Digital Commons Network^™

Associations Between Alcohol Consumption And Fasting Blood Glucose In Young Adults, Julie Ann Lucca

Master's Theses

Current research shows moderate alcohol consumption is associated with decreased risk of diabetes and excessive consumption or binge drinking can cause insulin resistance and diabetes. In 2010, diabetes was the seventh leading cause of death in the United Statesand was responsible for significant health complications: blindness, kidney failure, and limb amputations, and is a large national economic burden. Fasting blood glucose (FBG) is a tool used to help diagnose diabetes. Abnormally high FBG, ≥100 mg/dl, is indicative of diabetes and pre-diabetes. Few studies have observed diabetic prevalence among young adults or college students. Studying young adults can help provide added …

Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne

Articles

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …

Microproteinuria During Opisthorchis Viverrini Infection: A Biomarker For Advanced Renal And Hepatobiliary Pathologies From Chronic Opisthorchiasis, Prasert Saichua, Paiboon Sithithaworn, Amar R. Jariwala, David J. Diemert, Jiraporn Sithithaworn, Banchob Sripa, Thewarach Laha, Eimorn Mairiang, Chawalit Pairojkul, Maria V. Periago, Narong Khuntikeo, Jason Mulvenna, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of …

Human Prostatic Acid Phosphatase: Structure, Function And Regulation., Sakthivel Muniyan, Nagendra K. Chaturvedi, Jennifer G. Dwyer, Chad A. Lagrange, William G. Chaney, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via …

The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …

Anr And Its Activation By Plch Activity In Pseudomonas Aeruginosa Host Colonization And Virulence, Angelyca A. Jackson, Maegan J. Gross, Emily F. Daniels, Thomas H. Hampton, John H. Hammond, Isabelle Vallet-Gely, Simon L. Dove, Bruce A. Stanton, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine …

Cytotoxic Properties Of Novel Platinum Compounds, Bbr3610-Dach And Trans-4-Nbd In Tumor Cells: Cellular Effects Of 1, 2-Dach And Nbd Ligands, Vijay Menon

Theses and Dissertations

Platinum-based chemotherapeutics are used for the treatment of a wide range of cancers and a number of attempts have been made toward developing compounds with better cellular stability and similar or enhanced cytotoxicity as compared to their predecessors. The first part of the work reported here focuses on the cellular effects of the metabolically stable dinuclear platinum compound, BBR3610-DACH. Comet assay showed this compound to form interstrand crosslinks, a highly toxic DNA lesion in HCT116 cells, at equimolar concentrations to its parental compound, BBR3610. Cell cycle studies showed that BBR3610-DACH causes G1/S and G2/M cell cycle arrest with S phase …

Polyethylenimine-Enhanced Alumina Nanoscale Adjuvant For Cancer Vaccine, Naoko Uno, Haiyan Li, Hong-Ming Hu, Jun Jiao

Student Research Symposium

Aluminum oxide nanoparticles (Al2O3 NPs) have been shown to increase the efficiency of cell-mediated immune response. Specifically, CD8 and CD4 immune response is required for T cell activation by dendritic cells. These nanoparticles, when functionalized with peptides and other molecules, can be used as vaccine in cancer treatment. In this study, Al2O3 NPs were attached to E6/E7 proteins. HPV-induced cervical cancer expresses E6/E7 antigens. E6/E7 proteins were attached using surface modification of the Al2O3 NPs; different types of molecules were tested to see which adhered the highest amount of protein and produced the strongest cell response. Protein measurements were done …

Flurbiprofen Benzyl Nitrate (Nbs-242) Inhibits The Growth Of A-431 Human Epidermoid Carcinoma Cells And Targets Β-Catenin, Niharika Nath, Xiaoping Liu, Lloydine Jacobs, Khosrow Kashfi

Publications and Research

Background: The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer.

Methods: We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3.

Results: NBS-242 inhibited the growth of …

Vbp15, A Glucocorticoid Analogue, Is Effective At Reducing Allergic Lung Inflammation In Mice, Jesse M. Damsker, Blythe C. Dillingham, Mary C. Rose, Molly A. Balsley, Christopher R. Heier, Alan M. Watson, Erik J. Stemmy, Rosalyn A. Jurjus, Tony Huynh, Kathleen Tatem, Kitipong Uaesoontrachoon, Dana M. Berry, Angela S. Benton, Robert J. Freishtat, Eric P. Hoffman, John M. Mccall, Heather Gordish-Dressman, Stephanie L. Constant, Erica K.M. Reeves, Kanneboyina Nagaraju

Pharmacology and Physiology Faculty Publications

Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Diabetic Db/Db Mice Exhibit Central Nervous System And Peripheral Molecular Alterations As Seen In Neurological Disorders., A. Ernst, Ajaykumar Narayan Sharma, Khalid M. Elased, P. C. Guest, H. Rahmoune, S. Bahn

