Medical Sciences Commons^™

Analysis Of Gaba And Glutamate In The Mouse Dorsal Striatum, Stella Wisidagamage

Wayne State University Theses

ABSTRACT

ANALYSIS OF GABA AND GLUTAMATE IN MICE BRAIN

by

STELLA WISIDAGAMA

May 2011

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Master of Science

GABA and glutamate are the predominant inhibitory and excitatory amino acid neurotransmitters in the central nervous system (CNS), respectively. However, their altered levels cause several neurological diseases including Parkinson's and Huntington's disease, schizophrenia, and epilepsy. It is important to measure their levels in the extra- and intracellular environments to better understand and develop improved therapeutics that will treat these neurological disorders. The principle aim of this study is to study the impacts of different endogenous …

Rhodococcus Equi Venous Catheter Infection: A Case Report And Review Of The Literature, Rosalinda Guerrero, Ashish Bhargava, Zeina Nahleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Rhodococcus equi is an animal pathogen that was initially isolated from horses and is being increasingly reported as a cause of infection in humans with impaired cellular immunity. However, this pathogen is underestimated as a challenging antagonist and is frequently considered to be a mere contaminant despite the potential for life-threatening infections. Most case reports have occurred in immunocompromised patients who have received organ transplants (for example kidney, heart, bone marrow) or those with human immunodeficiency virus infection. Infections often manifest as pulmonary involvement or soft tissue abscesses. Bacteremia related to R. equi infections of tunneled central venous …

Spatial-Temporal Analysis Of Non-Hodgkin Lymphoma In The Nci-Seer Nhl Case-Control Study, David C. Wheeler, Anneclaire J. De Roos, James R. Cerhan, Lindsay M. Morton, Richard Severson, Wendy Cozen, Mary H. Ward

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL.

Methods

We conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors …

Rad6b Acts Downstream Of Wnt Signaling To Stabilize Β-Catenin: Implications For A Novel Wnt/Β-Catenin Target, Brigitte Gerard, Larry Tait, Pratima Nangia-Makker, Malathy Pv Shekhar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Aberrant Wnt/β-catenin signaling is associated with breast cancer even though genetic mutations in Wnt signaling components are rare. We have previously demonstrated that Rad6B, an ubiquitin conjugating enzyme, stabilizes β-catenin via polyubiqutin modifications that render β-catenin insensitive to proteasomal degradation. Rad6B is a transcriptional target of β-catenin, creating a positive feedback loop between Rad6B expression and β-catenin activation.

Methods

To isolate subpopulations expressing high or low Rad6B levels, we transfected MDA-MB-231 or WS-15 human breast cancer cells with ZsGreen fluorescent reporter vector in which the expression of ZsGreen was placed under the control of Rad6B promoter. ZsGreen^{high …}

Histone Deacetylases (Hdacs) In Xpc Gene Silencing And Bladder Cancer, Xiaoxin S. Xu, Le Wang, Judith Abrams, Gan Wang

Wayne State University Associated BioMed Central Scholarship

Abstract

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. …

Phylogeny And Adaptive Evolution Of The Brain-Development Gene Microcephalin (Mcph1) In Cetaceans, Michael R. Mcgowen, Stephen H. Montgomery, Clay Clark, John Gatesy

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Representatives of Cetacea have the greatest absolute brain size among animals, and the largest relative brain size aside from humans. Despite this, genes implicated in the evolution of large brain size in primates have yet to be surveyed in cetaceans.

Results

We sequenced ~1240 basepairs of the brain development gene microcephalin (MCPH1) in 38 cetacean species. Alignments of these data and a published complete sequence from Tursiops truncatus with primate MCPH1 were utilized in phylogenetic analyses and to estimate ω (rate of nonsynonymous substitution/rate of synonymous substitution) using site and branch models of molecular evolution. We also tested …

Unfolded Protein Response In Cancer: The Physician's Perspective, Xuemei Li, Kezhong Zhang, Zihai Li

Wayne State University Associated BioMed Central Scholarship

Abstract

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic …

A Supermatrix Analysis Of Genomic, Morphological, And Paleontological Data From Crown Cetacea, Jonathan H. Geisler, Michael R. Mcgowen, Guang Yang, John Gatesy

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.

Results

We combined new nuclear DNA sequences, including segments of six genes (~2800 …

Bio::Phylo-Phyloinformatic Analysis Using Perl, Rutger A. Vos, Jason Caravas, Klaas Hartmann, Mark A. Jensen, Chase Miller

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Phyloinformatic analyses involve large amounts of data and metadata of complex structure. Collecting, processing, analyzing, visualizing and summarizing these data and metadata should be done in steps that can be automated and reproduced. This requires flexible, modular toolkits that can represent, manipulate and persist phylogenetic data and metadata as objects with programmable interfaces.

Results

This paper presents Bio::Phylo, a Perl5 toolkit for phyloinformatic analysis. It implements classes and methods that are compatible with the well-known BioPerl toolkit, but is independent from it (making it easy to install) and features a richer API and a data model that is …

Analysis Of Positional Candidate Genes In The Aaa1 Susceptibility Locus For Abdominal Aortic Aneurysms On Chromosome 19, John H. Lillvis, Yoshiki Kyo, Gerard Tromp, Guy M. Lenk, Ming Li, Qing Lu, Robert P. Igo Jr, Natzi Sakalihasan, Robert E. Ferrell, Charles M. Schworer, Zoran Gatalica, Susan Land, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database.

Methods

Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. …

A Protein Network-Guided Screen For Cell Cycle Regulators In Drosophila, Stephen T. Guest, Jingkai Yu, Dongmei Liu, Julie A. Hines, Maria A. Kashat, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Large-scale RNAi-based screens are playing a critical role in defining sets of genes that regulate specific cellular processes. Numerous screens have been completed and in some cases more than one screen has examined the same cellular process, enabling a direct comparison of the genes identified in separate screens. Surprisingly, the overlap observed between the results of similar screens is low, suggesting that RNAi screens have relatively high levels of false positives, false negatives, or both.

Results

We re-examined genes that were identified in two previous RNAi-based cell cycle screens to identify potential false positives and false negatives. We …

Effects Of Managed Care On The Health And Health-Care Of The Non-Elderly With Diabetes, Meihua Lu

Wayne State University Dissertations

This dissertation attempts to examine the quality effect of managed care plans (as compared with traditional fee-for-service plans, or FFS) on the health outcome and health care use of patients with diabetes. As the number of diabetics is growing rapidly with many of them are relying on managed care plans, knowing better the effects of different plans on health status and health care utilization is of great interest and significance to consumers, employers, and policymakers, especially at a time that universal health care is under being implemented.

Using up-to-date data from MEPS, a nationally representative survey, I compared 484 HMO …

Frazzled And Abelson Interact To Regulate The Actin Cytoskeleton In Drosophila, Bridget Elsa Varughese

Wayne State University Dissertations

Guidance receptors such as Frazzled affect cell shape and motility by directly or indirectly modulating the cytoskeleton. Fra is particularly needed for the formation of the posterior commissures in a developing Drosophila embryo. The cytoplasmic tyrosine kinase, Abelson Kinase (Abl) enhances the loss of commissures observed in fra mutant. Abl physically interacts with Frazzled to help guide commissural axons across the midline. Furthermore, the loss of commissural axons is only seen when the actin dynamics are perturbed. Abl is also known to regulate actin-dependent processes underlying formation of filopodia, microspikes and membrane ruffles. So, we established a Drosophila S2 cell …

Mechanisms Of Translation Arrest Following Focal Brain Ischemia, Monique K. Lewis

Wayne State University Dissertations

MECHANISMS OF TRANSLATION ARREST FOLLOWING FOCAL BRAIN

ISCHEMIA

by

MONIQUE K. LEWIS

August 2011

Advisor: Dr. Donald DeGracia

Major: Physiology

Degree: Doctor of Philosophy

The loss of blood flow to the brain is termed ischemia and the subsequent resumption of blood flow is termed reperfusion. Brain ischemia and reperfusion (I/R) occurs primarily following resuscitation from cardiac arrest and stroke and presents one of the most significant clinical challenges. At present, there are no clinically effective pharmacologic interventions to halt brain damage following I/R. The major Aim of this dissertation will be to investigate possible mechanisms involved in neuron death following …

Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma

Wayne State University Dissertations

During peripheral nervous system development, successful communication between axons and glial cells including Schwann cells in peripheral nervous system and oligodendrocytes in central nervous system, is required for the proper functions of both neurons and glia. Three types of alternatively-spliced proteins belonging to the neuregulin1 (NRG1) gene family of growth and differentiation factors are essential for Schwann cell survival and peripheral nerve development. While membrane-bound NRG1 forms (type III) has been strongly implicated in the regulation of myelination process at late stage of Schwann cell development, little is known about the role of soluble, heparin-binding forms of NRG1 (type I/II) …

Expression Of Microbial Rhodopsins In Retinal Neurons With Subcellular Targeting Motifs: For The Study Of The Structure/Function Of Aii Amacrine Cells And For Vision Restoration, Chaowen Wu

Wayne State University Dissertations

Protein-targeting motifs serve as addresses for subcellular protein localization. This feature of targeting-motifs was used to study the retina. The first part of the dissertation reports in the axonless spiking AII amacrine cell of the mammalian retina a dendritic process sharing organizational and functional similarities with the axon initial segment, the typical site of action potential initiation. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP (ChR2-GFP) with the AIS-targeting motif of sodium channels (NavII-III) and was shown to be the site of spike initiation. The second part of the dissertation aimed to improve microbial rhodopsin-mediated gene therapy for vision …

Mechanisms Of Persistent Translation Arrest Following Global Brain Ischemia And Reperfusion, Jill Theresa Jamison

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION

by

JILL T. JAMISON

December 2011

Advisor: Donald J. DeGracia, Ph.D.

Major: Physiology

Degree: Doctor of Philosophy

The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is …

Processing Random Signals In Neuroscience, Electrical Engineering And Operations Research, Kalyan Raman

Wayne State University Dissertations

The topic of this dissertation is the study of noise in electrical engineering, neuroscience, biomedical engineering, and operations research through mathematical models that describe, explain, predict and control dynamic phenomena. Noise is modeled through Brownian Motion and the research problems are mathematically addressed by different versions of a generalized Langevin equation. Our mathematical models utilize stochastic differential equations (SDEs) and stochastic optimal control, both of which were born in the soil of electrical engineering. Central to this dissertation is a brain-physics based model of cerebrospinal fluid (CSF) dynamics, whose structure is fundamentally determined by an electrical circuit analogy. Our general …

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. …

Compensation Crisis Related To The Onsite Adequacy Evaluation During Fna Procedures-Urgent Proactive Input From Cytopathology Community Is Critical To Establish Appropriate Reimbursement For Cpt Code 88172 (Or Its New Counterpart If Introduced In The Future), Inderpreet Dhillon, Martha B. Pitman, Richard M. Demay, Pamela Archuletta, Vinod B. Shidham

Department of Pathology

The confusion centered around appropriate use of the CPT billing code 88172 is addressed in the commentary from the Economic and Government Affairs Committee of the American Society of Cytopathology (ASC) who have written a timely commentary in this issue of Cytojournal,“Adequate Reimbursement is Crucial to Support Cost-Effective Rapid Onsite Cytopathology Evaluations”. Currently, lack of standardized use within and between pathology departments is stirring unhealthy practices of denying reimbursements for this critical and legitimate cytopathology service. This editorial discusses the important concerns raised in this commentary and recommends immediate corrective action. (See also Al-Abbadi MA, et al. Adequate reimbursement is …

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …

Regulation Of Neuronal Excitability: New Mechanisms For Slow Afterhyperpolarization Activation And Modulation, Claudio Alberto Villalobos

Wayne State University Dissertations

One of the most characteristic features of pyramidal cells in the prefrontal cortex (PFC) is that they present a slow afterhyperpolarizing current (I_sAHP) that plays a critical role in the regulation of neuronal excitability. This current is modulated by receptors acting via GΑ_q/11 G proteins, thus it is thought that neurotransmitters regulate neuronal excitability through the inhibition of this current. I_sAHP is known to be mediated by calcium-activated potassium channels, however, neither the identity of the channel underlying this current nor its mechanism of activation are yet well understood. Recent reports have questioned a direct role …

Beyond The Dvh - Spatial And Biological Radiotherapy Treatment Planning, Bo Zhao

Wayne State University Dissertations

Purpose: Both spatial and biological information are necessary in order to perform true optimization of a treatment plan and for predicting clinical outcome. The goal of this work is to develop an enhanced treatment plan evaluation tool which incorporates biological parameters and retains spatial dose information.

