Medical Specialties Commons^™

Development Of A Conditional Mesd (Mesoderm Development) Allele For Functional Analysis Of The Low-Density Lipoprotein Receptor-Related Family In Defined Tissues, Andrew V. Taibi, Janet K. Lighthouse, Richard C. Grady, Kenneth R. Shroyer, Bernadette Holdener

Department of Biomedical Engineering Faculty Publications

The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in …

Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 mu M after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 mu M, 78.7 …

High Dose, Variable Length, N-Acetylcysteine (Hinac) Therapy For Late-Presenting Acetaminophen Poisoning, Jessica K. Eygnor Do, Suprina Dorai Md, Philip W. Moore Do, J Ward Donovan Md, Keith K. Burkhart Md

Department of Emergency Medicine

No abstract provided.

Method For Enhancing Specific Immunotherapies In Cancer Treatment, Peter G. Traber, William L. Redmond, Eliezer Zomer, Anatole Klyosov, Stefanie N. Linch

Technology Transfer - Patents

Methods and compositions of the invention relate to the enhancement of specific immunotherapies in cancer treatment. In particular, aspects of the invention relate to novel approaches to boost immune function using a complex carbohydrate pharmaceutical compound alone or in combination with other targeted immunotherapy to increase the efficacy of immunotherapy of cancer.

Pseudomonas Aeruginosa Exotoxin Y-Mediated Tau Hyperphosphorylation Impairs Microtubule Assembly In Pulmonary Microvascular Endothelial Cells, Ron Balczon, Nutan Prasain, Cristhiaan Ochoa, Jason Prater, Bing Zhu, Mikhail Alexeyev, Sarah Sayner, Dara W. Frank, Troy Stevens

University Faculty and Staff Publications

Pseudomonas aeruginosa uses a type III secretion system to introduce the adenylyl and guanylyl cyclase exotoxin Y (ExoY) into the cytoplasm of endothelial cells. ExoY induces Tau hyperphosphorylation and insolubility, microtubule breakdown, barrier disruption and edema, although the mechanism(s) responsible for microtubule breakdown remain poorly understood. Here we investigated both microtubule behavior and centrosome activity to test the hypothesis that ExoY disrupts microtubule dynamics. Fluorescence microscopy determined that infected pulmonary microvascular endothelial cells contained fewer microtubules than control cells, and further studies demonstrated that the microtubule-associated protein Tau was hyperphosphorylated following infection and dissociated from microtubules. Disassembly/reassembly studies determined that …

Resistance Of Human Cytomegalovirus To Cyclopropavir Maps To A Base Pair Deletion In The Open Reading Frame Of Ul97, Brian G. Gentry, Laura E. Vollmer, Ellie D. Hall, Katherine Z. Borysko, Jiri Zemlicka, Jeremy P. Kamil, John C. Drach

Oncology Faculty Publications

Human cytomegalovirus (HCMV) is a widespread pathogen in the human population, affecting many immunologically immature and immunocompromised patients, and can result in severe complications, such as interstitial pneumonia and mental retardation. Current chemotherapies for the treatment of HCMV infections include ganciclovir (GCV), foscarnet, and cidofovir. However, the high incidences of adverse effects (neutropenia and nephrotoxicity) limit the use of these drugs. Cyclopropavir (CPV), a guanosine nucleoside analog, is 10-fold more active against HCMV than GCV (50% effective concentrations [EC₅₀s] = 0.46 and 4.1 μM, respectively). We hypothesize that the mechanism of action of CPV is similar to that …

Chronic Cadmium Exposure Stimulates Sdf-1 Expression In An Erα Dependent Manner, Esmeralda Ponce, Natalie B. Aquino, Maggie Louie

Collected Faculty Scholarship

Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell …

Coupling S100a4 To Rhotekin Alters Rho Signaling Output In Breast Cancer Cells, Min Chen, Anne R. Bresnick, Kathleen L. O'Connor

Markey Cancer Center Faculty Publications

Rho signaling is increasingly recognized to contribute to invasion and metastasis. In this study, we discovered that metastasis-associated protein S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway. Glutathione S-transferase pull-down and immunoprecipitation assays demonstrated that S100A4 specifically and directly binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to Rhotekin is calcium-dependent and uses residues distinct from those bound by active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex with active RhoA. Using RNA interference, we determined that suppression of both S100A4 and …

Metastatic Castration-Resistant Prostate Cancer: Critical Review Of Enzalutamide, Joelle El-Amm, Nihar Patel, Ashley Freeman, Jeanny B. Aragon-Ching

Medicine Faculty Publications

Enzalutamide, previously known as MDV300, is an oral, second-generation androgen receptor (AR) signaling inhibitor or antagonist that was approved by the Food and Drug Administration in 2012 for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) postdocetaxel. Preclinical studies have demonstrated impressive affinity to the AR compared to the first-generation AR inhibitors. The landmark Phase III AFFIRM trial demonstrated improved overall survival benefit compared to placebo in addition to improvement in all tested parameters. Enzalutamide is currently being studied in several trials prechemotherapy and in earlier settings of prostate cancer. This review will discuss the mechanism of action of enzalutamide, …

Effects Of Prior Acute Exercise On Circulating Cytokine Concentration Responses To A High-Fat Meal, Josef Brandauer, Rian Q. Landers-Ramos, Nathan T. Jenkins, Espen E. Spangenburg, James M. Hagberg, Steven J. Prior

Health Sciences Faculty Publications

High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before …

Efficacy Of Gold Silica Nanoshells And Gold Nanorods For Photothermal Therapy Of Human Glioma Spheroids, Suyog Jung Chhetri

UNLV Theses, Dissertations, Professional Papers, and Capstones

Gold-based nanoparticles including gold-silica nano-spheres and gold nano-rods have been investigated for a number of therapeutic and diagnostic applications. The ability of these nanoparticles to convert light into heat energy makes them particularly appealing for photothermal therapy in which cancer cells are destroyed via light-induced heat generation. The overall objective of the study is to compare the efficacy of gold-silica nano-spheres and gold nano-rods in an in vitro system consisting of human brain tumor (glioma) spheroids.

Delivery of the nanoparticles to the spheroids was accomplished using murine macrophages. Nanoparticles (spheres or rods) were incubated with macrophages for 24 hours. Thereafter, …

The Relationship Among Ankle Function, Functional Capacity, And Body Composition To Balance In Geriatric Populations, Joseph Robert Chaney

Graduate Theses and Dissertations

The primary purpose of this research study was to identify significant relationships among measures of ankle strength, ankle range of motion, body composition, and functional capacity to balance ability in geriatric populations which may potentially assist in identifying older individuals with increased risk of falling. A battery of five test (ankle strength assessments, ankle range of motion , DXA, functional fitness, and balance) were administered to 20 participants (6 males, 14 females, mean age 69.78 ± 3.98) that had indicated to be at least 65 years of age or older and no history of falls within the previous 12 months. …

Illuminating The Dark Side--Vitamin D Status In Different Localities Of Karachi, Romaina Iqbal, Lena Jafri, Ali Haroon, Aysha Habib Khan

Department of Medicine

This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value < 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification.

Population Genetics And Drug Resistance Markers: An Essential For Malaria Surveillance In Pakistan, Afsheen Raza, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, …

Effect Of A Lateral Wedge Insole Over A One Week Period In A Healthy Population, Sarah E. Sudheimer

Human Movement Studies & Special Education Theses & Dissertations

Medial knee osteoarthritis is a disease that is projected to affect approximately 45% of the U.S. population and is associated with significant morbidity, chronic pain, and limited activity. Laterally wedged insoles are used as an intervention to laterally shift the mechanical axis of the limb and decrease the external knee adduction moment, possibly indicating a shift in load distribution to the lateral compartment of the knee. The aim of this study was to examine the acute effects of a laterally wedged insole in those with valgus and normally aligned knees and to determine prolonged effects after the insole was worn …

Vitamin D And The Athlete: Risks, Recommendations, And Benefits, Dana Ogan, Kelly Pritchett

All Faculty Scholarship for the College of the Sciences

Vitamin D is well known for its role in calcium regulation and bone health, but emerging literature tells of vitamin D’s central role in other vital body processes, such as: signaling gene response, protein synthesis, hormone synthesis, immune response, plus, cell turnover and regeneration. The discovery of the vitamin D receptor within the muscle suggested a significant role for vitamin D in muscle tissue function. This discovery led researchers to question the impact that vitamin D deficiency could have on athletic performance and injury. With over 77% of the general population considered vitamin D insufficient, it’s likely that many athletes …

Neuropathogenic Escherichia Coli K1 Does Not Exhibit Proteolytic Activities To Exert Its Pathogenicity, Junaid Iqbal, Mehak Rajan, Ruqaiyyah Siddiqu, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

Background: Proteases are well-known virulence factors that promote survival, pathogenesis and immune evasion of many pathogens. Several lines of evidence suggest that the blood-brain barrier permeability is a prerequisite in microbial invasion of the central nervous system. Because proteases are frequently associated with vascular permeability by targeting junctional proteins, here it is hypothesized that neuropathogenic Escherichia coli K1 exhibit proteolytic activities to exert its pathogenicity.
Methods: Zymographic assays were performed using collagen and gelatin as substrates. The lysates of whole E. coli K1 strain E44, or E. coli K-12 strain HB101 were tested for proteolytic activities. The conditioned media were …

Qcm Aptasensor For Rapid And Specific Detection Of Avian Influenza Virus, Luke Brockman

Graduate Theses and Dissertations

There has been a need for rapid detection of avian influenza virus (AIV) H5N1 due to it being a potential pandemic threat. Most of the current methods, including culture isolation and PCR, are very sensitive and specific but require specialized laboratories and trained personnel in order to complete the tests and are time-consuming. The goal of this study was to design a biosensor that would be able to rapidly detect AIV H5N1 using aptamers as biosensing material and a quartz crystal microbalance (QCM) for transducing method. Specific DNA aptamers against AIV H5N1 were immobilized, through biotin and streptavidin conjugation, onto …

Malignant Vascular Tumours Associatedwith The Breast: A Study Of 7 Cases, Azizun-Nisa, Zeeshanuddin, Naila Kayani

Department of Pathology and Laboratory Medicine

Angiosarcomas account for less than 0.05% of the malignant neoplasms of the breast. We present here 7 cases of malignant vascular neoplasms of the breast, including 2 cases of postmastectomy Stewart-Treves syndrome. In this case series, most of the patients were young. Tumour was bilateral at presentation in one case. The size of the tumours ranged from 1.6 cm to 11 cm. Although breast angiosarcomas are rare neoplasms, with the increasing use of radiation therapy for breast cancer patients, post-radiation skin lesions should not be ignored.

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey

Dissertations and Theses (Open Access)

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.

HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.

METHODS: 253 individuals with an …

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 …

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 …

A Home-Based Exercise Program For The Foot And Ankle To Improve Balance, Muscle Performance And Flexibility In Community Dwelling Older Adults: A Pilot Study, Laurel Long, Kurt Jackson, Lloyd L. Laubach

Physical Therapy Faculty Publications

Background and purpose: Strength and range of motion of the foot and ankle have been shown to be related to measures of balance and fall risk in older adults. The primary purpose of this pilot investigation was to evaluate the feasibility of a 6-week home-based exercise program focusing on the foot and ankle and any associated changes in balance, muscle performance and range of motion in older adults. Methods: This single-group repeated measures study involved a convenience sample of 21 healthy communitydwelling older adults age 60-90. Nineteen participants completed all phases of the testing and training. The intervention was a …