Pharmacology and Toxicology Faculty Publications

The db/db mouse is a widely used preclinical model in diabetes research. Recent studies have shown that these mice also display aspects of psychosis and depression-like behaviors as seen in some psychiatric disorders. Here, we have performed multiplex immunoassay and liquid chromatography mass spectrometry profiling of the plasma and brain samples from db/db and control mice to identify altered pathways, which could be related to these behavioral abnormalities. This is the first study to carry out profiling of the brain proteome in this model. Plasma from the db/db mice had increased levels of leptin and insulin, decreased levels of peptide …

Effect Of Coconut Oil On Ulcerative Colitis In The Mouse Model, Pranav Chandra Alok

Masters Theses & Specialist Projects

Ulcerative colitis (UC) is a chronic disease of the colon or large intestine that causes inflammation and ulceration of the inner lining of the colon and rectum. In patients with ulcerative colitis, the body’s immune system overreacts and the body mistakes food, bacteria or other internal materials in the colon for an invading substance. The immune system attacks the material, thus irritating the colon. Limited knowledge of inflammatory conditions coupled with a narrow range of therapeutic options necessitates investigating the role of natural products. This study describes the effect of natural coconut oil on chemically-induced acute and chronic disease in …

Algorithms And A Software Application For The Discovery Of Heparin-Binding Proteins For Chemical Analysis, Christopher Dempewolf

Computer Science and Computer Engineering Undergraduate Honors Theses

Heparin is a biological molecule that plays a vital role in anticoagulation. As such, it is used for the prevention of blood clotting in a variety of medical disorders. However, it is easily contaminated with foreign substances, and this can prove fatal for a person receiving heparin. In order to prevent this, proteins that easily bind to heparin need to be added to the solution. Then, the unwanted substances can easily be filtered out. Certain sequences or patterns of amino acids are known to have a high probability of binding to heparin. Thus, proteins that contain large numbers of these …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

Influence Of Genetic Variation On Birth Defects In Caenorhabditis Elegans, Daniel Robert Kepple

Renée Crown University Honors Thesis Projects - All

In my Renee Crown Honors Capstone project, I studied how genetic variation influences birth defects that cause death in C. elegans embryos. I performed high-throughput hatching assay experiments of recombinant inbred advance intercross lines of C. elegans. These lines are genetically distinct from each other. I found significant variation in birth defects causing embryo death in these recombinant inbred advanced intercross lines. My results give evidence that gene interaction may play a significant role in causing birth defects resulting in death. My data also provides a starting point for studies making statistical arguments linking these birth defects to specific …

The Effect Of Nerve Growth Factor (Ngf) Incorporation Into Swine Intestinal Submucosa (Sis) Suture Material On The Healing Process In Gastrocnemius Muscle, Nicole K. Alexander

PCOM Biomedical Studies Student Scholarship

The repair of gastrocnemius muscle incisions were evaluated histologically in a rat model. Comparisons were made between carbon dioxide laser and scalpel incisions closed with sutures prepared from Swine Intestinal Submucosa (SIS) with and without added Nerve Growth Factor. This study was conducted in conjunction with two other studies, one comparing epidermal repair and the other comparing kinesthetic changes post-operatively in the same animal model. Thirty-five days post-surgery the animals were euthanized and an area of muscular tissue encompassing the operative site was excised and evaluated microscopically for the following: presence of macrophages, integrity of the muscle, leukocytes present within …

Ccaat-Binding Factor As A Transcriptional Regulator Of Cyc1 In Candida Albicans, Carmen S. Padilla-Marcia

Graduate Theses and Dissertations

Candida albicans is a normal commensal of the human flora; however, under appropriate circumstances this organism can become pathogenic to the host and cause life threatening conditions. In fact, Candida species are the fourth most common nosocomial infection in the Unites States with a mortality rate of over 30%

The CCAAT binding factor is a multi-protein transcription factor highly conserved in eukaryotes. It binds specifically to the consensus sequence 5'-CCAAT-3' in promoters and it is one of the most common cisacting elements in eukaryotes promoters. This transcription factor is composed of three DNA binding subunits; Hap2p, Hap3p and Hap5. In …

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 …

Role Of Mir-19a Released By Inflammatory Breast Cancer Cells In The Regulation Of Dendritic Cell Functions: In Vitro Model Of Crosstalk In The Tumor Microenvironment Of Inflammatory Breast Cancer, Simone Anfossi

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is a rare but very aggressive form of locally advanced breast cancer (1-6% of total breast cancer patients in United States), with a 5-year overall survival rate of only 40.5%, compared with 85% of the non-IBC patients. So far, a unique molecular signature for IBC able to explain the dramatic differences in the tumor biology between IBC and non-IBC has not been identified. As immune cells in the tumor microenvironment plays an important role in regulating tumor progression, we hypothesized that tumor-associated dendritic cells (TADC) may be responsible for regulating the development of the aggressive characteristics …

Effects Of Short Term High Fat Diet On Obesity And Perivascular Adipose Structure And Function In Mice : Role Of Aldose Reductase, And Aldehyde Metabolizing Enzyme., Daniel Alan Murphy

College of Arts & Sciences Senior Theses

This study was undertaken to determine the effects of high fat diet and aldose reductase deficiency on the structure and function of murine perivascular adipose tissue. Wild type (WT) (C57 bl/6) and aldose reductase knockout (AR-null) mice were aged to 8 or 18 weeks on a normal chow diet then some were switched to a high fat diet for 4 weeks while others remained on the control diet for the same amount of time. Following 4 weeks, mice were euthanized PVAT was analyzed. High fat feeding significantly increased body fat percentage in both age groups of mice and the area …

Concurrent Neurological And Behavioral Assessment Of Number Line Estimation Performance In Children And Adults, Joseph Michael Baker

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Understanding the brain’s response to common math-learning activities may help improve math education. For example, by imaging the brains of typically developing children and adults throughout a number line estimation task, it is possible to establish a baseline of what “typical” brains do in such situations. Thus, comparisons may be made to determine the degree to which brain functioning differs between typical and atypical math learners. Moreover, by identifying methods that may increase the brain’s response to real-world math activities, it may be possible to improve the math learning process for typical and atypical learners alike.

Brain imaging devices such …

Oxidative Stress For An Acute Bout Of Bikram Yoga In Healthy, Trained Adults, Kimberly Anne Trocio

UNLV Theses, Dissertations, Professional Papers, and Capstones

BACKGROUND:Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original "hot" yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate …

Improving Cervical Cancer Nodal Boost Radiation Therapy By Quantifying Uncertainties And Exploring Advanced Radiation Therapy Modalities, Zhiqian Yu

Dissertations and Theses (Open Access)

Radiation therapy for patients with intact cervical cancer is frequently delivered using primary external beam radiation therapy (EBRT) followed by two fractions of intracavitary brachytherapy (ICBT). Although the tumor is the primary radiation target, controlling microscopic disease in the lymph nodes is just as critical to patient treatment outcome. In patients where gross lymphadenopathy is discovered, an extra EBRT boost course is delivered between the two ICBT fractions. Since the nodal boost is an addendum to primary EBRT and ICBT, the prescription and delivery must be performed considering previously delivered dose. This project aims to address the major issues of …

The Impact Of Family History On Medullary Thyroid Cancer In Men2a Patients, Nicole D. Mohrbacher

Dissertations and Theses (Open Access)

The American Thyroid Association recently classified all MEN2A-associated codons into increasing risk levels A-C and stated that some patients may delay prophylactic thyroidectomy if certain criteria are met. One criterion is a less aggressive family history of MTC but whether families with the same mutated codon have variable MTC aggressiveness is not well described. We developed several novel measures of MTC aggressiveness and compared families with the same mutated codon to determine if there is significant inter-familial variability. Pedigrees of families with MEN2A were reviewed for codon mutated and proportion of RET mutation carriers with MTC. Individuals with MTC were …

Gene Therapy And Stem Cell Therapy To Improve The Outcome Of Human Islet Transplantation, Hao Wu

Theses and Dissertations (ETD)

Since its first introduction in 1990s, the Edmonton Protocol for human islet transplantation has helped more than 500 patients with type 1 diabetes worldwide and met great success from bench to bedside. The Edmonton Protocol involves isolating islets from a cadaveric donor pancreas by enzymatic digestion and infusing into the patient's portal vein. Each recipient usually receives islets from two or three donors for an optimal outcome and is dosed with two immunosuppressive drugs, sirolimus and tacrolimus and a monoclonal antibody drug daclizumab to prevent the graft rejection. However, despite the administration of immunosuppressive drugs and the recent improvement in …

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.

The Role Of Il-8-Mediated Src Family Kinase Activation In Tumor-Tumor And Tumor-Stromal Interactions In Metastasis Of Prostate Cancer, Lynnelle Thorpe

Dissertations and Theses (Open Access)

Men with localized prostate cancer (PCa) have a 100% five-year survival rate, but this rate drops to 33% for men with metastatic disease. A better understanding of the metastatic process is needed to develop better therapies for PCa. Aberrant activation of protein tyrosine kinases, including Src Family Kinases (SFKs) contribute to metastasis through numerous functions, one of which leads to increased expression of cytokines, such as IL-8. However, the relationship between Src activity and IL-8 regulation is not completely understood. In cell line models, I determined that IL-8 activates Src and in turn Src activates IL-8 demonstrating a feed forward …

Novel Therapeutic Targets Identified By High-Throughput Technologies For Triple-Negative Breast Cancer, Christine Shiang

Dissertations and Theses (Open Access)

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to …

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 …