Medical Specialties Commons^™

Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra

Dissertations and Theses (Open Access)

The anaplastic lymphoma kinase (ALK) is a single chain transmembrane receptor tyrosine kinase that belongs to the insulin receptor superfamily. Other members of this superfamily include the insulin receptor (IR), type I insulin-like growth factor receptor (IGF-IR), and the leukocyte tyrosine kinase. The common structural finding among these tyrosine kinases is the YXXXYY motif present within their respective tyrosine kinase domains. Binding of its ligands causes ALK receptor homodimerization and protein kinase activation. ALK has been previously shown to play a significant role during early developmental stages. In human embryos, the expression of ALK is mainly seen in …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations and Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …

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 …

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 …

Connecticut's Elderly Population: An In-Depth Analysis Of Current And Future Trends In Elder Care, With A Focus On Dementia And Cognitive Decline, Emily J. Snodgrass

Honors Scholar Theses

The aging population in Connecticut currently represents ~15% of the state’s population but is anticipated to rapidly increase over the next 20 years. My thesis is an examination of the types of interventions and programs currently available for elderly persons with memory impairment and cognitive decline, as well as the challenges associated with caring for a larger elderly population. Data collected from interviews with CT healthcare and research professionals representative of the diverse specialties of aging together with an analysis of current research literature are used to demonstrate the importance of continued research and expansion of appropriate and accessible services …

Oseltamivir-Warfarin Interaction In Hypoplastic Left Heart Syndrome: Case Report And Review., Jonathan B. Wagner, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

An 8-year-old boy with hypoplastic left heart syndrome with a previous history of thrombosis within the inferior vena cava receiving stable warfarin dosing for anticoagulation was diagnosed with influenza B. He was subsequently placed on oseltamivir therapy according to the Centers for Disease Control and Prevention clinical practice guidelines. During the hospitalization, his international normalized ratio steadily increased to supratherapeutic levels and returned to baseline after discontinuation of oseltamivir therapy. This case represents a drug-drug interaction that has not been previously reported in children or adolescents. An extensive review of the pharmacokinetic and pharmacodynamic literature did not uncover a definitive …

Characterization Of Low Density Intracranial Lesions Using Dual-Energy Computed To Mography, Jessica L. Nute

Dissertations and Theses (Open Access)

Calcific and hemorrhagic foci of susceptibility are frequently encountered on routine brain MR studies. Both etiologies cause variations in local magnetic field strength, leading to dark regions on the MR images that cannot be classified. Single-energy CT (SECT) can be used to identify lesions with attenuation over 100 HU as calcific, however lesions with lower attenuation cannot be reliably identified. While calcific lesions are unlikely to cause harm, hemorrhagic lesions carry a risk of subsequent intracranial bleeding; as such, identification of hemorrhage is vital in preventing the inappropriate use of anticoagulant medications in patients with hemorrhagic lesions.

Given there currently …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations and Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

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 …

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, …

Refractory Case Of Esophageal Web In A Male Patient With Alcoholic Liver Disease, Bonnie Patek Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

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 …

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.

Mindfulness-Based Stress Reduction And Transcendental Meditation: Current State Of Research, Adam Holt

Journal of Patient-Centered Research and Reviews

This article summarizes the current state of meditation research, specifically focusing on mindfulness-based stress reduction and transcendental meditation. Despite significant methodological problems with the studies reported to date on the subject, there is consistent evidence that meditation can produce changes in the nervous system and physiology of the meditator, and can help with various psychological markers of well-being. Regarding improvement in specific clinical diseases, research is generally mixed and preliminary. Strong recommendations cannot be made based on current evidence, and further studies are needed. In general, there is a stronger body of evidence supporting mindfulness-based stress reduction than for transcendental …

Acute Superior Vena Cava Syndrome In The Setting Of An Intravascular Device, Rachel Kinney Do, Matthew Miles Do, Shannon Davis Do, Jennifer Rovella Do

Department of Medicine

No abstract provided.

Libman-Sacks Endocarditis “A Wolf In Sheep’S Skin”, Philip Dunn Do, Ryan Rogers Do, James Ross Md

Department of Medicine

No abstract provided.

Pacemaker Induced Takotsubo Cardiomyopathy, Jalaj Garg Md, Kailyn Mann Do, James Kimber Do

Department of Medicine

No abstract provided.

An Unlikely Cause Of Possible Hormone-Dependent Abdominal Pain In Young Fertile Females: A Case Series, Bonnie Patek Do, Hiral Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Coculture Of Staphylococcus Aureus With Pseudomonas Aeruginosa Drives S. Aureus Towards Fermentative Metabolism And Reduced Viability In A Cystic Fibrosis Model, Laura M. Filkins, Jyoti A. Graber, Daniel G. Olson, Emily L. Dolben, Lee Lynd, Sabin Bhuju, George A. O'Toole

Dartmouth Scholarship

The airways of patients with cystic fibrosis are colonized with diverse bacterial communities that change dynamically during pediatric years and early adulthood. Staphylococcus aureus is the most prevalent pathogen during early childhood, but during late teens and early adulthood, a shift in microbial composition occurs leading to Pseudomonas aeruginosa community predominance in ∼50% of adults. We developed a robust dual-bacterial in vitro coculture system of P. aeruginosa and S. aureus on monolayers of human bronchial epithelial cells homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutation to better model the mechanisms of this interaction. We show that P. …

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 …

Disseminated Mycobacterium Tuberculosis With Ulceronecrotic Cutaneous Disease Presenting As Cellulitis, Kelly L. Reed Do, Nektarios I. Lountzis Md

Department of Medicine

No abstract provided.

