Digital Commons Network^™

Creation Of Non-Human Primate Neurogenetic Disease Models By Gene Targeting And Nuclear Transfer, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Genetically modified rhesus macaques are necessary because mouse models are not suitable for a number of important neurogenetic disorders; for example, Kallmann's syndrome, Lesch-Nyhan's disease and Ataxia-Telangiectasia. Mouse models may not be suitable because there may be no mouse ortholog of the human gene of interest, as is the case for Kallmann's syndrome, or because mutant mice do not exhibit the same phenotype observed in humans, as is the the case for Lesch-Nyhan's disease and Ataxia-Telangiectasia. Non-human primate models of neurogenetic diseases are expected to more closely resemble human diseases than existing mouse models. Genetically modified rhesus macaques can be …

Nf04-598 Rabies In Nebraska, Annette K. Bredthauer, David R. Smith

University of Nebraska-Lincoln Extension: Historical Materials

Rabies is a deadly virus infection that can attack the central nervous system of most warm blooded animals, including humans. Rabies is a very old disease. The first recorded description of the disease dates from the 23rd century BC in Babylon. It was rampant in Europe in the 19th century and was carried to the Americas by animals on the early ships.

This NebFact describes rabies in animals and explains how people can protect themselves, as well as their pets or livestock from rabies exposure.

Prophylactic Defibrillator Implantation In Patients With Nonischemic Dilated Cardiomyopathy, Alan H. Kadish, Alan Dyer, James P. Daubert, Rebecca Quigg, N. A. Mark Estes, Kelley P. Anderson, Joseph H. Levine

Office of the President Publications and Research

No abstract provided.

Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated By Hypoxia-Inducible Factor 1Α, Hdm2, And P70s6k1 In Response To Phosphatidylinositol 3-Kinase/Akt Signaling, Heath D. Skinner, Jenny Z. Zheng, Jing Fang, Faton Agani, Bing-Hua Jiang

Faculty & Staff Scholarship

No abstract provided.

Etoposide Differentially Affects Bone Marrow And Dermal Derived Endothelial Cells, S. W. Adams, Lin Wang, J. Fortney, Laura F. Gibson

Faculty & Staff Scholarship

Chemotherapy alteration of the bone marrow microenvironment has the potential to influence hematopoietic recovery following transplantation. To discern the effect of specific drugs on components of the complex marrow microenvironment, in vitro models have significant utility. In the current study we sought to determine whether dermal (HMEC-1) and marrow derived endothelial cells (BMEC-1) respond differently to identical chemotherapy exposure. BMEC-1 cells were consistently more sensitive to etoposide exposure than HMEC-1 cells, measured as reduced viability. BMEC-1 also had reduced focal adhesion kinase (FAK) and VCAM-1 protein expression following chemotherapy, in contrast to dermal derived endothelial cells in which neither protein …

The Moral Authority Of Symbolic Appeals In Biomedical Ethics, Sharon Sytsma

Faculty Articles, Papers, and Other Scholarship

No abstract provided.

Surveillance For Waterborne-Disease Outbreaks Associated With Recreational Water--United States, 2001-2002, Jonathan S. Yoder, Brian G. Blackburn, Gunther F. Craun, Vincent Hill, Deborah A. Levy, Nora Chen, Sherline H. Lee, Rebecca L. Calderon, Michael J. Beach

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting and periodically reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs) related to drinking water; tabulation of recreational water-associated outbreaks was added to the surveillance system in 1978. This surveillance system is the primary source of data concerning the scope and effects of waterborne disease outbreaks on persons in the United States.

REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with recreational water that occurred during January 2001-December 2002 and on …

Content And Criterion Validity Evaluation Of National Public Health Performance Standards Measurement Instruments., Joyce Beaulieu, F. Douglas Scutchfield, Ann V. Kelly

Preventive Medicine and Environmental Health Faculty Publications

OBJECTIVE: The Centers for Disease Control and Prevention's National Public Health Performance Standards Program (NPHPSP) has developed instruments to measure the performance of local and state public health departments on the 10 "Essential Services of Public Health," which have been tested in several states. This article is a report of the evaluation of the content and criterion validity of the local public health performance assessment instrument, and the content validity of the state public health performance assessment instrument.

METHODS: Health department performance is measured using a set of indicators developed for the 10 Essential Services of Public Health and a …

The Triterpenoid Cddo Inhibits Expression Of Matrix Metalloproteinase-1, Matrix Metalloproteinase-13 And Bcl-3 In Primary Human Chondrocytes, Sarah Elliott, Ezra Hays, Michael Mayor, Michael Sporn, Matthew P. Vincenti

Dartmouth Scholarship

A synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), has been reported to have anti-inflammatory properties and to decrease the interleukin-1 (IL-1)-induced expression of matrix metalloproteinase-1 (MMP-1) and MMP-13. We have shown previously that IL-1 induces expression of the inhibitor of NF-κB (IκB) family member Bcl-3, and that this contributes to MMP-1 expression. To quantify the effects of CDDO on IL-1-induced MMP-1, MMP-13 and Bcl-3 expression, we stimulated the chondrosarcoma cell line SW-1353 and human primary chondrocytes with IL-1, in the presence or absence of CDDO. Harvested RNA was subjected to quantitative real-time reverse-transcriptase polymerase chain reaction. In SW-1353 cells, 300 nM CDDO …

Compromised Constitutions: The Iranian Experience With The 1918 Influenza Pandemic., Amir Afkhami

Psychiatry and Behavioral Sciences Faculty Publications

The global demographic impact of the 1918-19 influenza pandemic continues to fascinate researchers and scholars. This paper examines the social and demographic effects of this outbreak on Iranian society, through a comprehensive investigation of the modes of transmission and propagation, mortality rates, and other distinctive features of the region, and reveals the importance of taking a country's unique sociopolitical settings into account. Iran was one of the regions hit hardest by the pandemic, with mortality rates significantly higher than in most regions of the world. Though globally the victims of influenza lived primarily in urban areas, it was Iran's rural …

Is Hp1 An Rna Detector That Functions Both In Repression And Activation?, Rebecca Kellum

Biology Faculty Publications

Heterochromatin is defined as regions of compact chromatin that persist throughout the cell cycle (Heitz, 1928). The earliest cytological observations of heterochromatin were followed by ribonucleotide labeling experiments that showed it to be transcriptionally inert relative to the more typical euchromatic regions that decondense during interphase. Genetic studies of rearrangements that place euchromatic genes next to blocks of heterochromatin also pointed out the repressive nature of heterochromatin (Grigliatti, 1991; and references therein). The discovery of the heterochromatin-enriched protein heterochromatin protein 1 (HP1) by Elgin and co-workers in the mid-1980s suggested that the distinct cytological features of this chromatin may be …

Regulation And Localization Of Endogenous Human Tristetraprolin, Anna-Marie Fairhurst, John E. Connolly, Katharine A Hintz, Nicolas J Goulding

Dartmouth Scholarship

Tumor necrosis factor (TNF) has been implicated in the development and pathogenicity of infectious diseases and autoimmune disorders, such as septic shock and arthritis. The zinc-finger protein tristetraprolin (TTP) has been identified as a major regulator of TNF biosynthesis. To define its intracellular location and examine its regulation of TNF, a quantitive intracellular staining assay specific for TTP was developed. We establish for the first time that in peripheral blood leukocytes, express

Genomic And Proteomic Profiling Of Responses To Toxic Metals In Human Lung Cells, Angeline S. Andrew, Amy J. Warren, Aaron Barchowsky, Kaili A. Temple, Linda Klei, Nicole V. Soucy, Kimberly A. O'Hara, Joshua W. Hamilton

Dartmouth Scholarship

Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expression following low-dose, acute exposures of cadmium, chromium, arsenic, nickel, or mitomycin C (MMC) in BEAS-2B human bronchial epithelial cells. Total RNA was isolated from cells exposed to 3 M Cd(II) (as cadmium chloride), 10 M Cr(VI) (as sodium dichromate), 3 g/cm2 Ni(II) (as nickel subsulfide), 5 M or 50 M As(III) (as sodium arsenite), or …

Cell-Cycle Regulatory Proteins In Podocyte Cell In Idiopathic Nephrotic Syndrome Of Childhood., Tarak Srivastava, Robert E. Garola, J M. Whiting, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The podocyte cell is believed to play an important role in idiopathic nephrotic syndrome (INS) of childhood. In adults with cellular and collapsing focal segmental glomerulosclerosis (FSGS), the expression of cell-cycle regulatory proteins such as p27, p57, and cyclin D is decreased and expression of cyclin A, Ki-67, and p21 is observed in podocyte cells suggestive of a dysregulated podocyte phenotype. We investigated for alterations in the expression of cyclin kinase inhibitors, p27, p57, p21, and cyclins D and A in the podocyte cell of children with INS.

