Digital Commons Network^™

Adiponectin Attenuates Lung Fibroblasts Activation And Pulmonary Fibrosis Induced By Paraquat., Rong Yao, Yu Cao, Ya-Rong He, Wayne Bond Lau, Zhi Zeng, Zong-An Liang

Department of Emergency Medicine Faculty Papers

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different …

Frederic E. Mohs, M.D. (1910-2002): Physician And Innovator., Nicholas A. Ross, B.A., Nazanin Saedi, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

Frederic “Fred” E. Mohs was an “honest and good man, a ferocious and courageous worker.”1 Husband, father of three, prolific writer, and speaker, Dr. Mohs was a pioneer in many fields. His desire to do good was fueled by his enthusiasm for scientific advancement (Frederic E. Mohs Jr., personal communication, 2014). He is most remembered for Mohs Micrographic Surgery, formerly chemosurgery, which allows visualization and examination of all tissue margins achieving skin cancer cure rates of 98 to 99 per cent.

Fibroblast Growth Factor 9 Regulation By Micrornas Controls Lung Development And Links Dicer1 Loss To The Pathogenesis Of Pleuropulmonary Blastoma, Yongjun Yin, Angela M. Castro, Marrit Hoekstra, Thomas J. Yan, Ajay C. Kanakamedala, Louis P. Dehner, D. Ashley Hill, David M. Ornitz

Pathology Faculty Publications

Pleuropulmonary Blastoma (PPB) is the primary neoplastic manifestation of a pediatric cancer predisposition syndrome that is associated with several diseases including cystic nephroma, Wilms tumor, neuroblastoma, rhabdomyosarcoma, medulloblastoma, and ovarian Sertoli-Leydig cell tumor. The primary pathology of PPB, epithelial cysts with stromal hyperplasia and risk for progression to a complex primitive sarcoma, is associated with familial heterozygosity and lesion-associated epithelial loss-of-heterozygosity of DICER1. It has been hypothesized that loss of heterozygosity of DICER1 in lung epithelium is a non-cell autonomous etiology of PPB and a critical pathway that regulates lung development; however, there are no known direct targets of epithelial …

Consequence Of The Tumor-Associated Conversion To Cyclin D1b., Michael A Augello, Lisa D Berman-Booty, Richard Carr, Akihiro Yoshida, Jeffry L Dean, M J Schiewer, Felix Y Feng, Scott A Tomlins, Erhe Gao, Walter J Koch, Jeffrey L Benovic, John Alan Diehl, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Clinical evidence suggests that cyclin D1b, a variant of cyclin D1, is associated with tumor progression and poor outcome. However, the underlying molecular basis was unknown. Here, novel models were created to generate a genetic switch from cyclin D1 to cyclin D1b. Extensive analyses uncovered overlapping but non-redundant functions of cyclin D1b compared to cyclin D1 on developmental phenotypes, and illustrated the importance of the transcriptional regulatory functions of cyclin D1b in vivo. Data obtained identify cyclin D1b as an oncogene, wherein cyclin D1b expression under the endogenous promoter induced cellular transformation and further cooperated with known oncogenes to promote …

Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik

Dartmouth Scholarship

Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of …

Prevalence Of Neurocognitive Test Failure Following Exertion In Athletes Recovering From Concussion, Caitlin Laura Zaring

Health, Human Performance and Recreation Undergraduate Honors Theses

The current return-to-play (RTP) protocol in place for an athlete recovering from a concussion is based on the subjective measure of self-report rather than more objective tools such as computerized neurocognitive testing. Because of this, it is possible that athletes downplay or lie about symptoms they are experiencing in order to expedite the RTP process. The purpose of the current study was to examine the frequency of post-exertional neurocognitive test failure in a sample of high school athletes recovering from concussion that underwent a standardized exertional RTP protocol. This research project used a de-identified medical records review of neurocognitive data …

Management Of Complications Of Wrist Arthroplasty And Wrist Fusion., Michael P. Gaspar, Patrick M Kane, Eon K. Shin

Department of Orthopaedic Surgery Faculty Papers

The human wrist joint is unique from functional and anatomic standpoints. Numerous articulations exist within the wrist that allow for many options for partial wrist fusion and arthroplasty. In cases of pancarpal disease, fusion or arthroplasty of the entire wrist joint can be performed. Because of the high functional demand of the wrist, many of these surgical options can fail, leading to devastating complications. This article addresses the types of fusions and arthroplasties available for the wrist and discusses the potential complications associated with each. Methods to prevent these complications are presented and those to treat them once they have …

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …

Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque

Department of Emergency Medicine

ABSTRACT Aluminum phosphide is commonly used as a rodenticide and insecticide and is one of the most fatal poisons. The active ingredient is Phosphine gas which inhibits cytochrome oxidase and cellular oxygen utilization. The clinical symptoms are due to multiorgan involvement including cardiac toxicity which is the most common cause of mortality. Severity of clinical manifestations depends upon the amount of the gas to which a person is exposed. There is no specific antidote available. High index of suspicion and early aggressive treatment is the key to success. We report 2 cases of aluminum phosphide toxicity in 2 families due …

Cancer Associated Fibroblast Derived Angiogenic Factor Mfap5 In Ovarian Cancer Progression, Sze Lee Cecilia Leung

Dissertations and Theses (Open Access)

Advanced stage ovarian cancer is the most lethal gynecologic malignancy. No major improvement on patient survival has been achieved in the past decade. Therefore, identification of predictive or prognostic markers and further understanding of the molecular mechanisms in ovarian cancer progression are of paramount importance.

While cancer cells have always been the targets for the identification of prognostic and predictive markers, the potential for developing new diagnosis and treatments based on the tumor supporting stromal microenvironment is relatively unexplored. Using transcriptome profiling analysis on microdissected stromal and epithelial components of normal and malignant ovarian tissues, we identified a gene signature …

Gene Set Analysis Of Post-Lactational Mammary Gland Involution Gene Signatures In Inflammatory And Triple Negative Breast Cancer, Arvind Bambhroliya

Dissertations and Theses (Open Access)

With each cycle of pregnancy and lactation, the mammary gland undergoes dramatic changes. Clarkson et al. (2004) and Stein et al. (2004) conducted a detailed analysis of these changes in the mouse mammary gland. Their results showed that tissue remodeling during post-lactational involution period mimics wound healing and tumorigenesis like pathological conditions. This indicates that post-lactational involution may create the microenvironment that initiates the development of precancerous mammary cells and promotes the progression of precancerous cells into cancer cells. Moreover, epidemiological studies have found that triple-negative (TN) breast cancer (BC) is associated with lower frequency and duration of breastfeeding compared …

Central Line-Associated Blood Stream Infections In Pediatric Intensive Care Units: Longitudinal Trends And Compliance With Bundle Strategies., Jeffrey D. Edwards, Carolyn T. Herzig, Hangsheng Liu, Monika Pogorzelska-Maziarz, Philip Zachariah, Andrew W. Dick, Lisa Saiman, Patricia W. Stone, E. Yoko Furuya

College of Nursing Faculty Papers & Presentations

BACKGROUND: Knowing the temporal trend central line-associated bloodstream infection (CLABSI) rates among U.S. pediatric intensive care units (PICUs), the current extent of central line bundle compliance, and the impact of compliance on rates is necessary to understand what has been accomplished and can be improved in CLABSI prevention.

METHODS: This is a longitudinal study of PICUs in National Healthcare Safety Network hospitals and a cross-sectional survey of directors and managers of infection prevention and control departments regarding PICU CLABSI prevention practices, including self-reported compliance with elements of central line bundles. Associations between 2011-2012 PICU CLABSI rates and infection prevention practices …

Urinary Phthalate Metabolite Concentrations And Blood Glucose Levels During Pregnancy, Candace A. Robledo, Jennifer D. Peck, Julie A. Stoner, Antonia M. Calafat, Hélène Carabin, Linda Cowan, Jean R. Goodman

School of Medicine Publications

Purpose: To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM).

Methods: Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine …

Local Modulation And Measurement Of Macrophage-Derived Bioactive Proteins From Implanted Biomaterials In Rat, Geetika Bajpai

Graduate Theses and Dissertations

Fibrosis around the implanted medical devices is a severe problem that can plague long-term device reliability. Activation of macrophage phenotype (macrophage polarization) has emerged as a new and possible means for reducing fibrosis in the fields of biomaterials and regenerative medicine. Macrophages are phagocytic cells that respond to microenvironmental cues that direct their phenotype. Macrophage activation has been widely studied in mouse and human in the context of tumor biology, yet little information is available regarding how macrophage activation could be used in a biomaterials context. Further, rats rather than mice are the common subjects in biomaterials experiments. A significant …

Killer Cell Activation By A Novel Multifunctional Protein: An Immuno/Gene Therapy For Cancer, Ashlee Tietje

All Dissertations

One of the characteristics of advanced tumors is the evasion of the immune system. There are multiple methods that tumor cells employ to achieve this including reducing the expression of activating ligands on the cell surface and a shift in the tumor microenvironment toward pro-tumor cytokines. The purpose of this research is to develop a novel bifunctional fusion protein that will target these two deficiencies in the tumor microenvironment and activate killer cells that are already present. The proposed protein combines the extracellular domain of a ligand for the killer cell activating receptor NKG2D and Interleukin-12 (IL-12). It is hypothesized …

Evaluation Of Tulane Virus As A Surrogate For The Study Of Human Norovirus, Sabastine Eugene Arthur

Graduate Theses and Dissertations

Among all known causes of acute gastroenteritis, human noroviruses (HuNoV) are the primary cause (68%) of outbreaks and are associated with 78% of illnesses, 46% of hospitalizations, and 86% of deaths. The main obstacle to studying the pathogenesis of HuNoV is the lack of cell culture system and small animal model. Murine norovirus (MNV) and feline calicivirus (FCV) have been utilized as model surrogate viruses to study HuNoV. In this research, a more recent surrogate virus, Tulane virus (TV), was evaluated for physicochemical stability and environmental persistence. The primary goal was to determine the suitability of TV as a surrogate …

Characterization And Investigation Of Fungi Inhabiting The Gastrointestinal Tract Of Healthy And Diseased Humans, Mallory J. Suhr

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Gastrointestinal microbiome studies have failed to include fungi in total community analyses. As a result, their diversity and function in the gut is poorly understood. Recent work has begun to uncover the role intestinal fungi play in diet, immune system development, interactions with other microorganisms in the gut, and pathogenesis of diseases. Advances in sequencing technologies allow for the ability to profile the fungal gut microbiome (“mycobiome”) in healthy and diseased states. This thesis explores the mycobiome in 1) healthy humans with a vegetarian diet and 2) pediatric small bowel transplant recipients that develop fungal bloodstream infections.

The gut mycobiome …

Compensatory Fetal Membrane Mechanisms Between Biglycan And Decorin In Inflammation., Luciana Batalha De Miranda De Araujo, Casie E Horgan, Abraham Aron, Renato V. Iozzo, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, …

Epidemiology Of Karachi Road Traffic Crash Mortality In 2013, Rashid Jooma, Masood Ali Shaikh

Department of Surgery Docs

Abstract

Road Traffic Crash (RTC) is the eighth leading cause of death globally. In a recent World Health Organization report, there were 5,192 RTC deaths reported from Pakistan in 2010. The Road Traffic Injury Research and Prevention Center (RTIRPC) is a unique public-private public health enterprise in Karachi, and collects data from five major public and private hospitals' emergency departments in the city. Cumulatively, 1130 deaths were recorded in the year 2013. Males accounted for 981 (86.8%) deaths. The most vulnerable decades of life were twenties and thirties; accounting for 307 (27.2%) of all deaths. In terms of involvement of …

Loss Of Cbl And Cbl-B Ubiquitin Ligases Abrogates Hematopoietic Stem Cell Quiescence And Sensitizes Leukemic Disease To Chemotherapy., Wei An, Scott A. Nadeau, Bhopal C. Mohapatra, Dan Feng, Neha Zutshi, Matthew D. Storck, Priyanka Arya, James E. Talmadge, Jane L. Meza, Vimla Band, Hamid Band

Journal Articles: Pathology and Microbiology

Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is unclear. Here we demonstrate that HSC expansion and MPD development upon combined Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated that DKO HSCs exhibit reduced quiescence associated with compromised reconstitution …

Powerful Anti-Tumor And Anti-Angiogenic Activity Of A New Anti-Vascular Endothelial Growth Factor Receptor 1 Peptide In Colorectal Cancer Models, Valeria Cicatiello, Ivana Apicella, Laura Tudisco, Valeria Tarallo, Luigi Formisano, Annamaria Sandomenico, Younghee Kim, Ana Bastos-Carvalho, Augusto Orlandi, Jayakrishna Ambati, Menotti Ruvo, Roberto Bianco, Sandro De Falco

Ophthalmology and Visual Science Faculty Publications

To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit …

Youtube As A Source For Patient Education Regarding Percutaneous Mitraclip, Katie Mastoris Do, Jalaj Garg Md, Nainesh C. Patel Md

Department of Medicine

No abstract provided.

Antiviral Activity Of The Human Cathelicidin, Ll-37, And Derived Peptides On Seasonal And Pandemic Influenza A Viruses., Shweta Tripathi, Guangshun Wang, Mitchell White, Li Qi, Jeffery Taubenberger, Kevan L. Hartshorn

Journal Articles: Pathology and Microbiology

Human LL-37, a cationic antimicrobial peptide, was recently shown to have antiviral activity against influenza A virus (IAV) strains in vitro and in vivo. In this study we compared the anti-influenza activity of LL-37 with that of several fragments derived from LL-37. We first tested the peptides against a seasonal H3N2 strain and the mouse adapted H1N1 strain, PR-8. The N-terminal fragment, LL-23, had slight neutralizing activity against these strains. In LL-23V9 serine 9 is substituted by valine creating a continuous hydrophobic surface. LL-23V9 has been shown to have increased anti-bacterial activity compared to LL-23 and we now show slightly …

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

The Effects Of Adderall On Maternal And Fetal Health, Alyson Brady

Honors Theses

Information available for woman prescribed Adderall to treat ADHD and the effects that it may have on her fetus is limited. However, Adderall and methamphetamine have similar pharmacological and addictive qualities. This paper is concerned with whether there is an adequate approach to treatment that balances the needs of the mother and the fetus. With Adderall use becoming more prevalent, it is essential that society is aware of the physiology and pharmacology of this drug, as well as, the need for more research on this subject to be produced.

Kinase-Independent Role Of Cyclin D1 In Chromosomal Instability And Mammary Tumorigenesis., Mathew C Casimiro, Gabriele Disante, Marco Crosariol, Emanuele Loro, William Dampier, Adam Ertel, Zuoren Yu, Elizabeth A Saria, Alexandros Papanikolaou, Z Li, Chenguang Wang, Sankar Addya, Michael P. Lisanti, Paolo Fortina, Robert D Cardiff, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1-/- mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led …

Crosstalk Between Desmoglein 2 And Patched 1 Accelerates Chemical-Induced Skin Tumorigenesis., Donna M Brennan-Crispi, Claudia Hossain, Joya Sahu, Mary Brady, Natalia A Riobo, M G Mahoney

Department of Biochemistry and Molecular Biology Faculty Papers

Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 on Ptc1+/lacZ background enhanced epidermal proliferation and interfollicular activation of the Hh pathway. Furthermore, in response to DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous …

Irreversible Electroporation Of Malignant Lesions: An Institution Experience, Benjamin Bates, Minia Hellan, Shannon Kauffman, James R. Ouellette

Department of Surgery Faculty Publications

Background: Irreversible electroporation (IRE) is a tumor ablation technique where short, high-voltage pulses are applied to tumors to permeabilize the cell membranes. Since no thermal energy is created, it can be used near vital structures. We report our experience in a wide array of anatomic locations and on diverse oncologic processes.

Methods: We performed a retrospective review of all IRE cases performed at our institution from September 2010 to September 2013. Patients were evaluated for peri-operative morbidity, mortality, and oncologic outcome.

Results: Twenty-seven patients underwent IRE during 16 laparotomies and 12 CT guided percutaneous procedures. Anatomic locations: 9 liver, 7 …

What Did We Learn About Vads In 2014?, Maya Guglin

The VAD Journal

No abstract provided.