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Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala

Wayne State University Dissertations

N5-Carboxyaminoimidazole ribonucleotide synthetase (N5-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report structural and functional studies on the Aspergillus clavatus N5-CAIR synthetase and identification of inhibitors for the enzyme. In collaboration with Dr. Hazel Holden of the University of Wisconsin, the three-dimensional structure of Aspergillus clavatus N5-CAIR synthetase was solved in the presence of either Mg2ATP or MgADP and AIR. These structures, determined to 2.1 …

A Study Of The Associations Between Childhood Obesity And Three Forms Of Social Capital, Cynthia Bala-Brusilow

Wayne State University Dissertations

Purpose: The purpose of the study was to expand the understanding of childhood obesity in American children by examining the associations between obesity in children and measures of social capital.

Context: Persons between 2 and 20 years of age are categorized as "obese" if their BMI is in 95th percentile or above for their age and sex using the Center for Disease Control and Prevention (CDC) BMI-for-age growth charts. Obesity prevalence has more than quadrupled in the last 40 years in the United States for children. Social capital, in the study of health, can be defined as resources accrued and/or …

The Effects Of Gestalt And Cognitive-Behavioral Therapy Group Interventions On The Assertiveness And Self-Esteem Of Women With Physical Disabilities Facing Abuse, Cilene Susan Adam Rita

Wayne State University Dissertations

The purpose of this study was to examine the differential effects of Gestalt and Cognitive-Behavioral group therapy interventions on assertiveness and self-esteem among women with physical disabilities facing abuse. The eleven women, who met the study criteria, were randomly assigned to one of two experimental conditions, Gestalt Therapy (GT) and Cognitive-Behavioral Therapy (CBT) group interventions. The Demographic Questionnaire (Adam Rita, 2009) documented personal characteristics of the participants. The criterion instruments were: a) RAS (Rathus, 1973), and b) CFSEI-2 (Form AD, Battle, 1992) measuring assertiveness and self-esteem respectively and were administered pre-and-post treatment. The research was conducted over a period of …

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 …

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 …

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 …

Synergistic Effects Of Garcinol And Gemcitabine In Enhancing Therapeutic Efficacy In Pancreatic Adenocarcinoma Cells And Its Effect On Microrna Profile, Mansi Anand Parasramka

Wayne State University Dissertations

SYNERGISTIC EFFECTS OF GARCINOL AND GEMCITABINE IN ENHANCING THERAPEUTIC EFFICACY IN PANCREATIC ADENOCARCINOMA CELLS AND ITS EFFECT ON MICRORNA PROFILE

By

MANSI PARASRAMKA

ADVISOR: DR. SMITI V. GUPTA

MAJOR: NUTRITION AND FOOD SCIENCE

DEGREE: DOCTOR OF PHILOSPHY

Human Pancreatic Cancer (PaCa) is one of the most hostile and fourth leading cause of cancer deaths in the United States. Current standard chemotherapeutic agent for advanced PaCa is gemcitabine, a cytotoxic nucleoside analogue which results in modest response due to high degree of inherent and acquired chemo resistance. Forthcoming evidence strongly supports that non-nutritive food components have therapeutic benefits attributable to pleiotropic …

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 …

Perceptions Of Sexuality By African American Patients On Hemodialysis, Merry Ann Stewart

Wayne State University Dissertations

ABSTRACT

PERCEPTIONS OF SEXUALITY BY AFRICAN AMERCIAN PATIENTS ON HEMODIALYSIS

by

MERRY STEWART

May 2010

Advisor: Dr. Ramona Benkert

Major: Nursing

Degree: Doctor of Philosophy

Sexuality is central to who we are as sentient beings and transcends physical sex acts. Sexuality concerns are reported as common for individuals receiving hemodialysis; yet, sexuality-related research for this population has been limited to a focus on altered physical sexuality. Little is known about the effects of hemodialysis on perceptions of personal identity, family-social roles as men or women, and intimate relationships. African Americans make up a disproportionate percentage of chronic hemodialysis patients and …

Jordanian Adolescent Cannabis Use: Patterns, Risks, And Protective Factors, Sukaina A. Alzyoud

Wayne State University Dissertations

ABSTRACT

JORDANIAN ADOLESCENT CANNABIS USE:

PATTERNS, RISKS, AND PROTECTIVE FACTORS

by

SUKAINA ALZYOUD

Month, 2010

Advisor: Dr. Stephanie Schim

Major: Nursing

Degree: Doctor of Philosophy

Background: Cannabis is considered to be the most commonly used substances worldwide. Its use is not only common among adolescents but is increasing in developing countries such as Jordan. Cannabis use among adolescents has been linked to unintentional injuries, physical fights, academic problems, and illegal behavior such as driving under the influence. Studies of cannabis use patterns, risks, and protective factors are limited in developing countries. Therefore, the purpose of this study is to determine …

Patients Safety Culture: A Baseline Assessment Of Nurses' Perceptions In A Saudi Arabia Hospital, Ahmad E. Aboshaiqah

Wayne State University Dissertations

ABSTRACT

PATIENT SAFETY CULTURE: A BASELINE ASSESSMENT OF NURSES' PERCEPTIONS IN A SAUDI ARABIA HOSPITAL

by

AHMAD E. ABOSHAIQAH

May 2010

Advisor: Dr. Stephen J. Cavanagh

Major: Nursing

Degree: Doctor of Philosophy

Patient safety (the avoidance and prevention of patient injuries or adverse events resulting from the processes of health care delivery) has become a major academic and public concern in healthcare. In order to promote and sustain a culture of safety in a healthcare organization, healthcare professionals stress the need to understand both individual and system contributions to error events. However, in Saudi Arabia, little is known about nurses' …

Identification Of Neuroblastoma And Its Prognostic Markers Using Raman Spectroscopy, Rachel Kast

Wayne State University Dissertations

Introduction: Neuroblastoma is the most common cancer of infancy. It is one of several peripheral nervous system tumors, including ganglioneuroma, peripheral nerve sheath tumor, and pheochromocytoma. It is commonly situated on the adrenal gland. It displays similar histology to other small round blue cell tumors, including non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma. One method of judging neuroblastoma aggressiveness uses tumor histology factors, including mitosis-karyorrhexis index, Schwannian stromal development, degree of differentiation, and patient age. Tumor aggressiveness can also be judged based on the amplification of certain genes, including MYCN. Raman spectroscopy is a physics-based method which identifies the biochemical …

The Role Of Employment Status, Work Disruption, Leisure, And Resources In The Mental Health Of Demenita Caregiving Daughters, Lisa Jones Ficker

Wayne State University Dissertations

Employment has been consistently identified as a role strain among dementia caregivers. This study sought to examine the patterns and context of employment and work disruption among dementia caregiving daughters and learn the extent to which work disruption influences mental health through hypothesized reductions in financial resources and leisure activities. This study was a cross-sectional design that extracted data of 486 daughter caregivers from a dataset that gathered information from Caucasian, African American, and Latina dementia caregivers at six research sites across the nation.

Results indicated that caregiving daughters who were employed reported the lowest number of depressive symptoms and …

The Contribution Of Nmda Receptors Within The Central Nucleus Of The Amygdala To The Suppression Of Pain Affect, Catherine Ann Spuz

Wayne State University Dissertations

The amygdala processes stimuli that threaten an individual and organizes the execution of affective behaviors designed to cope with the threat. The prototypical threat to an individual is exposure to a noxious stimulus. The central nucleus of the amygdala (CeA) receives nociceptive afferents and exhibits neuronal activation in response to noxious peripheral stimulation. NMDA receptors within CeA mediate this noxious-evoked neural excitation, and previous studies in the laboratory have shown that blockade of CeA NMDA receptors via the antagonist APV elevates the threshold for noxious tail-shock-induced vocalization afterdischarges (VADs), a validated measure of pain affect in the rat. The present …

Predicting Adolescent Risk-Taking And Goal-Oriented Behaviors: An Ecological Perspective, Joshua Jon Tynan

Wayne State University Dissertations

An important aspect of human development is adolescence. It has been well documented that adolescence is a time during which individuals partake in the greatest amount of risk-taking behaviors. These behaviors often include having unsafe sex, drug and alcohol use, smoking and recklessness. On the other hand, goal oriented behaviors are also developing, although these have been less well studied. The current study explored several key contexts that adolescents are concurrently exposed to, including parenting behaviors, peer relationships, religion, and media. The outcomes of interest were risk-taking behaviors and goal-oriented behaviors. Ultimately the purpose of this study was to compile, …

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 …

Spirituality And Spiritual Self-Care: Expanding Self-Care Deficit Nursing Theory, Mary Louise White

Wayne State University Dissertations

The purpose of this study was to extend the theory of self-care deficit nursing by including specific constructs of religion, spirituality, and spiritual self-care practices within the structure suggested by Orem's self-care deficit nursing theory. Based on an extensive literature review, practice experience, and a discovery theory-building approach, a new mid-range theory called White's theory of spirituality and spiritual self-care (WTSSSC) was developed. To begin to test this mid-range theory, empirical indices of many of the main concepts were identified from prior studies and one new instrument (the Spiritual Self-Care Practice Scale) was developed. Hypothesized relationships among the main concepts …

Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka

Wayne State University Dissertations

Myelin is a multilamellar membrane structure surrounding axons in both the CNS and PNS that facilitates nerve conduction. In the CNS, myelin is synthesized by oligodendrocytes, while in the PNS, myelin is synthesized by Schwann cells. In the CNS, Proteolipid protein 1 (PLP1), an integral membrane protein, is the major protein component of myelin, constituting ~50% of myelin protein. Mutations of the PLP1 gene in man cause a spectrum of neurological disease, ranging from the severe Pelizaeus-Merzbacher disease (PMD), that typically begins during infancy with nystagmus, seizures and hypotonia and evolves into spastic quadriparesis, cognitive impairment and ataxia, to ¡¥pure¡¦ …

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 …

The Influence Of Religion And Spirituality On Rehabilitation Outcomes Among Traumatic Brain Injury Survivors, Brigid Waldron-Perrine

Wayne State University Dissertations

The long-term consequences of traumatic brain injury affect millions of Americans, many of whom report using religion and spirituality to cope. Little research, however, has investigated how various elements of the religious and spiritual belief systems affect rehabilitation outcomes. The present study sought to assess the use of specifically defined elements of religion and spirituality as coping resources in a sample of traumatically brain injured adults. Furthermore, various mechanisms by which religion and spirituality may affect outcome were explored.

The sample included 88 adults with brain injury from 1 to 20 years post injury and their knowledgeable significant others (SOs). …

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. …

Adaptive Radiation Therapy Of Prostate Cancer, Ning Wen

Wayne State University Dissertations

ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT.

The dose from CBCT was measured in phantom using TLD and ion chamber techniques …

Examining The Relationship Between Spiritual Resources, Self-Efficacy, Life Attidues, Cognition, And Personal Characteristics Of Homeless African American Women, Jean Gash

Wayne State University Dissertations

African Americans comprise 12% of the American population and 45% of the homeless sheltered population (United States Department of Housing and Urban Development [HUD], 2007). The fastest growing segment is African American women and African American women with children. The purpose of this study was to examine the relationship between spiritual resources, self-efficacy, life attitudes, cognition, and personal characteristics (e.g., physical and mental health, age, marital status, number of children, number and length of times homeless and perceptions of being at risk for serious illness) of homeless African American women from 30 years of age and older who were trying …

Is Private Long-Term Care Insurance Affordable For Older Adults?, Nayoung Kim

Wayne State University Dissertations

Nationwide there are fewer than 7 million long-term care (LTC) insurance policies in force. Why do so few Americans buy private long-term care (LTC) insurance? Several theories have been offered as possible explanations, including the availability of Medicaid, misperceptions that Medicare or other policies cover LTC, beliefs that one's own risk of needing LTC services is small, or desires to simply rely on children and spouses for LTC. This study examines another possible explanation - that private LTC insurance is simply "unaffordable" for most older Americans, which may be why they don't buy it.

This study begins by investigating the …

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 Experience Of Chronic Pain As Described By African American Indigent Adults Attending An Urban Primary Care Clinic, Jamie Alexandra Crawley

Wayne State University Dissertations

Background: Inadequate chronic pain control has far-reaching implications including costs for missed time at work; utilization of health care resources and reduced quality of life. People at highest risk for inadequate pain control include indigent adults and minorities. Newman's theory health as expanding consciousness views the chronic pain experience as a life pattern within health. Qualitatively examining chronic pain from participants' perspectives may improve chronic pain care.

Purpose: The purpose of this study was to examine the experiences of chronic pain as described by African American indigent adults attending an urban, primary care clinic.

Methods: 13- participants (7 men and …

A Vignette Study Examining The Accuracy Of Diagnosis: The Role Of Patient And Practitioner Gender And Race Match, Kevin Johnson

Wayne State University Dissertations

ABSTRACT

DIAGNOSING MENTAL ILLNESS

By

KEVIN JOHNSON

2010

Advisor: Dr. Janet R. Hankin

Major: Medical Sociology

Degree: Doctor of Philosophy in Sociology

A convenience snowball sample of 228 mental health practitioners were surveyed and administered two vignettes of persons with mental illness and a 12-question survey that included occupational background and attitudinal questions about diagnosing mental illness. The gender and race of the patients were randomly altered, while the symptoms and characteristics of mental illness remained constant for each vignette. Each practitioner assigned a DSM-IV diagnostic label for axis I and axis II on both vignettes. The surveys were coded …

Physical Activity Levels In Obese And Non-Obese Women And Their Relationship With Body Mass Index, Perceived Self-Efficacy, Perceived Benefits And Barriers Of Exercise, And Commitment To A Plan Of Action, Rose Lange

Wayne State University Dissertations

The purpose of this descriptive correlational study was to examine relationships among selected variables and concepts within the Health Promotion Model (perceived benefits, perceived barriers to exercise, self-efficacy, commitment to plan of action) in non-obese and obese women with a focus on the behavioral outcome of physical activity (leisure & lifestyle). A group of 137 women, aged 18-50 participated in this study. BMI was found to be positively correlated to an individual's perceived barriers to action. Findings did not support the hypothesis that as BMI increases perceived benefits, self-efficacy, commitment to a plan of action and physical activity levels would …