Medicine and Health Sciences Commons^™

Identification Of Enzymes Causing Redox Cycling, Causing Oxidative Stress And Damaging Mitochondria, Kiran Sebastian

Honors College Theses

Oxidative stress is thought to contribute to the death of dopamine neurons and the consequential progression of Parkinson’s disease. Redox cycling of quinones, including compounds formed by dopamine oxidation, can lead to oxidative stress and damaging of the mitochondria. Which enzymes catalyze the redox cycling of quinones is unknown, however. Inhibitors of the mitochondrial respiratory chain (cyanide, rotenone) do not inhibit redox cycling. Mitochondrial NAD(P)H:quinone oxidoreductases are likely candidates, but dicumarol, a common inhibitor of such enzymes is not effective. We observed that Cibacron Blue does indeed inhibit NADH-dependent redox cycling to an extent. Our data shows that the rate …

Physical Activity And Exercise During Adolescence And Young Adulthood Can Act As Preventative Measures Against The Development Of Osteoporosis In Elderly People, Christine C. Center

Honors College Theses

Osteoporosis, “the silent killer,” is responsible for 8.9 million annual fractures. Although not bound to these factors, osteoporosis typically targets females that are post-menopausal and have a family history of the disease. Osteoporosis is caused by a decrease in bone mass density. Physical activity and exercise and often spoken about when the topic of osteoporosis is discussed because of the impact they have on maintaining bone mass density in an effort to delay osteoporosis. This paper first provides an overview of osteoporosis, explanation of methods of diagnosing osteoporosis, risk factors, complications and treatment for osteoporosis. Topics covered include, bone mass …

Characterization Of High-Voltage-Activated Calcium Channels In Retinal Bipolar Cells, Qi Lu

Wayne State University Dissertations

Retinal bipolar cells, conveying visual information from photoreceptors to ganglion cells, segregate visual information into multiple parallel pathways through their diversified cell types and physiological properties. Voltage-gated Ca²⁺ channels could be particularly important underlying the diversified physiological properties of different BCs. In this dissertation, I investigated the high-voltage-activated (HVA) calcium current in retinal bipolar cells in mice. In the first part of my dissertation, I characterized multiple bipolar cell-expressing GFP and/or Cre transgenic mouse lines. In the second part of my dissertation, by performing whole-cell patch-clamp recordings, I examined the electrophysiological properties of HVA calcium currents among CBCs and …

Impact Of Cryoablation On Tumor Immunity, Jesse Veenstra

Wayne State University Dissertations

Background and Objectives: Percutaneous cryoablation is a minimally invasive procedure for tumor debulking, which has the potential to initiate or amplify tumor immunity through the release of tumor-associated antigens and endogenous danger signals. However, enhanced immunity is rarely observed in treated patients, suggesting the need for mechanistic analysis. The goal is to determine how cryoablation affects tumor specific immunity and if the response can be improved through exogenous TLR9 stimulation.

Methodology: We evaluated anti-Her2/neu immunity following cryoablation in wt BALB/c and tolerant NeuT mice inoculated with neu or Her2 expressing mammary tumors TUBO and D2F2/E2 respectively. Mice were treated with …

Roles Of Neuregulin1 In Neuromuscular Junction Development, Jiajing Wang

Wayne State University Dissertations

Neuromuscular junction (NMJ) development is a multistep process mediated by coordinated interactions between nerve terminals, target muscles, and peri-synaptic glial cells, and thus requires reciprocal signals derived from every cell type. Neuregulin1s (NRG1s) are a family of predominantly neuronal growth and differentiation factors that are important for many aspects of nervous system development. In this thesis, both the effects of NRG1 on NMJ development and reciprocal effects of neurotrophic factors on NRG1 expression were studied as a means to define the complex regulatory communication at the NMJ. Using the chicken embryo as a model, methods were developed to study the …

The Experiences Of Self-Managing Perceived Blood Pressure Changes In Women With Hypertension, Mary Margaret Franklin

Wayne State University Dissertations

The purpose of this qualitative study was to describe the experiences of women with HTN self-managing their perceived BP changes. van Manen's phenomenology methodology and method guided the inquiry, and also guided the existential reflection of the impact of perceived BP changes on the participants' lifeworlds (e.g, lived space, lived body, lived time, and lived relations).

Seven African American and six European American women with HTN who were able to tell if their BP changed based on their symptoms were recruited from community settings and were interviewed once with a semi-structured guide. Participants were middle-aged (M=50.5 years, SD=9.62), experienced in …

Structural Processing Of Language Components: Detection And Comprehension, Samantha Rose Crow

Wayne State University Theses

Although music and language share many perceptually functional characteristics, research endeavors are still focusing on the underlying neural circuitry. Past research has indicated a distinction of hemispheric lateralization between music and language processing. Recently, efforts have shifted to the notion of an initial general shared pathway in the brain with auditory stimuli differentiated in later processing to specialized regions. Therefore, both linguistic and musical components have been examined in numerous experiments to discern the possible influence of music and language components on auditory perception and comprehension, including their potential interaction. However, the effects of sentential prosody on early language structural …

Adolescent Dating Violence And Romantic Relationship Attachment In Young Adulthood: The Effects Of Relationship Commitment And Perceptions Of Alterability, Jennifer Marie Pierce

Wayne State University Theses

Romantic relationships are crucial to adolescents' development. These relationships fulfill numerous goals such as independence and intimacy (Bouchey & Furman, 2003; Sanderson & Cantor, 1995; Zimmer-Gembeck & Petherick, 2006). Because these relationships determine adolescents' successful attainment of important developmental objectives, negative relationships or experiences may impact later behavior, attitudes, beliefs and expectations (Connolly, Furman, & Konarski, 2000; Crockett & Crouter, 1995; Deal & Wampler, 1986; Furman, 2002; Magdol, Moffitt, Caspi, & Silva, 1998). Physical and sexual violence within adolescent romantic relationships is quite common; studies suggest that up to half of all girls have experienced dating violence (Arriaga & Foshee, …

Characterization Of Antimicrobial-Resistant Staphylococcus Spp. In Food Animals And Retail Meat, Kanika Bhargava

Wayne State University Dissertations

Antimicrobial resistance in Staphylococcus spp. is a worldwide epidemic concern in hospital and community settings. Food animals and retail meat are important reservoirs of these pathogens that can pose potential threat to humans. In this dissertation, we aimed to investigate the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Coagulase-negative Staphylococci (MRCoNS) in food animals and retail meat to provide insight into the role of agricultural environment in transmitting bacteria of human clinical significance. Furthermore, the potential application of phytochemicals as antimicrobials and antimicrobial adjuvants to control MRSA infections was explored.

CoNS recovered from food animals were characterized by …

Expression And Regulation Of Map Kinase Phosphatases 1 And 2 In Breast Cancer Tamoxifen Sensitivity, Kelly Haagenson

Wayne State University Dissertations

ABSTRACT

EXPRESSION AND REGULATION OF MAP KINASE PHOSPHATASES 1 and 2 IN BREAST CANCER TAMOXIFEN SENSITIVITY

by

KELLY K. HAAGENSON

May 2013

Advisor: Dr. Malathy Shekhar

Co-Advisor: Dr. Gen Sheng Wu

Major: Cancer Biology

Degree: Doctor of Philosophy

The deregulation of cell signaling is a very important component in the development and progression of cancer. One group of signaling molecules that has been implicated in these processes is the Mitogen-Activated Protein Kinase (MAPK) family which consists of three major branches in mammalian cells: ERK, JNK and p38. The activity of these kinases has wide-ranging effects within the cell and must …

Fatty Acid Fate In Determining Oxidation And Inflammation In Adipose Tissue, Emilio Patrick Mottillo

Wayne State University Dissertations

Adipose tissue (AT) is a critical regulator of energy balance through its ability to store or oxidize free fatty acids (FFAs). White adipose tissue (WAT) functions as an anabolic organ to sequester and release FAs, in contrast brown adipose tissue (BAT) is a catabolic organ that oxidizes FAs. However, a comprehensive understanding of the role that FFAs play in the function of WAT and BAT is needed. Here we demonstrate that intracellular FAs enhance the expression of inflammatory cytokines by β3-AR activation in adipocytes, in which the expression of PAI-1 is partly mediated by the de novo synthesis of ceramides/sphingolipids. …

The Lived Experience Of Weight Retention Among Postpartum African American Adolescents, Thelma Mae Phillips

Wayne State University Dissertations

Background: Obesity presents a public health challenge and is a serious chronic medical condition, which is associated with multiple co-morbidities and reduced survivability/longevity (Davis, Stange, & Howitz, 2010). African American adolescents who retain weight after pregnancy are at the highest risk of becoming obese adults. Obesity is expected to cost the United States health care system over 237 million dollars (National Institutes of health, 2011) within the next decade.

The prevalence of obesity is cause for concern because of its costs to the economic base of the country and its toll in human suffering due to related morbidity and mortality. …

The Role Of Tissue Sound Speed As A Surrogate Marker Of Breast Density, Mark Sak

Wayne State University Dissertations

Breast density is one of the strongest predictors of breast cancer risk as women with the densest breasts have a three- to five-fold increase in risk compared to women with the least dense breasts. Breast density is currently measured by using mammography, the current gold standard for breast imaging. There are many shortcomings to using mammography to measure breast density, including the use of ionizing radiation. Ultrasound tomography (UST) does not use ionizing radiation and can create tomographic breast sound speed images. These sound speed images are useful because breast density is proportional to sound speed. The purpose of this …

Predictors Of Psychosocial Adaptation To Pregnancy Among Urban African-American Primiparas, Joan M. Visger

Wayne State University Dissertations

Psychosocial adaptation to pregnancy among urban African-American women has not been well-researched. The purpose of this study was to examine predictors of psychosocial adaptation to pregnancy and to explore relationships among socioeconomic status, experiences and frequency of discrimination, personal control beliefs, social support, planned pregnancy, and model of health care among urban African-American primiparas using life course theory and Lederman's model of psychosocial adaptation to pregnancy as the framework.

One hundred and nine women participated in this descriptive, cross-sectional, correlational study. Participants were recruited from three clinical sites that provided care using medical and/or midwifery models of care. Study variables …

An Exploration Of The Relationships Among Demographics, Risk Factors, Perceived Self-Efficacy, And Fall Prevention Behaviors In Community-Dwelling Thai Older Adults, Kanyarat Ubolwan

Wayne State University Dissertations

Background: Worldwide, falls among older adults lead to significant physical, psychological, and social problems. Studies have described fall prevalence, risk factors, and the impact of falls in Thailand. Although fall prevention requires significant self-care abilities, insufficient knowledge exists about how to prevent falls in Thai community settings or the predictors of fall prevention behaviors among Thai Older adults.

Purpose: Orem's Self-Care Theory was used: 1) to examine the relationships among the basic conditioning factors (BCFs) of age, gender, falls, comorbidity, mental and physical health status, self-care agency (i.e., self-efficacy), and fall prevention self-care behaviors and 2) to determine the predictors …

Subordinate-Supervisor Demographic And Perceived Value Similarity: Relationships To Subordinate Perceptions Of Organizational Justice, Charles Levi Wells, Iv

Wayne State University Dissertations

The purpose of this study was to examine the empirical relationship between subordinate-supervisor demographic and value similarity with subordinate perceptions of organizational justice using three structural equation models. The first model indicated that subordinate-supervisor demographic and value similarity were directly related to subordinate perceptions of organizational justice (Direct Model). The second model indicated that subordinate perceived value similarity with their supervisor mediated the relationship between the subordinate-supervisor demographic similarity and subordinate perceptions of organizational justice (Mediated Model). The last model indicated subordinate perceived value similarity with their supervisor moderated the relationship between subordinate-supervisor demographic similarity and subordinate perceptions of organizational …

Facilitation Of Language Acquisition Viewed Through An Interpretative Lens: The Role Of Authenticity, Melanie Ann Harper

