Medicine and Health Sciences Commons^™

Genetic Analysis Of The Promoter Region Of The Serotonin Receptor 5ht2b And Its Contribution To Pulmonary Hypertension Syndrome In Broiler-Type Chickens, Khaloud Awada Alzahrani

Graduate Theses and Dissertations

Pulmonary Arterial Hypertension (PAH) is a sever disorder characterized by high pulmonary artery pressure and pulmonary vascular resistance along with specific histological changes. Idiopathic PAH is a human disease of unknown origin that showed common characteristics to PHS/ascites in chicken. PHS/ascites is a condition found in broilers causing right ventricular hypertrophy, valvular insufficiency, increased venous pressure, variable liver changes, accumulation of fluids in the abdominal cavity, and finally lung and heart failure. Currently, there is no acceptable animal model for human PAH. Our group has been validating the chicken as the medical animal model for human PAH, thus we have …

Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White

Dissertations and Theses (Open Access)

The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the FDA-approved proteasome inhibitor bortezomib (Velcade®) in solid tumor cells, we demonstrated that perhaps the most critical response to proteasome inhibition is repression of global protein synthesis by phosphorylation of the eukaryotic initiation factor 2-α subunit (eIF2α). In a panel of 10 distinct human pancreatic cancer cells, we showed marked heterogeneity in the ability of cancer cells to induce …

Molecular Diagnosis Of Metabolic Fast Growth Related Diseases In Broiler, Adnan Ali Khalaf Al-Rubaye

Graduate Theses and Dissertations

Pulmonary Hypertension Syndrome (PHS) and lameness are important metabolic diseases that affect rapidly growing broilers. The research reported in the first section of this dissertation focused on developing qPCR assays to identify differences in the expression levels of four candidate genes possibly associated with PHS: angiotensin II type 1 receptor (AGTR1): urotensin receptor 2D (UTS2D); serotonin receptor/transporter type 2Bn (HTR2B); and angiotensinogen cleaving enzyme (ACE). Expression levels of these candidate genes were examined in four different tissues. We established ribosomal protein S14 (RPS14) and RNA polymerase subunit 2B (RP2B) as suitable reference genes because they showed the most consistent deltaCt …

Cinacalcet As Adjunctive Therapy For Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets., Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism from inadequate calcium absorption in the gut, is the underlying pathophysiology for rachitic changes in hereditary vitamin D-resistant rickets (HVDRR). We describe a novel use of Cinacalcet to treat a child with HVDRR in whom conventional modes of therapy had to be discontinued. Cinacalcet therapy with high-dose oral calcium effectively normalized the metabolic abnormalities and bone condition. The relative ease of administration of the calcimimetic as a once- or twice-daily oral preparation, compared with traditional intravenous calcium administration, should encourage its move to the frontline of treatment of the disorder.

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Evolution Of Human Immunodeficiency Virus Type 1 Clade C Envelope V1–V5 Region During Disease Progression In Non-Human Primate Model, For Yue Tso

School of Biological Sciences: Dissertations, Theses, and Student Research

Human immunodeficiency virus type 1 (HIV-1) clade C strain is the fastest spreading HIV-1 strain globally, especially in Africa. It has been decades since the acquired immune deficiency syndrome (AIDS) pandemic first started. However, an effective anti-HIV-1 vaccine is not yet available, which is partly due to the highly variable nature of HIV-1 envelope gene and the absence of a suitable animal model. Strengthening of the understanding of envelope evolution during disease progression will contribute significantly towards future anti-HIV-1 treatment and preventions.

Non-human primates have been an essential animal model for many biomedical research areas. Using simian-human immunodeficiency virus (SHIV) …

A Home-Based Exercise Intervention To Increase Physical Activity Among People Living With Hiv: Study Design Of A Randomized Clinical Trial, Jason R. Jaggers, Wesley Dudgeon, Steven N. Blair, Xuemei Sui, Stephanie Burgess, Sara Wilcox, Gregory A. Hand

Faculty and Staff Scholarship

Background

While combination antiretroviral therapy has extended the life expectancy of those infected with human immunodeficiency virus (HIV), there is a high prevalence of comorbidities that increase the risk of cardiovascular morbidity and mortality among people living with HIV/AIDS (PLWHA). The side effects associated with antiretroviral therapy (ART) lead to multiple metabolic disorders, making the management of these metabolic issues and risk of cardiovascular disease (CVD) in those treated with ART a critical issue. Clinical research trials, primarily clinical exercise, rarely include this population due to unique challenges in research methods with underserved minority populations living with a life threatening …

Proteomic Studies Of The Influenza Virus-Human Cell Interactions: The Responses Of Host Cell Protein Expression To Viral Infection And The Novel Host Proteins That Interact With Virus Protein Ns1, Yimeng Wang

Graduate Theses and Dissertations

Influenza A viruses (IAVs) continue to be a threat to human health. Despite extensive studies, the mechanisms underlying the IAVs-host interactions during IAV infection remain elusive. We employed quantitative proteomic methods to systematically explore the host cell protein expression responses to IAV infection and examine the function of a critical IAV protein called NS1 by identifying its host binding partners. Specifically, we used a 2-dimentional gel electrophoresis (2-DE) based proteomic method to screen host proteins whose expression was substantially altered by IAV. One critical protein named IκB kinase-gamma (IKKγ) was found to be significantly down-regulated during IAV infection. Functional studies …

Design And Implementation Of Wireless Point-Of-Care Health Monitoring Systems: Diagnosis For Sleep Disorders And Cardiovascular Diseases, Se Chang Oh

Graduate Theses and Dissertations

Chronic sleep disorders are present in 40 million people in the United States. More than 25 million people remain undiagnosed and untreated, which accounts for over $22 billion in unnecessary healthcare costs. In addition, another major chronic disease is the heart diseases which cause 23.8% of the deaths in the United States. Thus, there is a need for a low cost, reliable, and ubiquitous patient monitoring system. A remote point-of-care system can satisfy this need by providing real time monitoring of the patient's health condition at remote places. However, the currently available POC systems have some drawbacks; the fixed number …

Development Of A Predictive Modeling System For Validation Of The Cumulative Mirobial Inactivation Of The Salmonellae In Pepperoni Utilizing A Non-Pathogenic Surrogate Microorganism (Enterococcus Faecalis), Scott Donald Stillwell

Graduate Theses and Dissertations

Salmonellosis is the most frequently occurring bacterial foodborne illness in the United States and the human case rate has not improved for the past two decades. The federal agency responsible for oversight of meat and poultry processors has announced the intent to extend existing pathogen reduction performance standards for Salmonella spp. to cover all classes of products including fermented sausages that are currently produced under HACCP plans that are validated for control of Escherichia coli O157:H7. The proposed regulatory modifications will require processors to revalidate HACCP plan controls to achieve either a 6.5 or a 7.0 log10 inactivation of the …

Bronchial Thermoplasty In The Endoscopy Unit Reducing Smooth Muscle Hypertrophy Asthmatic, Marie Porter Rn, Bsn, Cgrn

Patient Care Services / Nursing

No abstract provided.

Functional Study Of Hemogen Knockout Mouse Model, Peng Gao

Theses and Dissertations (ETD)

Mouse Hemogen (Hemgn) is regarded as a homologue of human Erythroid Differentiation Associated Gene (EDAG). EDAG overexpression has been postulated for association with some leukemia cases. Meanwhile, Hemgn has been found to contribute to Hoxb4 mediated hematopoietic stem cell expansion. Based on these postulations and evidences, a Hemgn knockout mouse model has been generated to study its function in normal and stress hematopoiesis. I confirmed the Hemgn expression in hematopoietic organs including bone marrow and spleen, as well as round spematids in testis. Hemgn is expressed in mouse hematopoietic stem cells and erythroid progenitor cells. Moreover, Hemgn was also found …

Efficacy Of Probiotics For Reducing The Incidence Of Lameness In Broilers Grown On Wire Flooring, John Matthew Stark

Graduate Theses and Dissertations

Growing broilers on wire flooring provides an excellent experimental model for reproducibly triggering significant levels of lameness. In Pilot Study #1 using broilers from Line C grown on wire flooring, adding the Biomin probiotic PoultryStar® to the feed reduced the percentage of lameness by half when compared with broilers that received the control diet alone. In Pilot Study # 2 using broilers from Line B grown on wire flooring, adding the PoultryStar® probiotic reduced the percentage of lameness to 8% when compared with 28% lameness in broilers that received the control diet alone. The objective of this study was to …

Efficacy Of Selected Disinfectants Against Salmonella Isolates From Broiler Breeders, Arslan Aslam

Graduate Theses and Dissertations

Salmonella have been causing huge losses in the poultry industry and have been a major cause food borne illness for many years. Salmonella infections in humans from poultry have been increasing. Good hygiene and biosecurity measures can reduce the incidence of Salmonella infections at poultry farms. Disinfection is a most important measure taken to prevent Salmonellosis in poultry. This research was conducted to determine the efficacy of 12 disinfectants against seven Salmonella isolates in the presence and absence of organic matter. A bacterial solution of a specific optical density value was prepared and .05x, .1x and .2x concentrations of disinfectants …

Landscape Epidemiology And Machine Learning: A Geospatial Approach To Modeling West Nile Virus Risk In The United States, Sean Gregory Young

Graduate Theses and Dissertations

The complex interactions between human health and the physical landscape and environment have been recognized, if not fully understood, since the ancient Greeks. Landscape epidemiology, sometimes called spatial epidemiology, is a sub-discipline of medical geography that uses environmental conditions as explanatory variables in the study of disease or other health phenomena. This theory suggests that pathogenic organisms (whether germs or larger vector and host species) are subject to environmental conditions that can be observed on the landscape, and by identifying where such organisms are likely to exist, areas at greatest risk of the disease can be derived. Machine learning is …

Oxidation Of Thrombomodulin Methionine 388 In Cigarette Smokers, Samrat B. Thapa

Graduate Theses and Dissertations

This work tested the hypothesis that oxidation of methionine 388 in thrombomodulin is higher in cigarette smokers, and thus a likely contributor towards the hypercoagulable state in smokers. Thrombomodulin, a protein cofactor found on endothelial cell surfaces, regulates the activity of thrombin. Thrombin bound to thrombomodulin no longer converts fibrinogen to fibrin, but instead activates Protein C which, in turn, stops the coagulation cascade by inactivation of clotting factors. The oxidation of methionine 388 of thrombomodulin has been shown in vitro to dramatically decrease the anticoagulant cofactor activity of thrombomodulin. The blood of cigarette smokers is more prone to clot …

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 …

Liposomal Fasudil, A Rho-Kinase Inhibitor, For Prolonged Pulmonary Preferential Vasodilation In Pulmonary Arterial Hypertension, Vivek Gupta, Nilesh Gupta, Imam H. Shaik, Reza Mehvar, Ivan F. Mcmurty, Masahiko Osa, Eva Nozik-Grayck, Fakhrul Ahsan

Pharmacy Faculty Articles and Research

Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were …

Effects Of Clostridium Difficile On The Human Immune Response, Mike Mcgovern

Honors Projects in Science and Technology

Clostridium difficile is a bacterium that is rapidly becoming a large issue in the medical community due to its tendency to infect hospital patients and its resistance to antibiotics. By studying the way in which the pathogen interacts with the human immune system, it is possible to better understand how the body naturally fights off the disease. This knowledge can allow medical professionals to develop treatments that can help curtail the infection before serious symptoms occur. Working under a grant program alongside Professors Kirsten Hokeness and Chris Reid, I was able to research the effects that exposure to the C. …

An In-Depth Look At Recent Influenza Seasons And Vaccine Effectiveness, Ariana Ricci

Honors Projects in Science and Technology

This paper aims to present an in-depth exploration of immunology, the influenza virus, vaccination, and vaccination’s effectiveness with respect to influenza. It also delves into the possible causes behind the large increase in early childhood deaths during the 2003-2004 influenza season, which was a turning point in terms of influenza incident reporting. Finally, data analysis on the relationship between childhood flu vaccine coverage and childhood outpatient ILI (influenza-like illness) visits by region is presented as a measurement of vaccine effectiveness and identifier of trends. Although this relationship was not statistically significant (alpha=0.05) regionally, this simply points to alternate factors that …

A Key New Ally In The Search For Huntington’S Disease Treatments, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Discrimination In Medical Settings And Attitudes Toward Complementary And Alternative Medicine: The Role Of Distrust In Conventional Providers, Tetyana Shippee, Carrie Henning-Smith, Nathan Shippee, Jessie Kemmick Pintor, Kathleen T. Call, Donna Mcalpine, Pamela Jo Johnson

Journal of Health Disparities Research and Practice

This study examines the relationship between racial/ethnic discrimination in medical settings, distrust in conventional medicine, and attitudes toward complementary and alternative medicine (CAM) among a racially/ethnically diverse sample. We also investigate how this relationship differs by nativity. Data are from a 2008 statewide stratified sample of publicly insured adults in Minnesota (N=2,194). Discrimination was measured as self-reported unfair treatment in medical settings due to race, ethnicity, and/or nationality. Outcomes are trust in conventional providers/medicine and attitudes toward CAM modalities. Discrimination in medical settings was positively associated with 1) distrust in conventional providers and 2) favorable attitudes toward CAM. Foreign-born …

Mccormack, Joseph Nathaniel, 1847-1922 (Sc 1005), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid and full-text scan (Click on "Additional Files" below) for Manuscripts Small Collection 1005. Letter addressed to “Dear Doctor”, sent by secretary Joseph Nathaniel McCormack of the Kentucky State Board of Health, Bowling Green, Kentucky, extolling the merit of the Rosenow-Mayo vaccine for the prevention of influenza and pneumonia. Dr. Lillian South is noted as the one in charge of the vaccine distribution.

Testosterone, Cardiovascular, Men, Trial, Lin Xu, Guy Freeman, Benjamin J. Cowling, Mary Schooling

Publications and Research

Background
Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease.

Methods
A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, …

Feeling The Hope, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Isolation Of Lesbian, Gay, Bisexual, And Transgender Youth: A Dimensional Concept Analysis, Michael Johnson, Elaine Amella

Interdisciplinary Research Scholarship Day

Present the findings of a dimensional concept analysis of isolation within the context of LGBT youth. LGBT youth are at greater risk for negative health outcomes as compared to heterosexual youth, including depression, anxiety, suicide, substance abuse, and HIV/AIDS. Some studies suggest LGBT feeling and being isolated is related to some negative health outcomes. Other research reveals a relationship between isolation and negative health

Pilot Study Of Cyp2b6 Genetic Variation To Explore The Contribution Of Nitrosamine Activation To Lung Carcinogenesis, Catherine Wassenaar, Qiong Dong, Christopher Amos, Margaret Spitz, Rachel F. Tyndale

Dartmouth Scholarship

We explored the contribution of nitrosamine metabolism to lung cancer in a pilot investigation of genetic variation in CYP2B6, a high-affinity enzymatic activator of tobacco-specific nitrosamines with a negligible role in nicotine metabolism. Previously we found that variation in CYP2A6 and CHRNA5-CHRNA3-CHRNB4 combined to increase lung cancer risk in a case-control study in European American ever-smokers (n = 860). However, these genes are involved in the pharmacology of both nicotine, through which they alter smoking behaviours, and carcinogenic nitrosamines. Herein, we separated participants by CYP2B6 genotype into a high- vs. low-risk group (*1/*1 + *1/*6 vs. *6/*6). Odds ratios estimated …

Quickening The Pace Towards A Huntington’S Disease Gene-Silencing Clinical Trials: Pharma Giant Roche, Isis Enter Partnership, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Parasitological Prevalence Of Bovine Trypanosomosis In Kubo Division Of Kwale County Of Coastal: Baseline Survey, N. Mbahin, H. Affognon, J. Andoke, M. Tiberius, D. Mbuvi, J. Otieno, P. Muasa, R. K. Saini

All Peer-Reviewed Publications

Prior to field trials of large scale tsetse repellent technology validation in July 2011, a cross-sectional survey of bovine trypanosomosis and its vectors was carried out to know the disease level in Kwale County of Coastal Kenya. A total of 584 adult cattle were examined at ten different Locations. The trypanosome prevalence in cattle with regard to age, sex, location and apparent tsetse density was investigated. The overall trypanosome prevalence in cattle in Kubo Division of Kwale County was 33.9%. Two types of infections were recorded in various parts of the Division in the following proportions: T. congolense 61.1%, T. …