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Update - September 1994, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Ritualized Genital Mutilation the Procedure
-- A Cultural Perspective
-- Female Genital Mutilation: A Question of Fundamental Human Rights
-- Ethics When Cultures Clash
-- Ethics Consultation (Review)

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 …

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 …

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 …

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 …

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.

Determination Of Pancreatic And Salivary Amylase By Enzyme Immunoassay And Their Prevalence In Hyperamylasemic Patients, Sabdra Borgens Ward

Theses and Dissertations in Biomedical Sciences

Currently, amylase determinations are nonspecific for the organ source and are based entirely on the enzymatic properties of amylase to produce a measurable product or byproduct. The determination of pancreatic amylase is important in the diagnosis of acute pancreatitis. Most commercially available tests for amylase employ the measurement of the change in NADH absorbance at 280 nm or of the p-nitrophenol released from a maltotetrose substrate. These are nonspecific measurements of pancreatic amylase and often necessitate other tests to be run such as a serum lipase.

The two predominant isoenzymes of amylase are pancreatic (p-amylase) and salivary (s-amylase); the most …

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 …

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 …

Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott

Loma Linda University Electronic Theses, Dissertations & Projects

The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change …

Comparative Toxicities Of Aminonitriles, Timothy Lester Lacy

Theses and Dissertations - UTB/UTPA

This study examined the comparative toxicities and metabolism of four selected aminonitriles namely aminoacetonitrile, $\beta$-aminopropionitrile, $N,N\sp\prime$-dimethylaminopropionitrile, and $\beta ,\beta\sp\prime$-iminodipropionitrile. Various experiments in this study include time course of the metabolism of these nitriles to cyanide, thiocyanate, and cyanoacetic acid. All of the nitriles studied were metabolized to cyanide and thiocyanate and the levels of these metabolites remained at a significantly high level even 5 days after dosing. Except aminoacetonitrile all the nitriles were metabolized to cyanoacetic acid. Experiments on the role of vehicles on the toxicity and metabolism of nitriles showed that all of the vehicles studied significantly affected nitrile …

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 …

Signal Transduction In Bacterial Chemotaxis, Edward Heath Rowsell

Loma Linda University Electronic Theses, Dissertations & Projects

This study investigated the site of ATP utilization in the signal transduction pathway of bacterial chemotaxis and localized the point of convergence of a methylation-independent system of chemotaxis with the methylation-dependent system. The identity of the signal originating from the phosphotransferase system was investigated by substituting the fructose-inducible HPr-like protein FPr for HPr in transport and chemotaxis. In addition, a novel chemoattractant, glycerol, was identified for Salmonella typhimurium. Histidine-auxotrophic S. typhimurium strains ST23 (hisF) and ST171 (hisF cheB) were depleted for ATP. The times required for the bacteria to adapt to a step increase in serine, …

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 …

Technology Transfer: A View From The Trenches, Harvey Drucker

RISK: Health, Safety & Environment (1990-2002)

Dr. Drucker, who has lab-wide responsibility for technology transfer at Argonne National Laboratory, argues that transferring rights in discoveries made through tax supported research to private entities can contribute to public welfare in many ways.

Origins Of The Human Genome Project, Robert Mullan Cook-Deegan

RISK: Health, Safety & Environment (1990-2002)

Dr. Cook-Deegan recounts some of the scientific and political history leading to controversy about the proper mix of private and public roles in pursuing genome research and bringing its fruits to bear, e.g., in preventing and curing disease.

Update - March 1994, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- The Human Genome Project: A Molecular Approach to Defining Humanity
-- Some Legal Ramifications for Newborns
-- Ethical and Legal Ramifications of Predictive Genetic Information
-- Graduate program combines biomedical and clinical ethics

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 …

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 …

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 …

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.

Cloning Of The Cellular Receptor For Amphotropic Murine Retroviruses Reveals Homology To That For Gibbon Ape Leukemia Virus, Daniel G. Miller, Robert H. Edwards, A. Dusty Miller

Biomedical and Pharmaceutical Sciences Faculty Publications

The host and tissue specificity of retrovirus infection is largely determined by specific cellular receptors that mediate virus entry. Genes encoding these receptors are widely distributed in the genome, and the receptors identified to date show no sequence similarity. We have identified the cellular receptor for amphotropic murine retroviruses, Ram-1, by screening a rat cDNA expression library introduced into amphotropic virus-resistant hamster cells. The 656-amino acid receptor is homologous to the gibbon ape leukemia virus receptor at both hydrophobic termini but is highly divergent in the central hydrophilic region. Both receptors appear to be integral membrane proteins having multiple membrane-spanning …

Control Of Cationic Amino Acid Transport And Retroviral Receptor Functions In A Membrane Protein Family, Michael Kavanaugh, Hao Wang, Zheng Zhang, Weibin Zhang, Yan-Na Wu, Esther Dechant, R. Alan North, David Kabat

Biomedical and Pharmaceutical Sciences Faculty Publications

A partial cDNA sequence indicated that the T lymphocyte early-activation gene (Tea) encodes a protein related to the dual-function ecotropic retrovirus receptor/cationic amino acid transporter (ecoR/CAT1), and RNA blots suggested highest Tea expression in T lymphocytes and liver (MacLeod, C.L., Finley, K., Kakuda, D. Kozad, C.A., and Wilkinson, M.F. (1990) Mol. Cell. Biol. 7, 3663-3674). The sequence of full-length Tea cDNA from liver (3683 bases) predicts a 657-amino-acid protein (CAT2 alpha) with 12-14 transmembrane domains. A long (515 base) region with six initiation codons and termination codons precedes the translation start codon. The liver Tea cDNA is identical to Tea …

Functional Expression Of Two Glucose Transporter Isoforms From The Parasitic Protozoan Leishmania Enriettii, Chris K. Langford, Brian M. Little, Michael Kavanaugh, Scott M. Landfear

Biomedical and Pharmaceutical Sciences Faculty Publications

The parasitic protozoan Leishmania enriettii contains a family of tandemly repeated genes, designated Pro-1, that encode proteins with significant sequence similarity to mammalian facilitative glucose transporters. Pro-1 mRNAs are expressed almost exclusively in the promastigote or insect stage of the parasite life cycle. The Pro-1 tandem repeat encodes two isoforms of the putative transporter, iso-1 and iso-2, which have identical predicted amino acid sequences except for their NH2-terminal hydrophilic domains. We have now expressed both iso-1 and iso-2 by microinjecting their RNAs into Xenopus oocytes and assaying these oocytes for transport of various radiolabeled ligands. Both iso-1 and iso-2 transport …

Cell-Surface Receptors For Gibbon Ape Leukemia Virus And Amphotropic Murine Retrovirus Are Inducible Sodium-Dependent Phosphate Symporters, Michael Kavanaugh, Daniel G. Miller, Weibin Zhang, Wendy Law, Susan L. Kozak, David Kabat, A. Dusty Miller

Biomedical and Pharmaceutical Sciences Faculty Publications

Cell surface receptors for gibbon ape leukemia virus (Glvr-1) and murine amphotropic retrovirus (Ram-1) are distinct but related proteins having multiple membrane-spanning regions. Distant homology with a putative phosphate permease of Neurospora crassa suggested that these receptors might serve transport functions. By expression in Xenopus laevis oocytes and in mammalian cells, we have identified Glvr-1 and Ram-1 as sodium-dependent phosphate symporters. Two-electrode voltage-clamp analysis indicates net cation influx, suggesting that phosphate is transported with excess sodium ions. Phosphate uptake was reduced by > 50% in mouse fibroblasts expressing amphotropic envelope glycoprotein, which binds to Ram-1, indicating that Ram-1 is a major …

Optimizing Conditions For Cloning Cdna From Chicken Brain, Stephen Clark

Masters Theses & Specialist Projects

Acoustic over stimulation can lead to hair cell loss in the auditory epithelium. Hair cell loss or damage in mammals often results in decreased auditory sensitivity which is irreversible. However for birds, hair cells which are damaged by acoustic trauma or ototoxic drugs may be replaced by regeneration. As the first step in determining the molecular mechanisms of hair cell regeneration, gene expression techniques including cDNA synthesis and cloning were attempted first with the chicken brain. The initial attempts at making cDNA libraries were elusive; therefore, experiments were performed to identify problems and enhance the efficiency of specific steps. These …

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 …

Accessing Genomic Information For Nonmedical Purposes, George P. Smith Ii

Scholarly Articles

No abstract provided.