Medicine and Health Sciences Commons^™

Association Of Genetic Variation, Gene Expression, And Protein Abundance Within The Natriuretic Peptide Pathway, Bipin Sunkara

Honors College Theses

Background: The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure, but there is marked individual variability in its functioning which may be genetic in origin. We investigated how genetic variations in NP pathway genes correlate with gene expression and protein abundance.

Methods: DNA, RNA, and tissue from human kidney (n=77) were obtained. Kidney was chosen as target tissue because each of the four candidate genes and proteins (natriuretic peptide receptor 1 (NPR1), NPR2, NPR3 and membrane metallo-endopeptidase (MME)) are expressed there. DNA samples were genotyped for 120 single nucleotide polymorphisms (SNP) in these four genes using …

Prenatal Genetic Diagnosis Using Transcervically Derived And Immunomagnetically Isolated Trophoblast Cells, Swati Bajpayee

Honors College Theses

Trophoblast cells migrate from the placenta into the endocervical canal early in the first trimester and can be collected non-invasively by transcervical sampling (TCS), potentially providing fetal DNA for prenatal genetic diagnosis. Experiments were conducted to separate fetal cells from maternal cells within the TCS specimens and use the fetal cells to perform genetic analysis. Trophoblast cells were efficiently isolated from TCS specimens during weeks 5-18 of gestation using HLA-G antibody coupled to magnetic nanoparticles. Immunofluorescence microscopy revealed that 99% of isolated cells expressed the chorionic gonadotropin β subunit (β-CG), while the non-bound cell fraction expressed none. Immunomagnetically isolated cells …

North American Bioactive Plants For Human Health And Performance, Maria Pontes Ferreira, Fidji Gendron, Katrina C. Mcclure, Kelly Kindscher

Nutrition and Food Science Faculty Research Publications

Native and naturalized bioactive plants of the Canadian and American temperate biome are examined for their health and performance enhancement properties. Some of these plants are now being used as natural health products, and many have a long history as traditional foods and/or medicines with indigenous groups. This paper reviews the medicinal/cultural uses and bioactive properties of selected plant families: the Holly family (Aquifoliaceae) as stimulants, the Celery family (Apiaceae) as normoglycemic aids and analgesics, the Ginseng family (Araliaceae) as energy- boosting aids, the Sunflower family (Compositae) as anti-inflammatory aids, and the Legume family (Fabaceae) and Nightshade family (Solanaceae) as …

Chronic Hepatitis B And C Co-Infection Increased All-Cause Mortality In Haart-Naive Hiv Patients In Northern Thailand, N. Tsuchiya, P. Pathipvanich, A. Rojanawiwat, N. Wichukchinda, I. Koga, M. Koga, W. Auwanit, P. E. Kilgore, K. Ariyoshi, P. Sawanpanyalert

Department of Pharmacy Practice

A total of 755 highly active antiretroviral therapy (HAART)-naive HIV-infected patients were enrolled at a government hospital in Thailand from 1 June 2000 to 15 October 2002. Census date of survival was on 31 October 2004 or the date of HAART initiation. Of 700 (92.6%) patients with complete data, the prevalence of hepatitis B virus (HBV) surface antigen and anti-hepatitis C virus (HCV) antibody positivity was 11.9% and 3.3%, respectively. Eight (9.6%) HBV co-infected patients did not have anti-HBV core antibody (anti-HBcAb). During 1166.7 person-years of observation (pyo), 258 (36.9%) patients died [22.1/100 pyo, 95% confidence interval (CI) 16.7–27.8]. HBV …

Construct-Validity Of The Engagement With Challenge Measure For Adolescents: Structural- And Criterion-Validity Evidence, E. Whitney G. Moore, David Hansen

Kinesiology, Health and Sport Studies

For adolescents, engaging with challenge is a key developmental task, hypothesized to support development of adult-like competencies (e.g., agency and self-direction; Larson, 2000). This study aimed to assess the construct-validity (structural- and concurrent-validity) of a new self-report measure assessing adolescents’ engagement with challenge to help researchers understand how different settings and the conditions in these settings support adolescents’ development. The sample consisted of 337 adolescents in 10 FFA programs along with the adult advisors in each program. Adolescents completed a questionnaire, which included the Engagement with Challenge measure and the following criterion variables: number of contests completed, participation frequency, and …

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

The Role Of Micrornas In Breast Cancer Migration, Invasion And Metastasis, Joy Tang, Fazlul H. Sarkar, Aamir Ahmad

Honors College Theses

MicroRNAs (miRNAs) are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been implicated in several human cancers, including breast cancer. miRNAs are known to regulate cell cycle and development, and thus may serve as useful targets for exploration in anticancer therapeutics. The link between altered miRNA signatures and breast cancer development and metastasis can be observed either through the loss of tumor suppressor miRNAs, such …

Open Access Journals: A Good Way To Go?, Joshua Neds-Fox, Alexandra Sarkozy

Library Scholarly Publications

Presentation to the faculty of the Wayne State University College of Nursing, Office of Health Research Brown Bag Series, on issues pertaining to publishing in open access nursing journals and implications for tenure, citation, copyright, etc.

The Enhanced Pneumococcal Lamp Assay: A Clinical Tool For The Diagnosis Of Meningitis Due To Streptococcus Pneumoniae, Dong Wook Kim, Paul E. Kilgore, Eun Jin Kim, Soon Ae Kim, Dang Duc Anh, Bai Qing Dong, Jung Soo Kim, Mitsuko Seki

Department of Pharmacy Practice

Background: Streptococcus pneumoniae is a leading cause of invasive bacterial disease in developed and developing countries. We studied the loop-mediated isothermal amplification (LAMP) technique to assess its suitability for detecting S. pneumoniae nucleic acid in cerebrospinal fluid (CSF).

Methodology/Principal Findings: We established an improved LAMP assay targeting the lytA gene (Streptococcus pneumoniae [Sp] LAMP). The analytical specificity of the primers was validated by using 32 reference strains (10 Streptococcus and seven non-Streptococcus species) plus 25 clinical alpha-hemolytic streptococcal strains, including four S. pneumoniae strains and 21 other strains (3 S. oralis, 17 S. mitis, and …

Prospective Patterns And Correlates Of Quality Of Life Among Women In Substance Abuse Treatment, Elizabeth M. Tracy, Alexandre Laudet, Meeyoung Oh Min, Hyunsoo Kim, Suzanne Brown, Min Kyoung Jun, Lynn Singer

Social Work Faculty Publications

Background Quality of life (QOL) is increasingly recognized as central to the broad construct of recovery in sub- stance abuse services. QOL measures can supplement more objective symptom measures, identify specific service needs and document changes in functioning that are associated with substance use patterns. To date however, QOL remains an under investigated area in the addictions field, especially in the United States.

Methods This study examines patterns and predictors of QOL at 1 and 6 months post treatment intake among 240 women enrolled in substance abuse treatment in Cleveland, Ohio. The World Health Organization Quality of Life (WHOQOL-BREF) measure …

Nursing Science Research Consulting: A Multidisciplinary Framework, Thomas N. Templin

Nursing Faculty Research Publications

Nursing science research is at the intersection of the social and medical sciences and statistical developments in many different disciplines are relevant. A framework for nursing science statistics which recognizes and builds upon the statistical contributions from biostatistics, quantitative psychology, epidemiology, econometrics, survey research, computer science and statistics is presented. A broad eclectic framework is necessary to take advantage of new developments in statistical and research design methodology addressing specific problems common to a given area. This framework recognizes that awareness of differences in established expectations (conventions, guidelines, regulations, etc.) with regard to statistical methodology across different research areas is …

Urban High-School Girls' Sense Of Relatedness And Their Engagement In Physical Education, Bo Shen, Nate Mccaughtry, Jeffrey J. Martin, Mariane Fahlman, Alex C. Garn

Kinesiology, Health and Sport Studies

A sense of relatedness is individuals' views about themselves as connected to others and worthy of love and respect from others. Using the Self-System Model of Motivational Development as the framework, this study was designed to examine associations of urban high-school girls' relatedness toward teachers and peers with their behavioral and emotional engagements in physical education. Participants (N = 184, ages 15-18) completed questionnaires assessing relevant psychological and behavioral constructs while their teachers also completed corresponding measures during classes. Regression analyses revealed that relatedness toward teachers and peers had direct and interactive roles in both behavioral and emotional engagements. …

Caudate Nucleus Volume Mediates The Link Between Cardiorespiratory Fitness And Cognitive Flexibility In Older Adults, Timothy D. Verstynen, Brighid Lynch, Destiny L. Miller, Michelle W. Voss, Ruchika Shaurya Prakash, Laura Chaddock, Chandramallika Basak, Amanda Szabo, Erin A. Olson, Thomas R. Wojcicki, Jason Fanning, Neha P. Gothe, Edward Mcauley, Arthur F. Kramer, Kirk I. Erickson

Kinesiology, Health and Sport Studies

The basal ganglia play a central role in regulating the response selection abilities that are critical formental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, …

Resource Availability, Mortality And Fertility: A Path Analytic Approach To Global Life History Variation, Mark A. Caudell, Robert J. Quinlan

Human Biology Open Access Pre-Prints

Humans exhibit considerable diversity in timing and rate of reproduction. Life history theory suggests that ecological cues of resource richness and survival probabilities shape human phenotypes across populations. Populations experiencing high extrinsic mortality due to uncertainty in resources should exhibit faster life histories. Here we use a path analytic approach informed by life history theory to model the multiple pathways between resources, mortality rates, and reproductive behavior in 191 countries. Resources that account for the most variance in population mortality rates are predicted to explain the most variance in total fertility rates. Results indicate that resources (e.g., calories, sanitation, education, …

Association Among Obesity-Related Anthropometric Phenotypes: Analyzing Genetic And Environmental Contribution, Aline Jelenkovic, Esther Rebato

Human Biology Open Access Pre-Prints

Obesity has become a public health and policy problem in many parts of the world. Epidemiological and population studies in this field are usually based on different anthropometric measures, however, common genetic and environmental factors between these phenotypes have been scarcely studied. The objective of this work is to assess the strength of these factors on the covariation among a large set of obesity-related traits. The subject group consisted of 533 nuclear families living in the Greater Bilbao (Spain), and included 1702 individuals aged 2-61 years. Detailed anthropometric measurements (stature, breadths, circumferences and skinfolds) were carried out in each subject. …

Substance Abuse Treatment Stage And Personal Networks Of Women In Substance Abuse Treatment, Elizabeth M. Tracy, Hyunsoo Kim, Suzanne Brown, Meeyoung Oh Min, Min Kyoung Jun, Christopher Mccarty

Social Work Faculty Publications

This study examines the relationship among 4 treatment stages (i.e., engagement, persuasion, active treatment, relapse prevention) and the composition, social support, and structural characteristics of personal networks. The study sample includes 242 women diagnosed with substance dependence who were interviewed within their first month of intensive outpatient treatment. Using EgoNet software, the women reported on their 25 alter personal networks and the characteristics of each alter. With one exception, few differences were found in the network compositions at different stages of substance abuse treatment. The exception was the network composition of women in the active treatment stage, which included more …

Comparative Tuberculosis (Tb) Prevention Effectiveness In Children Of Bacillus Calmette-Guérin (Bcg) Vaccines From Different Sources, Kazakhstan, Michael Favorov, Mohammad Ali, Aigul Tursunbayeva, Indira Aitmagambetova, Paul Kilgore, Shakhimurat Ismailov, Terence Chorba

Department of Pharmacy Practice

Background: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization.

Methods/Findings: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years …

Book Review: Reproduction And Adaptation: Topics In Human Reproductive Ecology, Geoff Kushnick Phd

Human Biology Open Access Pre-Prints

Reproduction and Adaptation: Topics in Human Reproductive Ecology. Edited by C.G. Mascie-Taylor and Lyliane Rosetta. Cambridge Studies in Biological and Evolutionary Anthropology, Vol. 59. Cambridge: Cambridge University Press. 2011. 282 pp. $99.00 (hardback). ISBN 978-0-521-50963-3.

Perioperative Experience Of Adolescents, Janean Carter Monahan

Wayne State University Dissertations

Research has shown that preoperative stress is associated with poorer health outcomes in adults and young children, but there is little in the literature about the stress experienced by adolescents. Clinical experience, however, has shown that adolescents behave differently throughout the perioperative experience than either adults or children. For example, common behaviors of adolescent's emerging from anesthesia include combativeness, thrashing, and crying. To promote adolescent health and to provide adolescents with appropriate interventions that will support a positive surgical outcome, research is needed to discover the perceptions and meanings adolescents attribute to the perioperative experience.

The purpose of this hermeneutic …

Patients' And Caregivers' Inside Perspectives: Living With A Left-Ventricular Assist Device As Destination Therapy, Linda Marcuccilli

Wayne State University Dissertations

Left-ventricular assist devices (LVADs) have improved the quality of life for many patients with advanced heart failure. Past research focused on technology issues and survival rates, but patients' and caregivers' perspectives of living with an LVAD as a destination therapy (e.g., permanent alternative to transplant) was not explored. Roy's adaptation model provided a framework to guide an understanding of how participants adjusted and accepted living with destination therapy. A hermeneutic-phenomenology as described by van Manen was used to explore and describe the essence of destination therapy from patients' and caregivers' perspectives in order to understand the meaning of this experience. …

A Role For Reactive Oxygen Species In Photodynamic Therapy, Michael Price

Wayne State University Dissertations

Photodynamic therapy (PDT) is based on the ability of certain photosensitizing agents to selectively localize in neoplastic cells and their vasculature. Subsequent irradiation at a wavelength corresponding to a photosensitizer absorbance band excites the photosensitizer molecules, leading to energy transfer reactions and fluorescence. It was initially concluded that the phototoxic effect occurred when energy from the excited state of the photosensitizer was transferred to dissolved oxygen to form singlet oxygen. This product has a very brief half-life and will cause cellular damage only in the immediate vicinity of its formation. But an excited-state photosensitizer can also interact with oxygen to …

The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin

Wayne State University Dissertations

Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …

Identification Of Transcriptional Mechanisms Downstream Of Nf1 Gene Defeciency In Malignant Peripheral Nerve Sheath Tumors, Daochun Sun

Wayne State University Dissertations

Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma that occurs in carriers of mutations in the neurofibromatosis type I gene (Nf1) as well as sporadically. Plexiform neurofibromas in NF1 patients have a significant risk of developing into MPNSTs leading to increased morbidity and mortality from this syndrome. Surgery is the primary intervention but it is not always effective due to the tendency of MPNSTs to infiltrate the surrounding tissue or grow in an inoperable location. Neurofibromin, the protein coded by the Nf1 gene, functions as a GTPase activating protein (GAP) whose mutation leads to constitutive …

Longitudinal Outcomes Of Distortion Product Otoacoustic Emissions And Wideband Reflectance In Infants, Virginia Ramachandran

Wayne State University Dissertations

Clinical practice has shown that some infants are born with, or develop a temporary conductive hearing loss characterized by the absence of measurable otoacoustic emissions (OAEs) but normal sensorineural hearing. This transient situation interferes with the process of universal newborn hearing screening and identification.

The purpose of this prospective, longitudinal study was to describe outcomes of distortion product OAE (DPOAE) screening in infants at birth, and one, four, eight, and twelve weeks of age. In addition, wideband reflectance (WBR) measures, which have the potential to help characterize outer-ear canal and middle-ear function, were examined to determine their potential utility in …

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

Sex Differences In The Dopaminergic Regulation Of Courtship, But Not Pairing Behaviors In Zebra Finches, Erin Marie Lowrey

Wayne State University Theses

Dopamine is one of the key ingredients in the glue that cements social bonds in vertebrates. The D2 dopamine receptor has been implicated in the regulation of monogamous pair bonding in the prairie vole. While dopamine affects courtship behaviors in the male zebra finch, the behavioral role of dopamine acting at D2 receptors in both males and females deserves further attention. We hypothesized that the D2 receptor would regulate courtship and pairing behaviors in the male and female zebra finch. Sixteen males and females were tested using a repeated measures design. On day 1, the zebra finches were injected with …

How To Write An Article: Preparing A Publishable Manuscript!, Vinod B. Shidham, Martha B. Pitman, Richard M. Demay

Department of Pathology

Most of the scientific work presented as abstracts (platforms and posters) at various conferences have the potential to be published as articles in peer-reviewed journals. This DIY (Do It Yourself) article on how to achieve that goal is an extension of the symposium presented at the 36th European Congress of Cytology, Istanbul, Turkey (presentation available on net at http://alturl.com/q6bfp). The criteria for manuscript authorship should be based on the ICMJE (International Committee of Medical Journal Editors) Uniform Requirements for Manuscripts. The next step is to choose the appropriate journal to submit the manuscript and review the 'Instructions to …

Copy Number Variation Signature To Predict Human Ancestry, Melissa Pronold, Marzieh Vali, Roger Pique-Regi, Shahab Asgharzadeh

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Copy number variations (CNVs) are genomic structural variants that are found in healthy populations and have been observed to be associated with disease susceptibility. Existing methods for CNV detection are often performed on a sample-by-sample basis, which is not ideal for large datasets where common CNVs must be estimated by comparing the frequency of CNVs in the individual samples. Here we describe a simple and novel approach to locate genome-wide CNVs common to a specific population, using human ancestry as the phenotype.

Results

We utilized our previously published Genome Alteration Detection Analysis (GADA) algorithm to identify common ancestry …

Network Insights On Oxaliplatin Anti-Cancer Mechanisms, Osama M. Alian, Asfar S. Azmi, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Oxaliplatin has been a crucial component of combination therapies since admission into the clinic causing modest gains in survival across multiple malignancies. However, oxaliplatin functions in a non-targeted manner, posing a difficulty in ascertaining precise efficacy mechanisms. While previously thought to only affect DNA repair mechanisms, Platinum-protein adducts (Pt-Protein) far outnumber Pt-DNA adducts leaving a big part of oxaliplatin function unknown. Through preliminary network modeling of high throughput data, this article critically reviews the efficacy of oxaliplatin as well as proposes a better model for enhanced efficacy based on a network approach. In our study, not only oxaliplatin’s function …

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …