Life Sciences Commons^™

Temporal Trends In Serum Concentrations Of Polychlorinated Dioxins, Furans, And Pcbs Among Adult Women Living In Chapaevsk, Russia: A Longitudinal Study From 2000 To 2009, Olivier Humblet, Oleg Sergeyev, Larisa Altshul, Susan A. Korrick, Paige L. Williams, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Mary M. Lee, Boris Revich, Andrey Shelepchikov, Denis Feshin, Russ Hauser

Mary M. Lee

BACKGROUND: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.

METHODS: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.

RESULTS: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the …

Parental Mastery Of Continuous Subcutaneous Insulin Infusion Skills And Glycemic Control In Youth With Type 1 Diabetes, Kathleen Mitchell, Kimberley Johnson, Karen Cullen, Mary M. Lee, Olga T. Hardy

Mary M. Lee

OBJECTIVE: The purpose of this study is to determine whether parental knowledge of the continuous subcutaneous insulin infusion (CSII) device affects glycemic control as measured by hemoglobin A1c (A1C) level. SUBJECTS AND METHODS: Parents of children with type 1 diabetes mellitus (T1DM) using CSII completed a 14-item questionnaire. Questions 1-10 were knowledge-based questions that required the parent to extract specific information from their child's CSII device. Questions 11-14 asked parents to provide a self-assessment of their CSII knowledge. RESULTS: Twenty-two parents of youth with T1DM participated in the study. Ten of the youth were in the Low-A1C group (A1C/=8%). Parents …

Evidence For Transfer Of Membranes From Mesenchymal Stem Cells To Hl-1 Cardiac Cells, Robert Boomsma, David Geenen

Funded Articles

This study examined the interaction of mouse bone marrow mesenchymal stem cells (MSC) with cardiac HL-1 cells during coculture by fluorescent dye labeling and then flow cytometry. MSC were layered onto confluent HL-1 cell cultures in a 1 : 4 ratio. MSC gained gap junction permeant calcein from HL-1 cells after 4 hours which was partially reduced by oleamide. After 20 hours, 99% MSC gained calcein, unaffected by oleamide. Double-labeling HL-1 cells with calcein and the membrane dye DiO resulted in transfer of both calcein and DiO to MSC. When HL-1 cells were labeled with calcein and MSC with DiO, …

Chromosomal Abnormalities In Primary Myelodysplastic Syndrome, Anila Rashid, Mohammad Khurshid, Usman Shaikh, Salman Adil

Department of Pathology and Laboratory Medicine

Objective: To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome (MDS) using conventional karyotyping. Study Design: Case series. Place and Duration of Study: The Clinical Laboratory, The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Methodology: Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature (ISCN, 1995) and described as frequency percentage. Results: …

Preliminary Efficacy Of Group Medical Nutrition Therapy And Motivational Interviewing Among Obese African American Women With Type 2 Diabetes: A Pilot Study, Stephania T. Miller, Veronica J. Oates, Malinda A. Brooks, Ayumi Shintani, Tebeb Gebretsadik, Darlene M. Jenkins

Human Sciences Faculty Research

Objective. To assess the efficacy and acceptability of a group medical nutritional therapy (MNT) intervention, using motivational interviewing (MI). Research Design & Method. African American (AA) women with type 2 diabetes (T2D) participated in five, certified diabetes educator/dietitian-facilitated intervention sessions targeting carbohydrate, fat, and fruit/vegetable intake and management. Motivation-based activities centered on exploration of dietary ambivalence and the relationships between diet and personal strengths. Repeated pre- and post-intervention, psychosocial, dietary self-care, and clinical outcomes were collected and analyzed using generalized least squares regression. An acceptability assessment was administered after intervention. Results. Participants (n = 24) were …

Circulating Microrna Profiles In Human Patients With Acetaminophen Hepatotoxicity Or Ischemic Hepatitis, Jeanine Ward, Chitra Kanchagar, Isana Veksler-Lublinsky, Rosalind C. Lee, Mitchell R. Mcgill, Hartmut Jaeschke, Steven C. Curry, Victor R. Ambros

Victor R. Ambros

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as …

The Role Of Ape/Ref-1 In Hepatocellular Carcinoma Progression, Zhen Yang, Sun Yang, Bobbye J. Misner, Feng Liu-Smith, Frank L. Meyskens