Darkening And Eruptive Nevi During Treatment With Erlotinib, Stephen Hemperly Do, Tanya Ermolovich Do, Nektarios I. Lountzis Md, Hina A. Sheikh Md, Stephen M. Purcell Do

Department of Medicine

No abstract provided.

Phylogenetic Tree Construction And “Truncal Loss” Analysis Reveal Hidden Associations Between Loss Of Protein Expression In Swi/Snf Complex Components And Tumor Stage And Survival In Clear Cell Renal Cell Carcinoma (Ccrcc), Wei Jiang, Md, Phd, Essel Dulaimi, Karthik Devarajan, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Robert Uzzo, Joseph R. Testa, Haifeng Yang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Polybromo-1 (PBRM1), a targeting subunit of the SWI/SNF chromatin remodeling complex, is mutated at a rate of ~40% in clear cell Renal Cell Carcinoma (ccRCC), second only to VHL. Whether its mutation is correlated with tumor stage is controversial. As other components of the SWI/SNF complex were also reported to be mutated in ccRCC, we aim to examine the protein expression patterns of PBRM1, ARID1A, BRG1, and BRM in ccRCC, and to investigate possible association between their loss of expression and tumor stage, as well as survival. We also included a histone modifier, SETD2, which is recently discovered to …

Assessment For Risk Factors Associated With Local Recurrence In Chordoma, John A. Abraham, Md, Wei Jiang, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Chordoma is a rare but locally aggressive malignant neoplasm showing notochordal differentiation. The clinical differential diagnoses can be extensive, and definitive diagnosis often relies on histopathologic evaluation. Histologically, chordoma shows dual epithelial and mesenchymal differentiation, with various morphologies. Despite surgical resection and use of adjuvant radiation therapy, the local recurrence rate of chordoma remains high. We aim to establish factors associated with the increased risk of recurrence and help guide treatment decisions.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Certain General Anesthetics Used In Pediatrics Hinder Neurological Development In Infants, Michael R. Hirschi

Selected Honors Theses

General anesthetics act by either blocking N-methyl-d-aspartate (NMDA) receptors or over stimulating γ-aminobutyric acid (GABA) receptors.^1–3 The actions of these receptors are responsible for the anesthetized state and are also crucial in the neurological development of infants.^2,4–8 Animal studies, although limited, provide vital information about general anesthesia’s neurotoxicity its hindrance of neurological development. Exposure to general anesthesia can severely hinder proper neuronal migration, synaptogenesis, and can drastically increase neuronal apoptosis in infant animals.^9–16 General anesthetics are more neurotoxic to infant animals in combination compared to individually.^10,16,17 Additionally, multiple exposures to general anesthesia tend to have compounding …

The Therapeutic Role Of Turmeric In Treatment And Prevention Of Alzheimer’S Disease, Rylan M. Mcquade

Selected Honors Theses

As a devastating neurological condition that expends millions of lives each year, Alzheimer’s disease (AD) is a subject of intense investigation.¹ Although AD has been known for over a century, the precise mechanisms that underlie AD pathogenesis and development are still poorly understood. The Alzheimer phenotype is typified by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), causing researchers to notice several key enzymes implicated in this process.¹ Most notable are β and γ secretases (which drive Aβ plaque production) and phospholipase

A₂ (which stimulates major cascade activation through the specific cleavage of fatty acyl esters). …

C-Anca Positive Necrotizing Crescentic Glomerulonephritis With Linear Immunoglobulin Staining, Akshita Mehta

GW Research Days 2015

Necrotizing crescentic glomerulonephritis is found in anti-glomerular basement membrane (GBM) disease (Type 1), immune complex (Type 2) deposition and anti-neutrophil cytoplasmic (ANCA)-related disease (Type 3).

ANCA positive glomerulonephritis is typically characterized on renal biopsy as pauci-immune, with mild or absent glomerular staining for immunoglobulin, or complement staining by immunofluorescence.

Rare cases of concomitant p-ANCA plus linear immunofluorescence pattern staining have been discussed, however none with prior association with c-ANCA.

We report a case of systemic c-ANCA pulmonary-renal syndrome with anti-GBM-disease-typical linear staining on renal biopsy immunofluorescence.

The Cognitive Effects Of Chronic Malnutrition And Environment On Working Memory And Executive Function In Children, Kristiana E. Morgan

Independent Study Project (ISP) Collection

Chronic malnutrition, or stunting, occurs frequently in many developing countries such as Uganda. Stunting hinders physical growth and has been associated with delayed cognitive development, especially in young children. This study examined the effect of stunted growth on the function of cognitive processes involving the working memory and executive functions using neuropsychological assessments. Additionally, this study compared cognitive performances among rural and urban populations to analyze the environmental background differences which may affect cognition.

Population samples of fifteen five year old children classified as rural adequately nourished, rural stunted and urban adequately nourished were examined. Tests for working memory and …