Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

Activation Of Tumor Cell Death Program By Targeting The Ubiquitin-Proteasome Pathway: Significance In Cancer Treatment And Prevention, Michael Joseph Frezza

Wayne State University Dissertations

ACTIVATION OF TUMOR CELL DEATH PROGRAM BY TARGETING THE UBIQUITIN-PROTEASOME PATHWAY: SIGNIFICANCE IN CANCER TREATMENT AND PREVENTION

by

MICHAEL FREZZA

August 2010

Advisor: Dr. Q. Ping Dou

Major: Cancer Biology

Degree: Doctor of Philosophy

The ubiquitin-proteasome pathway serves as a quality control mechanism to regulate the degradation of intracellular proteins involved in a wide array of cellular processes including tumorigeneis. Thus targeting key features of protein turnover responsible for the growth and proliferation of cancer have emerged as a favorable approach in cancer therapy. Both in vitro and in vivo experimental and clinical results have demonstrated the potential use of …

Comparison Of Mitotic Cell Death By Chromosome Fragmentation To Premature Chromosome Condensation, Joshua B. Stevens, Batoul Y. Abdallah, Sarah M. Regan, Guo Liu, Steven W. Bremer, Christine J. Ye, Henry H. Heng

Wayne State University Associated BioMed Central Scholarship

Abstract

Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost …

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 Globin Gene Family Of The Cephalochordate Amphioxus: Implications For Chordate Globin Evolution, Bettina Ebner, Georgia Panopoulou, Serge N. Vinogradov, Laurent Kiger, Michael C. Marden, Thorsten Burmester, Thomas Hankeln

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The lancelet amphioxus (Cephalochordata) is a close relative of vertebrates and thus may enhance our understanding of vertebrate gene and genome evolution. In this context, the globins are one of the best studied models for gene family evolution. Previous biochemical studies have demonstrated the presence of an intracellular globin in notochord tissue and myotome of amphioxus, but the corresponding gene has not yet been identified. Genomic resources of Branchiostoma floridae now facilitate the identification, experimental confirmation and molecular evolutionary analysis of its globin gene repertoire.

Results

We show that B. floridae harbors at least fifteen paralogous globin genes, …

Mapping Haplotype-Haplotype Interactions With Adaptive Lasso, Ming Li, Roberto Romero, Wenjiang J. Fu, Yuehua Cui

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it …

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 …

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …

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, …

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 …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

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 …

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 …

Development And Validation Of A Measurement Scale To Analyze The Environment For Evidence-Based Medicine Learning And Practice By Medical Residents, Fangqiong Mi

Wayne State University Dissertations

A growing number of residency programs are instituting curricula to include the component of evidence-based medicine (EBM) principles and process. However, these curricula may not be able to achieve the optimal learning outcomes, perhaps because various contextual factors are often overlooked when EBM training is being designed, developed, and implemented. The purpose of the study was to develop and validate an instrument, the EBM Environment Scale, to analyze the environment for EBM learning and practice as perceived by medical residents.

The development of the EBM Environment Scale underwent the process of content domain identification, item generation, review by content experts …

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 …

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. …

Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia, Amanda Larson Gedman

Wayne State University Dissertations

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric ALL cases and is associated with early relapse and inferior outcome. The poorer prognosis of T-ALL compared to B-precursor ALL may in part reflect the lack of unique features on which to base therapy. NOTCH1 mutations are of particular interest since these were reported in 37-71% of T-ALLs. The prognostic value of NOTCH1 mutations remains controversial as both favorable and unfavorable associations were reported, whereas in other studies, there were no associations between NOTCH1 mutations and treatment outcome. We explored the impact of mutations in NOTCH1, FBW7 and PTEN on …

Primate Phylogenomics: Developing Numerous Nuclear Non-Coding, Non-Repetitive Markers For Ecological And Phylogenetic Applications And Analysis Of Evolutionary Rate Variation, Zuogang Peng, Navin Elango, Derek E. Wildman, Soojin V. Yi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Genetic analyses are often limited by the availability of appropriate molecular markers. Markers from neutrally evolving genomic regions may be particularly useful for inferring evolutionary histories because they escape the constraints of natural selection. For the majority of taxa however, obtaining such markers is challenging. Advances in genomics have the potential to alleviate the shortage of neutral markers. Here we present a method to develop numerous markers from putatively neutral regions of primate genomes.

Results

We began with the available whole genome sequences of human, chimpanzee and macaque. Using computational methods, we identified a total of 280 potential …

Incorporation Of Membrane-Bound, Mammalian-Derived Immunomodulatory Proteins Into Influenza Whole Virus Vaccines Boosts Immunogenicity And Protection Against Lethal Challenge, Andrew S. Herbert, Lynn Heffron, Roy Sundick, Paul C. Roberts

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.

Results

We have evaluated the immunogenicity of inactivated cytokine-bearing influenza …

Development And Evaluation Of New Mask Protocols For Gene Expression Profiling In Humans And Chimpanzees, Donna M. Toleno, Gabriel Renaud, Tyra G. Wolfsberg, Munirul Islam, Derek E. Wildman, Kimberly D. Siegmund, Joseph G. Hacia

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Cross-species gene expression analyses using oligonucleotide microarrays designed to evaluate a single species can provide spurious results due to mismatches between the interrogated transcriptome and arrayed probes. Based on the most recent human and chimpanzee genome assemblies, we developed updated and accessible probe masking methods that allow human Affymetrix oligonucleotide microarrays to be used for robust genome-wide expression analyses in both species. In this process, only data from oligonucleotide probes predicted to have robust hybridization sensitivity and specificity for both transcriptomes are retained for analysis.

Results

To characterize the utility of this resource, we applied our mask protocols …

Differential Effects Of Th1, Monocyte/Macrophage And Th2 Cytokine Mixtures On Early Gene Expression For Molecules Associated With Metabolism, Signaling And Regulation In Central Nervous System Mixed Glial Cell Cultures, Robert P. Lisak, Joyce A. Benjamins, Beverly Bealmear, Liljana Nedelkoska, Diane Studzinski, Ernest Retland, Bin Yao, Susan Land

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS) in multiple sclerosis (MS).

Methods

We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M).

Results

In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, …

Autoimmune-Induced Preferential Depletion Of Myelin-Associated Glycoprotein (Mag) Is Genetically Regulated In Relapsing Eae (B6 × Sjl) F1 Mice, Dusanka S. Skundric, Rujuan Dai, Vaagn L. Zakarian, Weili Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Experimental autoimmune encephalomyelitis (EAE) is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS). Four distinct autoimmune mechanisms with subsequently distinct patterns of demyelination have been recognized in acute MS lesions. EAE correlates for those distinct patterns of MS lesions are unknown. An excessive loss of myelin-associated glycoprotein (MAG), as a result of distal oligodendrogliopathy, is found exclusively in the subtype III lesion. We sought to answer if types of demyelination in acute lesions during onset and relapse of EAE can replicate the specific patterns observed in MS acute lesions. …

Relation Between Nodule Size And 18F-Fdg-Pet Suv For Malignant And Benign Pulmonary Nodules., Majid Khalaf, Hani Abdel-Nabi, John Baker, Yiping Shao, Dominick Lamonica, Jayakumari Gona

Wayne State University Associated BioMed Central Scholarship

Abstract

The most common semiquantitative method of evaluation of pulmonary lesions using ¹⁸F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules.

Methods

Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a …

Droid: The Drosophila Interactions Database, A Comprehensive Resource For Annotated Gene And Protein Interactions, Jingkai Yu, Svetlana Pacifico, Guozhen Liu, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, Drosophila melanogaster. …

A Phylogenomic Profile Of Hemerythrins, The Nonheme Diiron Binding Respiratory Proteins, Xavier Bailly, Stefano Vanin, Christine Chabasse, Kenji Mizuguchi, Serge N. Vinogradov

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Hemerythrins, are the non-heme, diiron binding respiratory proteins of brachiopods, priapulids and sipunculans; they are also found in annelids and bacteria, where their functions have not been fully elucidated.

Results

A search for putative Hrs in the genomes of 43 archaea, 444 bacteria and 135 eukaryotes, revealed their presence in 3 archaea, 118 bacteria, several fungi, one apicomplexan, a heterolobosan, a cnidarian and several annelids. About a fourth of the Hr sequences were identified as N- or C-terminal domains of chimeric, chemotactic gene regulators. The function of the remaining single domain bacterial Hrs remains to be determined. In …

Analytical Approaches To Detect Maternal/Fetal Genotype Incompatibilities That Increase Risk Of Pre-Eclampsia, Neeta Parimi, Gerard Tromp, Helena Kuivaniemi, Jyh Nien, Ricardo Gomez, Roberto Romero, Katrina Ab Goddard

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear.

Methods

Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based …

A Stable Explant Culture Of Her2/Neu Invasive Carcinoma Supported By Alpha-Smooth Muscle Actin Expressing Stromal Cells To Evaluate Therapeutic Agents, Marie P. Piechocki

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

To gain a better understanding of the effects of therapeutic agents on the tumor microenvironment in invasive cancers, we developed a co-culture model from an invasive lobular carcinoma. Tumor cells expressing HER2/neu organize in nests surrounded by alpha-Smooth Muscle Actin (α-SMA) expressing tumor stroma to resemble the morphology of an invading tumor. This co-culture, Mammary Adenocarcinoma Model (MAM-1) maintains a 1:1 ratio of HER2/neu positive tumor cells to α-SMA-reactive stromal cells and renews this configuration for over 20 passages in vitro.

Methods

We characterized the cellular elements of the MAM-1 model by microarray analysis, and immunocytochemistry. We developed …