Digital Commons Network^™

Role Of Reactive Oxygen Species And P53 In Chromium(Vi)-Induced Apoptosis, Jianping Ye, Suwei Wang, Stephen S. Leonard, Yongyut Rojanasakul

Faculty & Staff Scholarship

No abstract provided.

Resurgence Of Sleeping Sickness In Tambura County, Sudan, Anne Moore, Michaleen Richer, Mario Enrile, Edward Losio, Jacquelin Roberts, Deborah A. Levy

Journal Articles: Epidemiology

Endemic foci of human African trypanosomiasis are present in southern Sudan. In 1996 and 1997, trypanosomiasis increased sharply in Tambura County. To define the magnitude and geographic distribution of the outbreak, we conducted a prevalence survey using population-based cluster sampling in 16 villages: 1,358 participants answered questions about routine activities and tsetse fly contact and received serologic testing. Seroprevalence in the surveyed area was 19.4% (95% confidence interval = 16.9%, 21.8%). We confirmed infection in 66% of seropositive persons who received one parasitologic examination and in 95% of those who had serial examinations of lymph node fluid and blood. Activities …

Wild Boy (1998) By Mordicai Gerstein, Gareth B. Matthews

Picture Books

Once there was a boy who lived alone, without a mother or father or any friends, in a forest in Southern France. He was naked. He didn’t even know what clothes were. He didn’t know he was a boy. He didn’t know what people were. He was wild. When a group of hunters discovered the boy, they delivered him to scientists in Paris, who eventually gave up trying to communicate with him. The boy was taken in by Dr. Itard and his housekeeper, Madame Guerin, who taught him to dress himself, to read and write simple words, and help around …

Inhibition Of Fibronectin Matrix Assembly By The Heparin-Binding Domain Of Vitronectin, Denise C. Hocking, Jane Sottile, Thomas Reho, Reinhard Fässler, Paula J. Mckeown-Longo

Biology

The deposition of fibronectin into the extracellular matrix is an integrin-dependent, multistep process that is tightly regulated in order to ensure controlled matrix deposition. Reduced fibronectin deposition has been associated with altered embryonic development, tumor cell invasion, and abnormal wound repair. In one of the initial steps of fibronectin matrix assembly, the amino-terminal region of fibronectin binds to cell surface receptors, termed matrix assembly sites. The present study was undertaken to investigate the role of extracellular signals in the regulation of fibronectin deposition. Our data indicate that the interaction of cells with the extracellular glycoprotein, vitronectin, specifically inhibits matrix assembly …

Camp-Induced Phosphorylation And Inhibition Of Na + /H + Exchanger 3 (Nhe3) Are Dependent On The Presence But Not The Phosphorylation Of Nhe Regulatory Factor, Mirza Zizak, Georg Lamprecht, Deborah Steplock, Nadeem Tariq, Shirish Shenolikar, Mark Donowitz, C. H. Chris Yun, Edward J. Weinman

Faculty & Staff Scholarship

No abstract provided.

The Leukemic Protein Core Binding Factor Beta (Cbfbeta)-Smooth-Muscle Myosin Heavy Chain Sequesters Cbfalpha2 Into Cytoskeletal Filaments And Aggregates, Neeraj Adya, Terryl Stacy, Nancy A. Speck, Pu Paul Liu

Dartmouth Scholarship

The fusion gene CBFB-MYH11 is generated by the chromosome 16 inversion associated with acute myeloid leukemias. This gene encodes a chimeric protein involving the core binding factor β (CBFβ) and the smooth-muscle myosin heavy chain (SMMHC). Mouse model studies suggest that this chimeric protein CBFβ-SMMHC dominantly suppresses the function of CBF, a heterodimeric transcription factor composed of DNA binding subunits (CBFα1 to 3) and a non-DNA binding subunit (CBFβ). This dominant suppression results in the blockage of hematopoiesis in mice and presumably contributes to leukemogenesis. We used transient-transfection assays, in combination with immunofluorescence and green fluorescent protein-tagged proteins, to monitor …

Trophectoderm Differentiation In The Bovine Embryo: Characterization Of A Polarized Epithelium., L C Barcroft, A Hay-Schmidt, A Caveney, E Gilfoyle, E W Overstrom, P Hyttel, A J Watson

Obstetrics & Gynaecology Publications

Blastocytst formation is dependent on the differentiation of a transporting epithelium, the trophectoderm, which is coordinated by the embryonic expression and cell adhesive properties of E-cadherin. The trophectoderm shares differentiative characteristics with all epithelial tissues, including E-cadherin-mediated cell adhesion, tight junction formation, and polarized distribution of intramembrane proteins, including the Na-K ATPase. The present study was conducted to characterize the mRNA expression and distribution of polypeptides encoding E-cadherin, beta-catenin, and the tight junction associated protein, zonula occludens protein 1, in pre-attachment bovine embryos, in vitro. Immunocytochemistry and gene specific reverse transcription--polymerase chain reaction methods were used. Transcripts for E-cadherin and …

Identification Of Putative Cytoskeletal Protein Homologues In The Protozoan Host Hartmannella Vermiformis As Substrates For Induced Tyrosine Phosphatase Activity Upon Attachment To The Legionnaires' Disease Bacterium, Legionella Pneumophila, Chandrasekar Venkataraman, Lian-Yang Gao, Subbarao Bondada, Yousef Abu Kwaik

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires' disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the …

Molecular Basis For Effects Of Carcinogenic Heavy Metals On Inducible Gene Expression, Joshua W. Hamilton, Ronald C. Kaltreider, Olga V. Bajenova, Michael A. Ihnat, Jennifer Mccaffrey, Bruce W. Turpie, Erin E. Rowell, Jannet Oh, Michael J. Nemeth, Carrie A. Pesce, Jean P. Lariviere

Dartmouth Scholarship

Certain forms of the heavy metals arsenic and chromium are considered human carcinogens, although they are believed to act through very different mechanisms. Chromium(VI) is believed to act as a classic and mutagenic agent, and DNA/chromatin appears to be the principal target for its effects. In contrast, arsenic(III) is considered nongenotoxic, but is able to target specific cellular proteins, principally through sulfhydryl interactions. We had previously shown that various genotoxic chemical carcinogens, including chromium (VI), preferentially altered expression of several inducible genes but had little or no effect on constitutive gene expression. We were therefore interested in whether these carcinogenic …

Current Concepts Review - Corrosion Of Metal Orthopaedic Implants, Joshua J. Jacobs, Jeremy L. Gilbert, Robert M. Urban

Biomedical and Chemical Engineering - All Scholarship

No abstract provided.

Differential Expression Of Human Metallothionein Isoform I Mrna In Human Proximal Tubule Cells Exposed To Metals, S H Garrett, S Somji, J H Todd, M A Sens, D A Sens

Faculty & Staff Scholarship

No abstract provided.

Detection And Characterization Of Sp1 Binding Activity In Human Chondrocytes And Its Alterations During Chondrocyte Dedifferentiation., Rita M. Dharmavaram, Gang Liu, Sheryl D. Mowers, Sergio A. Jimenez

Department of Medicine Faculty Papers

We have detected DNA binding activity for a synthetic oligonucleotide containing an Sp1 consensus sequence in nuclear extracts from human chondrocytes. Changes in the levels of Sp1 oligonucleotide binding activity were examined in nuclear extracts from freshly isolated human chondrocytes, from chondrocytes that had been cultured under conditions that allowed the maintenance of a chondrocyte-specific phenotype on plastic dishes coated with the hydrogel poly(2-hydroxyethyl methacrylate), and from chondrocytes induced to dedifferentiate into fibroblast-like cells by passage in monolayer culture on plastic substrata. It was observed that Sp1 binding was 2-3-fold greater in nuclear extracts from dedifferentiated chondrocytes than in nuclear …

Anticoagulation And Elective Surgery., J. Spandorfer, G. Merli

Department of Medicine Faculty Papers

No abstract provided.

Intrinsic And Extrinsic Control Of Hemopoietic Stem Cell Numbers: Mapping Of A Stem Cell Gene, Gerald De Haan, Gary Van Zant

Markey Cancer Center Faculty Publications

We evaluated in vivo interactions between extrinsic (growth factor induced) and intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle kinetics were assessed in eight strains of inbred mice using the cobblestone area–forming cell (CAFC) assay. A strong inverse correlation was observed between mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in the femur. The population size of primitive stem cells (CAFC day 35) varied widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling and quiescent), which were similar. Administration of …

Phosphorylation Regulates The Assembly Of Numa In A Mammalian Mitotic Extract, Alejandro Saredi, Louisa Howard, Duane A. Compton

Dartmouth Scholarship

NuMA is a 236 kDa nuclear protein that is required for the organization of the mitotic spindle. To determine how NuMA redistributes in the cell during mitosis, we have examined the behavior of NuMA in a mammalian mitotic extract under conditions conducive to the reassembly of interphase nuclei. NuMA is a soluble protein in mitotic extracts prepared from synchronized cultured cells, but forms insoluble structures when the extract becomes non-mitotic (as judged by the inactivation of cdc2/cyclin B kinase and the disappearance of mpm-2-reactive antigens). These NuMA-containing structures are irregularly shaped particles of 1–2 microm in diameter and their assembly …

Choosing Ignorance In The Manufacture Of Toxic Products , Wendy E. Wagner

Cornell Law Review

No abstract provided.

Section 8(C) Of The Proposed Restatement (Third) Of Torts: Is It Really What The Doctor Ordered , Jeffrey D. Winchester

Cornell Law Review

No abstract provided.

Loss Of Dcc Expression And Glioma Progression., M Reyes-Mugica, K Rieger-Christ, H Ohgaki, B C Ekstrand, M Helie, G Kleinman, Alan M. Yahanda Md, Facs, E R Fearon, P Kleihues, M A Reale

PCI Publications and Projects

The deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene on chromosome 18q21, encodes a neural cell adhesion molecule family protein that is most highly expressed in the nervous system. To address the hypothesis that DCC may play a role in glioma development and/or progression, we examined DCC expression by immunohistochemistry in 57 resected human astrocytic tumors. Overall, low-grade astrocytomas were predominantly DCC positive (15 of 16, or 94%), whereas high-grade tumors significantly less often expressed the DCC protein (27 of 41, or 66%; P = 0.03). We were able to directly assess the relationship between DCC expression …

Ifn-Gamma, Igif, And Iddm., Nora Sarvetnick

Journal Articles: Regenerative Medicine

No abstract provided.

The History Of The Present Illness As Treatment: Who's Listening, And Why Does It Matter?, Herbert M. Adler, Md, Phd

Department of Family & Community Medicine Faculty Papers

BACKGROUND: The history of the present illness (HPI) is examined as a narrative communication that has the potential to be therapeutic.

METHODS: The general principles that influence the therapeutic potential of the HPI are induced from participant observation of personal experience and natural observations of conventional social interaction. These principles are corroborated by evidence from cross-cultural healing practices, clinical experience, and experimental psychology.

RESULTS: To facilitate a therapeutic HPI, the clinician should convey a sense of safety, sensitivity, affective competence, and cognitive competence. Furthermore, the effective clinician joins the patient in coprocessing the illness experience.

CONCLUSIONS: The (HPI) is not …

Opposing Motor Activities Are Required For The Organization Of The Mammalian Mitotic Spindle Pole, Tirso Gaglio, Alejandro Saredi, James B. Bingham, M Josh Hasbani, Steven R. Grill, Trina A. Schroer, Duane A. Compton

Dartmouth Scholarship

We use both in vitro and in vivo approaches to examine the roles of Eg5 (kinesin-related protein), cytoplasmic dynein, and dynactin in the organization of the microtubules and the localization of NuMA (Nu-clear protein that associates with the Mitotic Apparatus) at the polar ends of the mammalian mitotic spindle. Perturbation of the function of Eg5 through either immunodepletion from a cell free system for assembly of mitotic asters or antibody microinjection into cultured cells leads to organized astral microtubule arrays with expanded polar regions in which the minus ends of the microtubules emanate from a ring-like structure that contains NuMA. …

Pancreatic Expression Of Interleukin-4 Abrogates Insulitis And Autoimmune Diabetes In Nonobese Diabetic (Nod) Mice., Regula Mueller, Troy Krahl, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Diabetes in nonobese diabetic (NOD) mice is a T cell-dependent autoimmune disease. The destructive activities of autoreactive T cells have been shown to be tightly regulated by effector molecules. In particular, T helper (Th) 1 cytokines have been linked to diabetes pathogenesis, whereas Th2 cytokines and the cells that release them have been postulated to be protective from disease. To test this hypothesis, we generated transgenic NOD mice that express interleukin (IL) 4 in their pancreatic beta cells under the control of the human insulin promoter. We found that transgenic NOD-IL-4 mice, both females and males, were completely protected from …

Efficient Vasoactive Intestinal Polypeptide Hydrolyzing Autoantibody Light Chains Selected By Phage Display, Sonia Tyutyulkova, Qing-Sheng Gao, Austin Thompson, Stephen I. Rennard, Sudhir Paul

Journal Articles: Pulmonary & Critical Care Med

An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The …

Cloning Of The Mammalian Type Ii Iodothyronine Deiodinase. A Selenoprotein Differentially Expressed And Regulated In Human And Rat Brain And Other Tissues., Walburga Croteau, Jennifer C. Davey, Valerie Anne Galton, Donald L. St Germain

Dartmouth Scholarship

The deiodination of thyroid hormones in extrathyroidal tissues plays an important role in modulating thyroid hormone action. The type II deiodinase (DII) converts thyroxine to the active hormone 3,5,3'-triiodothyronine, and in the rat is expressed in the brain, pituitary gland, and brown adipose tissue (BAT). Complementary DNAs (cDNAs) for the types I and III deiodinases (DI and DIII, respectively) have been isolated and shown to code for selenoproteins. However, information concerning the structure of the mammalian DII remains limited, and the pattern of its expression in human tissues is undefined. We report herein the identification and characterization of rat and …

A Novel Iron-Regulated Metal Transporter From Plants Identified By Functional Expression In Yeast., David Eide, Margaret Broderius, Jeanette Fett, Mary Lou Guerinot

Dartmouth Scholarship

Iron is an essential nutrient for virtually all organisms. The IRT1 (iron-regulated transporter) gene of the plant Arabidopsis thaliana, encoding a probable Fe(II) transporter, was cloned by functional expression in a yeast strain defective for iron uptake. Yeast expressing IRT1 possess a novel Fe(II) uptake activity that is strongly inhibited by Cd. IRT1 is predicted to be an integral membrane protein with a metal-binding domain. Data base comparisons and Southern blot analysis indicated that IRT1 is a member of a gene family in Arabidopsis. Related sequences were also found in the genomes of rice, yeast, nematodes, and humans. In Arabidopsis, …

Prefabrication Of A Secondary Tram Flap., Geoffrey G. Hallock Md

Department of Surgery

A secondary TRAM flap was prefabricated in a rat model using the rectus muscle. The right rectus muscle was elevated as an inferiorly pedicled muscle flap in one experimental group (n = 6) and as a superiorly pedicled muscle flap in a second group (n = 5) and then sandwiched between a silicone sheet and the abdominal skin. Two weeks later, the abdominal skin and attached rectus muscle were elevated over the silicone sheet as a secondary TRAM flap. The surviving skin paddle areas of these prefabricated TRAM flaps were compared with superiorly (n = 7) and inferiorly (n = …

Disruption Of The Cbfa2 Gene Causes Necrosis And Hemorrhaging In The Central Nervous System And Blocks Definitive Hematopoiesis., Qing Wang, Terryl Stacy, Michael M Binder, Miguel Marin-Padilla, Arlene H. Sharpe, Nancy A. Speck

Dartmouth Scholarship

The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption …

A Tandem Duplication Within The Fibrillin 1 Gene Is Associated With The Mouse Tight Skin Mutation., Linda D. Siracusa, Rodney Mcgrath, Qing Ma, John J. Moskow, Jayanthi Manne, Paul J. Christner, Arthur M. Buchberg, Sergio A. Jimenez

Department of Medicine Faculty Papers

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame …

Cd40-Cd40 Ligand Interactions In Experimental Allergic Encephalomyelitis And Multiple Sclerosis., Koen Gerritse, Jon D. Laman, Randolph J. Noelle, Alejandro Aruffo

Dartmouth Scholarship

We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological disease. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40-bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with …

Basics Of Research (Part 5): Ethics And Human Rights, Eric Davis, Edward A. Panacek, Cheryl Thompson

Journal Articles: College of Nursing

No abstract provided.