Digital Commons Network^™

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Study Of Mouse Induced Pluripotent Stem Cell Transplantation Intowistar Albino Rat Cochleae After Hair Cell Damage*, Mustafa Kürşat Gökcan, Selçuk Mülazi̇moğlu, Emre Ocak, Pinar Can, Murat Çalişkan, Ömer Beşalti, Serpi̇l Di̇zbay Sak, Gülşah Kaygusuz

Turkish Journal of Medical Sciences

Background/aim: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. Materials and methods: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the …

Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer

All ETDs from UAB

Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …

What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill

All ETDs from UAB

Staphylococcus aureus is known to cause disease in both human and animal populations. Many of the virulence factors important for S. aureus pathogenesis are found on mobile genetic elements known as S. aureus pathogenicity islands (SaPIs). SaPIs can transduce into surrounding cells, giving those cells the ability to produce virulence factors. Derepression allows SaPIs to be excised from S. aureus genome to initiate mobilization. Derepressors have been identified for multiple SaPIs, but it remains unknown if the same SaPI can be derepressed by multiple derepressors. It has been shown that SaPIbov1 can be derepressed by the type 1 dUTPase from …

Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham

All ETDs from UAB

Glioblastoma (GBM) is the most common and aggressive human primary malignant brain tumor with a 5-year survival rate of less than 5%. GBM is highly invasive, rendering complete surgical resection impossible. Additionally, this tumor type is relatively insensitive to radiotherapy. Thus, effective chemotherapeutic options present the last line of defense for GBM patients. Unfortunately, nearly 50% of all GBM tumors are resistant to the current chemotherapeutic standard, temozolomide (TMZ). TMZ is a DNA alkylating agent that promotes apoptosis via DNA damage. Resistance to TMZ-induced cell death is attributed to expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) resultant from …

Role Of Sulfiredoxin Interacting Proteins In Lung Cancer Development, Hedy Chawsheen

Theses and Dissertations--Toxicology and Cancer Biology

Sulfiredoxin (Srx) is an antioxidant enzyme that can be induced by oxidative stress. It promotes oncogenic phenotypes of cell proliferation, colony formation, migration, and metastasis in lung, skin and colon cancers. Srx reduces the overoxidation of 2-cysteine peroxiredoxins in cells, in addition to its role of removing glutathione modification from several proteins. In this study, I explored additional physiological functions of Srx in lung cancer through studying its interacting proteins. Protein disulfide isomerase (PDI) family members, thioredoxin domain containing protein 5 (TXNDC5) and protein disulfide isomerase family A member 6 (PDIA6), were detected to interact with Srx. Therefore, I proposed …

Seasonal Vitamin D Status And Endothelial Function In Healthcare Workers, Özlem Hali̇loğlu, Tolga Kasaci, Di̇lek Yavuz

Turkish Journal of Medical Sciences

Background/aim: Healthcare workers have long working hours indoors and are at risk of vitamin D deficiency. The aim of this study was to determine seasonal vitamin D status and its relationship with early atherosclerotic markers, endothelial function, and carotid intima-media thickness (CIMT) in healthcare workers of Marmara University Hospital, İstanbul. Materials and methods: One hundred and ninety healthy volunteer healthcare workers and 66 nonmedical volunteers of Marmara University Hospital were included in the study and 25-hydroxyvitamin D (25(OH)D), calcium, intact parathyroid hormone (PTH), endothelial function, and CIMT were measured twice during winter and summer seasons. Results: Mean vitamin D levels …

Higher Neutrophil To Lymphocyte Ratio Is Related To A Lower Ejectionfraction In Bicuspid Aortic Valve Patients, Haci Ahmet Kasapkara, Abdullah Nabi̇ Aslan, Hüseyi̇n Ayhan, Murat Can Güney, Murat Akçay, Zeynep Şeyma Turi̇nay, Tahi̇r Durmaz, Telat Keleş, Engi̇n Bozkurt

Turkish Journal of Medical Sciences

Background/aim: Inflammation plays an important role in the pathophysiology of vascular disease. In this study, we aimed to evaluate the associations of neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) with left ventricular ejection fraction and ascending aorta diameter in patients with a bicuspid aortic valve (BAV). Materials and methods: One hundred and thirty-nine consecutive patients with the diagnosis of BAV were enrolled in the study. Complete blood counts were analyzed for neutrophil and lymphocyte levels and NLR. The subjects were separated into two groups based on their ascending aorta diameter. The patients with ascending aorta diameter equal to …

