Digital Commons Network^™

Activation Of C-Myc And Cyclin D1 By Jcv T-Antigen And Β-Catenin In Colon Cancer, Michael J. Ripple, Amanda Parker Struckhoff, Jimena Trillo-Tinoco, Li Li, David A. Margolin, Robin Mcgoey, Luis Del Valle

School of Medicine Faculty Publications

During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein β-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear β-catenin …

A Collagen‐Glycosaminoglycan‐Fibrin Scaffold For Heart Valve Tissue Engineering Applications, Claire Brougham, Stefan Jockenhoevel, Thomas Flanagan, Fergal O'Brien

Conference Papers

The field of heart valve biology and tissue engineering a heart valve continue to expand. The presentatio ns at this meeting reflect the advances made in both areas due to the multi-disciplinary approach taken by many laboratories.

Evidence For Transfer Of Membranes From Mesenchymal Stem Cells To Hl-1 Cardiac Cells, Robert Boomsma, David Geenen

Open Access Publishing Support Funded Articles

This study examined the interaction of mouse bone marrow mesenchymal stem cells (MSC) with cardiac HL-1 cells during coculture by fluorescent dye labeling and then flow cytometry. MSC were layered onto confluent HL-1 cell cultures in a 1 : 4 ratio. MSC gained gap junction permeant calcein from HL-1 cells after 4 hours which was partially reduced by oleamide. After 20 hours, 99% MSC gained calcein, unaffected by oleamide. Double-labeling HL-1 cells with calcein and the membrane dye DiO resulted in transfer of both calcein and DiO to MSC. When HL-1 cells were labeled with calcein and MSC with DiO, …

Epidemiology Of Patients Presenting To The Emergency Centre Of Princess Marina Hospital In Gaborone, Botswana, Amit Chandra, Paul C. Mullan, Ari Ho-Foster, Antanoid Langeveldt, Ngaire Caruso, Joseph Motsumi, Andrew Kestler

Pediatrics Faculty Publications

No abstract provided.

West Virginia Nursing Homes: Are They Up To The Standard?, Guillermo Madero Md, Shirley M. Neitch Md

Internal Medicine

Quality measurement and performance monitoring are under continuous assessment in Nursing Homes (NH). Through this research project we assess the quality of care provided in the NH in the state of West Virginia by publicly accessible quality measurements. The methodology for this research study was through the retrieval of data from the Nursing Home Compare website in which a total of 80 NH were located and analyzed. The results demonstrate that more than 50% of NH in West Virginia are at or above the national average when compared using the Five Star Rating System by CMS, in overall rating (59%), …

Mir-638 Mediated Regulation Of Brca1 Affects Dna Repair And Sensitivity To Uv And Cisplatin In Triple Negative Breast Cancer, Xiaohui Tan, Jin Peng, Yebo Fu, Shejuan An, M. Katayoon Rezaei, Sana Tabbara, Christine B. Teal, Yan-Gao Man, Rachel F. Brem, Sidney W. Fu

Pathology Faculty Publications

Introduction

Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment.

Methods

Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal …

Understanding Patient Options, Utilization Patterns, And Burdens Associated With Breast Cancer Screening., Susan C Harvey, Ashok Vegesna, Sharon Mass, Janice L. Clarke, Alexandria Skoufalos

College of Population Health Faculty Papers

Abstract Despite ongoing awareness, educational campaigns, and advances in technology, breast cancer screening remains a complex topic for women and for the health care system. Lack of consensus among organizations developing screening guidelines has caused confusion for patients and providers. The psychosocial factors related to breast cancer screening are not well understood. The prevailing algorithm for screening results in significant rates of patient recall for further diagnostic imaging or procedures, the majority of which rule out breast cancer rather than confirming it. For women, the consequences of the status quo range from unnecessary stress to additional out-of-pocket expenses to indirect …

Implementation And Validation Of Aortic Remodeling In Hypertensive Rats, Shijia Zhao, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

A computational framework was implemented and validated to better understand the hypertensive artery remodeling in both geometric dimensions and material properties. Integrating the stress-modulated remodeling equations into commercial finite element codes allows a better control and visualization of local mechanical parameters. Both arterial thickening and stiffening effects were captured and visualized. An adaptive material remodeling strategy combined with the element birth and death techniques for the geometrical growth were implemented. The numerically predicted remodeling results in terms of the wall thickness, inner diameter, and the ratio of elastin to collagen content of the artery were compared with and fine-tuned by …

Fructose-2,6-Bisphosphate Synthesis By 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (Pfkfb4) Is Required For The Glycolytic Response To Hypoxia And Tumor Growth, Jason Chesney, Jennifer Clark, Alden C. Klarer, Yoannis Imbert-Fernandez, Andrew N. Lane, Sucheta Telang

Markey Cancer Center Faculty Publications

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than …

The Role Of Inflammation In Contrast-Induced Nephropathy, Elijah Kwasa, Sudhir Vinayak, Robert Armstrong

Imaging & Diagnostic Radiology, East Africa

Objective: Global incidence of contrast-induced nephropathy (CIN) is 2-5%, but a recent Kenyan study highlighted a local incidence of 12-14% without offering an explanation for the higher incidence. This study proposes that inflammatory states confer a higher relative risk for development of CIN. Our objective was to determine the risk of developing CIN given the presence of an inflammatory state in patients in Kenya.

Methods: Prospective cohort study of patients undergoing a contrast-enhanced CT (CECT) scan in a private university teaching hospital in Kenya and having no known risk factors for CIN. 423 patients were recruited and grouped into those …

Towards Highly-Integrated Stereovideoscopy For In Vivo Surgical Robots, Jay Carlson

Department of Electrical and Computer Engineering: Dissertations, Theses, and Student Research

When compared to traditional surgery, laparoscopic procedures result in better patient outcomes: shorter recovery, reduced post-operative pain, and less trauma to incisioned tissue. Unfortunately, laparoscopic procedures require specialized training for surgeons, as these minimally-invasive procedures provide an operating environment that has limited dexterity and limited vision. Advanced surgical robotics platforms can make minimally-invasive techniques safer and easier for the surgeon to complete successfully. The most common type of surgical robotics platforms -- the laparoscopic robots -- accomplish this with multi-degree-of-freedom manipulators that are capable of a diversified set of movements when compared to traditional laparoscopic instruments. Also, these laparoscopic robots …

Com Outlook Fall 2014, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Tumour-Stroma Crosstalk In The Development Of Squamous Cell Carcinoma., Yok Zuan Lim, Andrew P South

Department of Dermatology and Cutaneous Biology Faculty Papers

Squamous cell carcinoma (SCC) represents one of the most frequently diagnosed tumours and contributes significant mortality worldwide. Recent deep sequencing of cancer genomes has identified common mutations in SCC arising across different tissues highlighting perturbation of squamous differentiation as a key event. At the same time significant data have been accumulating to show that common tumour-stroma interactions capable of driving disease progression are also evident when comparing SCC arising in different tissues. We and others have shown altered matrix composition surrounding SCC can promote tumour development. This review focuses on some of the emerging data with particular emphasis on SCC …

Vital Signs, Fall 2014, Boonshoft School Of Medicine

Vital Signs

A sixty-four page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, a research spotlight, alumni notes, and more.

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …

Regulation Of L1 Expression And Retrotransposition By Melatonin And Its Receptor: Implications For Cancer Risk Associated With Light Exposure At Night., Dawn Deharo, Kristine J Kines, Mark Sokolowski, Robert T Dauchy, Vincent A Streva, Steven M Hill, John P Hanifin, George Brainard, David E Blask, Victoria P Belancio

Department of Neurology Faculty Papers

Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian …

Hypertensive Crisis, Burden, Management, And Outcome At A Tertiary Care Center In Karachi, Aysha Almas, Ayaz Ghouse, Ahmed Raza Iftikhar, Munawar Khursheed

Department of Medicine

Objectives:. Hypertension, if uncontrolled, can lead to hypertensive crisis. We aim to determine the prevalence of hypertensive crisis, its management, and outcome in patients presenting to a tertiary care center in Karachi.
Methods: This was a cross-sectional study conducted at the Aga Khan University, Karachi, Pakistan. Adult inpatients (>18 yrs) presenting to the ER who were known hypertensive and had uncontrolled hypertension were included.
Results. Out of 1336 patients, 28.6% (387) had uncontrolled hypertension. The prevalence of hypertensive crisis among uncontrolled hypertensive was 56.3% (218). Per oral calcium channel blocker; 35.4% (137) and intravenous nitrate; 22.7% (88) …

Low Zinc Levels Is Associated With Increased Inflammatory Activity But Not With Atherosclerosis, Arteriosclerosis Or Endothelial Dysfunction Among The Very Elderly, Ehimen Aneni, Khurram Nasir

All Publications

BACKGROUND:

Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, which are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall.

