Diseases Commons^™

Leptin Induces Proliferation And Notch Expression In Pancreatic Cancer, Felice Watson, Ruben Gonzalez-Perez, Phd

Journal of Health Disparities Research and Practice

Pancreatic adenocarcinoma (PA) is an aggressive cancer. It develops in a way that causes almost no detectable symptoms, which leads to a rapid progression and a short survival rate.

Researchers have discovered a link between pancreatic cancer (and other cancer types) and obesity. High levels of leptin, an appetite hormone secreted by adipocytes, have been found in obese people. Studies have shown that the absence of leptin in the body or severe leptin resistance can lead to uncontrolled eating and weight gain, hence, its connection to obesity. Consequently, our lab is analyzing the relationship between obesity and leptin and what …

The Association Between Food Insecurity, Glycemic Control, Self-Care, And Quality Of Life In Adults With Type 2 Diabetes, Allen Walters, Joni S. Williams, Md, Mph, Leonard E. Egede, Md, Ms

Journal of Health Disparities Research and Practice

Food insecurity is the inability to obtain adequate nutritious food. Therefore, the study assessed the relationship between food insecurity, glycemic control, self-care behaviors, and quality of life in adults with type 2 diabetes (T2DM).

Cross sectional study of 356 adults with T2DM recruited from an academic medical center and a veterans affairs medical center. The independent predictor was food insecurity, and the outcomes were glycosylated hemoglobin A1c, self-care behaviors, and quality of life (QOL). Logistic regression was used to assess the independent factors associated with food insecurity. Multiple linear regression was used to assess the association between food insecurity and …

Effects Of Acculturation On Quality Of Life, Chronic Diseases And Health Behaviors In Persons Of African Ancestry, Danielle Stephenson, Camille Ragin, Phd, Elizabeth Blackman, Mph

Journal of Health Disparities Research and Practice

The Black population in Philadelphia comprises of a diverse mix of persons with varied ancestry. We have established a non-cancer control registry (CAP3 study) which involves the collection of bio-specimens, epidemiological, lifestyle, quality of life, chronic conditions, culture and cancer prevention behaviors. Currently there are 707 participants enrolled, 95% from the African diaspora. In this study, the acculturation (the degree to which an individual holds onto their cultural norms) of new and pre-enrolled participants (n = 100) will be assessed and evaluations will be made to determine the relationship between acculturation, chronic conditions, health behaviors and quality of life.

Since …

Elucidating The Expression Profile Of Ezh2 Isoforms In Endometriosis: An Immunohistochemical Study, John Soto-Vargas, Idhaliz Flores, Phd, Mariano Colón-Caraballo, Andrés Velázquez-Garcia

Journal of Health Disparities Research and Practice

Endometriosis is an estrogen-dependent gynecological disease that affects 1 out of 10 women of reproductive age causing severe pelvic pain and infertility. Factors including genetics, environment, inflammation, and recently epigenetics have been shown to play roles in the pathophysiology of this disease. Histone methylation is an epigenetic modification that modulates gene expression by causing changes in the chromatin structure. Trimethylation of histone 3 at lysine residue 27 (H3K27me3) is a histone mark related to gene repression. EZH2 is the histone methyltransferase (HMT) responsible of catalyzing H3K27me3. It has been shown that the EZH2 is involved in carcinogenesis; however, the specific …

Glioblastoma Stem Cells, Michael Quintero, Qi Cui, Yanhong Shi, Phd

Journal of Health Disparities Research and Practice

Glioblastoma multiforme(GBM) is the most common and malignant primary brain tumor in humans. GBM accounts for 55% of all primary brain cancers, with a median survival rate of 14.6 months. The grim prognosis of GBM can be attributed to glioma stem cells (GSCs), which initiate tumor formation through the stem-like properties of self-renewal and differentiation. The ability of GSCs to resist radiation and chemotherapy contributes to the high rate of tumor recurrence in GBM patients. Consequently, novel therapies that effectively target the population of GSCs are of vital importance.

A promising is to induce the differentiation of GSCs. Previous studies …

Rgs2 And Human Adipogenesis, Kaia Partlow, Alma Madrigal, Yuanxiang Zhao, Phd

Journal of Health Disparities Research and Practice

Obesity is characterized by excess adipose tissue and is one of the leading public-health issues of the industrialized world. Gain of adipose tissue can result from accumulation of fat in existing adipocytes (fat cells), as well as increased commitment of stem cells into new adipocytes through a process known as adipogenesis. Although a number of key adipogenic transcription factors such as PPARgamma2 and CEBPalpha are well characterized, the temporal and spatial molecular and cellular events that occur during adipogenesis are still largely unknown. Better understanding of these events could have important implications in finding treatments for obesity.

Human mesenchymal stem …

Dietary Restriction In Drosophila Melanogaster Increases Flight Duration, Nelson Nunez, Mark Frye, Phd, Mehmet Keles, Phd Candidate

Journal of Health Disparities Research and Practice

Caloric restriction extends the lifespan in several model animals, including fruit flies, but less is known about the influence upon endurance and sensory-motor performance. For this experiment, all flies will be raised on standard media. At the point of eclosion, they will be transferred to rich, standard, or restricted media. The endurance of a fruit fly can be tested by monitoring how long it is able to maintain active flight. Flight power is quantified by measuring wing beats per second and total wing stroke amplitude. Sensory-motor performance is measured by the animal’s ability to actively fixate on a black bar …

Application Of The Transtheoretical Model In Hispanic And African American Populations To Assess Deceased Kidney Donor Noncompliance, Cynthia Mancilla, Amy D. Waterman, Phd, Crystal Kynard-Amerson, Mph, Aubre Parnicky, Msw

Journal of Health Disparities Research and Practice

Given existing health disparities such as financial barriers, lack of education and inadequate health care in minority communities, the rates of deceased kidney donation continues to decline. The transtheoretical model (TTM) assesses the patients’ willingness to pursue deceased kidney donation through application of a stage structured curriculum.

Patients are evaluated into five different stage groups; pre-contemplation, contemplation, preparation, action, and maintenance. This assessment of behavior change as applied to the willingness of a patient to pursue a deceased kidney donor transplant can be tracked over time and used to help determine what stage of change a patient is in during …

Exploration Of Antagonist Efficacy For Lpra2 Like Peptide, Ayobami Loye, Ruben R. Gonzalez-Perez, Phd

Journal of Health Disparities Research and Practice

Leptin is a small protein hormone that controls satiety and is produced by adipocytes. Obese people have increased levels of circulating leptin. Excessive leptin levels cause a break down in the control of leptin signaling pathways leading to increased angiogenesis, proliferation, cell migration, invasion, and anti-apoptotic events. Obesity and leptin signaling have been linked to cancer progression. Literature shows that LPrA2 is an effective leptin antagonist as it decreases proliferation of breast cancer cells in vitro.

This project compares the effectiveness of LPrA2 like compounds in breast cancer cell-line MDA-MB-468 (M-468 BCs). We hypothesize that the new peptide antagonists have …

Design And Optimization Of A Mycoplasma Detection Assay, Carlos J. León-Rodríguez, Richard J. Noel, Jr., Phd, Tirtsa Porrata-Doria, Ms

Journal of Health Disparities Research and Practice

Mycoplasma are among the smallest free living microorganisms. These bacteria grow slowly, lack a rigid cell wall and are not eliminated by filter sterilization methods used in tissue culture. Mycoplasma infection affects biochemical and genetic aspects of cultured cells, resulting in experimental inconsistency. Therefore, it is necessary to establish routine testing for mycoplasma contamination in tissue culture laboratories.

Our goal is to develop a reliable and cost-effective test for mycoplasma in cell culture based on established methods found in literature. We first cloned and sequenced a PCR product from a commercial mycoplasma detection kit. Sequencing revealed the 16s rRNA as …

Role Of Hiv-1 Nef Lysine Residues 4 And 7 In The Interaction With Calnexin And Inhibition Of Abca1 Activity, Valeria Kaufman, Michael Burkinsky, Md, Phd, Ruth Hunegnaw, Msc, Phd Candidate

Journal of Health Disparities Research and Practice

Patients infected with HIV are at increased risk of developing atherosclerosis, a result due partly to the functional impairment of cellular cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1). This transporter mediates efflux of cholesterol from cells to high density lipoprotein, thus allowing cells to maintain normal levels of cholesterol. When ABCA1 function is inhibited, cells, and in particular macrophages, accumulate cholesterol, resulting in formation of atherosclerotic plaques. The HIV-1 protein, Nef downregulates ABCA1 and inhibits the activity of this protein, thereby reducing cholesterol efflux and promoting atherosclerosis, but the molecular mechanism by which Nef inhibits ABCA1 is unknown.

Previous studies …

Collagen Iv Assembly: Production Of A Recombinant Construct For Mechanistic Studies, Kennedy Harris, Billy Hudson, Phd, Isi Ero-Tolliver, Phd, Kyle Brown, Phd

Journal of Health Disparities Research and Practice

Basement membranes, specialized extracellular matrix, provide mechanical support for epithelial cells and shape cell behavior by interacting with cell receptors. Collagen IV, the predominant component of basement membrane, comprises six genetically distinct alpha chains (α1 to α6) that assemble to form protomers, which associate to form hexamers, in the scaffold. Non-assembly due to mutations within alpha chains give rise to kidney diseases. Yet, the mechanism of assembly is poorly understood.

Preliminary data in our lab indicated that amino acid 78 of collagen IV α2 NC1 (non-collagenous) domains may play a role in a chloride-dependent switch that supports hexamer formation. We …

Sex Differences In The Sex Differences In The Effects Of Environmental Enrichment After An Early Life Stressor, Alfredo Gutierrez, Annelyn Torres-Reverón, Phd, Raura Doreste-Méndez

Journal of Health Disparities Research and Practice

Studies have shown that environmental enrichment can compensate for the effects of an early life stressor such as maternal separation. Behavioral responses and immunohistochemical markers in rats are affected by environmental enrichment after maternal separation. In this study we seek to investigate whether sex influences the behavioral responses of environmental enrichment after maternal separation.

Prior scientific evidence suggests that there are behavioral sex differences in: 1) neural processes underlying successful or failed fear extinction (Gruene et al, 2014); (2) prenatal stress exposure and response to behavioral anxiety tests (Said et al, 2015); and (3) glutamate receptor expression in response to …

Cox2 Plays An Important Role In Maintenance Of Mammary Cancer Stem Cell Population In Human Breast Cancer Cell Lines, Mayra Garcia, Shehla Pervin, Phd, Easter Thames, Meher Parveen, Phd, Melanie Baker

Journal of Health Disparities Research and Practice

Breast cancer is a malignant growth in the adipose-rich mammary gland. Initiation and progression of breast tumors involve multiple cell types, among which mammary cancer stem cells play an important role. There are two main types of adipocytes; white adipocytes have previously been found to influence the disease while brown adipocytes, which uniquely express uncoupling protein 1 (UCP1), were recently detected in breast tumors.

We have detected Myf5, a transcription factor, which is expressed in the progenitor population of brown adipocytes, in breast cancer cell lines. We also found an association between expression of Myf5 and COX2 (or Ptgs2), which …

The Role Of Integrin-Associated Protein “Pinch” In Kidney Development, Tyrone Gamble Jr, Roy Zent, Phd, Bertha C. Elias, Phd

Journal of Health Disparities Research and Practice

PINCH (a particularly interesting new cysteine-histidine-rich protein) is a protein that binds with Integrin-linked kinase and Parvin, to form an IPP complex. This complex is formed only when integrin molecules are activated upon interaction with the basement membrane. The IPP complex then acts as a platform for other proteins to come together and regulate cell signaling to and from the extracellular matrix (ECM). This allows for various cellular activities to progress like cell adhesion, migration, proliferation, etc. There are two types of PINCH proteins, PINCH-1 and PINCH-2. Studies from our group have shown that the lack of PINCH-1 in the …

Nitric Oxide And Cyclic Gmp Signaling In Cancer Therapy, Armond Dorsey, Ferid Murad, Md, Phd, Ka Bian, Md, Phd

Journal of Health Disparities Research and Practice

The nitric oxide-3’,5’-cyclic guanosine monophosphate signaling pathway (NO-cGMP signaling pathway) is a well-known signal transduction pathway which elicits several physiological processes including: cell proliferation, vasodilation, cardiac protection, etc. In this pathway, NO binds to the ferrous heme of histidine-105 on the prosthetic heme of the β₁ subunit of soluble guanylyl cyclase, resulting in the production of cGMP. This pathway, however, is inhibited in certain cancer cells—as observed in glioma cell lines. As a result, the production of cGMP is reduced. This mechanism may facilitate uncontrolled tumor cell growth.

The cancers under research—lung carcinoma, glioma, and pancreatic carcinoma—are all highly …

Potential Cost Savings Of Not Doing Cd4 Counts In Hiv Positive People In Rhode Island With An Undetectable Viral Load, Ruth Dele-Oni, Ferdinand Schumacher, Zachary Markus, Timothy Flanigan, Md

Journal of Health Disparities Research and Practice

CD4 cells fight infections in the body. When someone contacts Human Immunodeficiency Virus (HIV), their CD4 cells are taken over by HIV which turns them into manufacturers of many copies of the virus. The Viral Load (VL) measures the amount of virus in the blood. When HIV takes over the CD4 cells, the VL increases while the number of necessary CD4 cells decreases. When patients maintain stable treatment, their CD4 counts rise, and VLs may become undetectable, indicating the virus is too little to be detected in their blood. Knowing this, is frequent CD4 counts necessary for those with undetectable …

Defining The Role For Zbp-89 In Atm-Mediated Dna Damage Response To Irradiation In The Intestine, Christine Carethers, Juanita L. Merchant, Md, Phd

Journal of Health Disparities Research and Practice

ZBP-89 (ZNF148, Zfp148) is a zinc-finger transcription factor that inhibits cellular proliferation when overexpressed in cell lines. ZBP-89 forms a protein-protein interaction with p53 and Ataxia-telangiectasia mutated (ATM). However, it is unclear how the interaction modulates the function of these two proteins in vivo.

Double strand DNA breakage induced by -irradiation induces ATM phosphoinositol kinase activity, which initiates a cascade of events culminating in cell cycle arrest, DNA repair or apoptosis. Elevated levels of ZBP-89 induce growth arrest and apoptosis in gastrointestinal cell lines. Therefore, we hypothesize that ZBP-89 facilitates cell growth arrest and activation of the DNA repair pathway …

Induction Of Dusp9 In Xenografts From Human Breast Cancer Cell Lines Increases Mammary Cancer Stem Cells, Albert Barrios, Meher Parveen, Phd, Easter Thames, Melanie Baker, Shelha Pervin, Phd

Journal of Health Disparities Research and Practice

Breast cancer remains a complex disease that kills 40,000 women every year. Initiation and progression of breast cancer is influenced by heterogeneous groups of cells, including mammary cancer stem cells (MCSCs). Progression of this dreadful disease is driven by many signaling pathways among which MAPK pathway is highly prominent. Since targeting prominent kinases in MAPK pathway has been unsuccessful to control breast cancer, it is important to examine the phosphatases that regulate the activity of these kinases.

Using xenograft model from breast cancer cell lines, our lab has found that during the initial stages of xenograft development (week 1-4, 100-200mg …

Preparing Underrepresented High School Students To Increase Diversity In The Research And Health Professions, Dolores E. Caffey-Fleming, Ms, Mph, Christopher Reid, Md, Phd

Journal of Health Disparities Research and Practice

This article introduces the work that was done through the Coordinating Center at Charles R. Drew University of Medicine and Science.

The Step Up Program, Lawrence Agodoa, Md

Journal of Health Disparities Research and Practice

The Short-Term Research Experience Program for Underrepresented Persons (STEP-UP) was established as part of the NIDDK Strategic Plan on Minority Health Disparities. This article provides an overview and introduction of this program. All of the articles that are included in this special issue reflect the work of our coordinating centers, the mentors and their staff, as well as the students.

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

The Development Of Transforming Growth Factor-Beta 1 Associated Fibrosis In The Gastrocnemius Of Peripheral Artery Disease Patients And Response To Revascularization And Supervised Exercise Therapies, Duy M. Ha

Theses & Dissertations

Peripheral Artery Disease (PAD) affects over 200 million people worldwide with a 5-year mortality rate as high as 30%. Atherosclerotic blockages impair blood flow to the lower limbs, causing ischemic leg pain and dysfunction upon exercise that later progresses to ulcerations and gangrene and often requires amputation. The standard therapies, revascularization and exercise, allow patients to walk further and longer but are at best maintained short-term. One explanation may be the development of myopathic changes in the limb that progress despite improved hemodynamics—a paradigm shift in the classic view of PAD pathophysiology as solely a mismatch between blood supply and …

The Pathogenesis Of Natural Killer/T Cell Lymphoma, Bei Jiang

Theses & Dissertations

Extranodal natural killer/T-cell lymphomas (NKTCL) are uncommon lymphomas with poor prognosis. In order to gain a better understanding of the molecular pathogenesis of NKTCL, we obtained and compared the global gene expression profile, global somatic mutation profile, and global methylation profile of normal NK cells, malignant NK cell lines, and NKTCL patient samples. We showed that the JAK-STAT pathway was constitutively activated in NKTCL through the cooperation between activation of signal transducer and activator of transcription proteins (STATs) via activating mutations and inactivation of STAT suppressor protein suppressor of cytokine signaling 6 (SOCS6) through promoter hypermethylation. Activating STAT3 and STAT5B …

Role Of B Cell And Hematopoietic Cell Intrinsic Actions Of Erα In Lupus Pathogenesis, Dana E. Tabor

Theses & Dissertations

Lupus is a chronic autoimmune disease characterized by the presence of autoimmune B and T cells and the production of pathogenic antibodies against nuclear antigens. Lupus predominately affects women between menarche and menopause. There are both genetic and environmental risk factors which affect an individuals’ risk of developing lupus. Estrogens are a risk factor for developing lupus and are thought to contribute significantly to the initiation and progression of disease. In lupus-prone mice, genetic knockout of a receptor for estrogen, estrogen receptor alpha (ERα), causes significant attenuation of lupus. Previous studies have not identified the cell type or …

Leisure Time Physical Activity Preferences, Behaviors, And Hypertension: Evidence From The China Health & Nutrition Survey, 2004-2011, Junmin Zhou

Theses & Dissertations

Background: Physical activity has been continuously declining in China. At the same time, prevalence of hypertension has dramatically increased. The associations between leisure time physical activity preference, behavior, and development of hypertension in Chinese adults remained not fully understood and few studies have examined these associations using longitudinal data.

Objectives: This dissertation examined the interrelationships among leisure time activity preference, behavior, and the incidence of hypertension using longitudinal data from 2004 to 2011 in the China Health and Nutrition Survey. It also assessed the urban-rural disparities.

Methods: A total of 2,687 adults were included in the analysis. Multivariate logistic regressions …

The Role Of Inflammatory Monocytes In Post-Influenza Methicillin-Resistant Staphylococcus Aureus Pneumonia, Karl J. Fischer

Theses & Dissertations

Secondary bacterial infections following influenza can lead to poor clinical outcomes and mortality. It is widely accepted that susceptibility to secondary bacterial infections is attributable to a suppressed innate antibacterial immunity. In contrast, a dysregulated host inflammatory response may also contribute to disease severity. Inflammation induced by viral infection alone significantly affects lung pathology, potentially exacerbating the destruction of the respiratory tract. Interestingly, the role of inflammatory mediators such as inflammatory monocytes have been extensively studied during influenza infection alone; however, their role during secondary bacterial infection are still not fully established. The objective of this study was to analyze …

A Hypothesis For Using Pathway Genetic Load Analysis For Understanding Complex Outcomes In Bilirubin Encephalopathy, Sean M. Riordan, Douglas C. Bittel, Jean-Baptist Lepichon, Silvia Gazzin, Claudio Tiribelli, Jon F. Watchko, Richard P. Wennberg, Steven Shapiro

Manuscripts, Articles, Book Chapters and Other Papers

© 2016 Riordan, Bittel, Le Pichon, Gazzin, Tiribelli, Watchko, Wennberg and Shapiro.

Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. …