Medicine and Health Sciences Commons^™

Microrna Mir-155 Affects Antiviral Effector And Effector Memory Cd8 T Cell Differentiation, Ching-Yi Tsai, S. Rameeza Allie, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNAs are key regulators of the immune response, but their role in CD8 T cell differentiation in vivo is not known. We show that miR-155 is important in both effector and memory antiviral CD8 T cell responses. Without miR-155, there was a weaker effector response and a skewing toward memory precursor cells. At the memory stage, miR-155-deficient CD8 T cells preferentially differentiated into central memory cells and were capable of mounting a potent secondary response.

Myeloid-Derived Suppressor Cells In Murine Retrovirus-Induced Aids Inhibit T- And B-Cell Responses In Vitro That Are Used To Define The Immunodeficiency, Kathy A. Green, W. James Cook, William R. Green

Dartmouth Scholarship

Myeloid-derived suppressor cells (MDSCs) have been characterized in several disease settings, especially in many tumor systems. Compared to their involvement in tumor microenvironments, however, MDSCs have been less well studied in their responses to infectious disease processes, in particular to retroviruses that induce immunodeficiency. Here, we demonstrate for the first time the development of a highly immunosuppressive MDSC population that is dependent on infection by the LP-BM5 retrovirus, which causes murine acquired immunodeficiency. These MDSCs express a cell surface marker signature (CD11b Gr-1 Ly6C ) characteristic of monocyte-type MDSCs. Such MDSCs profoundly inhibit immune responsiveness by a cell dose- and …

Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang

Theses and Dissertations

Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, …

Glutaredoxin 2 (Grx2) Knockout Increases Sensitivity To Oxidative Stress In Mouse Lens Epithelial Cells, Hongli Wu, Liren Lin, Frank Giblin, Ye-Sheh Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin belongs to the oxidoreductase family with cytosolic glutaredoxin 1 (Grx1) and mitochondrial gluraredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper studied the effect of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild type (WT) mice. We found that both cell types showed similar growth patterns and morphology, and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin (Trx) expression but exhibited high sensitivity to oxidative stress. Under treatment …

Generating Forensic Dna Profiles, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Statistical Weights Of Single Source Dna Profiles, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Hematopoietic Stem Cell Threshold Sensing Controls Regulatory Pathways Facilitating Clinically Relevant Ex Vivo Expansion For Stem Cell Transplantation, Andrew D. Lasiter

Theses and Dissertations (ETD)

The ex vivo expansion of hematopoietic stem cells (HSCs) for transplantation has threefold importance: 1.) First, because of the rarity of stem cells there often isn’t a sufficient supply obtainable from common sources for larger children and adults. 2.) Secondly, patient morbidity and time to hematopoietic reconstitution following myeloablative preconditioning is improved by administering a larger pool of HSCs. 3.) Lastly, gene therapies for hematological diseases still require a robust supply of HSCs to offset varying degrees of inefficiency in vector mediated transfection protocols. These reasons, and others, have been an impetus for many discoveries made within four primary subdivisions …

Relaxation Thyroplasty – A Classical Surgical Approach For Puberphonia, Balasubramanian Thiagarajan, Karthikeyan Arjunan

Balasubramanian Thiagarajan

Abstract: The persistence of adolescent voice even after puberty in the absence of organic cause is known as puberphonia. 1,2,3 The condition is commonly seen in males.1-7 . This case report illustrates a novel surgical method “Retrusion thyroplasty” in the management of puberphonia. Introduction: The persistence of adolescent voice even after puberty in the absence of organic cause is known as puberphonia. 1,2,3 The condition is commonly seen in males.1-7 Normally adolescent males undergo voice changes due to sudden increase in length of vocal cords due to enlargement of thyroid prominence (Adam’s apple). This is uncommon in females because their …

Parenteral Nutrition Additive Shortages: The Short-Term, Long-Term And Potential Epigenetic Implications In Premature And Hospitalized Infants., Corrine K. Hanson, Melissa Thoene, Julie Wagner, Dean Collier, Kassandra Lecci, Ann Anderson-Berry

Journal Articles: Medical Nutrition

Nutrition support practitioners are currently dealing with shortages of parenteral nutrition micronutrients, including multivitamins (MVI), selenium and zinc. A recent survey from the American Society of Enteral and Parenteral Nutrition (ASPEN) indicates that this shortage is having a profound effect on clinical practice. A majority of respondents reported taking some aggressive measures to ration existing supplies. Most premature infants and many infants with congenital anomalies are dependent on parenteral nutrition for the first weeks of life to meet nutritional needs. Because of fragile health and poor reserves, they are uniquely susceptible to this problem. It should be understood that shortages …

New Fusion Transcripts Identified In Normal Karyotype Acute Myeloid Leukemia, Hongxiu Wen, Yongjin Li, Sami N. Malek, Yeong C. Kim, Jia Xu, Pei Xian Chen, Fengxia Xiao, Xin Huang, Xianzheng Zhou, Zhenyu Xuan, Shiva Mankala, Guihua Hou, Janet D. Rowley, Michael Q. Zhang, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Credentialing Success In Respiratory Therapy Education: Revisiting Bourdieu's Concepts Of Field And Capital, Karen Lightbody Shaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

The field of Respiratory Therapy (RT) is expected to experience a workforce shortfall over the next decade. The numbers of both program applicants and graduates have declined in recent years, necessitating strategies to improve board exam pass rates for future graduates. In response to the pending employment crisis, the Commission on Accreditation for Respiratory Care has published Programmatic Outcomes Data detailing individual program statistics. A theoretical framework adapted from Pierre Bourdieu's Concepts of Field and Capital was proposed to explain a possible re-stratification of RT programs. It states, in part, that a modification of position-takings within the RT educational field …

Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome of P. aeruginosa strain PAO579, an alginate-overproducing derivative of strain PAO381.

What Can Go Wrong With Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Observer Effects In Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Artifacts And Noise In Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Implications Of Database Searches For Dna Profiling Statistics, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Statistical Weights Of Mixed Dna Profiles, Dan E. Krane

Biological Sciences Faculty Publications

Presentation recording from December 2012 can be found at http://youtu.be/daRBTopFA1A.

Part of the Forensic DNA Profiling Video Series.

Dna Technology In Court, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Tumour Inflammasome-Derived Il-1b Recruits Neutrophils And Improves Local Recurrence-Free Survival In Ebv-Induced Nasopharyngeal Carcinoma, Lih-Chyang Chen, Li-Jie Wang, Nang-Ming Tsang, David M. Ojcius, Chia-Chen Chen, Chun-Nan Ouyang, Chuen Hsueh, Ying Liang, Kai-Ping Chang, Chiu-Chin Chen, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 …

Reversible Inhibition Of Chlamydia Trachomatis Infection In Epithelial Cells Due To Stimulation Of P2x4 Receptors, Matthew A. Pettengill, Camila Marques-Da-Silva, Maria Luisa Avila, Verissa W. Lam, Ikechukwu Ollawa, Ali Abdul-Sater, Robson Coutinho-Silva, Georg Hacker, David M. Ojcius, Suellen D'Arc Dos Santos Oliveira

All Dugoni School of Dentistry Faculty Articles

Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly …

Evaluation Of Polymer Gel Dosimeters For Measurements Of Dose And Let In Proton Beams, Kevin M. Vredevoogd

Dissertations & Theses (Open Access)

This project assessed the effectiveness of polymer gel dosimeters as tools for measuring the dose deposited by and LET of a proton beam. A total of three BANG® dosimeter formulations were evaluated: BANG®-3-Pro-2 BANGkits™ for dose measurement and two BANG®-3 variants, the LET-Baseline and LET-Meter dosimeters, for LET measurement. All dosimeters were read out using an OCT scanner. The basic characteristics of the BANGkits™ were assessed in a series of photon and electron irradiations. The dose-response relationship was found to be sigmoidal with a threshold for response of approximately 15 cGy. The active region of the dosimeter, the volume in …

Development Of A Beam-Specific Planning Target Volume And A Robust Plan Analysis Tool For Proton Therapy, Peter Park

Dissertations & Theses (Open Access)

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of …

Raman Micro Spectroscopy For The Characterisation Of Cervical Cancer., Nosheen Rashid

Doctoral

The primary purpose of this study is to evaluate the potential of FTIR and Confocal Raman micro spectroscopy (CRM) in elucidating the biochemical changes occurring in different layers of the cervical epithelium including basal, superficial and the underlying connective tissue known as stroma during the progression of Cervical Intraepithelial Neoplasia (CIN) to cancer. Initially the two techniques were compared and Raman was chosen based on its higher spatial and spectral resolution. The sample preparation and spectral measurement procedures were optimised and all samples were formalin fixed paraffin processed, dewaxed using xylene, and measured on calcium fluoride windows. Raman spectra were …

Scopolamine-Induced Dry Eye Model In Female Rats, Ryan Alderson

Masters Theses

The objective of this study will be to establish, validate, and characterize a dry eye model in female rats induced by continuous systemic administration of scopolamine via Alzet® osmotic pumps for 28 days. This study will use female rats as a model for dry eye and will be implanted with osmotic pumps that will continuously distribute scopolamine or saline systemically over 28 days. Scopolamine will be used to induce the dry eye condition and saline will be used as a negative control. The clinical signs of dry eye will be evaluated by tear volume measurements with sterilized phenol-red thread (FCI …

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

The Role Of Bip Nucleotide Exchange Factor Sil1 In Immunoglobulin Biosynthesis, Tyler Sanford

Theses and Dissertations (ETD)

BiP is an essential endoplasmic reticulum resident molecular chaperone of the HSP70 family that binds exposed hydrophobic regions of unfolded proteins. Substrates bound by BiP are protected from dangerous non-specific interaction with other unfolded proteins via their aggregation prone exposed hydrophobic regions, which are normally buried in the native state, and act as BiP binding targets. For these substrates to mature into the native state, BiP must be released. Like all HSP70 family members, cycles of BiP binding and release are nucleotide dependent and facilitated by two genres of cochaperones, HSP40s, and nucleotide exchange factors (NEFs). HSP40s function in stimulating …

Changes In Serum Interleukin-33 Concentration Before And After Treatment With Pegylated Interferon Alfa-2a Plus Ribavirin In Patients With Chronic Hepatitis C Genotype 1b Infection., Bruno Cacopardo, Marilia Rita Pinzone, Filippo Palermo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: IL-33 is a novel member of the IL-1 family, which has been shown to play an important role in T helper 2 (Th2)-associated immune responses. Recent studies have suggested a possible role for IL-33 in the pathogenesis of liver damage during acute and chronic hepatitis; furthermore, IL-33 may be involved in the development and progression of liver fibrosis.

OBJECTIVES: To evaluate serum IL-33 levels in a group of patients with chronic hepatitis C (CHC) genotype 1b at enrolment and after a course of pegylated (PEG)-IFN plus ribavirin.

PATIENTS AND METHODS: 60 patients with chronic hepatitis C (CHC) and 65 …

Development And Validation Of Sunlight Exposure Measurement Questionnaire (Sem-Q) For Use In Adult Population Residing In Pakistan, Quratulain Humayun, Romaina Iqbal, Iqbal Azam, Aysha Habib Khan, Amna Rehana Siddiqui, Naila Baig Ansari

Department of Pathology and Laboratory Medicine

Background: Vitamin D deficiency has been identified as a major public health problem worldwide. Sunlight is the main source of vitamin D and its measurement using dosimeters is expensive and difficult for use in population-based studies. Hence, the aim of this study was to develop and validate questionnaires to assess sunlight exposure in healthy individuals residing in Karachi, Pakistan.

Methods: Two questionnaires with seven important items for sunlight exposure assessment were developed. Fifty four healthy adults were enrolled based on their reported sunlight exposure (high = 17, moderate = 18, low = 19) from Aga Khan University, Karachi. Over four …

Metabotropic Glutamate Receptor 5 In The Medial Prefrontal Cortex: Role In Cocaine Sensitization And Addiction, Kristin Marie Timmer

Theses and Dissertations (ETD)

Cocaine sensitization is associated with cocaine-induced hyperexcitability of pyramidal projection neurons within the medial prefrontal cortex (mPFC). Such hyperexcitability presumably results in increased glutamatergic input to reward-affiliated brain regions such as the ventral tegemental area (VTA) and nucleus accumbens (NAc), consequently facilitating drugseeking behavior. Metabotropic glutamate receptor 5 (mGluR5) has been implicated in cocaine addiction and demonstrated to increase neuronal excitability, therefore, the aim of the present study was to investigate the effect of intra-mPFC mGluR5 manipulation on behavioral and neurochemical sensitization and drug-seeking. Bilateral cannulae were implanted into the mPFC of male Sprague-Dawley rats and mGluR5 antagonist MTEP (15 …