METHODS: Forty-two kidney biopsies were investigated; 14 with minimal-change disease (MCD), …

Human Acyl-Coenzyme A:Cholesterol Acyltransferase Expressed In Chinese Hamster Ovary Cells: Membrane Topology And Active Site Location, Song Lin, Xiaohui Lu, Catherine C.Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Acyl-CoA:cholesterol acyltransferase (ACAT) is a membrane-bound enzyme that produces cholesteryl esters intracellularly. Two ACAT genes (ACAT1 and ACAT2) have been identified. The expression of ACAT1 is ubiquitous, whereas that of ACAT2 is tissue restricted. Previous research indicates that ACAT1 may contain seven transmembrane domains (TMDs). To study ACAT2 topology, we inserted two different antigenic tags (hemagglutinin, monoclonal antibody Mab1) at various hydrophilic regions flanking each of its predicted TMDs, and expressed the recombinant proteins in mutant Chinese hamster ovary cells lacking endogenous ACAT. Each tagged ACAT2 was expressed in the endoplasmic reticulum as a single undegraded protein band …

Minus-End Capture Of Preformed Kinetochore Fibers Contributes To Spindle Morphogenesis, Alexey Khodjakov, Lily Copenagle, Michael B. Gordon, Duane A. Compton, Tarun M. Kapoor

Dartmouth Scholarship

Near-simultaneous three-dimensional fluorescence/differential interference contrast microscopy was used to follow the behavior of microtubules and chromosomes in living alpha-tubulin/GFP-expressing cells after inhibition of the mitotic kinesin Eg5 with monastrol. Kinetochore fibers (K-fibers) were frequently observed forming in association with chromosomes both during monastrol treatment and after monastrol removal. Surprisingly, these K-fibers were oriented away from, and not directly connected to, centrosomes and incorporated into the spindle by the sliding of their distal ends toward centrosomes via a NuMA-dependent mechanism. Similar preformed K-fibers were also observed during spindle formation in untreated cells. In addition, upon monastrol removal, centrosomes established a transient …

Glucuronidation Enzymes, Genes And Psychiatry, Jose De Leon

Psychiatry Faculty Publications

The phase I cytochrome P450 (CYP) isoenzymes have received substantial attention in the pharmacogenetic literature. Researchers are beginning to examine the role of the phase II UDP-glucuronosyltransferase (UGT) enzymes, which produce products that are more water-soluble, less toxic and more readily excreted than the parent compounds. Several reasons may have contributed to neglect of UGTs (compared to CYPs) including: (1) the overlapping activity of UGTs and lack of selective probes; (2) the complexity of the glucuronidation cycle; and (3) the difficulty in developing analytic methods to measure glucuronides. Current CYP knowledge is used as a model to predict advances in …

Effects Of Tacrolimus On Ischemia-Reperfusion Injury., Shawn D. St Peter, Adyr A. Moss, David C. Mulligan

Manuscripts, Articles, Book Chapters and Other Papers

In addition to efficacious immunosuppression for the benefit of organ transplantation, tacrolimus has diverse actions that result in amelioration of ischemia-reperfusion injury. Knowledge is accumulating rapidly on the mechanisms through which tacrolimus exerts these cytoprotective effects, including alterations in microcirculation, free radical metabolism, calcium-activated pathways, inflammatory cascades, mitochondrial stability, apoptosis, stress-response proteins, and tissue recovery. Within the nucleus, actions mediating the effects of tacrolimus appear to be dominantly influenced by interactions with the transcription factor, nuclear factor-kappaB. Because tacrolimus is a cornerstone agent in immunosuppression regimens throughout the world and knowledge of its cellular mechanisms is evolving, it is important …

Platelets Stimulate Fibroblast-Mediated Contraction Of Collagen Gels, Ulrika Zagai, Karin Fredriksson, Stephen I. Rennard, Joachim Lundahl, C. Magnus Sköld

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) contribute to this effect.

METHODS: Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing), were cast together with human lung fibroblasts in three-dimensional collagen gels. …

The Permeability Of The Endoplasmic Reticulum Is Dynamically Coupled To Protein Synthesis, Anirban Roy, William F. Wonderlin

Faculty & Staff Scholarship

No abstract provided.

An Author Co-Citation Analysis Of Medical Informatics, James E. Andrews

School of Information Faculty Publications

Objective: This study presents the results of an author co-citation analysis of the interdisciplinary field of medical informatics.

Methods: An author co-citation analysis was conducted for the years 1994 to 1998, using the fifty most-cited American College of Medical Informatics fellows as an author population. Co-citation data were calculated for every author pair, and multivariate analyses were performed to ultimately show the relationships among all authors. A multidimensional map was created, wherein each author is represented as a point, and the proximity of these points reflects the relationships of authors as perceived by multiple citers.

Results and Conclusion: The results …

Parenting Adolescents, Sandra L. D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

Rigorously Assessing Whether The Data Backs The Back School, David T. Vinh, Craig W. Johnson, Cynthia L. Phelps

Faculty, Staff and Student Publications

A rigorous between-subjects methodology employing independent random samples and having broad clinical applicability was designed and implemented to evaluate the effectiveness of back safety and patient transfer training interventions for both hospital nurses and nursing assistants. Effects upon self-efficacy, cognitive, and affective measures are assessed for each of three back safety procedures. The design solves the problem of obtaining randomly assigned independent controls where all experimental subjects must participate in the training interventions.

Randomized Comparisons Among Health Informatics Students Identify Hypertutorial Features As Improving Web-Based Instruction, Craig W. Johnson, Yan Xing, Lan Yang

Faculty, Staff and Student Publications

Hypertutorials optimize five features - presentation, learner control, practice, feedback, and elaborative learning resources. Previous research showed graduate students significantly and overwhelmingly preferred Web-based hypertutorials to conventional "Book-on-the-Web" statistics or research design lessons. The current report shows that the source of hypertutorials' superiority in student evaluations of instruction lies in their hypertutorial features. Randomized comparisons between the two methodologies were conducted in two successive iterations of a graduate level health informatics research design and evaluation course. The two versions contained the same text and graphics, but differed in the presence or absence of hypertutorial features: Elaborative learning resources, practice, feedback, …

Signaling And Regulation Of G Protein-Coupled Receptors In Airway Smooth Muscle., Charlotte K Billington, Raymond B Penn

Department of Medicine Faculty Papers

Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the …

Plasma Pge-2 Levels And Altered Cytokine Profiles In Adherent Peripheral Blood Mononuclear Cells In Non-Small Cell Lung Cancer (Nsclc), Giovanna E. Hidalgo, Li Zhong, Dennis E. Doherty, Edward A. Hirschowitz

Internal Medicine Faculty Publications

INTRODUCTION: PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC) and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile.

RESULTS: Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming …

Distinct Neural Systems Subserve Person And Object Knowledge, Jason P. Mitchell, Todd F. Heatherton, C. Neil Macrae

Dartmouth Scholarship

Studies using functional neuroimaging and patient populations have demonstrated that distinct brain regions subserve semantic knowledge for different classes of inanimate objects (e.g., tools, musical instruments, and houses). What this work has yet to consider, however, is how conceptual knowledge about people may be organized in the brain. In particular, is there a distinct functional neuroanatomy associated with person knowledge? By using event-related functional magnetic resonance imaging (fMRI), we measured neural activity while participants made semantic judgments about people or objects. A unique pattern of brain activity was associated with person judgments and included brain regions previously implicated in other …

Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein alpha subunit, has been shown to produce an additional protein, termed salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found predominantly at cellular plasma membranes, salpha(i2) has been localized to intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have been suggested to constitute a specific targeting signal. RESULTS: This paper proposes and examines an alternative hypothesis: disruption of the normal C-terminus of alpha(i2) produces an unstable protein that fails to localize to plasma …

Effectiveness Of Current Therapy Of Bacterial Vaginosis, Petya M Andreeva, Hatim A. Omar

Pediatrics Faculty Publications

The study was conducted in order to evaluate effectiveness of the treatment of bacterial vaginosis (BV) with different therapeutic regimes according to recommendations of the World Health Organization (WHO). During a one-year period (February 2000-February 2001) the Sexually Transmitted Diseases (STD) Center was visited by 482 women aged 14-51. The diagnosis of BV was established by standard methods: Amsel's clinical criteria and Gram stain of vaginal discharge. The first-line treatment was oral Metronidazole 2 g single dose. Second line was Metronidazole 500 mg twice daily orally for 7 days or oral Clindamycin 300 mg twice daily for seven days. BV …

Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

Dartmouth Scholarship

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …