Medicine and Health Sciences Commons^™

Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert

All ETDs from UAB

TLT2 is one of four receptors conserved between mouse and human within the TREM locus, and is expressed on B cells, macrophages, and neutrophils. TLT2 ligation on murine macrophages induces the production of chemokines and growth factors, as evidenced by ex vivo treatment with anti-TLT2 mAbs. This treatment did not lead to the upregulation of activation markers such as CD69 or costimulatory molecules such as CD80 and CD86, indicating a specific response following TLT2 ligation. This is recapitulated in vivo following injection of anti-TLT2 mAbs resulting in the production of chemokines and growth factors, which ultimately lead to enhanced neutrophil …

Ampa Receptor Trafficking In Schizophrenia, John Hammond

All ETDs from UAB

The glutamate hypothesis of schizophrenia is based primarily on NMDA receptor dysfunction. Recent studies have led to an expansion of this hypothesis to include AMPA receptors which are essential for neurotransmission through NMDA receptors. Examination of total AMPA receptor protein expression in schizophrenia has been inconsistent and led to examination of AMPA receptor interacting proteins and trafficking and subcellular localization of the receptors. AMPA receptors are highly trafficked from the endoplasmic reticulum to the synapse and in a complex system of endosomes. Alterations in the subcellular localization of these receptors may be a part of the underlying pathophysiology of schizophrenia. …

Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink

All ETDs from UAB

Bone Morphogenetic Protein (BMP) signaling pathways are imperative for proper heart development. BMP ligands bind serine threonine kinase receptors, which activate intracellular receptor-regulated SMAD proteins. SMAD1, SMAD5, and SMAD8 transduce BMP signals from the cytoplasm to the nucleus, where they regulate transcription. We have investigated two aspects of BMP signaling during mouse cardiogenesis: identifying SMAD1-interacting proteins and exploring the roles of a known BMP target, Mycn, in the developing myocardium. Chromodomain helicase DNA binding protein 7 (CHD7) is a highly conserved transcription factor that promotes protein synthesis, proliferation, and differentiation. Haploinsufficiency for CHD7 causes CHARGE syndrome, a developmental disorder characterized …

The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison

All ETDs from UAB

An estimated 70 million Americans have one or more types of cardiovascular disease (CVD). Although the sequence of events leading to CVD are still controversial, there is a general consensus that atherosclerotic lesions result from oxidative stress associated with risk factor. For this study, it was hypothesized that endogenous mitochondrial oxidative stress would influence susceptibility to atherogenesis and mitochondrial damage mediated by CVD risk factor exposure. To test this hypothesis, atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage were assessed in hypercholestoremic mice (apolipoprotein E null - apoE -/- SOD2 +/+) and mice with significantly decreased levels of the …

The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel

All ETDs from UAB

LL-37 is the only cathelicidin-derived anti-microbial peptide in humans and has been shown to stimulate proliferation, angiogenesis, cellular migration and inhibit apoptosis, in addition to serving as a chemoattractant for leukocytes. It is produced primarily by epithelial cells and leukocytes, and has recently been discovered to be over-expressed in breast, ovarian and lung cancers. Based on these findings, we compared levels of LL-37 expression in benign and cancerous human prostate tissues. Results of this investigation demonstrated that LL-37 is increasingly over-expressed in primary prostate tumors in a grade dependent manner and in metastatic lesions. Since the physiological mechanisms of LL-37 …

Protein Modifications And The Response To Oxidized Lipids In Cardiovascular Cells, Ashlee Higdon

All ETDs from UAB

Free radical catalyzed oxidation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid is increased in cardiovascular disease states, including atherosclerosis and heart failure. Oxidized lipids have been extensively studied and found to recapitulate several key steps in atherogenesis. However, clinical trials with antioxidants such as alpha-tocopherol have been less promising than originally predicted. Now appreciated as more than just biomarkers of disease, lipid peroxidation products have been shown to have roles in pathogenesis as well as physiology. Of particular interest are reactive lipid species that possess electrophilic carbonyls enabling them to act in a receptor-independent manner. To date, the …

Pax5 Controls B Lineage Specific Gene Expression Program Through Association With The Nuclear Matrix, Sang Yong Hong

All ETDs from UAB

Pax5 is an essential regulator for B lineage cell development and controls hundreds of positive and negative target genes. The nuclear matrix (NM) has long been proposed to provide a dynamic structural support for biological reactions inside of the nucleus, including DNA replication, RNA transcription, and RNA splicing. Although Pax5 binding sites have been identified in numerous Pax5 target genes, it is not clear how Pax5 controls so many target genes. In this dissertation, I demonstrate that Pax5 association with the NM is essential for regulation of the B lineage specific gene expression program. In part I, I found that …

The Role Of Cd19 In Follicular Dendritic Cell Activation, Riley Croom Myers

All ETDs from UAB

Germinal Centers (GC) are organized foci in secondary lymphoid organs of birds and mammals and are the principle sites of memory B cell generation and plasma cell formation. GC concentrate antigen within follicles to facilitate recognition by responding B cells to promote somatic hypermutation and affinity maturation. Follicular dendritic cells (FDC) reside within the light zones of GC and serve to facilitate B cell interactions with antigen, as well as B cell selection, proliferation, and survival. The work contained within this dissertation addresses the collaborative interactions between B cells and FDC. FDC within an active, GC-containing follicle express an array …

Protein Modification By Arginylation, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

The modification of protein by arginine catalyzed by arginyltransferases (ATE1) described by the Kashina group in this issue shows that arginylation of protein occurs widely in biology and is being recognized as a key regulatory reaction such as phosphorylation of proteins (Wang et al., 2011).

Mitochondrial Genome Sequence Analysis: A Custom Bioinformatics Pipeline Substantially Improves Affymetrix Mitochip V2.0 Call Rate And Accuracy., Hongbo M Xie, Juan C Perin, Theodore G Schurr, Matthew C Dulik, Sergey I Zhadanov, Joseph A Baur, Michael P King, Emily Place, Colleen Clarke, Michael Grauer, Jonathan Schug, Avni Santani, Anthony Albano, Cecilia Kim, Vincent Procaccio, Hakon Hakonarson, Xiaowu Gai, Marni J Falk

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate …

Protein Kinase C Δ Is Critical For Nucleotide Excision Repair Of Cyclobutane Pyrimidine Dimers, Christopher Michael Negro

Master's Theses

Nucleotide excision repair (NER) is the process by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP). NER in human cells is a complex biochemical process requiring several complementation groups. Defects in complementation group genes result in rare, autosomal recessive cancer syndromes such as xeroderma pigmentosum (XP), cockayne syndrome (CS), and trichothiodystrophy, supporting the tumor suppressive effects of NER. Protein Kinase C delta (PKCδ) expression is lost in squamous cell carcinomas where it functions as a tumor suppressor gene. Additionally, in response to UV radiation, PKCδ is …

Measuring The Symptom Burden Of Lung Cancer: The Validity And Utility Of The Lung Cancer Module Of The M D Anderson Symptom Inventory, Tito R Mendoza, Xin Shelley Wang, Charles Lu, Guadalupe R Palos, Zhongxing Liao, Gary M Mobley, Shitij Kapoor, Charles S Cleeland

Faculty, Staff and Student Publications

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health …

P16 Ink4a Immunocytochemistry On Cell Blocks As An Adjunct To Cervical Cytology: Potential Reflex Testing On Specially Prepared Cell Blocks From Residual Liquid-Based Cytology Specimens, Vinod B. Shidham, Ravi Mehrotra, George Varsegi, Krista L. D'Amore, Bryan Hunt, Raj Narayan

Department of Pathology

Background: p16 INK4a (p16) is a well-recognized surrogate molecular marker for human papilloma virus (HPV) related squamous dysplasia. Our hypothesis is that the invasive interventions and related morbidities could be avoided by objective stratification of positive cytologic interpretations by p16 immunostaining of cell block sections of cytology specimens.

Materials and Methods: Nuclear immunoreactivity for p16 was evaluated in cell block sections in 133 adequate cases [20 negative for intraepithelial lesion or malignancy, 28 high-grade squamous intraepithelial lesion (HSIL), 50 low-grade squamous intraepithelial lesion (LSIL), 21 atypical squamous cells, cannot exclude HSIL (ASC-H), and 14 atypical squamous cells of undetermined significance …

Regional Expression Of Hoxa4 Along The Aorta And Its Potential Role In Human Abdominal Aortic Aneurysms, John H. Lillvis, Robert Erdman, Charles M. Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A. Cox, Jianbin Shen, Richard S. Vander Heide, Guy M. Lenk, Leigh Hlavaty, Li Li, James R. Elmore, David P. Franklin, John L. Gray, Robert P. Garvin, David J. Carey, Wayne D. Lancaster, Gerard Tromp, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.