The Inhibitory Effect Of Bacteriocin Produced By Lactobacillus Acidophilusatcc 4356 And Lactobacillus Plantarum Atcc 8014 On Planktonic Cells And Biofilms Of Serratia Marcescens, Roya Vahedi Shahandashti, Rouha Kasra Kermanshahi, Parinaz Ghadam

Turkish Journal of Medical Sciences

Background/aim: The spread of antibiotic-resistant pathogens has resulted in the need for new treatments. The aim of the present study is to investigate the effect of bacteriocin from Lactobacillus acidophilus ATCC 4356 and Lactobacillus plantarum ATCC 8014 on planktonic and biofilm forms of Serratia marcescens strains. Materials and methods: The direct antagonism of the L. plantarum and L. acidophilus cell-free supernatant on S. marcescens cultures was determined using an optical density assay. The bacteriocin was partial purified by ammonium sulfate precipitation. Its molecular weight was analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The effect of bacteriocins on the biofilm …

Neuroprotective Effects Of Bone Marrow-Derived Mesenchymal Stem Cellsand Conditioned Medium In Mechanically Injured Neuroblastoma Cells, Mesut Mete, Işil Aydemi̇r, Ülkü Ünlü Ünsal, Yusuf Kurtuluş Duransoy, Mehmet İbrahi̇m Tuğlu, Mehmet Selçuki̇

Turkish Journal of Medical Sciences

Background/aim: Bone marrow-derived mesenchymal stem cells (BMSCs) possess self-renewal characteristics that distinguish them from other cell types. Recent studies have focused on the effects of conditioned medium (CM) that includes the extracellular matrix. Here we examined the neuroprotective effects of BMSCs and CM on damaged neuroblastoma cells. Materials and methods: The cells were divided into five groups: 1) healthy controls, 2) damaged cells alone, 3) damaged cells treated with BMSCs, 4) damaged cells treated with CM, and 5) damaged cells treated with both BMSCs and CM. Neuroprotective effects were then evaluated based upon the levels of oxidative stress, antitransforming growth …

Prevalence And Level Of Enterohemorrhagic Escherichia Coli In Culled Dairy Cows At Harvest, Zachary R. Stromberg, Gentry L. Lewis, Sharif S. Aly, Terry W. Lehenbauer, Joseph M. Bosilevac, Natalia Cernicchiaro, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

The primary objective of this study was to determine the prevalence and level of enterohemorrhagic Escherichia coli (EHEC) O26, O45, O103, O111, O121, and O145 (collectively EHEC-6) plus EHEC O157 in fecal, hide, and preintervention carcass surface samples from culled dairy cows. Matched samples (n=300) were collected from 100 cows at harvest and tested by a culture-based method and two molecular methods: NeoSEEK STEC (NS) and Atlas STEC EG2 Combo. Both the culture and NS methods can be used to discriminate among the seven EHEC types (EHEC-7), from which the cumulative prevalence was inferred, whereas the Atlas method can discriminate …

High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao

Nebraska Center for Virology: Faculty Publications

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29

grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high …

Stress-Induced Reinstatement Of Drug Seeking: 20 Years Of Progress, John R. Mantsch, David A. Baker, Douglas Funk, Anh D. Lê, Yavin Shaham

Biomedical Sciences Faculty Research and Publications

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, …

The Role Of Epidermal Stem/Progenitor-Like Cells In Hpv-Mediated Pre-Neoplastic Transformation, Yvon L. Woappi

Theses and Dissertations

The role of epidermal basal stem cells in dysplasia is a matter of great interest in the human papillomavirus (HPV)-driven cancers. To assess the relationship between “stemness” and HPV-mediated transformation, we made use of 3-D suspension culture and fluorescence activated cell sorting (FACS) to purify stem/progenitor-like cells from primary normal human keratinocyte (NHKc) cultures. We found that NHKc cells derived from multicellular keratinocyte spheroids were enriched for a basal subpopulation of epidermal stem-like cells, that could be maintained for prolonged time in culture and used to conduct transfection experiments with full-length HPV16 DNA. Thus, by using these stem cell enrichment …

การพัฒนาการเตรียมตัวอย่างแบบง่ายสำหรับการตรวจวิเคราะห์สายพันธุ์และการกลายพันธุ์ของเชื้อไวรัสฮิวแมนปาปิลโลมาโดยวิธี High-Throughput Sequencing, อุกฤษฏ์ ทองภูมิ

Chulalongkorn University Theses and Dissertations (Chula ETD)

มะเร็งปากมดลูกมีสาเหตุหลักมาจากการติดเชื้อไวรัสฮิวแมนปาปิลโลมาในกลุ่ม high risk genotype แต่สามารถพบการติดเชื้อในกลุ่ม low risk genotype ในผู้ป่วยมะเร็งปากมดลูกด้วย ซึ่งเทคนิคที่ใช้ในปัจจุบันไม่สามารถตรวจพบได้ ในขณะที่เทคโนโลยีที่มีประสิทธิภาพสูงอย่าง high-throughput sequencing สามารถตรวจพบสายพันธุ์ของไวรัสได้คลอบคลุมมากกว่าแต่มีข้อเสียในเรื่องค่าใช้จ่ายในการเตรียมตัวอย่างนั้นค่อนข้างสูง งานวิจัยนี้จึงมีวัตถุประสงค์เพื่อพัฒนาการเตรียมตัวอย่างสำหรับการตรวจวิเคราะห์สายพันธุ์ของเชื้อไวรัสฮิวแมนปาปิลโลมาโดยเทคนิค high throughput sequencing ที่ง่ายและใช้ต้นทุนต่ำกว่าการเตรียมตัวอย่างแบบเดิมรวมถึงเพื่อตรวจหาการกลายพันธุ์บนยีน L1 โดยใช้เทคนิคการเตรียมตัวอย่างที่พัฒนาขึ้น ในการศึกษาสายพันธุ์ของเชื้อไวรัสฮิวแมนปาปิลโลมานั้นจะใช้ความแตกต่างบนยีน L1 ในการจำแนกสายพันธุ์ ซึ่งงานวิจัยชิ้นนี้ได้ปรับแต่ง primer MY09/11 ให้มีโครงสร้างของ sequencing primer, index และ adapter ที่จำเป็นสำหรับการศึกษาด้วยเทคนิค high-throughput sequencing ผลการศึกษาพบว่าเทคนิคการเตรียมตัวอย่างที่พัฒนาขึ้นนั้นมีความสามารถในการตรวจพบสายพันธุ์ของเชื้อไวรัสฮิวแมนปาปิลโลมาได้ทั้งสองกลุ่มโดยปริมาณสารพันธุกรรมน้อยที่สุดที่เทคนิคนี้สามารถตรวจพบคือ 100 copies/µl มีความไวเท่ากับ 100% และความจำเพาะเท่ากับ 87.23% โดยสายพันธุ์ของเชื้อไวรัสส่วนใหญ่ที่พบในทุกระยะคือสายพันธุ์ 16 ซึ่งเป็นสายพันธุ์ที่มีอุบัติการณ์สูงในประเทศไทย นอกจากนี้สามารถตรวจพบการกลายพันธุ์บนยีน L1 ซึ่งทำให้เกิดการเปลี่ยนแปลงของกรดอะมิโนขึ้นและอาจส่งผลให้เชื้อไวรัสสามารถหลบเลี่ยงระบบภูมิคุ้มกันได้ โดยสรุปเทคนิคการเตรียมตัวอย่างที่พัฒนาขึ้นนี้นอกจากจะมีความสามารถในการตรวจพบสายพันธุ์ของเชื้อไวรัสฮิวแมนปาปิลโลมาทุกสายพันธุ์และตรวจพบการกลายพันธุ์บนยีน L1 แล้วยังช่วยลดค่าใช้จ่ายในการเตรียมตัวอย่างสำหรับการตรวจหาสายพันธุ์ของเชื้อไวรัสฮิวแมนปาปิลโลมาลงได้อีกด้วย

The Effect Of Caffeine On Migraine Headaches, Deborah Shimshoni

Honors Undergraduate Theses

As the most widely consumed drug around the globe, there is a vast array of contradicting research available on caffeine. One of the most debated and researched topics on caffeine is its effect on the brain. Meanwhile, the data on the neurological condition of migraine has information scattered throughout countless research articles and experiments.

Although neither migraine or caffeine are completely understood by the medical world, this analysis attempts to give a more coherent understanding of the relationship between the two. This is done by first understanding the known and theorized mechanisms of caffeine as well as the pathologies of …

The Role Of Sod1 Acetylation In Neurodegeneration, Michael Kaliszewski

Electronic Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Cu, Zn superoxide dismutase (SOD1), a cytoplasmic free radical scavenging enzyme, is mutated in familial ALS (fALS) and post-translational modification of the wild-type protein has been associated with sporadic ALS (sALS). Proteomic studies indicate that SOD1 is acetylated at Lys123; however, the role of this modification remains unknown. To investigate its function, we generated antibodies for Lys123-acetylated SOD1 (Ac-K123 SOD1). Sod1 deletion in Sod1-/- mice, K123 mutation, or preabsorption with Ac-K123 peptide suppressed immunoreactivity, confirming antibody specificity. In the normal central nervous system, Ac-K123 SOD1 maps to glutamatergic …

Simulation Of Cryolipolysis As A Novel Method For Noninvasive Fat Layer Reduction, Abbas Majdabadi, Mohammad Abazari

Turkish Journal of Medical Sciences

Background/aim: Regarding previous problems in conventional liposuction methods, the need for development of new fat removal operations was appreciated. In this study we are going to simulate one of the novel methods, cryolipolysis, aimed to tackle those drawbacks. Materials and methods: We think that simulation of clinical procedures contributes considerably in efficacious performance of the operations. To do this we have attempted to simulate temperature distribution in a sample fat of the human body. Using Abaqus software we have presented the graphical display of temperature-time variations within the medium. Results: Findings of our simulation indicate that tissue temperature decreases after …

Clinical Characteristics And Outcome Of Brucella Endocarditis, Na Du, Feng Wang

Turkish Journal of Medical Sciences

Background/aim: Brucella endocarditis, which is a rare condition, is the most common cause of death in human brucellosis, leading to severe cardiac complications. By collecting and analyzing clinical cases, we analyzed the clinical characteristics and outcome of Brucella endocarditis in endemic areas in China. Materials and methods: Presented here are 5 cases of Brucella endocarditis, all managed uniformly. We present the clinical, serological, and echocardiographic features; the therapeutic approach; and the follow-up of five patients with Brucella endocarditis. Results: There was a predominance of aortic involvement (4 cases) and a high incidence of left ventricular failure (5 cases). Polymerase chain …

Emergency Department Visits Caused By Adverse Drug Reactions: Results Of Aturkish University Hospital, Mehmet Can Gi̇rgi̇n, Sedat Yanturali, Mualla Ayli̇n Arici, Neşe Çolak Oray, Özgür Doylan, Yücel Demi̇ral, Yeşi̇m Tunçok

Turkish Journal of Medical Sciences

Background/aim: We aimed to evaluate adverse drug reaction (ADR)-related emergency department (ED) visits in the ED of the Dokuz Eylül University Hospital prospectively. Materials and methods: Patients who were admitted to the ED during 1-week periods of four different seasons between July 2010 and April 2011 were enrolled. Demographics of patients, previous ADR history, clinical progress, and outcomes were recorded. Causality assessment was done according to World Health Organization Uppsala Monitoring Centre categories. ADRs were categorized as certain, probable, or possible. Results: Patients who were on medications (26.5%, n = 1838) were evaluated for ADR-related ED admissions. ADRs accounted for …

Health Promotion Lifestyle Profile Scores Are Not Associatedwith Obesity In High School Students, Gi̇zem Li̇mni̇li̇, Ni̇lgün Özçakar, Mehtap Kartal

Turkish Journal of Medical Sciences

Background/aim: Obesity is a cause of preventable morbidity and mortality with an increasing prevalence. Health promoting lifestyle activities maintain or improve an individual?s health and in adolescence many habits are configured. The aim of this study was to determine the prevalence of overweight and obesity among adolescents and the relation between obesity and health promoting behaviors. Materials and methods: This is a cross-sectional study including 848 high school students aged 15?17. All students were administered a questionnaire including the Health Promotion Life-Style Profile Scale. Weight and height were measured and body mass index was calculated. Descriptive analysis, Pearson?s chi-square test, …

Herbal Self-Medication Use In Type 2 Diabetes Mellitus, Yusuf Aydin, Eli̇f Önder

Turkish Journal of Medical Sciences

No abstract provided.

Cerebrovascular Risk Factors, Arteriolar Sclerosis, And Cognitive Decline In The Kentucky Appalachian “Stroke-Belt”, Omar M. Al-Janabi

Theses and Dissertations--Medical Sciences

The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively using MRI to measure total white matter hyperintensity (WMH) volumes, would identify specific association of CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type, that represent the core features of vascular cognitive impairment in our cohort.

A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell

Theses and Dissertations--Physiology

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a G_s protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …

The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, Anita Kovacs-Kasa, Boris A. Gorshkov, Kyung-Mi Kim, Sanjiv Kumar, Stephen M. Black, David J. Fulton, Christiana Dimitropoulou, John D. Catravas, Alexander D. Verin

Bioelectrics Publications

The goal of this study was to investigate the role of MLC phosphatase (MLCP) in a LPS model of acute lung injury (ALI). We demonstrate that ectopic expression of a constitutively-active (C/A) MLCP regulatory subunit (MYPT1) attenuates the ability of LPS to increase endothelial (EC) permeability. Down-regulation of MYPT1 exacerbates LPS-induced expression of ICAM1 suggesting an anti-inflammatory role of MLCP. To determine whether MLCP contributes to LPS-induced ALI in vivo, we utilized a nanoparticle DNA delivery method to specifically target lung EC. Expression of a C/A MYPT1 reduced LPS-induced lung inflammation and vascular permeability. Further, increased expression of the …

Investigating The Roles Of Zinc-Binding Protein (Zbp-89) And Rela (Nfkb-P65) In The Regulation Of Matrix Metalloproteinase 1 (Mmp1) Gene Expression, Nelly Khaselev

PCOM Biomedical Studies Student Scholarship

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases with the unique ability to breakdown virtually the entire extracellular matrix (ECM). Through ECM remodeling, MMPs play an important role in normal development, tissue repair, angiogenesis, and apoptosis. Studies have shown that unregulated MMP expression plays a role in many cancers and chronic inflammatory diseases. Previous research has used gene sequence analysis ofthe MMP-1 promoter to identify a putative ZBP-89 binding site at -1969 bp. Chromatin immuneprecipitation experiments showed that both ZBP-89 and Re!A (p65) could bind to this binding site. In this thesis research, transfection experiments were used to explore …

The Role Of Tgfβ1 And Ep Receptors In The Differentiation Of Normal And Diseased Lung Fibroblasts, Madison A. Hexter

Williams Honors College, Honors Research Projects

Fibroblasts, and their differentiation into myofibroblasts, are important in the pathology of several lung diseases including asthma and idiopathic pulmonary fibrosis (IPF). The differentiation process is dependent on several factors, such as soluble factors like transforming growth factor beta 1 (TGFβ1) and mechanical signals such as matrix stiffness. Additionally, the soluble arachidonic acid metabolite Prostaglandin E₂ (PGE₂) prevents TGFβ1 induced differentiation of fibroblasts to myofibroblasts, but the molecular mechanism is not completely understood¹⁵. Transient Receptor Potential Vanilloid 4 (TRPV4), a mechanosensitive ion channel, has previously been implicated in the differentiation of cardiac fibroblasts^12,13. …

Antibiotic Efficacy And Interaction In Escherichia Coli During Varying Nutrient Conditions, Kristina K. Millar

Scripps Senior Theses

Due to the recent rise in antibiotic resistant pathogens, and the difficulties surrounding the quest for new antibiotics, many researchers have started revisiting antibiotic interactions in hopes of finding new treatment options. The primary outcome of this project was to examine the efficacy of concomitant antibiotic use under varying nutrient conditions, to identify variations in antibiotic interactions. Antibiotic interactions were studied, utilizing E. coli as a model bacterial system, grown in four different media types. E. coli cultures were treated with streptomycin, tobramycin, erythromycin, and amikacin individually and in a pairwise fashion at varying doses. We found that at least …

The Hormonal Regulation Of The Claudin Genes In The Ovary, Sean Gadson, April Binder, Kenneth Korach, Katherine Hamilton

All Master's Theses

The ovary is a dynamic organ that responds to many hormonal signals. When these hormonal signals are disrupted, ovarian dysfunction can occur. One such example is Polycystic Ovarian Syndrome (PCOS). PCOS patients suffer from high levels of testosterone. Excess testosterone may misregulate genes in the ovary and disrupt ovarian function. The Claudin (Cldn) 3 and Cldn11 genes have been shown to be regulated by androgens in the testis, while studies in ovarian cancer cells suggests a coregulatory mechanism for the expressions of Cldn3 and Cldn4 in the ovary. The objective of this study was to characterize the hormonal …