Wayne State University Dissertations

A paradigm is the conceptual framework or lens one uses to view reality. The field of speech-language pathology is traditionally rooted in the empirical paradigm, which believes that language can be fragmented into isolated skills and taught in a hierarchal fashion. This belief has resulted in service delivery models that remove students from naturalistic contexts for decontextualized exercises. Progress in language acquisition is measured objectively. The empirical belief is exemplified by the accountability requirements in special education law (e.g., IEP). It is compounded by the realities of public school speech-language pathologists (SLPs), such as high caseload numbers, multiple buildings, and …

Vascular Depression: An Early Indicator Of Decline, Daniel Lee Paulson

Wayne State University Dissertations

Women over the age of 80 represent a rapidly growing demographic group. While older women live longer than men, they do so with more years of disability and frailty. The emergence of geriatric disorders such as vascular disease, depression, frailty and cognitive decline in the aging US population place additional strain and expense on the already over-burdened public health care system. Meanwhile, integrated models of care are associated with preserved functional independence, reduced medical costs, and greater satisfaction for both health care providers and patients. Implementation of integrated care demands process-models of disease that contextualize symptoms within broader patterns of …

Multi-Modality Assessment Of Language Function, Erik Carmen Brown

Wayne State University Dissertations

The work presented as part of this dissertation represents a multi-modality study of language structure and function. The primary functional modality employed is task-related electrocorticography (ECoG). This is complemented by discussion and evaluation of previously published functional magnetic resonance imaging (fMRI) data. Language-related structure is explored using diffusion-weighted magnetic resonance imaging in conjunction with ECoG data. The scientific questions pursued are broad and include reevaluation of previously proposed theories.

We start by taking the first steps in validating our naming-related ECoG approach by comparing our results from a small cohort of patients to the clinical gold-standard technique of electrical brain …

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Sleep Homeodynamics And Wellbeing In Asymptomatic Hiv-Seropositive African American Women, Tabetha Lynn Gayton

Wayne State University Dissertations

SLEEP HOMEODYNAMICS AND WELLBEING IN ASYMPTOMATIC HIV–SEROPOSITIVE AFRICAN AMERICAN WOMEN

by

TABETHA LYNN GAYTON

December 2013

Advisor: Hossein N. Yarandi, PhD

Major: Nursing (Urban Health)

Degree: Doctor of Philosophy

BACKGROUND: HIV–related sleep disruption is a common complaint of persons with HIV infection. With the demographical shifts, African American women have now emerged as one of the fastest growing HIV populations today, yet they remain a vulnerable and underrepresented population in the sleep literature.

OBJECTIVE: The purpose of this pilot study was to explore the dynamics of HIV–related sleep disruption and wellbeing in asymptomatic HIV–seropositive AA women of childbearing age within …

The Effect Of Proalgazyme And Its Subfractions On Lipid Metabolism In Diet Induced Hypercholesterolemic Hamsters: Correlation With Plasma Metabolomic Profile, Andreea Geamanu

Wayne State University Dissertations

ABSTRACT

THE EFFECT OF PROALGAZYME AND ITS SUBFRACTIONS ON LIPID METABOLISM IN DIET INDUCED HYPERCHOLESTEROLEMIC HAMSTRES:

CORREALTION WITH PLASMA METABOLOMIC PROFILE

by

ANDREEA GEAMANU

December 2013

Advisor: Dr. Smiti Gupta

Major: Nutrition and Food Science

Degree: Doctor of Philosophy

Background: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the preventative effect of an algae infusion, ProAlgaZyme (PAZ) and its subfractions (F1, F2, F3, F4) on plasma HDL in a hamster model. Further, the study aimed to identify the biologically active fraction of PAZ and to determine the …

A Distinction Without A Moral Difference? An Essay On The Difference Between Palliative Sedation And Physician-Assisted Death, Patrick T. Smith

Wayne State University Dissertations

Professionals engaged in palliative care have a responsibility to treat their patients by aggressively managing pain and certain kinds of suffering within legal and professional ethical boundaries. Many medical professionals and ethicists, rightly or wrongly, have considered the practices of euthanasia and physician-assisted suicide, which can be categorized as instances of physician-assisted death (PAD), to be beyond the scope of ethically appropriate health care. Many of these same individuals who oppose PAD, and the professional organizations they sometimes represent, often embrace, at the same time, the practice of palliative/terminal sedation at the end of life. Palliative sedation is thought to …

Dispositional Mediators Of Burnout Syndrome In A Sample Of Direct Care Staff Employed At Group Homes In A Midwestern State, Cristovao Bartolo Carreira

Wayne State University Dissertations

The current research examined the dispositional characteristics that mediated burnout syndrome in a sample of direct care workers who were employed in group homes for the mentally ill in a Midwestern state. Specifically, the indirect effects that the direct care staff's attachment systems and problem solving ability were examined as they applied to their potential burnout status. Attachment theory, a contemporary psychodynamic theory of personality, was used to provide a context for the study. The researcher studied the interactions between construct subcomponents to address a criticism in the literature stating that only total scores were used to study burnout and …

Effect Of Garcinol On Change In Gene Expression In Pancreatic Cancer Mouse Model, Nurul Huda Razalli

Wayne State University Theses

Pancreatic cancer is currently ranked as the fourth leading cause of cancer-related deaths in The United States making it so important to develop new approaches in order to improve the prognosis of this lethal disease. Chemotherapy drugs as treatment for pancreatic cancer are known to have adverse toxic reactions. Thus, development of treatments for pancreatic cancer that are relatively nontoxic is warranted. This thesis reports the potential anticancer effect of garcinol, a compound extracted from Garcinia indica fruit rind which may have promise for treating this lethal malignancy. Using KPC mouse-model for pancreatic cancer, this study has evaluated the mRNA …

The Effect Of Alpha-Cyclodextrin On Acute Blood Lipid And Glycemic Responses To A Fat Containg Meal, Evan Neil Fletcher

Wayne State University Theses

Obesity and hyperlipidemia have become major concerns in the United States over the past 30 years. Alpha-Cyclodextrin (á-CD), a naturally occurring soluble dietary fiber, has been shown to reduce dietary fat absorption and improve blood lipid levels in an animal model (mouse and rat) and in human studies. In the current double blind study, 34 healthy male and female participants were recruited to test if á-CD had any acute effect on blood lipid and glycemic responses to a fat containing meal. The participants received the á-CD on one occasion and a placebo the other to determine if there was any …

Studies Of Regulated Exocytosis From Neuroendocrine Cells, Madhurima Das

Wayne State University Theses

In this thesis we study cargo release and fusion pore dilation during calcium triggered exocytosis and the co-localization of calcium sensing proteins essential for exocytosis, in neuroendocrine cells.

Pancreatic beta cells secrete several hormones, the most studied one being insulin. C-peptide is a protein which is co-stored with and secreted from the same vesicles as insulin. It is found in the soluble phase unlike insulin, which is found in the dense core. The pancreatic beta cells also secrete the Chromogranin B (CgB) which is mostly found in the dense cores of secretory vesicles. In chapter 1, we found that CgB, …

Anti-Cancer Effects Of Oil Palm Phenolics On Pancreatic Cancer - Histological Evidence, Poornima Gowthaman

Wayne State University Theses

Oil palm phenolics, a water soluble portion is obtained from the milling of palm oil. It has been proven to be a remarkable anti-oxidative agent which reduces the overall oxidative stress in the body and cardiovascular disease in mice. The aim of this study was to see whether OPP has any beneficial effects on the development or progression of pancreatic cancer. A total of 30 male LSL.KrasG12D/+; p53R172H/+; PdxCretg/+ were categorized into control (CP, KC=6) and treatment (KP, KG, KPG=6) groups. The control groups received the regular chow dietand the treatment groups revceived 5%OPP chow diet. 5µg of saline was …

Advanced Augmented Reality Telestration Techniques With Applications In Laparoscopic And Robotic Surgery, Stephen Dworzecki

Wayne State University Dissertations

The art of teaching laparoscopic or robotic surgery currently has a primary reliance on an expert surgeon tutoring a student during a live surgery. During these operations, surgeons are viewing the inside of the body through a manipulatable camera. Due to the viewpoint translation and narrow field of view, these techniques have a substantial learning curve in order to gain the mastery necessary to operate safely. In addition to moving and rotating the camera, the surgeon must also manipulate tools inserted into the body. These tools are only visible on camera, and pass through a pivot point on the body …