Results

We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic …

Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. …

Addressing The Fertility Needs Of Hiv-Seropositive Males, Brian A. Levine, Sahadat K. Nurudeen, Jennifer T. Gosselin, Mark V. Sauer

Psychology Faculty Publications

An increasing number of serodiscordant couples are utilizing advanced reproductive technologies to address their reproductive needs. Recent literature has demonstrated that it is not only technically possible but also safe to utilize sperm-washing techniques to allow for the creation of embryos, thereby preventing both horizontal and vertical transmission of HIV. This article addresses the strengths and weakness of various reproductive techniques and discusses our experience at Columbia University (NY, USA), the location of the largest HIV-focused fertility program in the USA.

Approaches For Enhancing Therapeutic Efficacy Of A Novel Il-10 Gene Family Member: Mda-7/Il-24, Belal Azab

Theses and Dissertations

Melanoma differentiation associated gene-7 (mda-7) was discovered in the Fisher laboratory by subtraction hybridization of temporally spaced subtracted cDNA libraries prepared from terminally differentiated human melanoma cells treated with human fibroblast interferon (IFN-β) and the protein kinase C activator mezerein (MEZ), an approach called ‘differentiation induction subtraction hybridization’ (DISH). mda-7 is located in human chromosome 1q32–33 and based on sequence homology, chromosomal localization, and its functional properties, the mda-7 gene is now classified as a member of the IL-10 family of cytokines and named IL-24. The mda-7/IL-24 cDNA encodes a protein of 206-amino acids with a predicted size of ~24-kDa, …

Differential Effects Of Isoflurane And Propofol Anesthesia On Neurogenesis In Young And Aged Rats, Diana Marcela Erasso

USF Tampa Graduate Theses and Dissertations

Worldwide, millions of young and elderly patients receive procedures that could not be performed without the use of anesthetics. Unfortunately, emerging animal and human data suggest an association between exposure to general anesthesia and impairment of cognitive function in pediatric and geriatric patients. Recent laboratory data have shown that general anesthetics are potentially damaging to the developing and aging brain. However, the mechanism by which this happens is still unknown. General anesthetics affect learning and memory, a brain function involving neural plasticity. An important form of neural plasticity receiving attention is postnatal neurogenesis. This process is highly regulated and involved …

The Role Of Hiv-1 Proteins In Alzheimer's Disease Pathology, Brian Nelson Giunta

USF Tampa Graduate Theses and Dissertations

Prevalence of HIV-associated cognitive impairment is rising, the worst form of which is HIV-associated dementia (HAD). The disease is fuiled by a chronic innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia. We first created an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. This activation, as measured by TNF-alpha and NO release, is synergistically attenuated through the alpha7nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA …

Repeated Binge Pattern Ethanol Administration During Adolescence Or Adulthood: Long-Term Changes In Voluntary Ethanol Intake And Mesolimbic Dopamine Functionality In Male Rats, Antoniette Michelle Maldonado-Devincci

USF Tampa Graduate Theses and Dissertations

Binge alcohol consumption is a rising concern in the United States, especially among adolescents as during this developmental period alcohol use is usually initiated and has been shown to cause detrimental effects on brain structure and function. These findings have been established through the use of binge models in animals, where animals are repeatedly administered high doses of ethanol typically over a period of three or four days. While such work has examined the effects of a four-day and repeated three-day binge, there has been almost no work conducted aimed at investigating the long-term behavioral and neurochemical and/or functional consequences …

The Effects Of Pre-Exercise Carbohydrate Supplementation On Resistance Training Performance During An Acute Resistance Training Session, Kelly Raposo

USF Tampa Graduate Theses and Dissertations

It appears that "carbohydrate loading" may enhance the performance of resistance training, but studies on CHO supplementation prior to a resistance-training bout are limited and have resulted in conflicting findings. PURPOSE: To investigate the effects of pre-exercise CHO supplementation on high-intensity (>75% 1RM) resistance training performance for resistance-trained women during an acute bout of resistance exercise. METHODS: Thirteen resistance trained female participants (21.9 ± 4.8 yrs; 64.5 ± 3.0 in; 137.0 ± 14.8 lbs) came to the Exercise and Performance Nutrition Laboratory on three separate occasions; the day of the Familiarization Trial (FT) and the two Exercise Testing sessions …

Secreted Factors From Human Umbilical Cord Blood Cells Protect Oligodendrocytes From Ischemic Insult, Derrick Rowe

