| A Search for New Therapeutic Targets: Using Yeast to Find the GEF for Rheb |
Jul-2008 |
6 pages |
| Authors:
Janet Leatherwood; STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION
|
 | The Tsc1/2 complex known as Hamartin/Tuberin is mutated in the human disease Tuberous Sclerosis and such mutation predisposes for cancer. Tsc1/2 complex has a clearly established chemical release a GTPase Activating Protein or GAP for the small GTPase Rheb. Rheb in turn regulates TOP. The Tor kinases and associated proteins are large complex units that integrate signals pertaining to nutrients and proliferation potential. Tor promotes growth and proliferation and thus ... |
|
| Activated Ras as a Direct Therapeutic Target for Neurofibromatosis Type 1: An Innovative Approach for Identifying Classes of Inhibitors |
DEC 2006 |
8 pages |
| Authors:
John Sondek; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Neurofibromatosis Type 1 (NF1) arises from the aberrant activation of Ras, a GTPases important controlling mitogenic potential. In an effort to control the aberrant activation of Ras to treat NF1 as well as other cancer, a high throughput screen was developed to screen for small molecule inhibitors of Ras activation by Sos1, a ubiquitous guanine nucleotide exchange factor that catalyzes the activation of Ras. Using this screen, several initial leads ... |
|
| Low Melatonin Production During Adulthood - Phase 2: Association with Levels of Hydroxyl Radical Scavenging and DNA Damage |
AUG 2005 |
8 pages |
| Authors:
Eugene Sobel; Zoreh Davanipour; FRIENDS RESEARCH INST INC BALTIMORE MD
|
| The primary purpose of the study was to develop cross-sectional evidence concerning whether or not lower melatonin production levels are associated with increased oxidative DNA guanine damage. Because the results of this study are supportive, confirmatory studies are warranted, followed by prospective chemoprevention studies of melatonin supplementation. Adjuvant cancer treatment studies have not identified any serious melatonin toxicities. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI MS/MS) was used to ... |
|
| Rational Design of Rho Protein Inhibitors |
SEP 2004 |
10 pages |
| Authors:
Rafael J. Rojas; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Rho GTPases are molecular switches that fluctuate between on and off states. When active, these proteins function to remodel the actin cytoskeleton by interacting with a number of downstream effector molecules. Recent studies have linked the activation of Rho GTPases with the acquisition of a metastatic phenotype in many types of cancers, including inflammatory breast cancer (IBC). This proposal incorporates a rational approach to target these signaling proteins using small ... |
|
| Low Melatonin Production During Adulthood - Phase 2: Association with Levels of Hydroxyl Radical Scavenging and DNA Damage |
AUG 2004 |
5 pages |
| Authors:
Eugene L. Sobel; Zoreh Davanipour; Henrik Poulsen; FRIENDS RESEARCH INSTITUTION INC LOS ANGELES CA
|
| The primary purpose of the proposed study is to develop cross-sectional evidence concerning whether or not lower melatonin production levels are associated with increased oxidative DNA guanine damage. If the results of this study are supportive, then confirmatory studies would be warranted, followed by prospective chemoprevention studies of melatonin supplementation. Adjuvant cancer treatment studies have not identified any serious melatonin toxicities. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI MS/MS) ... |
|
| Effect of a Single Nucleotide Polymorphism (NP) on Breast Cancer Invasion |
JUL 2003 |
19 pages |
| Authors:
Colby A. Wyatt; Constance E. Brinckerhoff; DARTMOUTH COLL HANOVER NH
|
| This study took several approaches to determine the influence of a single nucleotide polymorphism (SNP) in the matrix metalloproteinase 1 promoter on gene transcription in normal and breast cancer cell lines or tissue. The SNP consists of an extra guanine nucleotide that creates an ETS family transcription factor binding site (2G), and we previously demonstrated that the 2G SNP leads to an increase in transcriptional activity of the MMP-l promoters ... |
|
| Oligonucleofide Imprinting in Aqueous Environment |
21 MAY 2003 |
|
| Authors:
Dolly Batra; Kenneth J. Shea; CALIFORNIA UNIV IRVINE DEPT OF CHEMISTRY
|
 | The development of synthetic receptors that recognize nucleotide bases and their derivatives is an important area of research 1-3. Applications are envisioned in separation science, biosensors, drug therapy and genetic engineering. Previously in this laboratory, we have developed a molecularly imprinted synthetic receptor for 9-ethyladenine (9-EA). The network polymer has an affinity for adenine and its derivatives with an average association constant (K(a)) of 75,000 M(-1) in CHCl3. |
|
| Genetic Analysis of a Single Nucleotide Polymorphism in the Matrix Metalloproteinase 1 Promoter in Breast Cancer |
JUL 2002 |
18 pages |
| Authors:
Constance E. Brinckerhoff; DARTMOUTH COLL HANOVER NH
|
| Tumor invasion requires destruction of collagen, and is accomplished by matrix metalloproteinase-l (MMP-1). A single nucleotide polymorphism (SNP) in the MMP-1 promoter enhances transcription of this gene. The SNP is at - 1607 bp in the MMP-1 promoter, where an additional guanine (G) creates a binding site (5-AGGA-3 ) for the Ets transcription factors. Allele frequency is: 25% =1 G homozygous, 25% =2 G homozygous, and 50% = 1G/2G heterozygous. ... |
|
| EGF-Receptor Signaling in Endocytosis Deficient Cells |
JUL 2002 |
68 pages |
| Authors:
Brian Ceresa; Sandra L. Schmid; OKLAHOMA UNIV OKLAHOMA CITY
|
| Award DAMD-99-l-9367 seeks to understand the role of membrane trafficking in Epidermal Growth Factor Receptor (EGER) signal transduction. We have been using a tissue culture model system (HeLa cells) to isolate the activated EGER at distinct stages in the endocytic pathway. Our research has focused on rab5, a small molecular weight GTPase, implicated in the biogenesis of the early endosome. Mutations to modulate the guanine nucleotide binding properties of this ... |
|
| Applications of a Novel Nucleic Acid Detection Method in Breast Cancer: Analysis of Overexpression of HER-2/neu and FAK |
JUL 2002 |
44 pages |
| Authors:
Herbert H. Thorp; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The project "Applications of a Novel Nucleic Acid Detection Method in Breast Cancer: Analysis of Overexpression of Her-2/neu and FAK" is aimed at utilizing new biosensors based on guanine electron transfer to quantitate messenger RNA for breast cancer genes. In the first two years of the project, methods were developed for attaching nucleic acids to indium tin oxide electrodes and detecting these molecules electrochemically through the catalytic reaction. These methods ... |
|
| Biomarkers of Oxidative Injury and Their Modulation in Prostatic Tissue from Patients With Prostate Cancer |
MAR 2002 |
11 pages |
| Authors:
Theodore L. DeWeese; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer (PCa) continues to be the most frequently diagnosed cancer in men in the United States. The development of potent prevention strategies to diminish or eliminate this threat is in order and remains the long-term goal of this project. One possible etiologic factor in the development of PCa, is exposure to chronic oxidative stress, leading to the accumulation of potentially promutagenic oxidized DNA bases such as 8- hydroxydeoxyguanosine (8- ... |
|
| Using Genetic Means to Identify Factors That Affect Estrogen Receptor Function |
JAN 2002 |
52 pages |
| Authors:
Laura Su; Michael J. Garabedian; NEW YORK UNIV MEDICAL CENTER NY
|
| To identify novel components that affect the ER transcriptional response, we performed a genetic screen in yeast and identified RDIl, a Rho guanine nucleotide dissociation inhibitor, as a positive regulator of ER transactivation. In contrast, expression of constitutively active forms of RhoA, Racl, and Cdc42 decreases ER transcriptional activity, suggesting that Rho GDI increases ER transactivation by antagonizing ER inhibition by Rho GTpases. Our recent results indicate that the Rho ... |
|
| Indicator Based and Indicator - Free Electrochemical DNA Biosensors |
25 OCT 2001 |
|
| Authors:
Kagan Kerman; Burcu Meric; Dilsat Ozkan; Pinar Kara; Mehmet Ozsoz; EGE UNIV IZMIR (TURKEY) FACULTY OF PHARMACY
|
| The utility and advantages of an indicator free and MB based sequence specific DNA hybridization biosensor based on guanine and adenine oxidation signals and MB reduction signals have been demonstrated. Indicator free detection system is simple, cost-effective and provides rapid detection. The application of DPV at CPE fulfilled the expectations for the direct detection of hybridization between the known oligonucleotides. This procedure can be employed to detect specific gene sequences ... |
|
| A New Invasion and Metastasis Molecule, Tiam1 and its Interaction with the Cytoskeleton are Involved in Human Breast Cancer Progression |
AUG 2001 |
43 pages |
| Authors:
Lilly Y. W. Bourguignon; MIAMI UNIV FL
|
| In breast tumor cells (e.g., SP1 cells), the guanine nucleotide exchange factor (GEF, the dbl or DR family), Tiam1 (T lymphoma invasion and metastasis) is detected as a 200 kDa protein. Tiam1 is capable of catalyzing GDP/GTP exchange for Rac1. In particular, the aa393-aa738 sequence of Tiam1, which contains the NH2-terminal pleckstrin homology (PHn), a putative coiled coil region (CC) and an additional adjacent region (Ex) (designated as PHn-CC-Ex domain ... |
|
| EGF-Receptor Signaling in Endocytosis Deficient Cells |
JUL 2001 |
24 pages |
| Authors:
Brian Ceresa; Sandra L. Schmid; OKLAHOMA UNIV HEALTH SCIENCES CENTER OKLAHOMA CITY
|
| Award DAMDl7-99-l-9367 seeks to understand the role of membrane trafficking in Epidermal Growth Factor Receptor (EGFR) signal transduction. We have been using a tissue culture model system (HeLa cells) to isolate the activated EGFR at distinct stages in the endocytic pathway. Our research has focused on rab5, a small molecular weight GTPase, implicated in the biogenesis of the early endosome. Mutations to modulate the guanine nucleotide binding properties of this ... |
|
| Effect of a Single Nucleotide Polymorphism (NP) on Breast Cancer Invasion |
JUL 2001 |
13 pages |
| Authors:
Colby A. Wyatt; Constance E. Brinckerhoff; DARTMOUTH COLL HANOVER NH
|
| The lethality of breast cancer is derived from its ability to metastasize, and matrix metalloproteinases (MMPs) facilitate cellular invasion by degrading the extracellular matrix. One component of MMP regulation is transcription. We have identified a single nucleotide polymorphism (SNP) that enhances the transcriptional activity of MMP-l promoters in transient transfections. The SNP consists of an extra guanine nucleotide that creates an ETS family transcription factor binding site (2G). We utilized ... |
|
| The Role of the Novel Nuclear Tyrosine Kinase, RAK, in Breast Cancer Biology |
JUL 2000 |
26 pages |
| Authors:
Paul Armistead; Holden Thorp; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The research supported by this grant is intended to investigate the feasibility of an electrocatalytic guanine oxidation reaction as an mRNA quantification method. This system is to be tested first by quantifying the mRNA of Rak nuclear tyrosine kinase in both cell culture and breast tissue samples. To accomplish this goal a competitive RT-PCR assay was designed to measure the absolute quantity of Rak mRNA in each sample. This absolute ... |
|
| Relationship Between Pak-Mediated Cell Death and Stress-Activated Kinase Signaling in Breast Cancer |
FEB 2000 |
|
| Authors:
Frank T. Zenke; SCRIPPS RESEARCH INST LA JOLLA CA
|
| P2L -ACTIVATED KINASES OR Pak's have been implicated in apoptosis as an upstream regulator with enhancing or suppressing influence and recognized as part of the cell death execution machinery. Here we show that a correlation exists in breast cancer cells between caspase- dependent cleavage of the Pak2 and activation of c-jun kinase. The mode of Pak kinase regulation has recently been identified. Small GTPases like Rac and Cdc42 or sphingoid-like ... |
|
| Sequence-Specific and Synergistic Binding of Drugs to DNA |
OCT 1999 |
126 pages |
| Authors:
Fu-Ming Chen; TENNESSEE STATE UNIV NASHVILLE
|
| Our goals were to study the sequence specific and synergistic binding of three drugs having distinctly different binding modes: actinomycin D (ACTD), an intercalator with GpC sequence preference; chromomycin A3 (CHR), a guanine specific minor groove binder; and distamycin A (DST), an A.T specific minor groove binder. These results formed the bases for designing suitable sequences for the synergistic binding study commenced during the later part of the grant period. ... |
|
| Structure Elucidation of the Rho-GTPase Activating DH-Homology Domain |
JUN 1999 |
19 pages |
| Authors:
Behzad Aghazadeh; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess an approximately 200 residue catalytic Dbl-homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human BetaPIX. The domain is ... |
|
| A New Invasion and Metastasis Molecule, Tiaml and Its Interaction with the Cytoskeleton are Involved in Human Breast Cancer Progression |
AUG 1998 |
31 pages |
| Authors:
Lilly Y. Bourguignon; MIAMI UNIV FL
|
| In this study we have examined the interaction between the guanine nucleotide exchange factor, Tiam1, and the cytoskeletal protein, ankyrin, in metastatic breast cancer cells (Met-1 cell line). Immunoblot assay using anti- Tiam1-specific antibody shows that Tiam1 is a 200 kDa polypeptide in Met-1 cells. Structural analysis indicates that the amino acid sequence, "(717) GEGTDAVKRS(727)L", in Tiam1 shares a great deal of structural homology with the ankyrin-binding domain located in ... |
|
| The Role of the Novel Nuclear Tyrosine Kinase, RAK, in Breast Cancer Biology |
JUL 1998 |
18 pages |
| Authors:
Paul M. Armistead; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The role of the RAK tyrosine kinase in breast cancer is unknown at this time. Over the past year efforts in our lab have been made to determine the level of expression of RAK mRNA in cultured cell lines. Two techniques were used to address this question. The first technique involved the use of S1 nuclease protection assays. It was concluded that the probes used in the assay ... |
|
| Ethanol Disruption of Synaptic Neurotransmission |
APR 1998 |
373 pages |
| Authors:
Robert S. Aronstam; DONALD GUTHRIE FOUNDATION FOR MEDICAL RESEARCH SAYRE PA
|
| The goal of this research program was to understand how acute and chronic ethanol administration disrupts synaptic transmission in the central nervous system. The overall hypothesis was that ethanol depresses neurotransmission at neurotransmitter receptors by disrupting receptor-G protein interactions. To this end, the influence of ethanol was measured on receptor- ligand binding (including the guanine nucleotide sensitivity of agonist binding) , receptor control of the G protein cycle, and receptor ... |
|
| Sequence Specific and Synergistic Binding of Drugs to DNA |
OCT 1997 |
15 pages |
| Authors:
Fu-Ming Chen; TENNESSEE STATE UNIV NASHVILLE
|
| Combination chemotherapy is one of the important strategies in cancer treatments. This is based on the observation that administering certain drugs together is more effective than giving individual drugs separately. Although the reason for such an effect is not understood, it may be related to the synergistic effect of their binding to biomacromolecules. Consequently, studies on the interplay among drugs capable of binding to different regions of DNA will be ... |
|
| AFRRI Reports, First - Second Quarters 1997 |
AUG 97 |
91 pages |
| Authors:
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
|
| This volume contains AFRRI Scientific Reports SR97-1 through SR97-10 for January-June 1997. |
|
| Seventh Symposium on Subtypes of Musccarinic Receptors |
97 |
276 pages |
| Authors:
Ruth R. Levine; BOSTON UNIV MA
|
| Partial Contents: Role of m1 Receptor-G Protein Coupling in Cell Proliferation in the Prostate; In Vivo Pharmacology of Butylthio2.2.2 (LY297802/ NNC11-11053), an Orally Acting Antinociceptive Muscarinic Agonist; In Vivo Consequences of M1-receptor Activation by Talsaclidine; Muscarinic m1 Receptor Agonists Increase the Secretion of the Amyloid Precursor Protein Ectodomain, and Muscarinic Agonists in Alzheimer's Disease. |
|
| Preliminary Experiments on a Possible Determination of the N7-Adduct of Guanine with Mustard Gas by Postla-Beling (Orieonterende experimenten naar de mogelijke bepaling van het N7-adduct van guanine met mosterdgas door postlabeling) |
DEC 96 |
|
| Authors:
H. Q. DE Vette; D. Noort; L. P. de Jong; PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)
|
| N7-(2-hydroxyethylthioethyl)-guanine (N7-HETE-Gua) was acetylated with acetic anhydride. The product obtained was identified as N7-(2- acetoxyethylthioethyl)-guanine (NMR). N7-HETE-Gua can be analyzed by using HPLC with radiometric detection after acetylation of the adduct with (3)H-acetic anhydride. The results obtained suggest that the sensitivity of this method will not be higher than that of a method already in use that is based on HPLC analysis with electrochemical detection, even at optimal conditions. ... |
|
| Sequence Specific and Synergistic Binding of Drugs to DNA |
OCT 96 |
14 pages |
| Authors:
Fu-Ming Chen; TENNESSEE STATE UNIV NASHVILLE
|
| Proposal was made to study the sequence specific binding and synergistic effect of three drugs having distinctly different binding modes: actinomycin D (ACTD), a guanine specific intercalator; chromomycin A3 (CHR), a guanine specific minor groove binder; and distamycin A, an A.T specific groove binder. To investigate the possible synergistic effects of drugs on DNA binding, it is essential that binding characteristics of each individual drug such as binding affinities, sequence ... |
|
| Bioaccumulation and Trophic Transfer of Long-Lived Radionuclides in Arctic Plankton |
AUG 96 |
22 pages |
| Authors:
Nicholas S. Fisher; STATE UNIV OF NEW YORK AT STONY BROOK MARINE SCIENCES RESEARCH CENTER
|
| The objectives of our research is to examine the bioaccumulation and trophic transfer of important radionuclides in important planktonic components of Arctic waters. This project has been assessing the extent to which select species of boreal copepod species bioconcentrate released radionuclides from water and from phytoplankton food. The rates and routes of uptake and depuration of isotopes in these animals, and the extent to which they can transfer their accumulated ... |
|
| Toxicokinetics of Sulfur Mustard and its DNA-Adducts in the Hairless Guinea Pig - DNA-Adducts as a Measure for Epithelial Damage |
MAR 96 |
|
| Authors:
Johannes P. Langenberg; Hendrik P. Benschop; Govert P. van der Schans; PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)
|
| In order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard (SM) the toxicokinetics of this agent as well as its major DNA-adduct, 7-SM-guanine, are studied in male hairless guinea pigs for the intravenous (i.v.), respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in blood and tissues was developed, involving gas chromatography with mass-spectrometric detection. Deuterated sulfur mustard (D8-SM) ... |
|
| AFRRI Report Third - Fourth Quarters 1996 |
96 |
57 pages |
| Authors:
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
|
| Table contents: Effect of chloral hydrate on in vivo KCl-induced striatal dopamine release in the rat. Effect of ionizing radiation on in vivo striatal release of dopamine in the rat. Transient and persistent experimental infection of nonhuman primates with Helicobacter pylori: Implications for human disease. Indomethacin attenuation of radiation-induced hyperthermia does not modify radiation-induced motor hypoactivity. Behavioral toxicity and radioprotective efficacy of WR-15l327 in combination with adenosine receptor antagonists. Chromatographic ... |
|
| Ethanol Disruption of Synaptic Neurotransmission |
OCT 95 |
112 pages |
| Authors:
Robert S. Aronstam; DONALD GUTHRIE FOUNDATION FOR MEDICAL RESEARCH SAYRE PA
|
| The goal of this research is to understand how acute and chronic ethanol administration disrupts synaptic transmission in the central nervous system. The underlying hypothesis is that ethanol depresses neurotransmission at neurotransmitter receptors by altering receptor- G protein interactions. The results provide partial support for our hypothesis. However, ethanol's actions were not universal, and receptor subtypes were not equally affected. The significance of ethanol's actions is indicated by the disruption ... |
|
| Sequence-Specific and Synergistic Binding of Drugs to DNA |
OCT 95 |
48 pages |
| Authors:
Fu-Ming Chen; TENNESSEE STATE UNIV NASHVILLE
|
| We had proposed to study the sequence specific binding and synergistic effect of three drugs having distinctly different binding modes: actinomycin D (ACTD), a guanine specific intercalator; chromomycin A3, a guanine specific minor groove binder; and distamycin A, an A.T specific groove binder. To investigate the possible synergistic effects of drugs on DNA binding, it is essential that binding characteristics of each individual drug such as binding affinities, sequence specificities, ... |
|
| Genotoxic Assessment of DNA and Cellular Fractions from Cancerous Tissues: A Prognostic Assay for Cancer Risk |
29 DEC 94 |
42 pages |
| Authors:
Donald C. Malins; PACIFIC NORTHWEST RESEARCH FOUNDATION SEATTLE WA
|
| Factors that elicit mutagenic damage to the DNA have been intensely studied for over 50 years. These reactions include the introduction of bulky substituents on the DNA bases which are products of two-electron oxidations (1) . Recent studies on these DNA changes suggest that they are more prone to blocking DNA replication and transcription than creating mutagenic lesions (2). A second means of creating potentially mutagenic changes to the DNA ... |
|
| Verification, Dosimetry, and Biomonitoring of Mustard Gas Exposure via Immunochemical Detection of Mustard Gas Adducts to DNA and Proteins |
JUL 93 |
|
| Authors:
H. P. Benschop; G. P. Van der Schans; PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)
|
| Convenient methods for diagnosis and dosimetry of exposure to chemical agents are not available, but are urgently needed. Immunochemical methods have now been developed for diagnosis and dosimetry of exposure to mustard gas. Exposure of calf-thymus DNA and human blood to mustard gas results in the formation of one major and two minor DNA adducts which were fully characterized. Monoclonal antibodies were raised against the major DNA adduct, i.e., the ... |
|
| NMR Structural Studies on a Nonnatural Deoxyribonucleoside Mediated Recognition of GC Base Pairs in Pyrimidine-Purine-Pyrimidine Triplexes |
01 JUN 93 |
21 pages |
| Authors:
Ishwar Radhakrishnan; Dinshaw J. Patel; E. S. Priestley; Huw M. Nash; Peter B. Dervan; CALIFORNIA INST OF TECH PASADENA DIV OF CHEMISTRY AND CHEMICAL ENGINEERING
|
| As a part of our ongoing efforts to define the structural aspects of unusual pairing alignments in DNA triplexes by Nuclear Magnetic Resonance spectroscopy, we have examined the structural role of a nonnatural deoxyribonucleoside, P1, that has been shown to mediate the recognition of GC base pairs in pyrimidine-purine-pyrimidine DNA triplexes. A qualitative interpretation of the NMR data indicates that this analog of protonated cytosines is readily accommodated in the ... |
|
| Dosimetry of Exposure to Sulfur Mustard of Human Skin: Immunofluorescence Microscopy of DNA-Adducts. |
13 MAY 1993 |
|
| Authors:
G. P. Van Der Schans; R. H. Mars-Groenendijk; H. P. Benschop; R. A. Baan; PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)
|
| The recent use and the present-day threat of use of sulfur mustard (HD) in the Middle East stress the need of unequivocal and sensitive methods to establish whether casualties have been exposed to HD. Moreover, a satisfactory treatment is not available for injuries caused by exposure to HD. In recent years, monoclonal antibodies have been raised against a major HD-DNA adduct, i.e. N7-(2'-hydroxyethylthioethyl)-guanine. These antibodies have been used to develop ... |
|
| Detection of Sulfur Mustard-Induced DNA Damage by a 32P-Postlabeling Method |
13 MAY 1993 |
10 pages |
| Authors:
D. B. Ludlum; P. Austin-Richie; D. Yu; MASSACHUSETTS UNIV MEDICAL CENTER WORCESTER
|
| We have applied the 32p-postlabeling technique to the detection of sulfur mustard-induced damage in white blood cell DNA. Red blood cells are lysed, and DNA is released from white cells by proteinase K treatment; proteins are removed by salt precipitation and DNA is collected by ethanol precipitation. Digestion to the 3'-deoxynucleotide level is performed with micrococcal nuclease and spleen phosphodiesterase, and the mixture of normal and modified nucleotides is labeled ... |
|
| Presynaptic Modulation of the Hippocampal Mossy Fiber Synapse |
14 SEP 92 |
21 pages |
| Authors:
David M. Terrian; EAST CAROLINA UNIV SCHOOL OF MEDICINE GREENVILLE NC
|
| During the first year of this research project, it was demonstrated that distinct of voltage-gated calcium channels are required for the exocytosis of glutamate and types dynorphin peptides. We were also to confirm that the release of glutamate from hippocampal mossy fiber terminals is regulated by a presynaptic receptor that is sensitive to L(+)aminophosphonobutyric acid. In the second year of this research project we tested several specific hypotheses concerning presynaptic ... |
|
| Biological (Molecular and Cellular) Markers of Toxicity |
15 DEC 91 |
|
| Authors:
L. R. Shugart; S. J. D'Surney; G. Gerrys-Hull; M. S. Greeley; OAK RIDGE NATIONAL LAB TN ENVIRONMENTAL SCIENCES DIV
|
| Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). A discontinuous DEN treatment inhibited the activity of a detoxication enzyme activity (ethoxyresorufin-O-deethylase) 65 percent and the activity of glutathione-S-transferase transferase 35 percent No 01-ethyl guanine adducts were detected, and a slight, but statistically significant, in DNA strand breaks ... |
|
| Evaluation of N-Methyl-n'-Nitroguanidine in Short-Term Genetic Toxicity Tests |
DEC 91 |
|
| Authors:
C. S. Godin; A. Thilagar; MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH
|
| N-Methyl-N'-nitroguanidine (MNG) is being considered as a component of Air Force explosive formulations. This chemical was evaluated in several bioassays to assess its potential genotoxic activity. The assays conducted were the Ames Salmonella/microsomal assay, the Chinese hamster ovary/hypoxanthine- guanine phosphoribosyltransferase forward mutation assay, and the mouse in vivo bone marrow micronucleus assay. Both in vitro assays were conducted in the presence and absence of S9 metabolic activation enzymes. The results ... |
|
| Verification , Dosimetry and Biomonitoring of Mustard Gas Exposure via Immunochemical Detection of Mustard Gas Adducts to DNA and Proteins |
DEC 91 |
|
| Authors:
Hendrik P. Benschop; PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)
|
| The use of mustard gas in the Iran-Iraq War has stressed the need of reliable methods for retrospective detection of poisoning with chemical warfare agents. We are developing methods to detect adducts of mustard gas to DNA and proteins, which may have a life span of many days after exposure. In order to achieve high sensitivity and specificity, immunochemical detection techniques are developed. As markers to detect adducts, we synthesized ... |
|
| Reaction of trans-2-Chlorovinylarsine Oxide with Polydeoxynucleotides |
89 |
|
| Authors:
Kilian Dill; Earle R. Adams; S. D. Davis; Richard J. O'Connor; Evelyn L. McGown; LETTERMAN ARMY INST OF RESEARCH PRESIDIO OF SAN FRANCISCO CA
|
| Trans-2-chlorovinylarsine oxide (in DCl/acetone-d6) was added to various polydeoxynucleotides. The arsenical did react with poly(dG).poly(dC), releasing guanine, and resulting in a partial apurinic duplex. Keywords: Chemical warfare agents, Reprints, Organic arsenicals, Cytotoxic action, Cellular sulfhydryl containing proteins, Enzymes, Thiols, Glutathione, Erythrocytes, Toxicity. (jg) ANNOTATION: Reprint: Reaction of trans-2-Chlorovinylarsine Oxide with Polydeoxynucleotides. |
|
| Isolation of Genomic Clone for Human Cholinesterase |
DEC 88 |
|
| Authors:
Oksana Lockridge; MICHIGAN UNIV ANN ARBOR DEPT OF PHARMACOLOGY
|
| Human serum cholinesterase is a scavenger of nerve gas, reacting rapidly to detoxify it. We have isolated the gene for human cholinesterase as well as full-length cDNA clones. The purpose for isolating these clones will be to use them in an expression system that can make active cholinesterase enzyme. The ultimate goal will be to make a small, stable peptide that has the detoxifying properties of the cholinesterase enzyme and ... |
|
| Effects of Anticholinesterase Exposure on Transport and Distribution of High versus Low Affinity Muscarinic Cholinergic Receptors |
14 NOV 87 |
|
| Authors:
James K. Wamsley; UTAH UNIV SALT LAKE CITY SCHOOL OF MEDICINE
|
| We have defined the exact conditions which allow clean separation of the binding of radioactive antagonists to a muscarinic type-1 (M1) and a muscarinic type-2 (M2) receptor population within the central nervous system. Both of these receptor populations appear to have a high and low affinity agonist states associated with them. These affinity states can be influenced by the ionic constituents of the incubation medium and the high affinity sites ... |
|
| Tolerance Following Organophophate Poisoning of Tracheal Muscle |
21 JUL 87 |
|
| Authors:
Jerry M. Farley; Terry M. Dwyer; MISSISSIPPI UNIV MEDICAL CENTER JACKSON DEPT OF PHARMACOLOGY AND TOXICOLOGY
|
| The effects of subacute exposure to the organophosphate acetylcholinesterase inhibitors (diisoprophylfluorophosphate, soman, sarin, and VX) on the binding properties of muscarinic receptors, the contractile responses, and the electrophysiological properties of swine tracheal smooth muscle were studied. Subacute organophosphate treatment decreased the number of muscarinic receptors in smooth muscle homogenates and in the surface membrane of isolated cells by 50-77%. DFP was the most potent, followed by sarin, VX, and soman. ... |
|
| Proceedings of the International Symposium on Quantum Biology and Quantum Pharmacology Held in Marineland, Florida on March 12-14, 1987 |
87 |
|
| Authors:
Per-Olov Loewdin; N. Y. Oehrn; John R. Sabin; Michael C. Zerner; FLORIDA UNIV ST AUGUSTINE WHITNEY LAB FOR EXPERIMENTAL MARINE BIOLOGY AND ME DICINE
|
| Contents: Some Remarks on Certain Magnetic Properties of Water in the Study of Cancer; Intercalative Binding and Antitumor Activity of Bisantrene and Derivatives; Ab Initio Investigation of the Structure of Hydrogen Halide-Amine Complexes in the Gas Phase and In a Polarizable Medium; an MNDO Molecular Orbital Study of the Reactions of Protonated Oxirane with Guanine; Application of the Quantum Mechanics and Free Energy Perturbation Methods to Study Molecular Processes; Equilibrium ... |
|
| Stabilization of Z-RNA under Physiological Conditions and Recognition by Anti-Z DNA Antibodies |
87 |
|
| Authors:
Charles C. Hardin; David A. Zarling; Joseph D. Puglisi; Mark O. Trulson; Peter W. Davis; CALIFORNIA UNIV OAKLAND NAVAL BIOSCIENCES LAB
|
| Radioimmunoassay and nitrocellulose filter-binding competition experiments were performed to determine the extent of recognition of Bromine- poly(r(C-G) by anti-Z-DNA antibodies. The polyclonal rabbit anti-Br-poly(d(C-G) igG preparations T4 and Z6 specifically recognize the Z-form of polyR(C-G, although the binding affinities are 10-to 100fold lower for Z-RNA than for various forms of Z-DNA. Competition RIA experiments verify the presence of a Z- DNA like determinant in left handed Br poly R(C-G) at ... |
|
| Protection against the Acute and Delayed Toxicity of Mustards and Mustard-Like Compounds |
SEP 85 |
|
| Authors:
David B. Ludlum; ALBANY MEDICAL COLL NY
|
| Both the acute and the delayed toxicities of sulfur mustards are evidently caused by damage which these inflict on cellular DNA. Bifunctional sulfur mustards crosslink DNA, but the toxicity of monofunctional agents indicates that other DNA modifications are also important. Genetic studies with sulfur mustards suggest that alkylation of the 6 position of guanine in DNA is responsible for some of this toxicity. Recently, a new enzyme, 0(6) -alkyl- guanine ... |
|
| Protection against the Acute and Delayed Toxicity of Mustards and Mustard-Like Compounds |
SEP 1983 |
|
| Authors:
D. B. Ludlum; ALBANY MEDICAL COLL NY
|
| The toxicity of sulfur mustards is evidently related to the damage they inflict on cellular DNA. Previous studies have shown that much of the acute toxicity of bifunctional mustards can be attributed to DNA cross-linking through two guanine moieties in opposite DNA strands. Analysis of the mutagenic effects of these compounds has indicated that delayed toxicity, on the other hand, may be caused by substitution in the 6 position of ... |
|
Reports by Keyword(s)
GUANINE