Methods: A software system named SABER (Spatial And Biological Evaluation for Radiotherapy) is developed which provides biological plan evaluation with a novel combination of features. It incorporates hyperradiosensitivity using the induced-repair model and applies the new concept of Dose Convolution Filter (DCF) to simulate dose wash-out …

Raman Spectroscopic Modeling Of T- Lymphocyte Activation And Detection Of Acute Renal Allograft Rejection, Kristian L. Brown

Wayne State University Dissertations

ABSTRACT

RAMAN SPECTROSCOPIC MODELING OF T-LYMPHOCYTE ACTIVATION AND DETECTION OF ACUTE RENAL ALLOGRAFT REJECTION

By

KRISTIAN L. BROWN

2010

Advisor: Gregory Auner, PhD

Major: Biomedical Engineering

Degree: Doctor of Philosophy

Despite the advances made in the area of kidney transplantation, the disparity between the demand and available donated organs remains a dominant and unresolved issue. Given the paucity of available renal allografts the preservation of existing grafts is vital. One factor that has negatively impacted renal allograft survival is acute rejection (AR). Traditionally, kidney transplant centers have used elevations in serum creatinine as a screening tool for detecting AR. However, …

Comparison Of Affective Analgesia And Conditioned Place Preference Following Cholinergic Activation Of, Elena Schifirnet

Wayne State University Dissertations

Activation of the dopaminergic mesolimbic reward circuitry that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress affective reactions to noxious stimuli (affective analgesia, AA). VTA dopamine neurons are activated via cholinergic inputs, and we have observed that microinjections of the acetylcholine agonist carbachol suppressed vocalizations of rats that occur following administration of brief (1 sec) tail-shocks (vocalization afterdischarges = VAD). VADs are a validated rodent model of pain affect. In addition, the capacity of carbachol to support reinforcement appears to be regionally dependent within VTA. Ikemoto and Wise (2002) reported that carbachol was self-administered in the …

Effect Of Dietary Folate Restriction On Colon Carcinogenesis In Dna Polymerase Β Haploinsufficient Mice, Lisa F. Ventrella Lucente

Wayne State University Dissertations

The data presented in this research is central to establishing the role that the base excision repair pathway (BER) plays in the development and progression of colon cancer when dietary folate is deficient. Both cellular folate restriction and BER deficiencies have been shown to result in the accumulation of endogenous damage and lesions that could eventually develop into carcinogenesis. In this study, a dietary folate deficiency (FD) resulted in a significant increase in aberrant crypt foci (ACF) formation and triggered liver tumorogenesis in wildtype (WT) animals, as did a BER deficiency in DNA polymerase Β haploinsufficient (Β-pol+/-) mice exposed to …

Loss Of The Sin3 Transcriptional Corepressor Results In Aberrant Mitochondrial Function, Valerie L. Barnes, Bethany S. Strunk, Icksoo Lee, Maik Hüttemann, Lori A. Pile

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

SIN3 is a transcriptional repressor protein known to regulate many genes, including a number of those that encode mitochondrial components.

Results

By monitoring RNA levels, we find that loss of SIN3 inDrosophilacultured cells results in up-regulation of not only nuclear encoded mitochondrial genes, but also those encoded by the mitochondrial genome. The up-regulation of gene expression is accompanied by a perturbation in ATP levels in SIN3-deficient cells, suggesting that the changes in mitochondrial gene expression result in altered mitochondrial activity. In support of the hypothesis that SIN3 is necessary for normal mitochondrial function, yeastsin3null mutants exhibit very poor …

The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier

Wayne State University Dissertations

Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …