Digital Commons Network^™

Microarray-Based Cancer Prediction Using Single Genes., Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Although numerous methods of using microarray data analysis for cancer classification have been proposed, most utilize many genes to achieve accurate classification. This can hamper interpretability of the models and ease of translation to other assay platforms. We explored the use of single genes to construct classification models. We first identified the genes with the most powerful univariate class discrimination ability and then constructed simple classification rules for class prediction using the single genes.

RESULTS: We applied our model development algorithm to eleven cancer gene expression datasets and compared classification accuracy to that for standard methods including Diagonal Linear …

Deregulation Of Micrornas By Hiv-1 Vpr Protein Leads To The Development Of Neurocognitive Disorders, Ruma Mukerjee, J Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya

School of Medicine Faculty Publications

Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic …

Zinc Supplementation As An Adjunct To Antibiotics In The Treatment Of Pneumonia In Children 2 To 59 Months Of Age, Batool A. Haider, Zohra S. Lassi, Amina Ahmed, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Diarrhoeal disorders and acute respiratory infections (ARIs), especially pneumonia, are the most common causes of death in low-income countries. Studies evaluating the impact of zinc supplementation as an adjunct in the management of pneumonia are limited and have shown variable results.
Objectives: To evaluate zinc supplementation, as an adjunct to antibiotics, in the treatment (clinical recovery) of pneumonia in children aged two to 59 months.
Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's and the Cochrane Infectious Diseases Group's Specialised …

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Background: Cerium oxide (CeO₂) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO₂ nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.

Methods and results: Compared with control animals, CeO₂ nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO₂nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO₂ nanoparticles.

Conclusion: Taken together, these data suggest that intratracheal instillation …

We Are… Bridging Medicine And Science Vol. 1, Issue 1, Fall 2011, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Formulation Of Buprenorphine For Sublingual Use In Neonates., Ellena A Anagnostis, Rania E Sadaka, Linda A Sailor, David E Moody, Kevin C Dysart, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVES: The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration.

METHODS: Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each …

Strain-Dependent Variation In The Early Transcriptional Response To Cns Injury Using A Cortical Explant System, David J. Graber, Brent T. Harris, William F. Hickey

Dartmouth Scholarship

While it is clear that inbred strains of mice have variations in immunological responsiveness, the influence of genetic background following tissue damage in the central nervous system is not fully understood. A cortical explant system was employed as a model for injury to determine whether the immediate transcriptional response to tissue resection revealed differences among three mouse strains. Immunological mRNAs were measured in cerebral cortex from SJL/J, C57BL/6J, and BALB/cJ mice using real time RT-PCR. Freshly isolated cortical tissue and cortical sections incubated in explant medium were examined. Levels of mRNA, normalized to β-actin, were compared using one way analysis …

Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina

Kimmel Cancer Center Faculty Papers

BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to …

The Use Of Targeted Charge-Reversal Nanoparticles (Tcrns) To Investigate Nuclear Delivery Of Fluorescent Agents To Cancer Cells: Implications For Novel Prostate And Breast Cancer Therapy, Mario Dance

Theses and Dissertations

Nanotechnology has recently emerged as a strong contributor toward research efforts to develop targeted systems of drug delivery in cancer therapy. Our work investigates the therapeutic potential of Targeted Charge-Reversal Nanoparticles (TCRNs), a novel nanoparticle with in vitro evidence of nuclear drug delivery. Using M12 prostate cancer cells, MDA-MB-231 breast cancer cells, and modified derivatives of these cell lines, we investigated the ability of Folic Acid-tagged TCRNs to deliver Nile Red and Dimethyl Indole Redfluorescent (DiR) fluorescent dyes to the nucleus of cells using confocal microscopy and in vivo biphontonic imaging using Xenogen® Technology. Confocal imaging with the SCP28 derivative …

Reciprocal Effects Of Oxidative Stress On Heme Oxygenase Expression And Activity Contributes To Reno-Vascular Abnormalities In Ec-Sod Knockout Mice, Tomoko Kawakami, Nitin Puri, Komal Sodhi, Lars Bellner, Toru Takahashi, Kiyoshi Morita, Rita Rezzani, Tim D. Oury, Nader G. Abraham

Biochemistry and Microbiology

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD^(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD^(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, …

Mast Cell Activation And Clinical Outcome In Pediatric Cholelithiasis And Biliary Dyskinesia., Craig A. Friesen, Nancy Neilan, James F. Daniel, Kim Radford, Jennifer Verrill Schurman, Ding-You Li, Linda Andre, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The current study was undertaken to determine the degree of activation of gallbladder mucosal mast cells, whether mast cell (MC) density or activation differ between patients with and without a positive clinical response to cholecystectomy, and whether either density or activation correlate with gallbladder emptying.

RESULTS: Fifteen biliary dyskinesia (BD) and 13 symptomatic cholelithiasis (CL) patients undergoing cholecystectomy were prospectively enrolled. Gallbladder wall MC density (by immunohistochemistry) and activation (by electron microscopy) were determined. Clinical response was evaluated 30 days post-cholecystectomy on a 5-point Likert-type scale. A complete or nearly complete clinical response was seen in 100% of CL …

Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar

Biochemistry and Microbiology

Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …

Biochemical And Functional Characterization Of The Ledgf/P75-Mecp2 Interaction In Tumor Cells, Lai Sum Leoh

Loma Linda University Electronic Theses, Dissertations & Projects

The lens epithelial derived growth factor p75 (LEDGF/p75) is a novel pro-survival and stress-inducible transcription co-activator that protects mammalian cells from various environmental stresses such as oxidative stress, heat shock, and serum starvation. This emerging cancer-related protein is highly expressed in prostate tumors and other tumor types and promotes resistance to chemotherapy in cancer cells. LEDGF/p75 is also involved in acquired immunodeficiency syndrome (AIDS) since it interacts with HIV-1 integrase to facilitate the integration and replication of the HIV virus in human cells. In addition, LEDGF/p75 has been shown to interact with MLL (mixed lineage leukemia)/menin transcription complex in leukemia …

Lateralization Of Emotion, Reaction Time, And Skin Conductance Responsiveness, Kimberley Erin Rose

Loma Linda University Electronic Theses, Dissertations & Projects

Bilateral presentations of brief (250 ms), unmasked emotional and neutral stimuli were examined in two experiments with primarily female samples. Reaction time and accuracy data were used to measure perception of emotion and skin conductance response (SCR) was used to measure experience of emotion. Both words and pictures were used to account for hemispheric differences in language and visuospatial dominance. Response time was faster to emotional pictures than words. Reaction time and speeded accuracy data did not support right hemisphere hypothesis (RHH) or valence hypothesis (VH) in the expected manner. Data suggested emotion caused greater interference under speeded conditions in …

Relationship Of Adipokines With Insulin Sensitivity In African Americans., Maria P Martinez Cantarin, Scott W Keith, Stephanie Deloach, Yonghong Huan, Bonita Falkner

Department of Medicine Faculty Papers

INTRODUCTION: Cytokines produced by adipose tissue, including adiponectin, have been associated with metabolic abnormalities. The purpose of this study was to examine the relationship of insulin sensitivity measured by euglycemic hyperinsulinemic insulin clamp with plasma adiponectin and other adipokines in young adult African Americans.

METHODS: Participants were healthy African Americans. Anthropometric measures, blood pressure, an oral glucose tolerance test and an euglycemic hyperinsulinemic insulin clamp were performed. Insulin sensitivity measurements were adjusted for percentage of fat mass. Plasma concentrations of adiponectin, plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6) were assayed on plasma from fasting blood samples. Pearson correlation coefficients and …

Antagonistic Effects Of Cellular Poly(C) Binding Proteins On Vesicular Stomatitis Virus Gene Expression, Phat X. Dinh, Lalit Beura, Debasis Panda, Anshuman Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Immunoprecipitation and subsequent mass spectrometry analysis of the cellular proteins from cells expressing the vesicular stomatitis virus (VSV) P protein identified the poly(C) binding protein 2 (PCBP2) as one of the P protein-interacting proteins. To investigate the role of PCBP2 in the viral life cycle, we examined the effects of depletion or overexpression of this protein on VSV growth. Small interfering RNA-mediated silencing of PCBP2 promoted VSV replication. Conversely, overexpression of PCBP2 in transfected cells suppressed VSV growth. Further studies revealed that PCBP2 negatively regulates overall viral mRNA accumulation and subsequent genome replication. Coimmunoprecipitation and immunofluorescence microscopic studies showed that …

Acute Fatty Liver Of Pregnancy: An Update On Mechanisms, Sathish Kumar Natarajan, Kavitha R. Thangaraj, Ashish Goel, C. E. Eapen, K. A. Balasubramanian, Anup Ramachandran

School of Veterinary and Biomedical Sciences: Faculty Publications

Acute fatty liver of pregnancy (AFLP), characterized by hepatic microvesicular steatosis, is a sudden catastrophic illness occurring almost exclusively in the third trimester of pregnancy. Defective fatty acid oxidation in the fetus has been shown to be associated with this disease. Since the placenta has the same genetic makeup as the fetus and as AFLP patients generally recover following delivery, we hypothesized that the placenta might be involved in pathogenesis of this disease. In an animal model of hepatic microvesicular steatosis (using sodium valproate), we found that microvesicular steatosis results in mitochondrial structural alterations and oxidative stress in subcellular organelles …

Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu

Dissertations and Theses (Open Access)

Atherosclerosis is a chronic, complex arterial disease characterized by intimal lipid accumulation and inflammation. A unique lipid-binding molecule, namely cluster of differentiation 1d (CD1d), may impact atherosclerosis. Structurally, CD1d acts as a nonpolymorphic cell-surface receptor, resembling the major histocompatibility complex-I (MHC-I). While MHC-I restricts peptide antigen presentation to T cells, CD1d presents lipid antigens to T cells named CD1d-restrictedd T cells. Although increased expression of CD1d has been found in human plaques, the exact nature of CD1d-recognized lipids in atherosclerosis remains to be determined. Three groups of lipids may undergo oxidation in atherosclerosis producing atherogenic lipids: phospholipids, fatty acids, and …

A Single Phenylalanine Residue In The Main Intracellular Loop Of Α1 Γ-Aminobutyric Acid Type A And Glycine Receptors Influences Their Sensitivity To Propofol, Gustavo Moraga-Cid, Gonzalo E. Yevenes, Günther Schmalzing, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

Background: The intravenous anesthetic propofol acts as a positive allosteric modulator of glycine (GlyRs) and γ-aminobutyric acid type A (GABA_ARs) receptors. Although the role of transmembrane residues is recognized, little is known about the involvement of other regions in the modulatory effects of propofol. Therefore, the influence of the large intracellular loop in propofol sensitivity of both receptors was explored. Methods: The large intracellular loop of α₁ GlyRs and α₁β₂ GABA_ARs was screened using alanine replacement. Sensitivity to propofol was studied using patch-clamp recording in HEK293 cells transiently transfected with …

A Non-Randomized, Observational Trial Of Short-Term Pre-Operative Endocrine Therapy In Er Positive Breast Cancer To Investigate Changes In Genomic Expression Using The Oncotype Dx® Recurrence Score®, Aaron D. Bleznak Md, Facs, Elizabeth A. Dellers Md, B G. Porter, Sharon R. Kimmel Phd, Mha, Heiwon Chung Md, Facs, Carl N. Yoshizawa, Emily Burke, D S. Davison, Calvin Chao

Department of Pathology & Laboratory Medicine

No abstract provided.

Spiking Patterns And Their Functional Implications In The Antennal Lobe Of The Tobacco Hornworm Manduca Sexta, Hong Lei, Carolina E. Reisenman, Caroline H. Wilson, Prasad Gabbur, John G. Hildebrand

Health Sciences and Kinesiology Faculty Articles

Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question …

Uncertain Progress On The Fuzzy Boundaries Of Alzheimer's Disease: Reading Between The Guidelines, Peter J. Whitehouse

Faculty Scholarship

No abstract provided.

Potential Applications Of Curcumin And Its Novel Synthetic Analogs And Nanotechnology-Based Formulations In Cancer Prevention And Therapy., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog (SHH)/GLIs and Wnt/β-catenin and downstream signaling elements …

Monoclonal Antibodies Recognizing The Non-Tandem Repeat Regions Of The Human Mucin Muc4 In Pancreatic Cancer., Maneesh Jain, Ganesh Venkatraman, Nicolas Moniaux, Sukhwinder Kaur, Sushil Kumar, Subhankar Chakraborty, Grish C. Varshney, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and …

Alpha-Defensins 1-3 Release By Dendritic Cells Is Reduced By Estrogen, Maria M. Escribese, Marta Rodríguez-García, Rhoda Sperling, Stephanie M. Engel

Dartmouth Scholarship

During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown …

Method And Apparatus For In Vivo Collection Of Circulating Biological Components, Dave S B Hoon, Bret Taback, Samuel Shaolian

Technology Transfer - Patents

The invention relates generally to in vivo collection of circulating molecules, tumor cells and other biological markers using a collecting probe. The probe is configured for placement within a living organism for an extended period of time to provide sufficient yield of biological marker for analysis. In some embodiments of the invention, active attraction of biological markers are provided. A partial or complete analytic/detection assembly may also be integrated with the probe.

Role Of Autophagy In Radiosensitization Of Breast Tumor Cells, Molly L. Bristol

Theses and Dissertations

In MCF-7 breast tumor cells, ionizing radiation promoted autophagy that was cytoprotective; pharmacological or genetic interference with autophagy induced by radiation resulted in growth suppression and/or cell killing (primarily by apoptosis). The hormonally active form of vitamin D, 1,25D3, also promoted autophagy in irradiated MCF-7 cells, sensitized the cells to radiation and suppressed the proliferative recovery that occurs after radiation alone. 1,25D3 also enhanced radiosensitivity and promoted autophagy in MCF7 cells that overexpress Her-2/neu as well as in p53 mutant Hs578t breast tumor cells. In contrast, 1,25D3 failed to alter radiosensitivity or promote autophagy in the BT474 breast tumor cell …

Mosaicism For Trisomy21: Utility Of Array-Based Technology For Its Detection And Its Influence On Telomere Length And The Frequency Of Acquired Chromosome Abnormalities, Chariyawan Charalsawadi

Theses and Dissertations

The primary aim of this study was to determine the effectiveness of array-based technology for detecting and quantifying the presence of mosaicism. This aim was achieved by studying individuals having mosaicism for Down syndrome. SNP arrays were performed on 13 samples from individuals with mosaicism for trisomy 21, 13 samples from individuals with normal chromosome 21complements (negative controls) and 5 samples from individuals with full or partial trisomy 21 (positive controls). In addition, BAC arrays were processed on 6 samples from individuals with mosaicism for trisomy 21, 3 negative controls and 1 positive control. These studies have shown that array-based …

Utilizing Induced Voxel Correlation In Fmri Analysis, Daniel B. Rowe, Andrew S. Nencka

Mathematics, Statistics and Computer Science Faculty Research and Publications

No abstract provided.

Discovery Of An Apoptosis Inducing Ligand For Burkitt Lymphoma, Carolyn Laymon, Kyla Bradylong, Mary Saunders, David Olivos, Kit Lam

STAR Program Research Presentations

One-bead two-compound (OB2C) combinatorial chemistry libraries enable the discovery of novel synthetic compounds which can be used to evoke specific signaling response in cells. The library configuration is composed of a fixed known cell adhesion ligand and a random chemical library displayed on the surface of Tentagel beads. The cell adhesion ligand binds to specific receptors located on the surface of cells enabling the random immobilized chemical molecules on each bead resin bead to evoke specific cellular responses such as apoptosis or cell death. To validate this concept, a OB2C combinatorial library comprised of an α4β1 integrin targeting ligand, LLP2A, …