induced by ischemia. A clot forms as a result of increase in the tissue factor, a direct result of CRP-provoked inflammation. The clot creates an hypoxic condition in tissues, namely of the brain, leading to infarction and an ischemic stroke. The severity and likelihood of atherosclerosis is determined genetically by a predisposition to obesity and increased adipose tissue, which correlates into a predisposition toward elevated CRP levels. Thus, CRP also plays an important role in the incidence of stroke. This research paper will explore in depth the link between adipose tissue, increased levels of CRP, the development of atherosclerosis, facilitation of thrombosis formation, and, ultimately, suffering an ischemic stroke.

 Combating trachoma in Chiapas, Mexico: An analysis of health workers' trachoma knowledge, attitudes, and practices.  Katelyn M. Perna, Department of International Health, School of Nursing and Health Studies, Georgetown University.
Trachoma, the world’s leading cause of preventable blindness, has long afflicted the indigenous population in the Highlands Region of Chiapas, Mexico. In order to combat and control this disease, the Chiapas State Program on the Prevention and Control of Trachoma relies on the activities of three brigadas to bring antibiotic treatment and health information to the endemic zone.  However, little is known about the brigada health workers knowledge, attitudes, and practices about trachoma. Twenty-two of twenty-three health workers from the three brigadas participated in a two-part cross-sectional study consisting of observations of community education workshops and eye revisions, as well as a self-administered knowledge, attitudes, and practices (KAP) survey. Responses to the survey indicated gaps in knowledge of prevention strategies, risk factors for trachoma, and treatment information. These knowledge gaps coincided with some poor quality practices observed during field activities, such as failure to wash hands before and after eye revisions and not explaining prevention strategies. Health workers specified the need for more medications and more support for their activities. This study recommends that the Trachoma Program procure treatment immediately and consider using tetracycline ointment rather than azithromycin. Health workers are also advised to be retrained in identifying risk factors and explaining prevention strategies; two concepts that must be better integrated into household visits and community workshops.

 The Role of the ErbB2/Pi 3-K/Akt1 Pathway in Antiestrogen Resistance as seen in Human Tumor Samples. Molly Proskine, Adriana Stoica, Ph.D., Department of Human Science, School of Nursing and Health Studies (M.P. and A.S.) and Department of Oncology (A.S.), Georgetown University.
One in seven women is diagnosed with breast cancer.  Estrogens are the most important etiological factor in predicting the diagnosis and prognosis of breast cancer.  Sixty to 80% of breast cancer patients have estrogen receptors in their tumors and its presence is a selection criterion for treatment.  Antiestrogen therapies can be used on those tumors with estrogen receptors.  However, only one-third of those patients benefit from this therapy and 5-10% of patients without the receptor respond.  This study is investigating the antiestrogen resistance mechanism in an effort to better target individual patients with the right medication.  There are numerous mechanisms that cause resistance to antiestrogen therapies.  This study particularly investigates the development of predominately ligand-independent-ER-mediated transcription.  This is the cross talk between ER and growth factor signaling.  Immunohistochemical and western blot analysis of human tumor cell samples demonstrated that Akt expression and activity is high.  Akt and pAkt staining occurred in ductal areas.  Akt expression and activity were higher in the cytoplasm (97%) than in the nucleus (64.5% and 35.5%).  In normal tissue, hyperplastic ducts and scattered end units were positive for p-Akt and Akt expression and Akt expression and activity was in general lower than in the tumor.  pAkt correlates with AKT1 expression, Tyr 1248 phosphorylation of ErbB2, an increase in ErbB2 and ErbB3 expression, and GSK3 phosphorylation.  From the data collected, it is hypothesized that during the development of antiestrogen resistance crosstalk between ER-α; and ErbB receptors signaling converges into the PI 3-K/Akt-1 pathway.  Estradiol binds to membrane ER-alpha and activates the ErbB2*ErbB3 heterodimer.  ErbB3 binds to PI 3-k, activating Akt1.  As a result, Akt1 phosphorylates ER-α, consequently altering its transcriptional activity and cell proliferation.  Therefore, a subset of 18 genes regulated by both Akt1 and estrogen may contribute to estrogen resistance.

 C-Reactive Protein and Heart Disease. Sydney Schacht, Martyna Skowron, Alex Weinstein, Jenna Winokur, Stephanie Zare, and Allan Angerio, Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
This review focuses on the role of C-Reactive Protein as a marker for early heart disease detection. Gender impacts CRP’s role in inflammation detection, with women displaying higher correlations between CRP levels and heart disease, holding age and body mass index as determinants. People genetically predisposed to heart disease displayed higher baseline CRP levels. The Framingham study compared men and women and the relationship between age, gender, and BMI in CRP’s role in detection of cardiovascular disease. CRP is a valuable marker of inflammation, but is most accurate when used in conjunction with other indicators. More research should be done to determine the most effective combinations with CRP. Diabetes, hypertension, high LDL levels, obesity, genetic predisposition, and smoking all impact CRP levels.

Key words: heart disease * C-reactive protein * inflammation* cholesterol* obesity* smoking * atherosclerosis* interleukin-6

 Role of CRP in Inflammatory Bowel Disease: Effective Marker for Diagnosis and Treatment? Kareen Shebaclo, Carolyn Yates, Agnes Usoro, Shana Talbot, and Allan Angerio Ph.D., Department of Human Science, School of Nursing and Health Studies, Georgetown University.
Inflammatory diseases, particularly Inflammatory Bowel Disease, trigger high morbidity and mortality rates in Americans every year. Therefore deciphering mechanisms to which clinicians can detect and diagnose these diseases could alleviate and possible even thwart the syndrome with early detection. C - reactive protein, an acute phase protein, has become a well-developed tool used to expose and identify IBD in patients. The objective of this paper seeks to discover first the link between elevated C-reactive protein values in relation to IBD, second the production of CRP, and finally the stimulation of auto-immunity. Methods included analyzing preceding research literal spanning a decade of findings. However, when investigating CRP, a myriad of additional benefits were observed. This discovery suggests that in addition to CRP values merely detecting IBD, clinicians can also predict the outcome of the disease, foretell any future relapses, and even determine the course of treatment. However, findings also pinpointed the flaws of CRP in that discrepancies arise in its use between Crohn’s Disease and Ulcerative Collitis, respectively 100% and 70% success rates.

 The Chemotactic Role of C-Reactive Protein in Stroke.  Whitney Sher, Michelle Vu, Danielle Toth, Brad White, Elizabeth Zagar, and Allan Angerio, Ph.D., School of Nursing and Health Studies, Georgetown University.
           C-Reactive Protein (CRP) is an immunoregulator. It is an inflammatory marker in strokes and therefore is a strong predictor of the risk for vascular events, namely ischemic stroke. Not only is CRP an indicator for strokes but actively participates in the pathophysiology of stroke. CRP attracts macrophages to injured arterial walls and exacerbates the process of cerebral atherosclerosis. Cerebral atherosclerosis promotes strokes. Our literature review shows that such illnesses as obesity, diabetes, and hypertension correlates with high levels of CRP and strokes. Drugs that lower CRP levels may have a beneficial effect on cerebral vascular disease.

Key Words: ischemia, stroke, C-reactive protein, macrophage, clotting, inflammation

 An analysis of the factors that influence the Health Seeking Behavior of people with eye ailments in the Highlands Region of Chiapas, Mexico. Camille Simmons, Department of International Health, School of Nursing and Health Studies, Georgetown University.
There are various factors that influence people‘s health seeking behavior.  An understanding of the reasons that determine why people choose to utilize health services when they are ill is critical to the success of a control initiative.  This study, through focus groups and an administered questionnaire, investigated the health seeking behavior of a sample population suffering from eye ailments in the Highlands Region of Chiapas, Mexico, in an effort to aid the Trachoma Program to eliminate the infectious disease.  It was found that factors such as the presence of the Trachoma Program in a town, general knowledge about health and diseases, distance to a health center, available resources, perceived gravity of an illness, and satisfaction with treatment all influenced the subjects’ decisions to seek care.  The health system, and in particular the Trachoma Program, need to recognize and minimize the factors that discourage people from seeking care and maximize the motives that encourage the population to utilize health services.