Physically Interactive Games Increase Vo2 Above Resting Metabolic Rate, Shaelee Allen, Jacob E. Barkley, Janet Dufek, Paul Hafen, Michael Jarrett, Krystina Moschella, James Navalta, Robert Rietjens, Richard Tandy, Antonio Santo

Interdisciplinary Research Scholarship Day

The purpose of this study was to determine the energy cost, beyond resting metabolic rate (RMR), of playing select games on the Nintendo Wii for 30 contiguous minutes. Physically interactive games (i.e. Basic Run and Basic Step) increase energy expenditure above resting values compared to a sedentary game (Tanks!) and therefore may help individual’s become more active. Furthermore, Basic Run and Basic Step elicited MET values of 3.9 and 3.2, respectively, which is considered moderate-intensity exercise and could be used to meet daily recommendations for physical activity.

Anti-Helicobacter Pylori Activity And Inhibition Of Helicobacter Pylori-Induced Release Of Il-8 In Ags Cells By Plant Extracts, Javed Yakoob, Zaigham Abbas, Rustam Khan, Muhammad Waqas Usman, Saeed Hamid, Safia Awan, Kanza Shamim, Syed Faisal Zaidi, Toshiro Sugiyama, Wasim Jafri

Section of Gastroenterology

Plants used in popular diet were studied for anti-Helicobacter pylori activity and their effect on the expression of interleukin-8 (IL-8) from H. pylori infected gastric epithelial cells. Extracts were prepared of Allium sativum (A. sativum), Cuminum cyminum (C. cyminum),Piper nigrum (P. nigrum) and their mix in two different dilutions. AGS cell line and H. pyloristrains were used for co-culture experiments. Extracts bactericidal activity was determined by a viable colony count. ELISA (Enzyme linked immunosorbent assay) was used to determine IL-8 expression. DNA extracted from bacterial cells was used for polymerase chain reaction (PCR) …

A Review Of G6pd Deficiency In Pakistani Perspective, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

Frequency Of Precancerous Lesions In Endoscopic Gastric Biopsies In Chronic Gastritis, Saroona Haroon, Naveen Faridi, Faisal Rashid Lodhi, Shafaq Mujtaba

Department of Pathology and Laboratory Medicine

Objective:
To determine the frequency of precancerous lesions in endoscopic gastric biopsies of patients with chronic gastritis.STUDY Design: A case series.
Place and duration of study:
Department of Histopathology, Liaquat National Hospital, Karachi, from July 2008 to January 2009.METHODOLOGY: Over 6 months, 375 endoscopic gastric biopsies of patients with age group of 15-65 years having endoscopic chronic gastritis were included. From final biopsy report, basic information like patient demographics and presence of precancerous lesions i.e. activity (chronic active gastritis), atrophy (atrophic gastritis), intestinal metaplasia and dysplasia were recorded on proforma. Results were described as proportions and frequency.
Results:
The frequency …

The Perfect Fit

Colby Magazine

From the classrooms and laboratories of Mayflower Hill, they found their niche in science. Microbiologist Carrie Harwood ’73, transplant surgeon Patrick Wood ’75, and marine biologist Paul Wade ’80 have passion for their professions.

A Comparison Of Upper Extremity Function Between Female Breast Cancer Survivors And Healthy Controls: Typical Self-Report Of Function, Motion, Strength, And Muscular Endurance, Mary Insana Fisher

Physical Therapy Faculty Publications

Many women who have experienced breast cancer (BC) report continued impairments in upper extremity (UE) function beyond the time required for normal healing after surgical treatment. Most research supporting this has not made comparisons between survivors of breast cancer (BCS) to a sample of healthy women. This lack of comparison to a healthy cohort prevents an understanding of whether continued deficits in UE function are due to normal aging or the BC treatment.

The purpose of this research was to compare quality of life (QOL) and UE function among long term breast cancer survivors and similar aged women without cancer. …