Medicine and Health Sciences Commons^™

The Toxoplasma Gondii Protein Rop2 Mediates Host Organelle Association With The Parasitophorous Vacuole Membrane, Anthony P. Sinai, Keith A. Joiner

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH₂-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is …

Guanylyl Cyclase C Agonists Regulate Progression Through The Cell Cycle Of Human Colon Carcinoma Cells., Giovanni Mario Pitari, M D Di Guglielmo, J Park, S Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, …

Internet Facilitation Of Opioid Dependence., D Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

No abstract provided.

An Open-Label Trial Of Tomoxetine In Pediatric Attention Deficit Hyperactivity Disorder., Christopher J. Kratochvil, Daryl Bohac, Martin Harrington, Natalie Baker, Diane E. May, William J. Burke

Journal Articles: Psychiatry

OBJECTIVE: To collect pilot data assessing the safety, tolerability, and efficacy of tomoxetine, a nonstimulant norepinephrine enhancer, in pediatric attention deficit hyperactivity disorder (ADHD).

METHODS: An open-label trial of tomoxetine in pediatric ADHD was conducted as part of a multisite clinical trial. Following a baseline assessment, an ascending dose titration was completed during 10 weekly visits.

RESULTS: Ten subjects were enrolled at baseline, with eight completing the study. Seven of the eight remaining subjects met efficacy criteria. Significant decreases in symptom severity ratings by parents and study investigators were found. The medication was well tolerated, with transient appetite suppression the …

Comparison Of The Quantification Of Caffeine In Human Plasma By Gas Chromatography And Elisa, A. B. Carregaro, W. E. Woods, Thomas Tobin, A. Queiroz-Neto

Veterinary Science Faculty Publications

In the present study we evaluated the precision of the ELISA method to quantify caffeine in human plasma and compared the results with those obtained by gas chromatography. A total of 58 samples were analyzed by gas chromatography using a nitrogen-phosphorus detector and routine techniques. For the ELISA test, the samples were diluted to obtain a concentration corresponding to 50% of the absorbance of the standard curve. To determine whether the proximity between the I₅₀ of the standard curve and that of the sample would bring about a more precise result, the samples were divided into three blocks according …

Association Of Viral Genome With Graft Loss In Children After Cardiac Transplantation., Girish S. Shirali, J Ni, R E. Chinnock, J K. Johnston, G L. Rosenthal, N E. Bowles, J A. Towbin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss.

METHODS: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence …

Regulation Of Blastocyst Formation., A J Watson, L C Barcroft

Obstetrics & Gynaecology Publications

Preimplantation or pre-attachment development encompasses the "free"-living period of mammalian embryogenesis, which directs development of the zygote through to the blastocyst stage. Blastocyst formation is essential for implantation, establishment of pregnancy and is a principal determinant of embryo quality prior to embryo transfer. Cavitation (blastocyst formation) is driven by the expression of specific sets of gene products that direct the acquisition of cell polarity within the trophectoderm, which is both the first epithelium of development and the outer cell layer encircling the inner cell mass of the blastocyst. Critical gene families controlling these events include: the E-cadherin-catenin cell adhesion family, …

Impact Of Smoking On The Outcome Of Anterior Cervical Arthrodesis With Interbody Or Strut-Grafting., Alan Hilibrand, Mark A. Fye, Sanford E. Emery, Mark A. Palumbo, Henry H. Bohlman

Rothman Institute Papers

BACKGROUND: An increased rate of pseudarthrosis has been documented following posterolateral lumbar spine grafting in patients who smoke. This same relationship has been assumed for anterior cervical interbody grafting, but to our knowledge it has never been proven. This study compared the long-term radiographic and clinical results of smokers and nonsmokers who had undergone arthrodesis with autogenous bone graft following multi-level anterior cervical decompression for the treatment of cervical radiculopathy or myelopathy, or both.

METHODS: One hundred and ninety patients were followed clinically and radiographically for at least two years (range, two to fifteen years). Fifty-nine of the patients had …

Clumping Factor A Mediates Binding Of Staphylococcus Aureus To Human Platelets, Ian R. Siboo, Ambrose L. Cheung, Arnold S. Bayer, Paul M. Sullam

Dartmouth Scholarship

The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro. When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. We have now characterized the gene disrupted in PS12 and its function in platelet binding. DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two …

Induction Of Beta3-Integrin Gene Expression By Sustained Activation Of The Ras-Regulated Raf-Mek-Extracellular Signal-Regulated Kinase Signaling Pathway., Douglas Woods, Holly Cherwinski, Eleni Venetsanakos, Arun Bhat, Stephan Gysin, Martine Humbert, Paul F. Bray, Vicki L. Saylor, Martin Mcmahon

Cardeza Foundation for Hematologic Research

Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf-MEK-extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of alpha6- and …

Aluminium Toxicokinetics: An Updated Minireview, Robert A. Yokel, Patrick J. Mcnamara

Pharmaceutical Sciences Faculty Publications

This MiniReview updates and expands the MiniReview of aluminium toxicokinetics by Wilhelm et al. published by this journal in 1990. The use of ²⁶Al, analyzed by accelerator mass spectrometry, now enables determination of Al toxicokinetics under physiological conditions. There is concern about aluminium in drinking water. The common sources of aluminium for man are reviewed. Oral Al bioavailability from water appears to be about 0.3%. Food is the primary common source. Al bioavailability from food has not been adequately determined. Industrial and medicinal exposure, and perhaps antiperspirant use, can significantly increase absorbed aluminium. Inhalation bioavailability of airborne soluble Al …

Patient Choice Modules For Summaries Of Clinical Effectiveness: A Proposal, Margaret Holmes-Rovner, Hilary Llewellyn-Thomas, Vikki Entwistle, Angela Coulter

Dartmouth Scholarship

No abstract provided.

Estrogen Protects Against The Synergistic Toxicity By Hiv Proteins, Methamphetamine And Cocaine, Jadwiga Turchan, Caroline Anderson, Kurt F. Hauser, Qinmiao Sun, Jiayou Zhang, Ying Liu, Phyllis M. Wise, Inna Kruman, William Maragos, Mark P. Mattson, Rosemarie Booze, Avindra Nath

Neurology Faculty Publications

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.

RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by …

Assessing The Body Composition Of 6-17 Year-Old Black And White Girls In Field Studies, John A. Morrison, Shumei S. Guo, Bonny L. Specker, Wm. Cameron Chumlea, Susan Z. Yanovski, Jack A. Yanovski

Ethel Austin Martin Program Publications

The purpose of the study was to develop ethnic-specific equations for fat-free mass (FFM) from selected anthropometric dimensions and bioelectrical impedance measures of resistance (R) and reactance (Xc) for use in the NHLBI Growth and Heath Study. Using dual-energy X-ray absorptiometry measures of body composition as the dependent variable and field measures of body composition by anthropometry and bioelectrical impedance as the explanatory variables, ethnic-specific prediction equations were developed on a sample of girls representing a wide range of ages and BMI. The equations were cross-validated using (1) the Prediction of Sum of Squares (PRESS) statistic and (2) an independent …

Eye Position Sense Contributes To The Judgement Of Slant., F M James, S Whitehead, G K Humphrey, M S Banks, T Vilis

Brain and Mind Institute Researchers' Publications

We measured monocular judgements of the slant of a cube face while varying eye position in the absence of stereoscopic and external lighting cues. Errors were found to be small, only 10% on average of the cube's eccentricity. Two factors appear to have contributed approximately equally to this error: an underestimate of cube slant as seen by the eye and an underestimate of eye position. When prism adaptation altered the sensed eye position, the pattern of slant judgements changed to reflect the altered sense of eye position.

Department Of Radiation Oncology And Kimmel Cancer Center, Thomas Jefferson University, The Intronic G13964c Variant In P53 Is Not A High-Risk Mutation In Familial Breast Cancer In Australia., Anna Marsh, Amanda B Spurdle, Bruce C Turner, Sian Fereday, Heather Thorne, Gulietta M Pupo, Graham J Mann, John L Hopper, Joseph F Sambrook, Georgia Chenevix-Trench

Department of Radiation Oncology Faculty Papers

BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in …

Central Chemosensitivity, Sleep, And Wakefulness, E. E. Nattie, A Li

Dartmouth Scholarship

No abstract provided.

Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel

Dartmouth Scholarship

No abstract provided.

Synaptopodin Expression 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: Synaptopodin is a proline-rich protein intimately associated with actin microfilaments present in the podocytes' foot processes. We investigated for synaptopodin expression in children with idiopathic nephrotic syndrome (INS), including minimal change disease (MCD), diffuse mesangial hypercellularity (DMH), and focal segmental glomerulosclerosis (FSGS); in children with congenital nephrotic syndrome of the Finnish type (CNF); and in normal kidney tissue. In particular, we examined whether an association exists between synaptopodin expression in podocyte cells and the response to steroids in INS, and whether synaptopodin expression can predict FSGS upon the initial kidney biopsy in children who progress from MCD or DMH …

Technology Evaluation: Pro-542, Progenics Pharmaceuticals Inc., Muhammad Mukhtar, Zahida Parveen, Roger J Pomerantz

Department of Medicine Faculty Papers

Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the …

Recognition Of Left Atrial Aneurysm By Fetal Echocardiography., R R. Fountain-Dommer, H B. Wiles, C O. Shuler, S M. Bradley, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Accessory Cell Defect In Unresponsiveness Of Neonates And Aged To Polysaccharide Vaccines., Subbarao Bondada, H Wu, D A Robertson, R L Chelvarajan

Microbiology, Immunology, and Molecular Genetics Faculty Publications

T independent antigens elicit antibody responses in the absence of carrier specific T helper cells but require signals from accessory cells (macrophages and dendritic cells) or specific cytokines. They are further subdivided into TI-1 and TI-2 categories based on the ability of TI-1 but not TI-2 antigens to elicit immune responses from neonates. Most bacterial polysaccharides including the pneumococcal polysaccharide vaccines belong to the TI-2 class. It is hypothesized that defects in accessory cell function play a critical role in the failure of neonates to respond to such TI-2 antigens. Immune responses to these TI-2 stimuli are also reduced in …

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

Role Perceptions Of Occupational Therapists Providing Support And Education For Caregivers Of Persons With Dementia., Susan Toth-Cohen

Department of Occupational Therapy Faculty Papers

OBJECTIVE: This pilot study explored occupational therapists' perceptions of their roles as interventionists providing education and support for caregivers of persons with dementia. The intervention was provided in caregivers' homes as part of a larger funded study.

METHOD: Interviews were conducted with four occupational therapists to elicit their reflections on practice and their views on occupational therapy services on the basis of their experiences providing support and education for caregivers in the funded study.

RESULTS: Key themes consisted of the contrasts between the therapists' roles in the study and their customary practices and the professional and personal impact of their …

Eye Position Signal Modulates A Human Parietal Pointing Region During Memory-Guided Movements., J F Desouza, S P Dukelow, J S Gati, R S Menon, R A Andersen, T Vilis

Brain and Mind Institute Researchers' Publications

Using functional magnetic resonance imaging, we examined the signal in parietal regions that were selectively activated during delayed pointing to flashed visual targets and determined whether this signal was dependent on the fixation position of the eyes. Delayed pointing activated a bilateral parietal area in the intraparietal sulcus (rIPS), rostral/anterior to areas activated by saccades. During right-hand pointing to centrally located targets, the left rIPS region showed a significant increase in activation when the eye position was rightward compared with leftward. As expected, activation in motor cortex showed no modulation when only eye position changed. During pointing to retinotopically identical …

Children Of Alcoholics: An Update., D Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

One of four children in the United States lives in a family in which the child is exposed to alcoholism. Children of alcoholics (COAs) are two to ten times more likely to develop alcoholism than non-COAs. This paper reviews studies that have attempted to identify risk factors that mediate the increased vulnerability and the protective factors that moderate the risk. Factors discussed include parental antisocial personality disorder, externalizing behavior, internalizing symptoms, differential response to the effects of alcohol, and positive and negative alcohol-related expectancies. The heterogeneous nature of COAs is emphasized, and some of the challenges related to treatment and …

Novel Function Of Phosphoinositide 3-Kinase In T Cell Ca2+ Signaling. A Phosphatidylinositol 3,4,5-Trisphosphate-Mediated Ca2+ Entry Mechanism., A L Hsu, T T Ching, G Sen, D S Wang, Subbarao Bondada, K S Authi, C S Chen

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This study presents evidence that phosphoinositide (PI) 3-kinase is involved in T cell Ca(2+) signaling via a phosphatidylinositol 3,4, 5-trisphosphate PI(3,4,5)P(3)-sensitive Ca(2+) entry pathway. First, exogenous PI(3,4,5)P(3) at concentrations close to its physiological levels induces Ca(2+) influx in T cells, whereas PI(3,4)P(2), PI(4, 5)P(2), and PI(3)P have no effect on [Ca(2+)](i). This Ca(2+) entry mechanism is cell type-specific as B cells and a number of cell lines examined do not respond to PI(3,4,5)P(3) stimulation. Second, inhibition of PI 3-kinase by wortmannin and by overexpression of the dominant negative inhibitor Deltap85 suppresses anti-CD3-induced Ca(2+) response, which could be reversed by subsequent …

Navigation-Related Structural Change In The Hippocampi Of Taxi Drivers, E A Maguire, D G Gadian, Ingrid Johnsrude, C D Good, J Ashburner, R S Frackowiak, C D Frith

Brain and Mind Institute Researchers' Publications

Structural MRIs of the brains of humans with extensive navigation experience, licensed London taxi drivers, were analyzed and compared with those of control subjects who did not drive taxis. The posterior hippocampi of taxi drivers were significantly larger relative to those of control subjects. A more anterior hippocampal region was larger in control subjects than in taxi drivers. Hippocampal volume correlated with the amount of time spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus). These data are in accordance with the idea that the posterior hippocampus stores a spatial representation of the environment …

Ubinuclein, A Novel Nuclear Protein Interacting With Cellular And Viral Transcription Factors., S Aho, M Buisson, T Pajunen, Y W Ryoo, J F Giot, H Gruffat, A Sergeant, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

The major target tissues for Epstein-Barr virus (EBV) infection are B lymphocytes and epithelial cells of the oropharyngeal zone. The product of the EBV BZLF1 early gene, EB1, a member of the basic leucine-zipper family of transcription factors, interacts with both viral and cellular promoters and transcription factors, modulating the reactivation of latent EBV infection. Here, we characterize a novel cellular protein interacting with the basic domains of EB1 and c-Jun, and competing of their binding to the AP1 consensus site. The transcript is present in a wide variety of human adult, fetal, and tumor tissues, and the protein is …

The Pl(A2) Polymorphism Of Integrin Beta(3) Enhances Outside-In Signaling And Adhesive Functions., K Vinod Vijayan, Pascal J. Goldschmidt-Clermont, Christine Roos, Paul F. Bray

Cardeza Foundation for Hematologic Research

Genetic factors are believed to influence the development of arterial thromboses. Because integrin alpha(IIb)beta(3) plays a crucial role in thrombus formation, we analyzed receptor adhesive properties using Chinese hamster ovary and human kidney embryonal 293 cells overexpressing the Pl(A1) or Pl(A2) polymorphic forms of alpha(IIb)beta(3). Soluble fibrinogen binding was no different between Pl(A1) and Pl(A2) cells, either in a resting state or when alpha(IIb)beta(3) was activated with anti-LIBS6. Pl(A1) and Pl(A2) cells bound equivalently to immobilized fibronectin. In contrast, significantly more Pl(A2) cells bound to immobilized fibrinogen in an alpha(IIb)beta(3)-dependent manner than did Pl(A1) cells. Disruption of the actin cytoskeleton …