 CRP as an indicator of Vascular Damage in Sickle-Cell Disease. Michael Simoneaux, Raluca Tavaluc, Jeanne Tchuenbou, Elizabeth Zielinski, and Allan Angerio, Ph.D, Department of Human Science (M.S., R.T. and E.Z) and Department of Nursing (J.T.), School of Nursing and Health Studies, Georgetown University
In this paper, we review the role of C-reactive protein in the sickle-cell crisis.  Sickle-cell anemia is a genetic disease that affects the oxygen-carrying hemoglobin molecule, resulting in abnormally-shaped erythrocytes.  When sickle-cell patients are exposed to hypoxic environments, the sickled erythrocytes tend to become occluded in capillaries throughout the body, resulting in a painful episode which is known as the sickle-cell crisis.  This vaso-occlusion causes ischemia in the tissues as well as damage to the endothelial lining of the blood vessel walls.  The endothelial damage initiates an inflammatory response, of which CRP is an integral part.  Through various chemical pathways, CRP both results from and contributes to this inflammation.  The concentration of CRP in the blood is a reliable indicator of the extent of the endothelial damage resulting from vaso-occlusion.  These conclusions suggest that the blood CRP level in patients with sickle-cell crisis is potentially a valuable tool for diagnosing the extent of the damage caused by the sickle-cell crisis, and for estimating the duration of the patient s recovery.

 Estradiol Increases Expression and/or Activity of ErbB Receptors, Akt, and GSK3 in MCF-7 Cells and Its Antiestrogen Resistant Variants. Heather Summe and Adriana Stoica, Ph.D., Department of Human Science (H.S and A.S.), School of Nursing and Health Studies and Department of Oncology (A.S.), Georgetown University.
The purpose of this research is to further define the mechanisms of cross-talk between ER-α; and epidermal growth factor family members (ErbBs) mediated by the PI 3-K/Akt pathway in breast cancer which cause 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- α; in their breast tissue and 2/3 of these patients have responded positively to hormone therapy. Furthermore, 5-10% of patients who are ER-α negative have benefited from the treatment. To define the role of ErbB2 and Akt1 in the development of hormone resistance, the in vitro model system MCF-7/LCC was used, in which sequential in vivo selection of MCF-7 cells (LCC1) with tamoxifen (LCC2) or ICI 182,780 (LCC9) led to endocrine resistance. For the in vitro samples, estradiol (similar to growth factors) was found to rapidly activate the PI 3-K/Akt1 pathway in the hormone dependent breast cancer cell line MCF-7. This non-genomic effect is mediated by membrane ER- α and ErBb2.  ErBb2 and Akt1 can also modify ER-α activity and expression. Expression and activity of ErbB2 (Tyr 1248), expression of ErbB3, and Akt activity were greater in LCC cells than MCF-7 cells. Estradiol increases ErbB2 expression and activity and ErbB3 expression in MCF-7 and LCC cells and basal EGFR expression increases in LCC cells. Tamoxifen and ICI 182,780 can not block the effect of estradiol on ErbBs expression and/or activity. Furthermore, estradiol rapidly activates Akt in MCF-7 and LCC cells. However, another peak of high Akt phosphorylation was observed at long-term treatment, paralleled by phosphorylation of GSK3. Growth of LCC cells treated with estradiol or antiestrogens was blocked by AG825 and the PI 3-K inhibitor, LY 294,002, suggesting that activation of the ErbB2/PI 3-K/Akt1 pathway can override the growth inhibitory antiestrogen effects.

 Perceptions and knowledge of trachoma and facial hygiene of two families in two indigenous communities in Chiapas, Mexico: An exploratory study. Meredith M. Welsch, Department of International Health, Georgetown University.
Trachoma is a little known but serious disease that is the leading cause of preventable blindness in the world (World Health Organization, 2005).  The objective of this study was to explore the basic hygiene practices, trachoma knowledge, and environmental and relationship dynamics of the families, as well as to encourage further research into this topic.  Facial hygiene has the potential to be among the most cost effective methods for reducing the risk of trachoma and preventing the progression of the population towards irreversible blindness.  Additionally, if channeled sensibly, knowledge of family relationships can facilitate prevention strategies in a community program.  Using structured interviews and through observation, information was gathered concerning water use, perceptions of facial hygiene, and knowledge and opinions of trachoma of two indigenous families.  In both communities, actual observed behaviors conflicted with interview findings.  The study’s findings have implications for the success of future preventive efforts of the Trachoma Program in Chiapas and those in similar regions.  Comprehensive observational studies should be conducted to expand knowledge of the most basic cultural beliefs and routines of this population.