Digital Commons Network^™

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

Progesterone And Preterm Birth Prevention: Translating Clinical Trials Data Into Clinical Practice, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE:

We sought to provide evidence-based guidelines for using progestogens for the prevention of preterm birth (PTB).

METHODS:

Relevant documents, in particular randomized trials, were identified using PubMed (US National Library of Medicine, 1983 through February 2012) publications, written in English, which evaluate the effectiveness of progestogens for prevention of PTB. Progestogens evaluated were, in particular, vaginal progesterone and 17-alpha-hydroxy-progesterone caproate. Additionally, the Cochrane Library, organizational guidelines, and studies identified through review of the above were utilized to identify relevant articles. Data were evaluated according to population studied, with separate analyses for singleton vs multiple gestations, prior PTB, or short …

Novel Napi-Iic Mutations Causing Hhrh And Idiopathic Hypercalciuria In Several Unrelated Families: Long-Term Follow-Up In One Kindred., Y Yu, S R. Sanderson, M Reyes, A Sharma, N Dunbar, Tarak Srivastava, H Jüppner, C Bergwitz

Manuscripts, Articles, Book Chapters and Other Papers

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous …

Significant Differences In Markers Of Oxidant Injury Between Idiopathic And Bronchopulmonary-Dysplasia-Associated Pulmonary Hypertension In Children, Kimberly B. Vera, Donald Moore, English Flack, Michael Liske, Marshall Summar

Pediatrics Faculty Publications

While oxidant stress is elevated in adult forms of pulmonary hypertension (PH), levels of oxidant stress in pediatric PH are unknown. The objective of this study is to measure F₂-isoprostanes, a marker of oxidant stress, in children with idiopathic pulmonary hypertension (IPH) and PH due to bronchopulmonary dysplasia (BPD). We hypothesized that F₂-isoprostanes in pediatric IPH and PH associated with BPD will be higher than in controls. Plasma F₂-isoprostanes were measured in pediatric PH patients during clinically indicated cardiac catheterization and compared with controls. F₂-Isoprostane levels were compared between IPH, PH due …

Ron - The Con In Colorectal Carcinoma, Shikha Tarang, J. Wang

Journal Articles: Eppley Institute

The recepteur d’origine nantais (RON) is a member of MET family of receptor tyrosine kinase (RTKs), an overexpression of which has been observed in several cancers. The expression of RON gene is required during embryonic development and also plays critical roles in regulating macrophage inflammatory response. In CRC, the overexpression of moderate RON activity contributes to their oncogenic potential by regulating several key processes such as proliferation, motility and resistance to apoptosis. Interestingly, an aberrant RON expression is often associated with the generation of several splice variants with unique transforming activities. The targeting of RON signaling pathway by the use …

Parkinson’S Disease: Molecular Mechanisms And Treatments, Delia Vahey

Senior Honors Theses

Parkinson’s disease is a motor system disorder that is caused primarily by the loss of dopamine-producing brain cells. The most affected brain structure is the pars compacta of the substantia nigra. This area of the brain is essential to the control of voluntary movement, and so its impairment leads to symptoms such as tremors, rigidity, and impaired balance. The neuronal protein alpha-synuclein has been shown to be heavily involved in the pathogenesis of the disease at the cellular level. The currently available treatments for PD mainly target dopamine regulation, and there been no cure developed for the disease at present. …

The Future Of Orthopedic Medicine, Brian M. Willie

Honors Theses

Orthopedic medicine is changing and advancing along with the rest of the medical field. There are new concepts developing in orthopedic trauma, tissue engineering, collagen, nano-orthopedics, biodegradable implants, robot-assisted surgery and more. The changes to orthopedics are focused on the changing needs of patients, and orthopedists are also changing their ways to keep up with the demand required of them. Advancements in fields such as stem cells, imaging technology, functional tissue engineering, and robotic assistance will further propel the diagnostic and treatment abilities of orthopedic medicine. In order to accomplish these advancements and provide for the needs of the future …

An Investigation Of The Effects Of Pitocin For Labor Induction And Augmentation On Breastfeeding Success, Megan J. Lewis

Scripps Senior Theses

Rates of labor induction and augmentation have been increasing in recent decades (Glantz, 2005). According to the Listening to Mothers II survey, half of all labors in the U.S. are induced or augmented with Pitocin or other synthetic form of the hormone oxytocin (Declercq et al., 2006). Oxytocin, a naturally occurring hormone released in the pituitary gland, is involved in the stimulation of uterine contractions during labor and in the milk ejection reflex during breastfeeding, and research suggests it also has various effects on the brain, such as eliciting maternal behavior. However, studies have shown that exogenous oxytocin can interfere …

Personal Construction Of Cough Medicine Among Young Substance Abusers In Hong Kong, Daniel T. L. Shek

Pediatrics Faculty Publications

Although cough medicine abuse is a growing problem in many places, there is no study examining the views of young substance abusers toward cough medicine. The objective of this study was to examine personal constructions of cough medicine abusers via the repertory grid tests (N = 11). Several observations are highlighted from the study. First, personal constructions of cough medicine were mixed, including the benefits and harmful effects of its abuse. Second, although the informants perceived cough medicine to be addictive and harmful, they perceived cough medicine to be less addictive and less harmful than did heroin. Third, while the …

John H. Moore Jr., Md Clinical Professor Of Plastic Surgery And Former Alumni Association President

Jefferson Surgical Solutions

John H. Moore Jr., MD, longtime clinical professor of plastic surgery at Jefferson and former president of the Jefferson Medical College (JMC) Alumni Association, died at home on September 26, 2011.

Born in Pittsburgh in 1953, Moore received his bachelor’s degree from the University of Virginia, where he stayed on for his medical degree. After completing his internship at Thomas Jefferson University Hospital in 1980, he completed a general surgery residency. He then participated in a fellowship in hand surgery and microsurgery at Jefferson and completed a plastic surgery residency at the Eastern Virginia Graduate School of Medicine.

In 1987, …

News In Brief

Jefferson Surgical Solutions

Alejandro Perez, MD, has joined the Jefferson Vascular Center at Methodist Hospital with a dual faculty appointment in the Departments of Medicine and Surgery at Thomas Jefferson University. Dr. Perez completed his residency and fellowship training in vascular medicine at the Cleveland Clinic. He specializes in deep vein thrombosis, pulmonary embolism and hyperbaric oxygen therapy.

Ehyal Shweiki, MD, FACS, has joined the Division of Acute Care Surgery. Dr. Shweiki is fellowship-trained in both cardiothoracic surgery (University of Louisville) and surgical critical care (Washington University/Barnes Jewish Hospital). He also holds an MS in Bioethics. He will serve patients at our …

Zhi Ven Fong, Jmc ’12 Secretary, Gibbon Surgical Society

Jefferson Surgical Solutions

Born and raised in Kuala Lumpur, Malaysia, Zhi Ven Fong spent his first two years of medical school at the International Medical University (IMU) in Malaysia before coming to Philadelphia to study at Jefferson Medical College. And while medical school alone would be enough to keep most students busy, Zhi, 23, has seized every opportunity to build his skills and knowledge as a physician scientist.

“I aspire to be a leader in an academic field like surgery, so I realized I needed experience in research,” Zhi says. “After consulting with senior students, I reached out to Dr. Ernest Rosato, who …

Building A Legacy Of Hope Against Ovarian Cancer

Jefferson Surgical Solutions

Cancer – let alone a rare form of ovarian cancer – wasn’t on Sandy Parvin’s radar when her 11-year-old daughter Sarah was nauseous and vomiting for a few days in the spring of 2005.

“Honestly, we thought she had the flu,” Sandy said. The virus had been going around so Sandy took her daughter to their family physician.

The doctor sent Sarah to the hospital to get some IV fluids. It quickly turned into a parent’s worst nightmare. Sarah was put on a heart monitor and four physicians were there asking questions. Her calcium levels were far too high.

“They …

Gerald A. Isenberg, Md, Facs

Jefferson Surgical Solutions

As Professor of Surgery, Division of Colorectal Surgery; Director, Surgical Undergraduate Education, Jefferson Medical College (JMC); Program Director, Colorectal Residency Program, Thomas Jefferson University Hospital; and Chair, Curriculum Committee, JMC, Gerald A. Isenberg, MD, FACS, is equally focused on – and passionate about – clinical practice and medical education.

Indeed, as he reflects on his career at Jefferson, which spans nearly 25 years, Dr. Isenberg is appreciative of the opportunity to build a busy and vibrant colorectal surgery practice. But he clearly also values his experiences as an educator – particularly the many opportunities to lead and innovate.