USF Tampa Graduate Theses and Dissertations

Oligodendrocytes (OL)s are the dominant cell type in the white matter and are integral for synaptic transmission essential for proper neuronal communication between brain areas. Previous studies have shown that intravenous administration of the mononuclear fraction of human umbilical cord blood (HUCB) cells in rat models of stroke reduced white matter injury, gray matter injury and behavioral deficits. Yet the mechanisms used by HUCB cells remain unknown in ischemic injury. These studies will investigate both in vitro and in vivo approaches to elucidate this mechanism in OLs. When mature primary OLs were coincubated with HUCB cells, HUCB cells secreted soluble …

The Effect Of Various Carbohydrate Supplements On Postprandial Blood Glucose Response In Female Soccer Players, Nina Pannoni

USF Tampa Graduate Theses and Dissertations

PURPOSE: The purpose of this study is to examine the effects of different types of carbohydrates on blood glucose response in collegiate soccer athletes at rest. This will help to determine the effectiveness of a carbohydrate supplement in providing sustained energy and maintained performance if ingested prior to a soccer match. METHODS: In a cross-over design, 10 female collegiate soccer players (n= 10, age 20.10 ± .99 years, height 65.55 ± 2.77 inches, weight 64.12 ± 8.36 kilograms) from the University of South Florida reported to the laboratory on five separate occasions after an overnight fast. Once a baseline blood …

Multivariate Anti-Inflammatory Approaches To Rescue Neurogenesis And Cognitive Function In Aged Animals, Sandra Antonieta Acosta

USF Tampa Graduate Theses and Dissertations

Studies have shown that there is a strong correlation between aging and neurodegenerative diseases. Aging is considered the number one risk factor to develop neuropathologies such as memory loss, senile dementia, Alzheimer's disease (AD), and Parkinson's disease. Neurodegenerative diseases tend to start during adulthood, and aggravate over time, making them difficult to prevent and to treat. In the Unites States, demographic studies by U.S. Bureau of the Census have determined that our aging population of >65 years is expected to increase from the present 35 million to 78 million in 2030. This would result, not only to an increase of …

Tdp-43 Potentiates Alpha-Synuclein Toxicity To Dopaminergic Neurons In Transgenic Mice., Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xugang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 proteinopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in …

Safe Patient Handling And Movement Programs:Implications For Occupational Therapy, Holly Ehrenfried Otr/L, Cht

Department of Medicine

No abstract provided.

Cellular Inhibitor Of Apoptosis 1 (Ciap-1) Degradation By Caspase 8 During Tnf-Related Apoptosis-Inducing Ligand (Trail)-Induced Apoptosis., Maria Eugenia Guicciardi, Justin L. Mott, Steven F. Bronk, Satoshi Kurita, Christian D. Fingas, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

TNF-related apoptosis-inducing ligand (TRAIL) is a potential chemotherapeutic agent with high selectivity for malignant cells. Many tumors, however, are resistant to TRAIL cytotoxicity. Although cellular inhibitors of apoptosis 1 and 2 (cIAP-1 and -2) are often over-expressed in cancers, their role in mediating TRAIL resistance remains unclear. Here, we demonstrate that TRAIL-induced apoptosis of liver cancer cells is associated with degradation of cIAP-1 and X-linked IAP (XIAP), whereas cIAP-2 remains unchanged. Lower concentrations of TRAIL causing minimal or no apoptosis do not alter cIAP-1 or XIAP protein levels. Silencing of cIAP-1 expression, but not XIAP or cIAP-2, as well as …

Human Chondrosarcoma Cells Acquire An Epithelial-Like Gene Expression Pattern Via An Epigenetic Switch: Evidence For Mesenchymal-Epithelial Transition During Sarcomagenesis., Matthew P. Fitzgerald, Francoise Gourronc, Melissa L.T. Teoh, Matthew J. Provenzano, Adam J. Case, James A. Martin, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers, E-cadherin,desmocollin 3, maspin, and 14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3σ in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3σ and displayed nearly complete DNA methylation. Robust activation of these genes was also …

The Utilization Of A Respiratory Care Journal Club To Facilitate State Continuing Division Of Educational Credits, Kenneth Miller Med, Rrt-Nps, Linda Cornman Bs, Rrt-Nps, Steven Pyne Rrt, Angela Lutz Bs, Rrt-Nps

Patient Care Services / Nursing

No abstract provided.

The Use Of Interval Division Of Education In The Navigation Of Breast Cancer Patients, Jane Zubia Rn, Ocn, Cbpn I-C, Laura Beaupre Bsn, Ocn, Cbpn-Ic, Diane Mchugh Bsn, Ocn, Cbpn-Ic, Raizalie Roman-Rosado Bsn, Ocn, Cmsrn, Nadesda Mack Rn, Bsn, Mba, Ocn

Department of Medicine

No abstract provided.