Medical Specialties Commons^™

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Biochemistry and Microbiology

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood.

RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Suppression Of Implanted Mda-Mb 231 Human Breast Cancer Growth In Nude Mice By Dietary Walnut, W. Elaine Hardman, Gabriela Ion

Biochemistry and Microbiology

Walnuts contain components that may slow cancer growth including omega 3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin. A pilot study was performed to determine whether consumption of walnuts could affect growth of MDA-MB 231 human breast cancers implanted into nude mice. Tumor cells were injected into nude mice that were consuming an AIN-76A diet slightly modified to contain 10% corn oil. After the tumors reached 3 to 5 mm diameter, the diet of one group of mice was changed to include ground walnuts, equivalent to 56 g (2 oz) per day in humans. The tumor growth rate from Day …

Decreased Expression Of Peroxiredoxins In Fuchs’ Endothelial Dystrophy, Ula V. Jurkunas, Ian Rawe, Maya Bitar, Cheng Zhu, Deshea L. Harris, Kathryn Colby, Nancy C. Joyce

Ophthalmology

Purpose: To compare the relative expression of peroxiredoxin (Prx) proteins in normal human corneal endothelium with endothelium in corneas affected by Fuchs’ endothelial dystrophy (FED) and between normal human endothelium and epithelial/stromal tissue.

Methods: Human corneal endothelial cell-Descemet’s membrane (HCEC-DM) complexes from normal and FED corneal buttons were dissected from the epithelium/stroma. For proteomic analysis, HCEC-DM protein extracts were separated by using two-dimensional gel electrophoresis. Relative differences in protein spot density was analyzed. Proteins of interest, including Prx isoforms, were identified by MALDI-TOF (matrix-assisted desorption ionization-time of flight) mass spectrometry. Western blot analysis compared the relative expression of Prx isoforms …

Increased Clusterin Expression In Fuchs’ Endothelial Dystrophy, Ula V. Jurkunas, Maya Bitar, Ian Rawe, Deshea L. Harris, Kathryn Colby, Nancy C. Joyce

Ophthalmology

Purpose: To compare the relative expression of peroxiredoxin (Prx) proteins in normal human corneal endothelium with endothelium in corneas affected by Fuchs’ endothelial dystrophy (FED) and between normal human endothelium and epithelial/stromal tissue.

Methods: Human corneal endothelial cell-Descemet’s membrane (HCEC-DM) complexes from normal and FED corneal buttons were dissected from the epithelium/stroma. For proteomic analysis, HCEC-DM protein extracts were separated by using two-dimensional gel electrophoresis. Relative differences in protein spot density was analyzed. Proteins of interest, including Prx isoforms, were identified by MALDI-TOF (matrix-assisted desorption ionization-time of flight) mass spectrometry. Western blot analysis compared the relative expression of Prx isoforms …

Study To Prospectively Evaluate Reamed Intramedually Nails In Patients With Tibial Fractures (S.P.R.I.N.T.): Study Rationale And Design, Franklin D. Shuler Md, Phd

Orthopaedics

Background: Surgeons agree on the benefits of operative treatment of tibial fractures – the most common of long bone fractures – with an intramedullary rod or nail. Rates of re-operation remain high – between 23% and 60% in prior trials – and the two alternative nailing approaches, reamed or non-reamed, each have a compelling biological rationale and strong proponents, resulting in ongoing controversy regarding which is better.

Methods/Design: The objective of this trial was to assess the impact of reamed versus non-reamed intramedullary nailing on rates of re-operation in patients with open and closed fractures of the tibial shaft. The …

Use Of Ultraviolet Light Irradiated Multiple Myeloma Cells As Immunogens To Generate Tumor Specific Cytolytic T Lymphocytes, Charles A. Gullo Phd, William Y.K. Hwang, Chye K. Poh, Melvin Au, Geraline Cow, Gerrard Teoh

Biochemistry and Microbiology

Background:

As the eradication of tumor cells in vivo is most efficiently performed by cytolytic Tlymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described.

Methods:

Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity.

Results: …

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Biochemistry and Microbiology

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …

The Function And Mechanism Of Chmp1a In Tumor Development, Jing Li

Theses, Dissertations and Capstones

Chmp1A (Chromatin modifying protein 1A/Charged multivesicular protein 1A) is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport) family, which mediates trafficking via MVB (multivesicular body) formation and sorting. Our studies suggest that Chmp1A is a novel tumor suppressor, especially in the pancreas. Knockdown of Chmp1A resulted in an increase of anchorage-independent growth of HEK 293T cells. Moreover, we showed that Chmp1A depleted HEK 293T cells forms tumor in xenograft mice. Knockdown of Chmp1A in PanC-1 cells promoted cell growth. In contrast, Doxycycline induced over-expression of Chmp1A in pancreatic cancer cells (PanC-1) resulted in cell growth inhibition, tumor …

Preventing And Treating Type 2 Diabetes Through A Physically Active Lifestyle, Raymond W. Leung, Jim Kamla, Man-Cheong Lee, Jennifer Y. Mak

Management Faculty Research

By the late 1960s, the increasing number of type 2 diabetic cases in children and adolescents rapidly presented a signifi cant public health issue recognized by the American Diabetes Association (2000). Since then, the prevalence of pediatric type 2 diabetes appears to be on the rise not only in the United States but all around the world (Gungor et al., 2005). In the United States, an increase from fewer than four percent to more than 50 percent of new cases of type 2 diabetes in the pediatric population was reported between the years of 1982 and 1998 (American Diabetes Association, …

A Case Study Of School Age Female Minority Athletes Who Became Pregnant, Floyd Jones Phd, Jennifer Y. Mak, Phyllis A. Jones Ed

Management Faculty Research

The purpose of this study is to provide an in-depth understanding of ''What had happened to the urban minority female athletes who became pregnant while playing high school basketball?'' The study wanted to provide a qualitative analysis of rich narrative data collected from questionnaire interviews of two separate groups (one in Pittsburgh, the other in New York City). The findings of this study suggest that in fact urban female African-Americans athletes still received benefits from sports participation.

Effects Of Retinoic Acid On Beta-Catenin Transcriptional Activity In Melanoma Cells, Fung Chan

Theses, Dissertations and Capstones

Melanoma is the most dangerous form of skin cancer and its incidence has been increasing in the United States. Most melanomas are resistant to current chemotherapies; therefore, understanding the mechanism of melanomagenesis is beneficial to treatment of the diseases. Accumulation of β-catenin has been shown in colon and other cancers, including melanomas, but the transcriptional role of β-catenin in melanomas is still unclear. All-trans retinoic acid (ATRA) is an anti-tumor agent that has an inhibitory effect on β-catenin, but this effect has not been studied in melanomas. It has been shown that Microphthalmia-associated transcription factor (MITF), a melanocyte specific protein, …

The Geriatric Residency Experience, Sabrina Camilo, Tamara Gravano, Karen Lagares, Gemma Longfellow

Physical Therapy Faculty Research

The Geriatric Residency in Physical Therapy program at St. Catherine's Rehabilitation Hospital and Villa Maria Nursing Center has graduated 4 residents since its inception in 2003. Recently, the 4 of us program graduates convened to talk about our experiences and discovered several similarities. We laearned about our individual reasons for choosing the residency, our experiences during the time we were residents, and our plans for continued professional development. But, of course, there were some differences that made the experience unique for each of us.

The Impact Of Title Ix On Athletics Development In The United States, Jennifer Y. Mak

Management Faculty Research

Nothing has had as much of an impact in the history of public education as Title IX of the Education Amendment of 1972. The increase in the popularity of collegiate sports, especially the revenue sports (football, basketball), has made Title IX and Athletics a hot topic. However, many members of the Title IX generations do not have a clear picture or fully understand the true meaning behind Title IX. This paper tries to close this gap by explaining the relationship between Title IX and Athletics in a timeline format: the birth of Title IX in 1972; Title IX and Athletics …

Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams

Biochemistry and Microbiology

Background

The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the …

Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors, Ivan L. Cameron, Nicholas Short, Luzhe Sun, W. Elaine Hardman

Biochemistry and Microbiology

Background

A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm³, it developed a well-vascularized capsule. Histological sections of tumors greater than 35 mm³were stained with PAS, with CD-31 antibody (an endothelial cell maker), or with hypoxia inducible factor 1α …

Dietary Omega-3 Fatty Acids And Ionizing Irradiation On Human Breast Cancer Xenograft Growth And Angiogenesis, W. Elaine Hardman, Luzhe Sun, Nicholas Short, Ivan L. Cameron

Biochemistry and Microbiology

Background

The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every second …

Defective B Cell Responses In The Absence Of Sh2d1a, Massimo Morra, Robert A. Barrington, Ana C. Abadia-Molina, Susumo Okamoto, Aimee Julien, Charles A. Gullo Phd, Anuj Kalsy, Matthew J. Edwards, Gang Chen, Rosanne Spolski, Warren J. Leonard, Brigitte T. Huber, Persephone Borrow, Christine A. Biron A. Biron, Abhay R. Satoskar, Michael C. Carroll, Cox Terhorst

Biochemistry and Microbiology

More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A-/- mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A-/- mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A-/- B cell functions were impaired. Using the adoptive …

Effects Of Aging On Pressure-Induced Mapk Activation In The Rat Aorta, Kevin M. Rice

Theses, Dissertations and Capstones

With age, the cardiovascular system experiences substantial alterations in cellular morphology and function. The factors regulating these changes are unknown; however, the mitogen activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6 month old), aged (30 month old) and very aged (36 month old) Fischer 344 x Brown Norway F1 Hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11% …

Effects Of Tamoxifen On Mitochondrial Nos Activity: Alteration In The Intramitochondrial Ca2+ Homeostasis, Sandeep S. Joshi

Theses, Dissertations and Capstones

Tamoxifen (Tam) is an anticancer drug that induces oxidative stress and apoptosis via mitochondria- and nitric oxide (NO)-dependent pathways. Here, we report that therapeutic concentrations of Tam stimulate the mitochondrial NO synthase (mtNOS) activity of isolated rat liver mitochondria by increasing the intramitochondrial ionized Ca²⁺ concentration ([Ca²⁺]_m). Tam decreases transmembrane potential (∆ψ) due to increased [Ca²⁺]_m that neutralizes the negative charges of the inner mitochondrial membrane. Thus, the present study reports a novel mechanism for the widely used anti- caner drug, Tam.

The Cell Surface Receptor Slam Controls T Cell And Macrophage Functions, Ninghai Wang, Abhay Satoskar, William Faubion, Susumu Okamoto, Stefan Feske, Charles A. Gullo Phd, Kareem Clarke, Miriam Rodriguez Sosa, Arlene H. Sharpe, Cox Terhorst

Biochemistry and Microbiology

Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be a coregulator of antigen-driven T cell responses and is one of the two receptors for measles virus. Here we show that T cell receptor–induced interleukin (IL)-4 secretion by SLAM−/− CD4+ cells is down-regulated, whereas interferon γ production by CD4+ T cells is only slightly up-regulated. Although SLAM controls production of IL-12, tumor necrosis factor, and nitric oxide in response to lipopolysaccharide (LPS) by macrophages, SLAM does not regulate phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as a coreceptor …

Diversion Of The Inferior Vena Cava Following Repair Of Atrial Septal Defect Causing Hypoxemia, Ellen A. Thompson, Silvestre Cansino, Dennis Moritz, Romaine Perdue Perdue

Internal Medicine

Atrial septal defects (ASDs) are a common congenital abnormality, and operative repair is a routine, safe procedure. Diversion of the inferior vena cava (IVC) into the left atrium is an unusual complication following ASD closure. We report a case that illustrates the problem created by this right-to-left shunt. A middle-aged woman underwent ASD repair. She developed hypoxemia postoperatively. A transthoracic echocardiogram confirmed a right-to-left shunt, found only with agitated saline injected into the femoral vein, not into the basilic vein. Surgical reexploration revealed a residual ASD diverting IVC flow into the left atrium, which was repaired with a pericardial patch. …

Antimicrobial And Spermicidal Activity Of Hydrogen Peroxide And Nonoxynol-9 Based Gel Preparations, Paul E. Grimmett

Theses, Dissertations and Capstones

Eighty gel formulations were prepared using five buffer systems (0.01M citrate, 0.02M citrate, 0.01M tartrate, 0.02M tartrate, and 0.01M citrate/0.01M tartrate), four hydrogen peroxide (H2O2) concentrations (0%, 0.3%, 0.9%, and 1.2%), and four nonoxynol-9 (N-9) concentrations (0%, 1%, 1.5%, and 2%). The eighty gel formulations were then tested for physio-chemical properties (viscosity and pH), antimicrobial effectiveness (Minimum Inhibitory Concentration Assay) against Candida albicans, Escherichia coli, and Streptococcus agalactiae, and finally, spermicidal effectiveness (Sander Cramer Assay). The gel formulation that contained the best combination of physio-chemical, antimicrobial, and spermicidal properties was a 0.01M citrate buffered hydrogel, which contained 0.9% H2O2 and …

Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson

Theses, Dissertations and Capstones

Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …

The Genetic And Molecular Characterization Of The Polycystic Kidney Disease-Causing Mouse Gene Bicc1, Sarah J. Price

Theses, Dissertations and Capstones

Polycystic kidney disease (PKD) is one of the most common hereditary diseases and is characterized by progressive cyst formation, substantial renal enlargement, and frequently, progression to end-stage renal disease. One way to learn more about the etiology of this disease is to study mouse models that imitate the human situation. The juvenile congenital polycystic kidney disease (jcpk) gene on mouse Chromosome 10 has been found to cause a severe, early onset form of PKD when inherited in an autosomal recessive manner (Flaherty et al., 1995). Previous genetic studies mapped the jcpk locus to a 1 cM region on mouse Chromosome …

Renal Basolateral Transport Of Glucuronides And Other Organic Anions In Rat In Vitro Models, Sarah L. Miles

Theses, Dissertations and Capstones

Glucuronidation is a common Phase II biotransformation reaction that increases the hydrophilicity, and thus elimination, of toxins, xenobiotics, and endogenous compounds. Previous studies suggest that the kidney can secrete glucuronide conjugates, but the renal transport mechanisms for glucuronide secretion have not been determined. Based on the chemical nature of glucuronide metabolites, it is hypothesized that organic anion transporter (OAT) proteins along the basolateral membrane of the renal proximal tubule promote renal accumulation of glucuronide conjugates. The purpose of this study was to develop a rat renal proximal tubule model which demonstrates OAT activity and by which the contribution of OAT …

Effect Of Low-Carbohydrate, Unlimited Calorie Diet On The Treatment Of Childhood Obesity: A Prospective Controlled Study, James R. Bailes Jr., Misty T. Strow, Joseph Werthammer, Richard A. Mcginnis, Yoram Elitsur

Pediatrics

Background: Childhood obesity has been recognized as the new epidemic in developed countries. Caloric restriction with physical activity is the main therapeutic treatment available for these children. We compared two different dietary protocols to assess treatment efficacy.

Methods: Obese children from the Pediatric Endocrinology clinic were prospectively recruited for the study. Children and their parents were allowed to choose one of two dietary protocols: (1) carbohydrate restricted diet (<30 g/day), with unlimited calories, protein, and fat (High protein, Low CHO Diet), and (2) calorie restricted diet (Low Cal Diet). Anthropometric data were measured at baseline and at the 2 month follow up appointment.

Results: Thirty-seven children completed the study of whom 27 chose High Protein, Low CHO Diet and 10 chose Low Cal diet. No differences in gender ratio, age, or …

High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

Background

d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …

Synergistic Interactions Of Chlorambucil, Dha, And Trail In Jurkat And H460 Human Cancer Cells, Jennifer Ellen Bush-O'Donnell

Theses, Dissertations and Capstones

Traditional chemotherapeutic drugs are prone to toxicity and may result in secondary cancers. In recent years much attention has been garnered by alternate methods of cancer treatment with fewer side effects, including immunotherapy and administration of ω-3 fatty acids, both of which have been shown to cause apoptosis in cancer cells. Docosahexaenoic acid (DHA), a fatty acid, is a normal component of cell membranes and is safe for systemic administration. The cytokine TRAIL (tumor necrosis factorrelated apoptosis-inducing ligand) is able to induce apoptosis in cancer cells while sparing normal tissue. In this study, the alkylating agent chlorambucil (CLB) was combined …

Utilization Of Emergency Policies And Procedures By Division I-A And Division I-Aa Intercollegiate Athletic Programs, Brandy A. Petty

Theses, Dissertations and Capstones

The need for an established emergency policy and procedures plan in the college and university setting has been confirmed by various organizations such as: National Safety Council (NSC), Federal Emergency Management Agency (FEMA), National Emergency Management Association (NEMA), National Athletic Trainers’ Association (NATA), National Collegiate Athletic Association (NCAA), and the American College of Sports Medicine (ACSM). The duty of these emergency policies and procedures is twofold. The first is to provide immediate care to student-athletes in an emergency situation. The second purpose is to avoid liability issues that may arise following an emergency situation. The premise behind the establishment and …

The Role Of Ap-1 Transcription Complex In Retinoic Acid-Dependent B16 Melanoma Cell Growth Arrest And Differentiation, Ying Huang

Theses, Dissertations and Capstones

Our laboratory has been studying the effects of all-trans retinoic acid (atRA) on the growth and differentiation of the B16 mouse melanoma cells. RA inhibits both anchorage-dependent and –independent growth and stimulates melanin production in B16 cells, which are accompanied by an increase in AP-1 activity. To further investigate the RA-induced AP-1 activity, I established clones of B16 stably expressing an AP-1-luciferase reporter gene. Treatment of these clones with phorbol dibutyrate (PDB), a known activator of AP-1, rapidly increased AP-1 activity which reached its maximum level at 2-4 h and returned to baseline level by 24 h. In contrast, RA …