Medicine and Health Sciences Commons^™

Sidedness Of H+ Action On K-Cl Cotransport In Dids Ph(I)-Clamped Low K Sheep Red Blood Cells With Reduced Mg(I), Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Dependence Of Thiol-Stimulated K-Cl Cotransport On Redox State Of Low K Sheep Red Blood Cells, Peter K. Lauf, Norma C. Adragna, Nihal S. Agar

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Progressive Cross-Linking Of Fibrin Gamma Chains Increases Resistance To Fibrinolysis, Kevin R. Siebenlist, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

In the presence of plasma transglutaminase (factor XIIIa) fibrin first undergoes intermolecular covalent cross-linking between its gamma chains to create gamma dimers followed by slower cross-linking among its alpha chains to form alpha polymers. Progressive cross-linking of gamma chain dimers occurs at the slowest rate, resulting in gamma trimers and gamma tetramers (“gamma multimers”). Most studies indicate that cross-linked fibrin clots become resistant to fibrinolysis, but the basis for this event is not clear. In this study, we explored the role of gamma chain multimerization compared with alpha polymerization as causal factors in time-dependent development of resistance to fibrinolysis. Fibrin …

Hypoglycemia And Hyperinsulinemia In Rodent Models Of Severe Malaria Infection, Khalid M. Elased, J. H. L. Playfair

Pharmacology and Toxicology Faculty Publications

Severe hypoglycemia developed during nonlethal Plasmodium chabaudi and lethal P. yoelii blood stage malaria infection in mice, always in association with hyperinsulinemia. Supernatants of lethal P. yoelii incubated overnight induced hypoglycemia and hyperinsulinemia in normal mice. In murine malaria, hypoglycemia may be largely secondary to increased insulin secretion.

Effects Of Natural Sequence Variation On Recognition By Monoclonal Antibodies Neutralize Simian Immunodeficiency Virus Infectivity, Weon Sang Choi, Catherine Collignon, Clotilde Thiriart, Dawn P. Wooley, E. J. Scott, Karen A. Kent, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

The determinants of immune recognition by five monoclonal antibodies (KK5, KK9, KK17, Senv7.1, and Senv101.1) that neutralize simian immunodeficiency virus infectivity were analyzed. These five neutralizing monoclonal antibodies were generated to native SIVmac251 envelope glycoprotein expressed by a vaccinia virus recombinant vector. All five recognize conformational or discontinuous epitopes and require native antigen for optimal recognition. These monoclonal antibodies also recognize SIVmac239 gp120, but they do not recognize gp120 of two natural variants of SIVmac239, 1-12 and 8-22, which evolved during the course of persistent infection in vivo (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843-1854, 1991). Recombinant viruses which …

Peculiar Histopathological Features Of Giardiasis In Distal Duodenal Biopsies, Z Abbas, A A. Qureshi, H Sheikh, S M. Jafri, A H. Khan

Department of Pathology and Laboratory Medicine

Histological changes in 20 Giardia positive duodenal biopsies (Group A) were compared with 50, Giardia negative duodenal biopsies (Group B), taken during the same period. Stool examinations in Group B were negative for Giardia. Surface epithelium, villous and crypt architecture and cellular infiltrates were examined and compared between the groups. Atrophic changes in the villi were more common in Group A as compared to B(P < 0.0001). Intraepithelial neutrophil infiltration (P < 0.001), infiltration of the lamina propria with plasma cells (P < 0.5), and presence of eosinophils in the lamina propria (P < 0.001) were significant findings in group A. Some of the changes were related to the density of Giardia colonization e.g., the goblet cell depletion (P < 0.05) and the density of plasma cell infiltration in lamina propria (P < 0.01). Erosions and ulcerations were less commonly seen in group A. Thus we conclude that giardiasis manifests its peculiar features in the distal duodenal mucosa and a biopsy of this region is an important diagnostic tool for detection of this disease.

A Randomized Comparison Of Coronary-Stent Placement And Balloon Angioplasty In The Treatment Of Coronary Artery Disease. Stent Restenosis Study Investigators., David L. Fischman, Martin B. Leon, Donald S. Baim, Richard A. Schatz, Michael P. Savage, Ian Penn, Katherine Detre, Lisa Veltri, Donald Ricci, Masakiyo Nobuyoshi, Michael Cleman, Richard Heuser, David Almond, Paul S. Teirstein, R. David Fish, Antonio Colombo, Jeffrey Brinker, Jeffrey Moses, Alex Shaknovich, John Hirshfeld, Stephen Bailey, Stephen Ellis, Randal Rake, Sheldon Goldberg

Department of Medicine Faculty Papers

BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes.

METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later.

RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who …

Molecular Cloning And Expression Of A Unique Receptor-Like Protein-Tyrosine-Phosphatase In The Leucocyte-Common-Antigen-Related Phosphatase Family, Wei-Ren Zhang, Naotake Hashimoto, Faiyaz Ahmad, Wendi Ding, Barry J. Goldstein

Department of Medicine Faculty Papers

Protein-tyrosine-phosphatases (PTPases) have been implicated in the regulation of certain tyrosine kinase growth factor receptors in that they dephosphorylate the activated (autophosphorylated) form of the receptors. In order to identify PTPases that potentially act on receptor targets in liver, we used the human leucocyte common antigen-related PTPase (LAR) cDNA [Streuli, Krueger, Hall, Schlossman and Saito (1988) J. Exp. Med. 168, 1523-1530] and isolated two closely related transmembrane PTPase homologues from a rat hepatic cDNA library. Both PTPases had large extracellular domains that contained three immunoglobulin-like repeats and eight type-III fibronectin repeats. Both enzymes had tandem homologous PTPase domains following a …

A Thyroid Hormone-Regulated Gene In Xenopus Laevis Encodes A Type Iii Iodothyronine 5-Deiodinase., Donald L. St Germain, Robert Schwartzman, Walburga Croteau, Akira Kanamori, Zhou Wang, Donald D. Brown, Valerie Galton

Dartmouth Scholarship

The type III iodothyronine 5-deiodinase metabolizes thyroxine and 3,5,3'-triiodothyronine to inactive metabolites by catalyzing the removal of iodine from the inner ring. The enzyme is expressed in a tissue-specific pattern during particular stages of development in amphibia, birds, and mammals. Recently, a PCR-based subtractive hybridization technique has been used to isolate cDNAs prepared from Xenopus laevis tadpole tail mRNA that represent genes upregulated by thyroid hormone during metamorphosis. Sequence analysis of one of these cDNAs (XL-15) revealed regions of homology to the mRNA encoding the rat type I (outer ring) 5'-deiodinase, including a conserved UGA codon that encodes selenocysteine in …

The Role Of Cd4+T Cells In The Immune Response To Trypanosoma Cruzi In Mice Held At Elevated Environmental Temperature, Qi Guo

Masters Theses & Specialist Projects

The immune response of mice infected with Trypanosoma cruzi (the causative agent of Chagas' disease) has been extensively studied, and it has been demonstrated that changes in environmental temperature can influence the resistance of infected mice to the parasite. In particular, several investigators have demonstrated an increased resistance to T. cruzi infection when infected mice are maintained at 36°C. This increased resistance is reflected in decreased parasitemias and increased longevity. In addition, this enhanced resistance has been shown to be an immunological phenomenon. CD4+ T cells play a very important role in immune responses to parasitic infections through the secretion …

Comparison Of Micrscan Identification And Susceptibility Testing Methods For Streptococcus Dysgalactiae To Conventional Biochemical Reactions And Kirby-Bauer Susceptibility Testing Methods, Anthony Hatcher

Masters Theses & Specialist Projects

A total of 100 isolates of Streptococcus dysgalact iae from bovine mastitis infections was used to evaluate and compare the biochemical reactions of the gram positive Combo Type 6 panel on the MicroScan autoSCANR system to a conventional procedure for identification of streptococci. Of the 100 isolates, 83.3% was identified as "Very Rare Biotype" by the MicroScan and classified as S. dysgalactiae by conventional methods. Of the remaining 16.7%, MicroScan identified 3.3% as Streptococcus morbillorum, 3.3% as Aerococcus viridians, 3.3% as Streptococcus constellatum/milleri, 1.7% as Streptococcus agalactiae, 1.7% as Streptococcus mitis, 1.7% as Streptococcus sanguis, and 1.7% as Streptococcus intermidis/rni …

The Role Of Cd8+T Cells In The Immune Response To Trypanosoma Cruzi In Mice Held At Elevated Environmental Temperature, Zhijan Ming

Masters Theses & Specialist Projects

When maintained at 36°C, T. cruzi infected C3H mice survive an infection that is lethal to mice maintained at room temperature. To study the role of CD8+ T cells in this phenomenon, anti-CD8 monoclonal antibody (MAb) was used to deplete CD8+ T cells in vivo. An IgG2a-producing rat hybridoma (designated 53-6.72) was adapted to serum free medium, and anti-CD8 MAb was purified from culture supernatant by ammonium sulfate precipitation. Mice were injected intraperitoneally with 200(ig of MAb for three consecutive days. On the fifth day, the result of the in vivo depletion of CD8+ T cells was determined by an …

Impairment Of The Cellular Immune Response In Acute Murine Toxoplasmosis: Regulation Of Interleukin 2 Production And Macrophage-Mediated Inhibitory Effects., Sakhina Haque, Imtiaz Khan, Azizul Haque, Lloyd Kasper

Dartmouth Scholarship

Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-1). Spleen cells from infected A/J mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg- and PTgB-infected A/J mice exhibited …

Adoptive Transfer Of Polyclonal And Cloned Cytolytic T Lymphocytes (Ctl) Specific For Mouse Aids-Associated Tumors Is Effective In Preserving Ctl Responses: A Measure Of Protection Against Lp-Bm5 Retrovirus-Induced Immunodeficiency., William R. Green, Kathy A. Green, Karen M. Crassi

Dartmouth Scholarship

Cytolytic T lymphocytes (CTL) can be raised against C57BL/6 B-cell lymphomas from mice with LP-BM5 murine leukemia virus-induced AIDS (MAIDS). Adoptive transfer of polyclonal anti-MAIDS tumor CTL or two CTL clones specific for the B6-1710 MAIDS lymphoma caused preservation of major histocompatibility complex-restricted and allogeneic CTL responses, which may be interpreted as indices of protection from LP-BM5 murine leukemia virus-induced immunodeficiency.

Polyclonal Infections Due To Mycobacterium Avium Complex In Patients With Aids Detected By Pulsed-Field Gel Electrophoresis Of Sequential Clinical Isolates., Alexander M. Slutsky, Robert D. Arbeit, Thomas W. Barber, Josiah Rich, C Fordham Von Reyn

Dartmouth Scholarship

Invasive infection with organisms of the Mycobacterium avium complex (MAC) is common among patients with advanced human immunodeficiency virus infection. In previous studies, we analyzed multiple individual colonies of MAC isolated from specimens obtained at the same time and observed that 14 to 20% of patients are simultaneously infected with more than one strain. In this study, we examined sequential isolates from 12 patients with AIDS who had two or more MAC isolates available from clinical specimens collected more than 1 week apart; the intervals between the first and last specimens ranged from 8 to 192 (median, 46) days. For …

Evaluation And Comparison Of Environmental Contaminants Present In Two Types Of Swine Rearing Facilities, Carolyn Crowe

Masters Theses & Specialist Projects

It has been reported that pigs weaned and moved into an isolated nursery have greater growth rates measured on an average daily gain, and thymus gland weights than do their counterparts in a conventional nursery. In this study I explored the association of this biological difference with environmental contaminants. Levels of total and respirable dust and endotoxin, carbon monoxide, carbon dioxide, ammonia, and temperature and percent relative humidity were measured in two types of swine rearing facilities: isolated nursery and nursery within a conventional farm. We found isolated nurseries have significantly (p<0.05) less total and respirable dust and endotoxin and greater growth rates. With few exceptions, our measurements of levels of total and respirable dust and total endotoxin were within published ranges. Levels of respirable endotoxin were higher than published ranges.

High Rates Of Frameshift Mutations Within Homo-Oligomeric Runs During A Single Cycle Of Retroviral Replication, Dawn P. Wooley, H. M. Temin

Neuroscience, Cell Biology & Physiology Faculty Publications

Homo-oligomeric runs were inserted into a spleen necrosis virus-based retrovirus vector to determine the nature and rate of mutations within runs of 10 to 12 identical nucleotides during a single replication cycle. Clones of helper cells containing integrated copies of retroviral vectors were used to produce virus for infection of target (nonhelper) cells. Proviral sequences from target cell clones were compared with proviral sequences from helper cell clones to study mutations that occurred during a single cycle of replication. In addition to the internal region spanning the homo-oligomeric inserts, a naturally occurring run of 10 T's in the long terminal …

The Cost Of Arm Autotomy In The Starfish Stichaster-Striatus, John M. Lawrence, A. Larrain

Integrative Biology Faculty and Staff Publications

Arm autotomy in asteroids, as tail autotomy in vertebrates, typically occurs when the animal is attacked and appears to facilitate escape. One assumes autotomy has a cost, but it rarely has been demonstrated in the field in vertebrates and never demonstrated in asteroids. The concentration of lipid was 40 % less and the amount of kilojoules 85 % less in the pyloric caeca of the asteroid Stichaster striatus Muller & Troschel (Echinodermata: Asteroidea) with autotomized arms than in those of individuals with intact arms collected in the field. as the pyloric caeca are used as nutrient reserves, individuals with autotomized …

Comparison Of Cytotoxic Properties Of Neonatal And Adult Neutrophils And Monocytes And Enhancement By Cytokines., E . R. Stiehm, R. L. Roberts, B. J. Ank, S. Plaeger-Marshall, N. Salman, L. Shen, M. W. Fanger

Dartmouth Scholarship

We studied cytotoxic capabilities of newborn polymorphonuclear leukocytes (PMNs) and monocytes and their enhancement by cytokines and antibodies. Umbilical cord PMNs were assessed for their ability to kill various target cells spontaneously, after activation with phorbol myristate acetate, in the presence of antiserum (antibody-dependent cellular cytotoxicity), and in the presence of dually specific antibody (heteroantibody-mediated cytotoxicity). Target cells included the K562 cell line (natural killer cell target), chicken erythrocytes (CRBCs), and herpes simplex virus-infected CEM cell lines. Newborn PMNs were equivalent to adult PMNs in their cytotoxic capacity in several cytotoxicity assays. Neither adult nor newborn PMNs lyse tumor cell …

Subunit Dynamics In Escherichia Coli Preprotein Translocase., John C. Joly, Marilyn R. Leonard, William T. Wickner

Dartmouth Scholarship

SecY, SecE, and band 1 copurify as the SecY/E integral membrane domain of Escherichia coli preprotein translocase. To measure the in vivo association of these polypeptides and assay possible exchange, plasmid-borne secY and secE genes were placed under control of the ara regulon and fused to DNA encoding the influenza hemagglutinin epitope. Cells were incubated with [35S]methionine, grown for a "chase" period, and then induced with arabinose to express epitope-tagged, nonradioactive SecY and SecE. Both the wild-type and epitope-tagged polypeptides assembled into functional, heterotrimeric SecY/E complex. However, immunoprecipitation with antibody to the epitope tag did not cross-precipitate radiolabeled SecY or …

Interleukin-12 Enhances Murine Survival Against Acute Toxoplasmosis., Imtiaz A. Khan, Tadashi Matsuura, Lloyd H. Kasper

Dartmouth Scholarship

Protective immunity against Toxoplasma gondii is mediated by the host cellular immune response. Interleukin-12 (IL-12), a recently described cytokine that stimulates NK cells to produce gamma interferon (IFN-gamma), is able to enhance host protection against this parasite in SCID mice. Administration of IL-12 to A/J mice significantly increased survival over that of control mice when IL-12 was delivered early in the course of acute infection. If it was administered at day 3 or thereafter, there was no observed difference in mortality between treated and control mice. Antibody depletion of IL-12 increased susceptibility to infection, as measured by mortality, only when …

The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine

Dartmouth Scholarship

High levels of the p53 tumor suppressor protein can block progression through the cell cycle. A model system for the study of the mechanism of action of wild-type p53 is a cell line (T64-7B) derived from rat embryo fibroblasts transformed by activated ras and a temperature-sensitive murine p53 gene. At 37 to 39 degrees C, the murine p53 protein is in a mutant conformation and the cells actively divide, whereas at 32 degrees C, the protein has a wild-type conformation and the cells arrest in the G1 phase of the cell cycle. Wild-type simian virus 40 large T antigen and …

Cd40 Ligand Expression Is Defective In A Subset Of Patients With Common Variable Immunodeficiency., Mary Farrington, Laura S. Grosmaire, Shigeaki Nonoyama, Susanna H. Fischer, Diane Hollenbaugh, Jeffrey A. Ledbetter, R. J. Noelle

Dartmouth Scholarship

Common variable immunodeficiency (CVI) is characterized by hypogammaglobulinemia and recurrent bacterial infections due to failure of CVI B cells to differentiate in vivo into immunoglobulin-secreting plasma cells. We hypothesized that T-cell dysfunction resulting in abnormal contact-mediated B-cell activation may play a prominent role in the failure of CVI B cells to produce specific antibody. We have previously shown that B-cell proliferation and IgE production after stimulation with anti-CD40 and interleukin (IL) 4 were normal in 22 CVI patients evaluated, indicating that CVI B cells respond to signals delivered via CD40. Here we report that CD40 ligand (gp39) mRNA expression by …

Separate Metabolic Pathways Leading To Dna Fragmentation And Apoptotic Nuclear Chromatin Condensation, D. Sun, Shibo Jiang, Li-Mou Zheng, David M. Ojcius, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Apoptosis is the predominant form of cell death observed in a variety of physiological and pathological conditions such as cancer involution, insect metamorphosis, the development of the immune and nervous systems, and embryogenesis. The typical nuclear changes taking place in apoptotic cells include extensive condensation of chromatin and internucleosomal DNA fragmentation into units of 200 base pairs. However, the mechanisms responsible for both chromatin condensation and DNA fragmentation have yet to be elucidated. In this study, micrococcal nuclease and the divalent cations, Ca2+ and Mg2+, were applied to isolated nuclei in an attempt to reconstitute in vitro the digestion of …

Morphometric Analysis Of Enteric Lesions In C3h/Hen Mice Inoculated With Serpulina Hyodysenteriae Serotypes 2 And 4 With Or Without Oral Streptomycin Pretreatment, Jagannatha V. Mysore, Gerald Duhamel

School of Veterinary and Biomedical Sciences: Faculty Publications

The segmental distribution and sequential progression and the role of the indigenous bacterial flora in the development of enteric lesions associated with Serpulina hyodysenteriae infection in laboratory mice have not been defined. We examined the distribution and sequential morphometric changes in the large intestine of mice orally inoculated with S. hyodysenteriae serotypes 2 and 4. To determine the role of colonization resistance conferred by the indigenous bacterial flora, 40 female C3H/HeN mice were administered water alone or water containing 5 mg/mL streptomycin sulfate ad libitum for seven days prior to orogastric inoculation either with S. hyodysenteriae or sterile trypticase soy …

Inactivation Of Hit Cell Ca2+ Current By A Simulated Burst Of Ca2+ Action Potentials, L. S. Satin, S. J. Tavalin, P. D. Smolen

Pharmacology and Toxicology Publications

ABSTRACT A novel voltage-clamp protocol was developed to test whether slow inactivation of Ca2+ current occurs during bursting in insulin-secreting cells. Single insulin-secreting HIT cells were patch-clamped and their Ca2+ currents were isolated pharmacologically. A computed ,3-cell burst was used as a voltage-clamp command and the net Ca2+ current elicited was determined as a cadmium difference current. Ca2+ current rapidly activated during the computed plateau and spike depolarizations and then slowly decayed. Integration of this Ca2+ current yielded an estimate of total Ca influx. To further analyze Ca2+ current inactivation during a burst, repetitive test pulses to + 10 mV …

Antiparasitic And Antiproliferative Effects Of Indoleamine 2,3-Dioxygenase Enzyme Expression In Human Fibroblasts., Sohan L. Gupta, Joseph M. Carlin, Padma Pyati, Wei Dai, Elmer R. Pfefferkorn, Martin J. Murphy Jr

Dartmouth Scholarship

Studies were carried out to evaluate the proposed role of indoleamine 2,3-dioxygenase (INDO) induction in the antimicrobial and antiproliferative effects of gamma interferon (IFN-gamma) in human fibroblasts. The INDO cDNA coding region was cloned in the pMEP4 expression vector, containing the metallothionein (MTII) promoter in the sense (+ve) or the antisense (-ve) orientation. Human fibroblasts (GM637) stably transfected with the sense construct expressed INDO activity after treatment with CdCl2 or ZnSO4, but cells transfected with the antisense construct did not. The growth of Chlamydia psittaci was strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment …

Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen

Dartmouth Scholarship

Two phorbol ester-inducible elements (beta E2 and beta E3) within the human T-cell receptor beta gene enhancer each contain consensus binding sites for the Ets and core binding factor (CBF) transcription factor families. Recombinant Ets-1 and purified CBF bound individually to beta E2 and beta E3, in which the Ets and core sites are directly adjacent. In this report, we show that CBF and Ets-1 bind together to beta E2 and beta E3 and that Ets-1-CBF-DNA complexes are favored over the binding of either protein alone to beta E2. Formation of Ets-1-CBF-DNA complexes increased the affinity of Ets-1-DNA interactions and …

Quinine And Quinidine Inhibit K-Cl Cotransport In Low K Sheep Erythrocytes, Norma C. Adragna, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Reactive Oxygen-Dependent Dna Damage Resulting From The Oxidation Of Phenolic Compounds By A Copper-Redox Cycle Mechanism, Y. Li, M. A. Trush

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.