METHODS:

Subjects (n = 201, 80-102 years) with uneventful cardiovascular history and who were not in use of anti-inflammatory treatments in the last 30-days were enrolled. Daily intake of zinc, lipid profile, plasma C-reactive protein (CRP), plasma zinc, flow-mediated dilation (FMD), carotid ultrasonography and cardiac computed tomography were obtained. Young's Elastic Modulus, Stiffness Index and Artery Compliance were calculated.

RESULTS:

There was no significant …

Method Of Using Ccr3 Binding Agents To Detect Choroidal Neovascularization, Jayakrishna Ambati, Mark E. Kleinman

Ophthalmology and Visual Science Faculty Patents

The results presented herein demonstrate the specific expression of CCR3 in CNV endothelial cells in humans with AMD, and despite the expression of its ligands, eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. The genetic or pharmacological targeting of CCR3 or eotaxins as disclosed herein inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation as it occurred in mice lacking eosinophils or mast cells and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing …

Identification Of A Cytotoxic Form Of Dimeric Interleukin-2 In Murine Tissues, Lucile E. Wrenshall, Suzanne E. Clabaugh, David R. Cool, Prakash Arumugam, William C. Grunwald Jr., Deandra R. Smith, Gino C. Liu, John D. Miller

Department of Surgery Faculty Publications

Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include “traditional” IL-2 …

Metabolomics Analysis Identifies Intestinal Microbiota-Derived Biomarkers Of Colonization Resistance In Clindamycin-Treated Mice, Robin L.P. Jump, Myreen Tomas, Abhishek Deshpande, Curtis J. Donskey

Faculty Scholarship

Background: The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment. Methods: To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of …

Blood-Based Biomarkers For Traumatic Brain Injury: Evaluation Of Research Approaches, Available Methods And Potential Utility From The Clinician And Clinical Laboratory Perspectives, Frederick G. Strathmann, Stefanie Podlog (Nee Schulte), Kyle Goerl, David J. Petron

Athletic Training Collection

Blood-based biomarkers for traumatic brain injury (TBI) have been investigated and proposed for decades, yet the current clinical assessment of TBI is largely based on clinical symptoms that can vary widely amongst patients, and have significant overlap with unrelated disease states. A careful review of current treatment guidelines for TBI further highlights the potential utility of a blood-based TBI biomarker panel in augmenting clinical decision making. Numerous expert reviews on blood-based TBI biomarkers have been published but a close look at the methods used and the astonishing paucity of validation and quality control data has not been undertaken from the …

Unmet Need For Contraception And Unintended Pregnancies Among Women Of Reproductive Age Group: A Situation Analysis, Sumera Aziz Ali, Savera Aziz Ali

School of Nursing & Midwifery

Each year approximately 210 million pregnancies occur worldwide and more than one-third (75 to 80 million) of these are unintended, more than half of these (46 million) unintended pregnancies undergo unsafe abortions. In Pakistan 16% of the births are reported to be unwanted and if the unwanted fertility is eliminated, total fertility in Pakistan would be 3.1 births per woman. Total demand for family planning in Pakistan is 55%, while the contraceptive prevalence rate is 35% and unmet need for family planning is 20%. Reasons for unmet need and unintended pregnancy include lack of permission, fear of side effects, poor …

Knowledge, Attitude And Perceptions About Tetanus And Rabies Among Family Physicians; Results Of A Survey At A Teaching Hospital In Karachi, Pakistan, Siddiqui Sj, Jehan F, Awan S S, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

To assess the knowledge, attitude and perception among family physicians about tetanus and rabies. Setting: This study was conducted at the International Family Physicians Conference held at the Aga Khan University. Method: It was a cross sectional study of convenient sampling. The participants were asked to fill a pre-tested questionnaire comprising of 26 questions. Both open and close ended questions were included. A total of 111 doctors fulfilling the inclusion criteria filled in the questionnaire.Result: Out of 111 doctors who participated in this study, vast majority were working in the urban area (86.5%). 59.5% had not seen a case of …

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …

Oncolog, Volume 59, Number 07, July 2014, Sarah Bronson, Joe Munch, Bryan Tutt, K. Stuyck

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Side Effects of Targeted Molecular Agents Vary According to Mechanism of Action: The main side effects of cytotoxic chemotherapy are notorious. But the side effects of newer, targeted molecular agents are less well known, so patients receiving such drugs may not know what to expect and may require additional guidance from physicians
• INBRIEF: Study Finds Less Frequent Bisphosphonate Treatment Equivalent to Standard Regimen
• RAS Mutation Status May predict Outcomes After Surgery for Colorectal Cancer Liver Metastases
• HPV Test Does Not Replace Pap Test for Cervical cancer Screening: The recent approval of a human papillomavirus (HPV) test for cervical cancer screening …

Division Of Rheumatology New Frontiers, Debra Bergman, John Keenan

New Frontiers

Table of Contents

• Nebraska Arthritis Outcomes Research Center puts UNMC on cutting edge
• Medical education: A fresh perspective
• The reader
• Lupus study becomes international affair
• The puzzle of ‘the loss of self-tolerance’
• An icon in rheumatology
• Registry, research offer insights into RA risk factors
• On the RISE
• RAIN man
• A top-tier team player
• Faculty Publications & Research Awards

Gendered Violence, Hiv Acquisition, And Clinical/Behavioral Research, Liz Barr, Michele Peake Andrasik, Claire Rappoport, Jessica Mooney, Annet Davis Vogel, Lisa Rossi, Amina Alio

Journal of Health Disparities Research and Practice

HIV incidence and prevalence rates for US women continue to increase, especially among Black and Latina women. In addition, the link between violence and HIV acquisition has been well documented. However, the interaction between violence, HIV risk, and HIV acquisition remains an under-addressed issue in current clinical and behavioral HIV research designs. Because violence against women plays an important role in HIV acquisition and transmission, it is imperative for clinical research to address violence in trial design and implementation. In this article, we discuss the prevalence of violence in women’s lives; the role violence plays in HIV acquisition; and the …

Il-4 Signaling Drives A Unique Arginase+/Il-1Β+ Microglia Phenotype And Recruits Macrophages To The Inflammatory Cns: Consequences Of Age-Related Deficits In Il-4rα After Traumatic Spinal Cord Injury, Ashley M. Fenn, Jodie C.E. Hall, John C. Gensel, Phillip G. Popovich, Jonathan P. Godbout

Spinal Cord and Brain Injury Research Center Faculty Publications

Alternative activation of microglia/macrophages (M2a) by interleukin (IL)-4 is purported to support intrinsic growth and repair processes after CNS injury. Nonetheless, alternative activation of microglia is poorly understood in vivo, particularly in the context of inflammation, injury, and aging. Here, we show that aged mice (18-19 months) had reduced functional recovery after spinal cord injury (SCI) associated with impaired induction of IL-4 receptor α (IL-4Rα) on microglia. The failure to successfully promote an IL-4/IL-4Rα response in aged mice resulted in attenuated arginase (M2a associated), IL-1β, and chemokine ligand 2 (CCL2) expression, and diminished recruitment of IL-4Rα⁺ macrophages to …

Targeting The Wnt/Β-Catenin Signaling Pathway In Liver Cancer Stem Cells And Hepatocellular Carcinoma Cell Lines With Fh535, Roberto Gedaly, Roberto Galuppo, Michael F. Daily, Malay B. Shah, Erin Colleen Maynard, Changguo Chen, Xiping Zhang, Karyn A. Esser, Donald A. Cohen, B. Mark Evers, Jieyun Jiang, Brett T. Spear

Surgery Faculty Publications

Activation of the Wnt/β-catenin pathway has been observed in at least 1/3 of hepatocellular carcinomas (HCC), and a significant number of these have mutations in the β-catenin gene. Therefore, effective inhibition of this pathway could provide a novel method to treat HCC. The purposed of this study was to determine whether FH535, which was previously shown to block the β-catenin pathway, could inhibit β-catenin activation of target genes and inhibit proliferation of Liver Cancer Stem Cells (LCSC) and HCC cell lines. Using β-catenin responsive reporter genes, our data indicates that FH535 can inhibit target gene activation by endogenous and exogenously …