In years …

Jefferson Researchers Identify Potential Diagnostic, Prognostic Tools For Pancreatic Cancer

Jefferson Surgical Solutions

When it comes to diagnosing and treating cancer, early detection is important. While other cancers can be identified through routine screenings, pancreatic cancer has been notoriously difficult to diagnose early. After pancreatic cancer is diagnosed, the optimal course of treatment is not always clear.

Hwyda Arafat, MD, PhD, Associate Professor of Surgery at Thomas Jefferson University and co-director of the Jefferson Pancreatic, Biliary and Related Cancers Center, and Jordan M. Winter, MD, Assistant Professor of Surgery, are working to change that.

Together with Mon-Li Chu, PhD, Professor and Vice Chair of the Department of Dermatology and Cutaneous Biology, Dr. Arafat …

Overview

Jefferson Surgical Solutions

Charles J. Yeo, MD, FACS

Samuel D. Gross Professor and

Chair, Department of Surgery

In this issue, Surgical Solutions focuses on our trauma expertise, recent progress in bench research, the contributions of Dr. Gerald Isenberg, insights from medical student Zhi Ven Fong, and pays tribute to Dr. John Moore. A very busy issue!

I was moved by a recent editorial in the New England Journal of Medicine dated February 16, 2012. In the piece entitled “What We Talk About When We Talk About Health Care Costs”, Peter Neumann of Tufts University quotes from the American College of Physicians Ethics Manual, …

Survival Motor Neuron Protein Deficiency Impairs Myotube Formation By Altering Myogenic Gene Expression And Focal Adhesion Dynamics, Katherine V. Bricceno, Tara Martinez, Evgenia Leikina, Stephanie Duguez, Terence A. Partridge, Leonid V. Chernomordik, Kenneth H. Fischbeck, Charlotte J. Sumner, Barrington G. Burnett

Pediatrics Faculty Publications

While spinal muscular atrophy (SMA) is characterized by motor neuron degeneration, it is unclear whether and how much survival motor neuron (SMN) protein deficiency in muscle contributes to the pathophysiology of the disease. There is increasing evidence from patients and SMA model organisms that SMN deficiency causes intrinsic muscle defects. Here we investigated the role of SMN in muscle development using muscle cell lines and primary myoblasts. Formation of multinucleate myotubes by SMN-deficient muscle cells is inhibited at a stage preceding plasma membrane fusion. We found increased expression and reduced induction of key muscle development factors, such as MyoD and …

Prioritizing Interventions And Research To Address The Cancer Disparities Of Arizona’S American Indian Population, Norman J. Petersen, Sujata Joshi, Tim Flood, Kathryn Coe

Journal of Health Disparities Research and Practice

The aim of the Southwest American Indian Collaborative Network (SAICN) is to reduce cancer disparities by closing the gap between community needs and the promise of cancer prevention and cure through participatory education, training and research programs. In an effort to provide evidence-based recommendations and promote the use of relevant data in tribal communities, the SAICN Data and Evaluation Core developed two comparison matrices that present scientifically sound practices for use by community health decision makers in prioritizing activities likely to reduce the irrespective community’s burden of cancer. In their current configurations, Matrix A considers those cancers for which prevention …

Genetics Of Clusterin Isoform Expression And Alzheimer's Disease Risk, I-Fang Ling, Jiraganya Bhongsatiern, James F. Simpson, David W. Fardo, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted …

Comparing Risk Factors Of Hiv Among Hijra Sex Workers In Larkana And Other Cities Of Pakistan: An Analytical Cross Sectional Study, Arshad Altaf, Aysha Zahidie, Ajmal Agha

Community Health Sciences

Background

In 2005, Pakistan was first labeled as a country with concentrated epidemic of Human Immunodeficiency Virus (HIV). This was revealed through second generation surveillance conducted by HIV/AIDS Surveillance Project (HASP). While injection drug users (IDUs) were driving the epidemic, subsequent surveys showed that Hijra (transgender) sex workers (HSWs) were emerging as the second most vulnerable group with an average national prevalence of 6.4%. An exceptionally high prevalence (27.6%) was found in Larkana, which is a small town on the right bank of river Indus near the ruins of Mohenjo-Daro in the province of Sindh. This paper presents the risk …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …

Regulation Of Natural Killer Cells: Ship-1, 2b4, And Immunomodulation By Lenalidomide, Nicole Renee Fortenbery

USF Tampa Graduate Theses and Dissertations

Natural Killer cells (NK) are critical components of the innate immune system. Often referred to by their morphology, these large granular lymphocytes (LGLs) are bone marrow-derived lymphocytes and can be found throughout the body. NK cells reside in the liver, lymph nodes, spleen, thymus, and mucosal-associated lymphoid tissues (MALT). Importantly, NK cells also circulate throughout the blood where they function as surveyors of the body and are armed to eliminate malignant, infected, damaged, or foreign cells.

NK cells function by a dual receptor system. That is, NK receptors are broadly categorized as inhibitory or activating. It is a fine balance, …

A Heuristic Solution Of The Identifiability Problem Of The Age-Period-Cohort Analysis Of Cancer Occurrence: Lung Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

BACKGROUND: The Age-Period-Cohort (APC) analysis is aimed at estimating the following effects on disease incidence: (i) the age of the subject at the time of disease diagnosis; (ii) the time period, when the disease occurred; and (iii) the date of birth of the subject. These effects can help in evaluating the biological events leading to the disease, in estimating the influence of distinct risk factors on disease occurrence, and in the development of new strategies for disease prevention and treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel approach for estimating the APC effects on disease incidence rates in the frame of …

Rituximab Induces Sustained Reduction Of Pathogenic B Cells In Patients With Peripheral Nervous System Autoimmunity., Michael A Maurer, Goran Rakocevic, Carol S Leung, Isaak Quast, Martin Lukačišin, Norbert Goebels, Christian Münz, Hedda Wardemann, Marinos Dalakas, Jan D Lünemann

Department of Neurology Faculty Papers

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal …

Com Outlook Spring 2012, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Malnutrition In Young Pakistani Children, Shela Akbar Ali Hirani

School of Nursing & Midwifery

Background: Pakistan is a developing country with the second highest infant and child mortality rate in South Asia. In this region, malnutrition underlies much of the high infant and under five child morbidity and mortality rates. Although struggle to tackle the issue of malnutrition among young Pakistani children has been going on since many decades, till yet a realistic solution for this growing problem has not been found.

Objective: This paper aims at reviewing literature to analyse the biological, maternal, socio-cultural, environmental, and politico-economical determinants of malnutrition among young children in Pakistan so that need based interventions can …

Psychostimulant Drug Abuse And Personality Factors In Medical Students, Joshua T. Buchner, Md, Duc M. Vu, Md, Mohammadreza Hojat

CRMEHC Faculty Papers

Purpose:

This study was designed to examine the prevalence of psychostimulant drug abuse among medical students and to test the hypothesis that medical students who use psychostimulant drugs for non-medical reasons are characterized by a sensation seeking and aggressive-hostility personality and exhibit lower empathy.

Dyschronic, A Drosophila Homolog Of A Deaf-Blindness Gene, Regulates Circadian Output And Slowpoke Channels., James E C Jepson, Mohammad Shahidullah, Angelique Lamaze, Drew Peterson, Huihui Pan, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause …

Oncolog, Volume 57, Number 04, April 2012, Joe Munch, Bryan Tutt

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

• Biology, More Than Chemotherapy Timing, Drives Locoregional Recurrence in Patients Who Undergo Breast-Conserving Therapy: The management of breast cancer, like that of many cancers, often requires a little bit of everything: surgery, radiation therapy, and systemic therapy with chemotherapeutic drugs or other agents
• New Treatments for Acute Myelogenous Leukemia May Improve Patient Outcomes: Acute myelogenous leukemia (AML) is an aggressive and deadly malignancy, nut new treatments are being developed that may prolong remissions
• HOUSE CALL: Controlling Nausea and Vomiting from Chemotherapy: Several techniques can be used to prevent or reduce this side effect

(Iv) Managing Bone Loss Of The Femur And Tibia In Revision Total Knee Arthroplasty, Glenn J. Kerr, M.D, Joseph A. Karam, M.D., Javad Parvizi, M.D., Frcs

Rothman Institute Papers

The number of primary and revision knee arthroplasty procedures performed yearly is steadily increasing. The management of bone loss at the time of revision surgery will play an integral role in the longevity and function of these knees into the future. There are a variety of options for addressing these defects varying from the use of polymethylmethacrylate bone cement, metal augments, sleeves, cones and large allograft replacements. This manuscript discusses the evaluation, classification and management of bone loss of the distal femur and proximal tibia.