Pharmacy Faculty Articles and Research

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell …

Imaging Luciferase-Expressing Viruses, Michael A. Barry, Shannon May, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Optical imaging of luciferage gene expression has become a powerful tool to track cells and viruses in vivo in small animal models. Luciferase imaging has been used to study the location of infection by replication-defective and replication-competent viruses and to track changes in the distribution of viruses in mouse models. This approach has also been used in oncolytic studies as a non-invasive means to monitor the growth and killing of tumor cells modified with luciferase genes. In this chapter, we describe the techniques used for luciferase imaging as have been applied to track replication-defective and replication-competent adenoviruses in mouse and …

Prediction Of Dengue Disease Severity Among Pediatric Thai Patients Using Early Clinical Laboratory Indicators, James A. Potts, Robert V. Gibbons, Alan L. Rothman, Anon Srikiatkhachorn, Stephen J. Thomas, Pra-On Supradish, Stephenie C. Lemon, Daniel H. Libraty, Sharone Green, Siripen Kalayanarooj

Alan Rothman

BACKGROUND: Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. METHODS AND FINDINGS: We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different …

The Plasmodium Bottleneck: Malaria Parasite Losses In The Mosquito Vector, Ryan C. Smith, Joel Vega-Rodríguez, Marcelo Jacobs-Lorena

Ryan C. Smith

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

30 Days On $200: A Cooking Guide For Tasty & Healthy Eating On A Budget, Benjamin J. Slocum

Osteopathic Medicine Student Projects

Meal planning and cooking guide created to help people on food assistance and others better utilize their resources. This book contains health information, grocery shopping tips, meal planning guides, and easy instruction on cooking and the use of leftovers. With simple-to-read, image-based instruction, it teaches the basics on how to budget, plan meals, make shopping lists, and prepare food. The book assumes no prior cooking experience, and while anyone can benefit from the book regardless of income level, it makes a particular effort to demonstrate preparation for foods commonly acquired at food pantries.

Th17 Cell-Associated Response To Borrelia Burgdorferi Outer Surface Protein A, Megan Elizabeth Johnson

Theses and Dissertations

Arthritis is a common symptom of Lyme disease, a debilitating condition resulting from infection with Borrelia burgdorferi. A protein found on the surface of B. burgdorferi, outer surface protein A (OspA), is known to elicit an inflammatory immune response involving T helper cells. T helper 17 (Th17) cells are associated with the inflammatory cytokines interleukin-17 (IL-17) and interleukin-23 (IL-23) and have been implicated in the development of Lyme arthritis. The objective of this thesis is to provide further characterization of the immune response to B. burgdorferi OspA. The central hypothesis of this thesis is: Vaccination with OspA will predispose mice …

Synthesis And Characterization Of Novel Platinum(Ii) And Platinum(Iv) Complexes Containing 4,4′--Disubstituted--2,2′--Bipyridine Ligands For The Treatment Of Cancer, Van Vo

UNLV Theses, Dissertations, Professional Papers, and Capstones

Three series of platinum(II) and platinum(IV) complexes containing 4,4′-disubstituted-2,2′-bipyridine ligands have been synthesized and characterized by 1H NMR, 13C NMR spectroscopy, elemental analysis, mass spectroscopy, and differential scanning calorimetry measurements. The MTS cell proliferation assay was used to examine the in vitro anti-proliferative activities of these complexes in various human breast, lung, and prostate cancer cells. The cell's response to the complexes varies between different cell lines; however, the low EC₅₀ values determined from the MTS data indicate that several of the complexes are much more potent than cisplatin.

Flow cytometric analysis of selected compounds revealed induction of apoptosis …

The Wetsuit Effect: Physiological Response To Wearing A Wetsuit, Aaron Prado

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to investigate the effects of wearing a wetsuit on resting cardiovascular parameters (mean arterial pressure (MAP), rate-pressure product (RPP), and heart rate variability (HRV)). Furthermore, the position (i.e., upright vs. prone) as well as the wetsuit size were explored as possible factors that influence the cardiovascular parameters. Twelve male participants (79.1±5.1 kg, 178.4±2.9 cm, 33.3±12.1 years) granted written consent and were assigned two wetsuits based on height, weight, and corresponding manufacturer recommendations. SWS signified the smallest possible wetsuit the subject could fit into according to recommendations, LWS signified the largest wetsuit the subject could …

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations & Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Review: Zinc’S Functional Significance In The Vertebrate Retina, Harris Ripps, Richard L. Chappell

Publications and Research

This review covers a broad range of topics related to the actions of zinc on the cells of the vertebrate retina. Much of this review relies on studies in which zinc was applied exogenously, and therefore the results, albeit highly suggestive, lack physiologic significance. This view stems from the fact that the concentrations of zinc used in these studies may not be encountered under the normal circumstances of life. This caveat is due to the lack of a zinc-specific probe with which to measure the concentrations of Zn2+ that may be released from neurons or act upon them. However, a …

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on the market. The …

Quantitative Ultrasound: Measurement Considerations For The Assessment Of Muscular Dystrophy And Sarcopenia, Michael O. Harris-Love, Reza Monfaredi, Catheeja Ismail, Marc R. Blackman, Kevin Cleary

Exercise and Nutrition Sciences Faculty Publications

Diagnostic musculoskeletal ultrasound has potential clinical utility in characterizing pathological muscle tissue. Sonography has been long proposed as method of assessing muscle damage due to neuromuscular diseases such as muscular dystrophy, and more recently, changes in body and tissue composition associated with muscle wasting disorders such as sarcopenia. The use of quantitative ultrasound as an adjunct diagnostic procedure has different technical challenges than the traditional use of ultrasound in clinical medicine. Operator-dependent technique and variation are critical considerations when obtaining measures of echointensity (i.e., tissue composition estimates) and tissue dimensions (i.e., muscle thickness) – key elements of the ultrasound assessment …

Sox11 Is Required To Maintain Proper Levels Of Hedgehog Signaling During Vertebrate Ocular Morphogenesis, Lakshmi Pillai-Kastoori, Wen Wen, Stephen G. Wilson, Erin Strachan, Adriana Lo-Castro, Marco Fichera, Sebastiano A. Musumeci, Ordan J. Lehmann, Ann C. Morris

Biology Faculty Publications

Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the …

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …

Blood-Based Biomarkers For Traumatic Brain Injury: Evaluation Of Research Approaches, Available Methods And Potential Utility From The Clinician And Clinical Laboratory Perspectives, Frederick G. Strathmann, Stefanie Podlog (Nee Schulte), Kyle Goerl, David J. Petron

Athletic Training Collection

Blood-based biomarkers for traumatic brain injury (TBI) have been investigated and proposed for decades, yet the current clinical assessment of TBI is largely based on clinical symptoms that can vary widely amongst patients, and have significant overlap with unrelated disease states. A careful review of current treatment guidelines for TBI further highlights the potential utility of a blood-based TBI biomarker panel in augmenting clinical decision making. Numerous expert reviews on blood-based TBI biomarkers have been published but a close look at the methods used and the astonishing paucity of validation and quality control data has not been undertaken from the …

Shifting Of Vitamin D Deficiency To Hypervitaminosis And Toxicity, Aysha Habib, Hafsa Majid, Romaina Iqbal

Department of Pathology and Laboratory Medicine

No abstract provided.

Tyrosine Kinase Inhibitors In Cancer Therapeutics: Great Expectations From Small Molecules, Zeeshan A Ansar, Tariq Moatter

Department of Pathology and Laboratory Medicine

No abstract provided.

Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson

Internal Medicine Faculty Publications

Activation of the phosphoinositide (PI) cycle generates the second messengers that control various aspects of cellular signaling. We have previously shown that two PI cycle enzymes, type II phosphatidylinositol 5-phosphate 4-kinase (PIPK IIα) and phosphoinositide 3-kinase (PI3K), are activated through light stimulation. In our earlier studies, we measured enzyme activities, instead of directly measuring the products, due to lack of sensitive analytical techniques. Cells have very low levels of PIs, compared to other lipids, so special techniques and sensitive analytical instruments are necessary for their identification and quantification. There are also other considerations, such as different responses in different cell …

Ampk Activation: A Therapeutic Target For Type 2 Diabetes?, Kimberly A. Coughlan, Rudy Valentine, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

Targeting The Wnt/Β-Catenin Signaling Pathway In Liver Cancer Stem Cells And Hepatocellular Carcinoma Cell Lines With Fh535, Roberto Gedaly, Roberto Galuppo, Michael F. Daily, Malay B. Shah, Erin Colleen Maynard, Changguo Chen, Xiping Zhang, Karyn A. Esser, Donald A. Cohen, B. Mark Evers, Jieyun Jiang, Brett T. Spear

Surgery Faculty Publications

Activation of the Wnt/β-catenin pathway has been observed in at least 1/3 of hepatocellular carcinomas (HCC), and a significant number of these have mutations in the β-catenin gene. Therefore, effective inhibition of this pathway could provide a novel method to treat HCC. The purposed of this study was to determine whether FH535, which was previously shown to block the β-catenin pathway, could inhibit β-catenin activation of target genes and inhibit proliferation of Liver Cancer Stem Cells (LCSC) and HCC cell lines. Using β-catenin responsive reporter genes, our data indicates that FH535 can inhibit target gene activation by endogenous and exogenously …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jonathan Balcombe, Ph.D.

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jonathan Balcombe, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …