MERCURY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Mercury: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-11072-5 1. Mercury-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on mercury. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON MERCURY .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Mercury ........................................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 73 Academic Periodicals covering Mercury.................................................................................... 116 CHAPTER 2. PATENTS ON MERCURY ............................................................................................ 117 Overview.................................................................................................................................... 117 Patents on Mercury ................................................................................................................... 117 Patent Applications on Mercury ............................................................................................... 120 Keeping Current ........................................................................................................................ 121 CHAPTER 3. BOOKS ON MERCURY ................................................................................................ 123 Overview.................................................................................................................................... 123 Book Summaries: Federal Agencies............................................................................................ 123 Book Summaries: Online Booksellers......................................................................................... 124 Chapters on Mercury ................................................................................................................. 124 CHAPTER 4. RESEARCHING MEDICATIONS .................................................................................. 127 Overview.................................................................................................................................... 127 U.S. Pharmacopeia..................................................................................................................... 127 Commercial Databases ............................................................................................................... 128 Researching Orphan Drugs ....................................................................................................... 128 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135 Other Commercial Databases..................................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 News Services and Press Releases.............................................................................................. 144 Newsletter Articles .................................................................................................................... 146 Finding Associations.................................................................................................................. 146 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 149 Overview.................................................................................................................................... 149 Preparation................................................................................................................................. 149 Finding a Local Medical Library................................................................................................ 149 Medical Libraries in the U.S. and Canada ................................................................................. 149 ONLINE GLOSSARIES................................................................................................................ 155 Online Dictionary Directories ................................................................................................... 156 MERCURY DICTIONARY........................................................................................................... 159 INDEX .............................................................................................................................................. 225
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with mercury is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about mercury, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to mercury, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on mercury. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to mercury, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on mercury. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON MERCURY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on mercury.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and mercury, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “mercury” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Urate and Calcium Stones: Picking Up a Drop of Mercury With One's Fingers? Source: American Journal of Kidney Diseases. 17(4): 426-430. April 1991. Summary: In this article, the evidence cited to support the suspicion that urinary urate is a predisposing factor in calcium oxalate (CaOx) stone formation is critically reviewed. Analysis of the relevant literature shows that speculation is based on the clinical impression that CaOx stone-formers appear to excrete more urate than do normal subjects, and that allopurinol reduces the rate of CaOx stone recurrences. The authors review the evidence for two theories that have dominated thinking in this area. The authors conclude that dissolved urate in urine, at normal physiological pH values, directly provokes CaOx crystal nucleation by the phenomenon of salting-out. 1 figure. 35 references. (AA-M).
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•
Mercury
Alzheimer's Disease, Dental Amalgam and Mercury Source: JADA: Journal of the American Dental Association. 130: 191-199. February 1999. Summary: Mercury (Hg) is a neurotoxin that may play a role in the pathogenesis of Alzheimer's disease (AD). This article describes an investigation that evaluated the relationship among AD, Hg levels in the brain, and exposure to dental amalgam. Dental amalgam is generally made up of approximately 50 percent Hg and releases low levels of Hg vapor making it a potential source of Hg for a large segment of the adult population. The authors studied 68 subjects with AD and 33 controls and ascertained dental amalgam status during life and at autopsy. They also determined Hg levels in multiple brain regions at autopsy and developed three dental amalgam index scores to use with the numbers of and surface area of dental amalgam restorations. The data showed no significant association of AD with the number, surface area, or history of dental amalgam restorations. The authors found no statistically significant differences in brain Hg level between subjects with AD and controls and conclude that Hg in dental amalgam restorations does not appear to be a neurotoxic factor in the pathogenesis of AD. This study demonstrated that brain Hg levels are not associated with current or previous dental amalgam history. 1 figure, 5 tables, 58 references (AA-M).
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Determination of Blood Mercury Concentrations in Alzheimer's Patients Source: Journal of Toxicology: Clinical Toxicology. 33(3): 243-247. 1995. Summary: This cross sectional study measured blood mercury in patients with diagnosed Alzheimer's disease (AD) as compared to people without known central nervous system and renal disorders. Researchers put all participants on a diet without any fish or seafood for a period of 3 months. At the end of this period, nursing staff collected 20 mL of blood from each participant for analysis. Blood mercury levels were determined by radiochemical neutron activation analysis, and selenium levels were determined through instrumental neutron activation analysis. Results suggest that blood mercury concentrations detected in subjects with AD were not statistically different than those of control subjects. Ratios of blood mercury to blood selenium also were determined, and no statistical difference was found between these two groups. 1 table, 23 references. (AA-M).
Federally Funded Research on Mercury The U.S. Government supports a variety of research studies relating to mercury. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to mercury.
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore mercury. The following is typical of the type of information found when searching the CRISP database for mercury: •
Project Title: A NEW APPROACH FOR BIOMEDICAL IMAGING Principal Investigator & Institution: Winefordner, James D.; Chemistry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 01-APR-2000; Project End 28-FEB-2005 Summary: (Verbatim from the Applicant's Abstract): The goal of this research program is to develop an ultranarrowband imaging detector which can be used for in vivo biomedical imaging. The device will be capable of providing real time velocity information in images of arterial blood flow and compositional information via selective Raman imaging. Functioning in the near infrared, it will be capable of obtaining images at tissue depths of up to several cm. The extremely high spectral resolution is achieved by using an atomic vapor as the active sensing element. Laser pumped multi-step resonance ionization provides a near unity quantum efficiency and a large solid angle for optical collection, approaching 2m sr, is possible. When coupled with a microchannel plate amplification stage and a CCD detector, such devices offer unparalleled performance for specialized imaging applications. This research project will develop and optimize resonance ionization image devices using mercury and cesium as active elements. Studies will include the ionization spectroscopy of Hg and Cs, optimization of the detector response function (spectral bandwidth, quantum efficiency, spatial resolution), design and development of functional devices for imaging in biomedical systems and finally, applications to imaging of arterial blood flow in patients with peripheral vascular disease and the Raman imaging of arterial plaque. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A NOVEL SENSOR FOR TOTAL MERCURY IN FISH TISSUE Principal Investigator & Institution: Sarangapani, Shantha; Innovative Chemical/Environmental Tech Environmental Technologies, Inc Norwood, Ma 02062 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 14-NOV-2003 Summary: (Applicant's abstract): There is a current need to monitor food and fish tissue samples for total mercury and other toxic metals, onsite, using portable instruments. Currently the determination of mercury requires complex instrumentation, which is beyond the means of potential users. Moreover, the samples have to be shipped to an accredited lab with typical turnaround times of 10 days or more. The fish tissue sample preparation involves a tedious procedure of hot, concentrated, acid digestion. This Phase I research will examine the feasibility of using screen-printed electrodes with dendrimer-gold nano composite for the "in situ" anodic stripping voltammetric analysis (ASV) of total mercury in fish tissue samples. Alternate methods of sample preparations will be tested. The dendrimeric structure due to its hydrophilicity and density of the molecular arms are expected to prevent the influx of large organic and biomolecules. With the advent of nano scale molecular reservoirs such as the dendrimers, and excellent opportunity exists to test the idea of rapid chemical sensing in a biomimetric manner. The screen-printed electrodes will be fabricated at the New Mexico State University Microfabrication Labs using our proprietary formulations. A thorough characterization of the proposed electrode, using certified fish tissue samples for "proof of the concept" will be carried out. The product from this research would be well suited
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Mercury
for portable automated commercial instruments such as the MetalyzerTM, SA-5000 or Tracelab TM systems using the current EPA protocols for mercury analysis by stripping methods. The cost of the proposed electrode strips is comparable to the current cost of electrodes. The ASV has remarkably low detection limits and can analyze a variety of toxic metals due to the unique stripping potentials for each metal. PROPOSED COMMERCIAL APPLICATION: The proposed electrodes strips have a massive potential for use in field tests for agriculture and food industry. Water quality as well as for routine monitoring of industrial waste water treatment facilities to monitor low levels of toxic mercury and other medals. Multianalyte sensing capabilities could be incorporated. The US and European market for the proposed sensors is projected to be close to 400 million dollars by the year 2005. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACETYLCYSTEINE: AN ANTIDOTE FOR METHYLMERCURY POISONING Principal Investigator & Institution: Simmons-Willis, Tracey A.; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2004 Summary: (provided by applicant): Chronic methylmercury (MeHg) exposure and toxicity continues to be of environmental concern. MeHg can cause severe neurological and developmental defects. Removal of MeHg from the body is the only effective remedy. Our recent work has shown that MeHg-L-cysteine is a substrate for the human amino acid transporters, LAT1 and LAT2, facilitating MeHg's rapid distribution in the body (Simmons-Willis et al. Biochem. Journal, in press). Recent work from our laboratory (Ballatori et al. Env. Health Perspectives, 106(5):267-271, 1998) demonstrated that N-acetylcysteine (NAC) added to drinking water of mice greatly increases the excretion of MeHg from the body. The molecular mechanism for this process was recently explored (Koh et al. Mol. Pharmacol., in press). This study indicates that a major renal organic anion transporter, Oat1, plays a significant role in MeHg removal from the kidney. The overall goals of the proposed work are to examine the mechanisms of MeHg elimination and determine the role of NAC as an antidote. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACTIVITIES NEPHROTOXIN
OF
BILIVERDIN
REDUCTASE-EFFECT
OF
Principal Investigator & Institution: Maines, Mahin D.; Professor; Biochemistry and Biophysics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 06-DEC-1985; Project End 31-AUG-2005 Summary: Biliverdin reductase (BVR) is a unique dual pH/cofactor-dependent enzyme that catalyzes the last step in the heme degradation pathway (i,e reduction of biliverdin to bilirubin). Biliverdin, the substrate for BVR, is generated, with carbon monoxide (CO), in the course of heme degradation by the stress/heat shock family of proteins: heme oxygenase (HO)-1 and HO-2. CO functions as NO. BVR is the ultimate regulator of heme metabolism, in that, biliverdin regulates HO activity in vivo. Biliverdin is also a liver tumor promoter and inhibits human Herpes virus-6 replication and HIV-1 proliferation. Bilirubin is a potent antioxidant; low levels of serum bilirubin are associated with increased risk of coronary artery heart disease and retinopathy of prematurity. We are the only laboratory in the country actively pursuing molecular toxicology research on BVR that, by virtue of being an -SH-dependent enzyme, is a
Studies
7
target for environmental agents and nephrotoxins. We have now discovered that BVR is a kinase and a protein kinase C (PKC)-interacting and -activating protein and translocates into the nucleus in response to nephrotoxins: such as mercury, bromobenzene and bacterial endotoxins (LPS) as well as in cancerous transformation. In addition, in human kidney tumors, ischemic rat brain and kidneys, and in kidneys of rats exposed to nephrotoxins, BVR levels are increased. Also, the ability to produce biliverdin in advanced human prostate tumor cells is increased. PKCs play an important role in the field of cancer research and are key components of cellular response to oxidative stress. Based on the ability of BVR to activate PKC, it is likely that BVR plays a significant role in modulating a multitude of cellular functions including cell growth and differentiation. The Specific Aims of the proposed studies are 1) To further characterize BVR for molecular properties and requirements of kinase and reductase activities. 2) To further investigate BVR/PKC interaction. 3) To characterize BVR interactive proteins in the cells and to identify the proteins that interact with BVR under normal and oxidative stress conditions, such as exposure to nephrotoxic agents and cancer. Also, to explore the nuclear function of BVR in the context of HO-1's response to oxidative stress. 4) To isolate the human BVR gene, characterize its promoter region and analyze its regulation by various toxins and effector agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADVANCED TECHNOLOGY
MERCURY
FREE
RESTORATIVE
ALLOYS
Principal Investigator & Institution: Lashmore, David S.; Synergy Innovations, Inc. Lebanon, Nh 03766 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): This application summarizes a new approach to Dental restoration using semi-automatic condensation of a silver containing slurry with new type of impacting Dental instrument. This instrument is unique in that it combines the functions of impact condensation, slurry feeding and waste liquid removal in a single ergonomic handpiece. This instrument employs the available expertise in magnetic design and consists of a solenoid driven impactor whose impact energy and frequency are independently selectable. Some design considerations are presented here. This instrument is unique in that it acts as both repetitive impact condensation device and a waste-solution removal device and will enable, for the first time, a mercury-free silver alloy to be used in commercial Dentistry. The driving forces for this program are the demonstrated superior properties of the pure silver restoration and the need to achieve reproducibly high restoration density independent of the skill of the operator and consistent with patient comfort. An additional obvious benefit of this mercury-free restoration is safety for Dentists and the environment. Using these mercury free alloys, Dentists would no longer need to handle, breath, or dispose of mercury containing waste products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AFRICAN HYPERTENSION
AMERICAN
STUDY
OF
KIDNEY
DISEASE
&
Principal Investigator & Institution: Randall, Otelio S.; Professor of Medicine; Medicine; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 30-JUN-2003
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Mercury
Summary: Hypertension is considered one of the major causes of end stage renal disease (ESRD) in the general population, and the number one cause in African Americans. Despite the availability of potent antihypertensive drugs, the number of hypertensive African Americans progressing to ESRD continues to rise. This disproportionately high prevalence of ESRD in African Americans cannot be explained by the higher prevalence of hypertension. Whether this is due to more susceptibility of the kidney of African Americans to hypertensive injury or due to concurrent existence of unidentified renal factors is not known. There is preliminary evidence suggesting that antihypertensive drugs may retard the progression of hypertensive renal disease, but no clinical trial has been conducted to test this hypothesis in African Americans. This proposed multi-center project is designed to study the following: if the pathological lesion in "hypertensive renal disease" is purely a result of persistent hypertension; if one anti-hypertensive drug is better than another in terms of preservation of renal function; and the level of blood pressure suitable for the survival of the kidney. Hypertensive African Americans, 18-70 years of age with no other known disease that can affect the kidney, will be screened for blood pressure qualification, and will undergo glomerular filtration rate (GFR) tests. Those who qualify, based on blood pressure levels and the GFR results will then be randomized in a double-masked fashion to one of the three major antihypertensive classes (converting enzyme inhibitor, calcium channel blocker, or beta blocker) and to one of two pressure levels: mean blood pressure greater than 92 millimeter of mercury (mmHg), or 102 to 107 mmHg. Other antihypertensive drugs will be added to keep the blood pressure at the desired level. The blood pressure of the randomized subjects will then be monitored on a monthly basis and compliance to medication(s) will be checked at the same time. Their renal function will also be tracked with periodic GFR tests throughout the study period, which will last approximately four years. All data will be collected and sent to the Data Coordinating Center (DCC) for analyses and interpretation. The goal of the African American Study of Kidney Disease and Hypertension (AASK) full- scale trial is to better understand the physiopathology of hypertensive renal disease in an effort to develop guidelines to prevent the increasing prevalence of ESRD in African Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AFRICAN AMERICAN STUDY OF KIDNEY DISEASE AND HYPERTENSIO Principal Investigator & Institution: Toto, Robert D.; Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 30-JUN-2003 Summary: (taken directly from the application) The African-American Study of Kidney Disease and Hypertension (AASK) is a multi-center, randomized double-blind controlled trial designed to determine whether long-term lowering of blood pressure to two different levels of mean arterial pressure (MAP) less than 92 versus 102-107 millimeters of mercury (mmHg) with a calcium channel blocker, an angiotensin converting enzyme inhibitor, or a beta-blocker can prevent deterioration in renal function in African-Americans with hypertensive nephrosclerosis and chronic renal insufficiency. The full-scale trial will involve 900 adult African-Americans of both sexes with hypertensive nephrosclerosis and a baseline glomerular filtration rate of 25-70 milliliters per minute per 1.73 meters squared. The study is designed to answer two key questions in this study population: 1) can long-term blood pressure control (102-107 mmHg) slow progression of renal disease; and 2) is strict blood pressure control (mean arterial pressure less than (92 mmHg) more effective than usual control (102-107 mmHg)
Studies
9
in preserving renal function? During the pilot study for AASK, the applicant reports that they have recruited and randomized 11 patients over a six and one- half month period. Eight of these patients have undergone successful renal biopsy. They report a 100 percent retention of randomized subjects with no serious adverse events thus far, and that the participants have been 100 percent compliant with protocol procedures and greater than 90 percent compliant with medications and have been able to achieve the blood pressure goal level in 9 out of 11 patients thus far. The team of investigators appears to have worked cooperatively with the data coordinating center and has been able to transmit data in a timely and efficient manner. The investigators report preliminary studies which suggest that the AASK protocol is acceptable and well tolerated by participants, and is feasible for application to the full- scale trial. The trial is unique because for the first time: 1) African- Americans with a single progressive renal disease will be studied in a multi-center trial; 2) the relative efficacy and safety of a calcium channel blocker, an angiotensin-converting enzyme inhibitor and a betablocker for preserving renal function will be assessed; and 3) investigators will obtain an assessment of the best methodologies for recruitment and retention of this population in a long-term clinical trial. The goal of the study is to provide a means by which the incidence of end stage renal disease can be effectively forestalled or prevented altogether in this high-risk population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALTERED GENE EXPRESSION BY MGCL2 IN TARGET ORGANS Principal Investigator & Institution: Mansour, Mahmoud M.; Tuskegee University Tuskegee Institute, Al 36088 Timing: Fiscal Year 2002; Project Start 01-JUN-1978; Project End 30-JUN-2006 Summary: (provided by applicant): Mercury is a significant contaminant of the environment and poses a serious systemic toxicity risk to humans, animals, and the aquatic food web. Published data indicate that inorganic mercury accumulates and induces strong renal toxicity and adversely affects spermatogenesis and fertility in male rats. Such effects underscore the threat to human health because mercury is ubiquitously present in the environment and is widely used in the industry. Hence, the long-term goal of this project is to understand how environmental exposure to mercury induces toxicity. The specific aim of this application is to determine the effects of mercuric chloride on differential gene expression in the kidney and two male reproductive organs. We hypothesize that the toxicity of mercuric chloride largely results from the loss of control of differential gene expression. This hypothesis is formulated based on published reports which indicated that mercuric chloride induced apoptosis, and transcriptional activation and/or suppression of several genes in the kidney, and based on our initial studies, that mercuric chloride down-regulated estrogen receptor alpha mRNA expression in the efferent ductules, and induced apoptosis in the testis of adult male rats. To test this hypothesis, we will test the effects of oral administration of mercuric chloride on differential expression of genes (repressed versus induced) using differential display PCR and relevant toxicity endpoints. Using micro-array, we will determine the effects of mercuric chloride on unique genes related to phase I and II metabolism, apoptosis, inflammation, DNA damage, cell transport, and oxidative stress in the kidney, efferent ductules, and the testis. Semi-quantitative PCR will be used to determine the effect on steroid hormone receptors (estrogen and androgen) in the efferent ductules and testis. The proposed experiments will identify pathways by which mercuric chloride causes toxicity, and identify molecular
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Mercury
biomarkers for exposure to inorganic mercury. Such approach will be valuable in the identification of new drug targets for treatment of mercuric chloride. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTOANTIGEN CLEAVAGE DURING APOPTOSIS AND NECROSIS Principal Investigator & Institution: Casiano, Carlos A.; Associate Professor; Medicine; Loma Linda University Loma Linda, Ca 92350 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Apoptosis and necrosis are two fundamental cell death pathways that may be the end result of response to physiologic activators, physical trauma, or environmental toxins and chemicals. These modes of cell death are associated with a wide range of human pathological conditions, including systemic autoimmunity, cancer, AIDS, and neurodegenerative disorders. Emerging evidence indicates that activation of cysteine proteases of the ICE/CED-3 family is a central mechanism in the execution of apoptosis. Although the mechanisms driving cell necrosis are still obscure, recent studies also point to activation of proteases as a key event in this cell death process. However, the nature of these proteases and their substrates remains largely unknown. Using human antinuclear autoantibodies as probes, we have demonstrated that both apoptosis and necrosis involve the selective, but distinctively different, proteolytic cleavage of a specific set of nuclear protein autoantigens. It is proposed that different proteolytic mechanisms underlie the execution of apoptosis and necrosis, and that dissecting these mechanisms should be helpful for establishing a clear distinction between these cell death processes. The broad, long term objectives of this research is to dissect and differentiate events associated with these mechanisms. Three specific aims are proposed to test our hypothesis. (1) To use a panel of antinuclear autoantibodies where the antigen targets are well characterized nuclear proteins, as probes to define and differentiate patterns of substrate proteolysis associated with Fas-mediated apoptosis and with necrosis induced by the toxic xenobiotic mercury. (2) To characterize proteolytic activities involved in the cleavage of specific autoantigens in both cell death processes. Cell free systems of apoptosis and necrosis will be used in these studies to analyze the inhibition profile of autoantigen cleavage and to determine whether activation of ICE/CED-3 proteases occurs during necrosis. The ability of purified proteases to cleave specific antigens and the identify of specific cleavage sites will be also investigated. (3) To exploit the differences in autoantigen cleavage observed in apoptosis and necrosis for the development of monoclonal antibodies which react specifically with epitopes associated with either apoptotic or necrotic cell death. It is anticipated that these studies should contribute to enhancing our understanding of cell death in molecular terms and establishing additional criteria that would help to differentiate between apoptosis and necrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CASA PIA STUDY OF DENTAL AMALGAMS IN CHILDREN Principal Investigator & Institution: Derouen, Timothy A.; Professor and Chairman; Dental Public Health Sciences; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: This proposed project is a competing renewal to the Casa Pia Study of the Health Effects of Dental Amalgams in Children, a cooperative agreement funded by the National Institute of Dental and Craniofacial Research as one component of the
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Children's Amalgam Trial. The University of Washington is the applicant organization with a subcontract to the University of Lisbon, Portugal, as the clinical site. The Study is a randomized clinical trial in which 507 children of ages 8 to 10 at entry with substantial dental treatment needs and who are students of Casa Pia Schools in Lisbon, have been randomized to the use or non-use of mercury amalgams in their dental treatment. The project is currently in the second year of follow-up, with 95% retention thus far in the study. Mercury exposure is measured from urine samples at baseline and follow-up exams at one-year intervals. Four primary endpoints are monitored from baseline at one-year intervals: three neurobehavioral (combined assessments from neurobehavioral tests for attention, memory, and motor/visual motor domains) and one neurological (nerve conduction velocities). Secondary endpoints include two renal (two Glutathione Transferase isozymes specific to renal tubular damage), a clinical neurological exam, porphyrin profiles, urinary albumin levels and the occurrence of sentinel health events. Comparison between the two groups of children for the four primary endpoints are made annually using a combination of Hotelling's T2 test and an extension of the O'Brien test for multiple endpoints adapted for longitudinal data and multiple tests over time. If significant adverse health effects of exposure to dental amalgams (or to the alternative dental material, composites) are detected during the course of the study, the children treated with the harmful material will be re-treated with the other. The purpose of this renewal application is to extend the funding period to cover the seven years of follow-up proposed in the original grant. We intend to continue collecting data in the study po2ulation for the same four endpoints currently in use, with the same methodology as during the initial 3 follow-up years, utilizing the same personnel currently employed. in obtaining the data, with only some minor revisions in the neurobehavioral tests to account for the maturation of the test, population. The introduction of some new secondary endpoints is proposed. This international collaboration has resulted in a study team that has demonstrated its expertise in all relevant areas and its capability to successfully complete this important study and settle the controversy over whether amalgam has even any subtle health effects associated with its use in the most susceptible population, children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CERAMIC WHISKER REINFORCEMENT OF DENTAL COMPOSITE RESINS Principal Investigator & Institution: Xu, Huakun; American Dental Association Foundation Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 15-SEP-1998; Project End 31-JUL-2004 Summary: Concerns about mercury in dental amalgam have created a need to extend the use of composite resins to posterior applications. However, current composites are not suitable for large stress-bearing applications involving cusps due to excessive wear and fracture. The glass fillers in resins provide only limited reinforcement because of their brittleness and rounded shapes. Preliminary studies with ceramic whiskers having high strength and elongated shapes showed a two-fold increase in composite strength and toughness, and promising results on polishability, water absorption and strength durability, enamel wear and esthetics. The goals of this project are to i) to investigate the whisker reinforcement mechanisms for dental resins; ii) to understand the key microstructural and processing variables that determine reinforcing efficacy; and iii) to develop optimized prototypes. To accomplish these goals, the following studies are proposed: (1) the effects of whisker size and aspect ratio will be evaluated to improve reinforcing efficacy and filler packing; (2) dental silicate fillers will be fused onto the
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Mercury
individual whiskers to minimize whisker entanglement, enhance silanization, and improve retention in matrix by providing rougher whisker surfaces; (3) the effect of whisker content will be systematically investigated on composite mechanical properties and reinforcing mechanisms, translucency, color and depth of cure; (4) the mechanical and physical properties of water-aged composites will be characterized to identify the reinforcing mechanisms and the key microstructural parameters, and this knowledge will be used as feedback to improve microstructural design; (5) three- and two-body enamel against composite wear will be evaluated to understand the effect of whiskers on wear mechanisms and wear rates; and (6) the whisker composite will be veneered with conventional composites and the effect of whisker reinforcement on properties of the final restoration will be evaluated by using Hertzian cyclic fatigue and flexural tests. This project will provide (1) an understanding of the effects of whisker- glass filler hybridization and fusion on composite properties; (2) mechanisms of whisker reinforcement for dental resins; (3) guidelines on microstructural design and processing of whisker-reinforced composite resins; and (4) a basis for the next generation of high performance composite resins for dental restorative and potentially other biomedical applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CEREBELLAR NEUROTOXICITY
GABA-A
AS
TARGETS
OF
MERCURY
Principal Investigator & Institution: Atchison, William D.; Professor; Pharmacology and Toxicology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 27-MAR-2002; Project End 28-FEB-2006 Summary: (provided by applicant): Methylmercury (MeHg) is a prominent environmental neurotoxicant which is responsible for several episodes of mass poisoning, and remains an environmental concern today- especially among populations with high dietary intake of fish. Cerebellar-based ataxia is a hallmark sign of MeHg poisoning. The granule cell layers of the cerebellum are particularly sensitive to MeHg especially during development. The primary objective of this project is to understand the basis for this unique sensitivity of cerebellar granule neurons to MeHg. Recent data from our lab suggest that GABAA receptor function is highly sensitive to inhibition by MeHg-particularly in cerebellar granule cells. Inasmuch as these cells express a unique phenotype of GABAA receptor, we propose to investigate the hypothesis that disruption of inhibitory GABAergic transmission at granule neuron synapses is uniquely sensitive to MeHg due to the presence of a unique phenotype of GABAA receptor expressed in these cells. GABAA receptors are heteropentameric membrane proteins consisting of combinations of several distinct subunits. They are responsible for mediating fast inhibitory synaptic transmission in the mammalian CNS by gating entry of Cl-. Typically, GABAA receptors consist of combinations of alpha, beta, gamma, or delta, subunits; multiple isoforms of many of the subunits exist. Subunit composition has been shown to affect pharmacological sensitive of GABAA receptors. Only granule cells contain the a6 subunit which lacks benzodiazapine agonist sensitivity; they frequently also contain the delta subunit. These two subunits also confer sensitive to Zn2+, which is released in cerebellar granule neurons by MeHg, and which inhibits GABAA receptor function. The approach will involve application of whole cell voltage clamp techniques to native cerebellar neurons in culture or in isolated slice to compare the sensitivity of the GABAA receptors to MeHg in granule cells and purkinje cells, which lack the alpha6 and delta subunit. Additionally, heterologous expression of cloned GABAA receptors in HEK 293 cells will be used to examine specifically the role
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that the alpha6 and delta subunit play in sensitivity to MeHg. Specific aims are to determine 1) Does MeHg differentially affect the functional properties of GABAA receptors in granule cells and Purkinje cells? If so, by what mechanism(s)? 2) Are recombinant GABAA receptors containing alpha6 subunits more sensitive to MeHg than those containing alpha1, subunits, and what if any role do other subunits, specifically gamma or delta subunits, play in MeHg-induced effects on GABAA receptors? 3) Are the effects of MeHg on cerebellar synaptic transmission, particularly inhibitory synaptic transmission, altered by knockout or mutation of genes for subunits such as the alpha6 or delta subunit which are unique to cerebellar granule cells? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENTISTRY
CLINICAL
EPIDEMIOLOGY OF
MERCURY
EXPOSURE
IN
Principal Investigator & Institution: Martin, Michael D.; Director; Oral Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The proposed Mentored Patient-Oriented Research Career Development Award would provide Michael D. Martin the opportunity to devote a minimum of 85 percent of his time to preparation toward becoming qualified as an independent clinical researcher. Dr. Martin is a dually trained dentist - epidemiologist on a tenure-track faculty position in the Department of Oral Medicine at the University of Washington's School of Dentistry with an adjunct appointment in the Department of Dental Public Health Sciences. Dr. Martin's focus of interest within epidemiology is on the epidemiology of mercury exposures from dental sources. He conducts clinical research that is of practical significance to dentistry/medicine and has theoretical importance to our understanding of the mechanisms-by which elemental mercury exposures affect the human. Prior projects have examined the risk factors for mercury exposure among dentists; the neurobehavioral effects of mercury among dentists; biomarkers for lowlevel mercury exposure; the effects of ethanol on mercury absorption in humans, and the relationship between dental metals (i.e., mercury amalgam) and mucosal disease, among others. He is currently participating in related projects including a large clinical trial of the effects of mercury amalgam in children; a study of the neurobehavioral effects of low-level mercury exposure among dentists; further study of biomarkers for mercury exposure, and in this application proposes a five year-plan which includes both didactic as well as practical clinical research training experiences directed toward his research plan involving continued work in the area of epidemiology of mercury exposure from dental sources and carrying it further forward into the area of autoimmune mucosal diseases and their relationship to dental metals. His primary goal is to achieve sufficient training and experience to become an independent researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE SURVEILLANCE OF OCCUPATIIONAL HEALTH IN NEW YORK Principal Investigator & Institution: Gelberg, Kitty H.; Bureau of Environmental Health 547 River St Troy, Ny 12180 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: New York, with the assistance of the SENSOR and ABLES programs, has established a structure for occupational disease surveillance and follow-up in New York State. Provisions of the New York State (NYS) Public Health Law mandate the reporting
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of a number of occupational conditions in NYS. Since 1981, the New York State Department of Health, Bureau of Occupational Health (BOH) has operated a Heavy Metals Registry for the reporting of cases of lead, mercury, arsenic, and cadmium poisoning, and an Occupational Lung Disease Registry for the reporting of cases of work related lung disease. Since 1991, BOH has operated a Pesticide Poisoning Registry and receives reports from healthcare providers of suspected pesticide poisonings. While all of these registries are operational, the extent to which there is active surveillance, with aggressive case finding, ascertainment and follow-up, varies. There are a number of reasons for this variability, including differences in how the diseases are diagnosed and the different reporting sources for the various registries. Additional federal resources will permit us to build upon existing reporting laws and infrastructure and expand current surveillance efforts to help us achieve the NIOSH standards for a model core surveillance system for a range of significant occupational conditions. We propose to conduct general surveillance of existing databases available to the Department of Health such as death certificates and hospital discharge data to assist with documenting the magnitude of occupational injuries and illnesses in New York, and to identify trends and industries occupations at elevated risk. Focus will be primarily upon upgrading our Occupational Lung Disease Registry; however, we will also focus more attention on conducting educational outreach for all of our registries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--NEUROTOXICOLOGY Principal Investigator & Institution: Cory-Slechta, Deborah; Professor; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: The basic research goal of the Neurotoxicology Core is to understand the nature of the effects of environmental chemicals on nervous system function, their consequences over the life span, the mechanisms by which these effects are produced, and the risks they pose to human health. A key element in this goal is to understand the contribution of combined effects of genetic predisposition and environmental chemical exposures on neurological dysfunctions, particularly as it relates to neurodegenerative diseases. The research within this Core involves both basic neuroscience research and neurotoxicology and explores the age spectrum from development to aging. The general theme of the Core is that both early and late stages of life represent periods of potentially enhanced vulnerability to neurotoxic effects. Embedded within this theme is the emerging concept that neurological effects of toxic exposures may not manifest themselves until years after exposure, and that toxicants interact in complex ways with the genetic composition of the human to influence the nature and severity of functional outcomes. The Core consists of seven members of which five are continuing members and two are new members, drawn from the Departments of Neurology, Environmental Medicine, and Obstetrics-Gynecology. The members have been chosen on the basis of their productivity, commitment to multidisciplinary neuroscience research, and experience in areas of thematic interest to the Center. In the past funding period, the Core was called the Neurobehavioral Toxicology Research Core to reflect its focus on behavioral toxicology. The present Core, now named the Neurotoxicology Core, has expanded its focus to include a broader spectrum of issues, ranging from mechanisms, genetic predispositions and contributions to human diseases, and human risk assessment, while maintaining strengths in behavioral toxicology. Of particular note are the inclusions of sophisticated molecular biology and neurochemistry into the battery of Core skills. The present proposal continues to advance the traditional strengths in metal
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neurotoxicology, while venturing into several new initiatives as well. A major change is the plan to recruit a new faculty to replace Dr. Cory-Slechta as Core Director. The individual will be selected to further integrate the neurotoxicology and basic neuroscience. Another change is the new initiative into molecular neuroscience and genetic-toxicant interactions, which has been developed through the addition of Drs. Federoff and Gelbard to the Core. This group will focus particularly on toxicant contributions to the development of neurodegenerative disorders. The major thematic areas of the Neurotoxicology Core are the following: 1) Neurochemical mechanism of lead-induced behavioral toxicology (Cory-Slechta). This project examines the neurochemical and neuroanatomical sites through which lead alters neural functions. Work had identified neurotransmitter alterations, neural pathways and behavioral deficits in animal models of lead exposure. 2) Environmental neurotoxicant genetic interaction: murine model (Federoff). This work would test the hypothesis that neurotoxicants interact with yet uncharacterized genetic determinants to produce selective vulnerability. Focusing on the dopamine transporter (DAT), the principal investigator will engineer a population of dopaminergic neurons overexpressing DAT by means of a somatic mosaic approach and directed gene expression to compare the responses of expressing and non-expressing neurons in the same animal. 3) A murine model of genetic and environmental neurotoxicant action (Richfield). This project would look at the role of the alpha-synuclein gene and gene product in Parkinson?s disease using the somatic mosaic approach. Studies will determine whether mice overexpressing alpha-synuclein show an enhanced dopaminerigic vulnerability when exposed to low does of paraquat. 4) Genotype and phenotype of autism spectrum disorders (Rodier). This project will continue the investigator?s work linking injury during early development (as early as neural tube fusion) and specific genes with the development of the autism disorders. Work will continue to examine the valproic acid model of brain injury (which phenocopies some aspects of autism spectrum disorders), and the toxicant involves the HOX family of genes. 5) The role of inflammation and oxidative stress in human immunodeficiency virus type 1- associated neurologic disease (Gelbard). This project has been investigating how HIV type 1 results in neurotoxicity. In the proposed research, the principal investigator would examine the role of tumor necrosis factor alpha (TNF-a) and platelet activating factor (PAF) in the pathogenesis of neurotoxicity. Future plans include the development of TNF-overexpressing mice by somatic mosaic methods, and subsequent examination of neuronal death under various challenges. 6) Neurobehavioral and developmental effects of methylmercury exposure (Clarkson). This represents a continuation of the large human study of methylmercury exposure via fish and its consequences on development. This is one of two definitive epidemiological studies of human methylmercury exposure, which will continue and expand during the next funding period. In addition, the project director will continue his involvement in a prospective study of mercury exposure via dental amalgams. 7) Persisting functional consequences of neurotoxicant exposure during early development (Weiss). This work will continue studies of developmental exposure to several classes of toxicants. These will include solvents in addition to ongoing work in metals, endocrine disruptors (e.g., TCDD), and drugs (e.g., cocaine). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEATH IMMUNOTOXICITY
RECEPTOR
SIGNALING
AND
MERCURY
Principal Investigator & Institution: Mccabe, Michael J.; Associate Professor; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627
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Mercury
Timing: Fiscal Year 2003; Project Start 03-APR-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Mercury (Hg) toxicity affects numerous organ systems including the immune system. The immunotoxicity of Hg is complex, in that, immunosuppression and immunostimulation occur upon exposure to this metal, and both of these outcomes may have adverse effects on human health. This proposal is constructed around the conceptual framework that Hg is an environmental agent that contributes to the development of autoimmune disease. Animal studies have established a connection between experimental exposure to Hg and lupus-like autoimmune disease. Similarly, case reports demonstrating a correlation between accidental Hg exposure and either the onset or the severity of autoimmune disease symptoms support a link between Hg intoxication and the etiology of human autoimmune disease. From this perspective, Hg is one of the few suspected environmental agents where a link between exposure to the agent and autoimmune disease has been indicated. However, the mechanisms whereby Hg initiates, potentiates, or perpetuates autoimmune responses have not been established. In particular, there is a dearth of information regarding the biochemical/molecular mechanisms involved in Hg-mediated autoimmunity. Accordingly, the long-term goal of our research is to identify biochemical/molecular mechanisms underlying Hg-mediated autoimmune disease. Non-cytotoxic concentrations of Hg2+ interfere with the CD95 apoptotic signaling pathway and also interfere with protein tyrosine mediated signaling. Thus, this proposal focuses on lymphocyte signaling pathways involved in the regulation of CD95-induced apoptosis. Since CD95-mediated apoptosis is involved in the regulation of peripheral tolerance, dysregulation of CD95-signaling by Hg may be one factor (together with other genetic or environmental factors) that contributes to autoimmune disease. The hypothesis guiding this proposal is that Hg2+ disrupts CD95-mediated apoptosis, which contributes to a breakdown in peripheral tolerance to autoantigens leading to the development of autoimmune disease. Using cell lines and human CD4+ lymphoblasts this hypothesis will be tested by determining; 1) the influence of Hg2+ on components of the CD95 apoptotic machinery and 2) the effects of Hg2+ on non-receptor kinase signaling pathways that may interact with and regulate CD95. A third specific aim will employ a mouse model to test whether disruption of CD95-mediated cell death by Hg intoxication in vivo enhances the survival of autoreactive T lymphocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENTAL AMALGAMS & NEUROPSYCHOLOGICAL FUNCTION Principal Investigator & Institution: Factor-Litvak, Pam R.; Associate Professor; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENTAL EFFECTS OF METHYLMERCURY Principal Investigator & Institution: Burbacher, Thomas M.; Associate Professor; Environmental and Occupational Health Studies; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 10-DEC-1986; Project End 31-JAN-2004 Summary: The broad, long-term objective of this research is to provide a comprehensive evaluation of the effects of in utero methylmercury (MeHg) exposure at different stages of the life span of Macaca fascicularis monkeys. Previous studies of Macaca fascicularis
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exposed in utero to MeHg and controls have described effects during infancy, adolescence and adulthood. The primary goal of the initial 2 years of this application is to continue to assess the effects of in utero MeHg exposure on the adult functioning of these same monkeys using operant procedures that are also sensitive to changes in function typically observed in primates during aging. The primary goal of the last 3 years is to provide housing and care for these monkeys to keep the group together for later studies of MeHg and aging effects on performance. The specific aims of the studies proposed in years 1 and 2 of this application are to test the following hypotheses: (1) In utero MeHg exposure results in high-frequency hearing impairment in adult Macaca fascicularis. MeHg exposed monkeys will exhibit elevated hearing thresholds at frequencies of 25,000 Hz and above on a test of pure tone detection, (2) In utero MeHg exposure slows the speed of information processing in adult Macaca fascicularis. MeHg exposed monkeys will exhibit increased reaction times compared to controls on a Choice Reaction Time test as the number of response choices increase, and (3) In utero MeHg exposure results in impaired spatial memory in adult Macaca fascicularis. MeHg exposed monkeys will exhibit significant decreases in % correct responses on an Indirect Delayed Response test that uses irrelevant stimuli to interfere with attention and memory. During years 3-5, the specific aims of the project are to: (1) provide housing and care for these monkeys to keep the group together for further studies after this grant period, and (2) evaluate visuospatial orientation, fine and gross motor coordination, menstrual cyclicity, and the general health status of these monkeys using observational techniques in order to detect gross changes related to MeHg exposure and/or aging. Future studies will be aimed at evaluating the effects of in utero MeHg exposure on the performance of these monkeys at a stage in the life span when impaired functions due to aging are typically observed. Exposure of the fetus to MeHg via maternal consumption of contaminated fish continues to be a major public health concern. The major focus of the public health concern regarding MeHg exposure is the possible immediate and longterm effects of in utero exposure on postnatal growth and function. This study was designed to complete our evaluation of the effects of in utero MeHg exposure on adult primate sensory and N cognitive functioning, while providing baseline data for studies of these monkeys after this grant period, when the monkeys are 19 years of age and over. The proposed studies take full advantage of the history of these monkeys and represents the best possible use of this valuable resource. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVICE FOR RAPID SCREENING OF PLASMA HOMOCYSTEINE Principal Investigator & Institution: Davies, Malonne I.; Bioanalytical Systems, Inc. (Basi) 2701 Kent Ave West Lafayette, in 479061389 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-MAY-2003 Summary: (Applicant's abstract) The objective of the proposed work is fast, sensitive integrated clinical analyzers for the diagnosis of two metabolism disorders, homocysteinuria and phenylketonuria (PKU). The assays are based on microchip capillary electrophoresis with electrochemical detection. This format has several advantages, including small sample requirements, fast analysis times, and inexpensive manufacture of multiple chips. Electrochemical detectors are ideally suited to microchip CE because they can be easily miniaturized and integrated into the analysis system. Monitoring phenylanlanine concentration in plasma samples of newborns is required by law. The current assay has a relatively high rate of failure (1:70) and requires instrumentation frequently not found in-house, especially in small hospitals. High levels of homocysteine in plasma has been associated with cerebrovascular, peripheral
18
Mercury
vascular, and coronary heart diseases. The assay for homocysteine involves online reduction of the protein-bound homocysteine with tris-(2-carboxyethyl)phosphine, separation by electrophoresis, and electrochemical detection at a gold/mercury electrode. Phenylalanine will be determined in plasma in a similar manner using a copper electrode. The chips will be used with a portable analysis system based on a battery-powered high voltage power supply, miniaturized potentiostat, and integrated data analysis system. The chips we develop will generate a foundation for other clinical assays based on electrochemical detection. PROPOSED COMMERCIAL APPLICATION: The current trend in clinical analysis is away form large centralized labs and toward point of care testing. Thus, a compact device for performance of assays for homocysteine and other clinically relevant animo acids in the clinic or physician's office has large commercial potential. Recently, the American Heart Association recommended homocysteine screening for patients at risk for cardiovascular disease. This should lead to a large demand for accurate and cost-effective assays for homocysteine similar to the current cholesterol screening assays. The development of a small, fast and reliable assay for phenylalanine in blood will make it possible to test infants quickly and accurately for PKU. The electrochemical based clinical analyzers developed here will provide a format that can be used for the development of a number of other assays for clinically important analytes. What is demonstrated with homocysteine and phenylalanine is just the beginning of a large array of clinical analyzers based on microchip CEEC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIGITAL X-RAY IMAGED BASED ON HGL2 POLYCRYSTALLINE FILMS Principal Investigator & Institution: Iwanczyk, Jan S.; Vice President; Photon Imaging, Inc. 19355 Business Center Dr, Ste 8 Northridge, Ca 91324 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-AUG-2003 Summary: The goal of this proposal is to develop a new detector technology for digital x-ray imaging based on HgI2 polycrystalline films coupled to large area flat panel amorphous silicon (a-Si:H) thin-film transistor (TFT)-addressed readout arrays. This novel imaging detector when optimized will provide order of magnitude improvements in sensitivity to x-rays and superior spatial resolution compared to detectors utilizing scintillating phosphors coupled to a-Si:H readout arrays. The increased sensitivity of the detector will allow for a ten-fold reduction in radiation dose to a patient for an equivalent quality image. The enhancement of the spatial resolution will have a direct impact on the quality of the image, which has paramount importance in many medical diagnostic procedures such as mammography. In addition, digital capabilities will allow for convenient film-less image acquisition, retrieval, and storage. Digital image processing, computer-assisted diagnosis, and the ability to provide real time images have distinct advantages in many medical diagnostics. During Phase I of this proposal we developed techniques for highly controlled growth of polycrystalline HgI2 films in terms of their thickness, sizes of the polycrystalline grains, uniformity of layers and good electrical properties. In the Phase II effort we will finalize the HgI2 film development and construct x-ray imaging detectors using initially small commercial flat panel a-Si:H readouts (approximately 2"x2"). Then we will scale up the film growth equipment and construct large area (approximately 14" x 17") x-ray imaging detector. The film growth process will be optimized for low production cost. This new x- ray imager will be characterized and compared with current commercial detectors in terms of spatial resolution, gain, linearity, noise, uniformity, and detective quantum efficiency. The imaging capabilities will be tested in our laboratory and at UCLA School of
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Medicine with the use of slits and phantoms. PROPOSED COMMERCIAL APPLICATIONS: There is a strong interest in application of digital radiographic detectors for medical diagnostic applications, nondestructive evaluation of materials, xray diffraction of biological and other material samples, and astronomical observations. Conservative estimates are that in the medical area alone there are over 600 x-ray images produced per 1000 population per year. The proposed detectors will be highly attractive to this enormous commercial market segment due to the order of magnitude performance improvements that they will offer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISRUPTION OF LYMPHOCYTE SIGNAL TRANSDUCTION BY HG+2 Principal Investigator & Institution: Rosenspire, Allen J.; Scientist; Biological Sciences; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 19-FEB-2002; Project End 30-NOV-2006 Summary: (provided by applicant): Mercury is a widespread environmental contaminant whose toxic potential to the nervous and immune systems is well known. Surprisingly little is known about its molecular mechanism of action. While high level exposure is no longer common, large segments of the population currently absorb low (.10 ug/day) levels of mercury as a result of ubiquitous environmental factors, including air, food, water, and dental amalgam. For about 3 percent of the population with no known special risk factors, blood levels of mercury exceed 0.25 uM. 4 percent of the population exceed 0.125 uM mercury in urine, with the highest concentrations reported in individuals with no known special risk factors to be about 1 uM. Preliminary and recently published results from our laboratories support our hypothesis that concentrations of inorganic mercury in the range of 0.1- 1.0 uM may directly impair immune system homeostasis, and contribute to autoimmune disease by interfering with protein tyrosine phosphorylation (PTK)mediated signal transduction, implying that substantial numbers of individuals may unknowingly be at risk. In this proposal it is our objective to critically and comprehensively test our hypothesis in several different cell systems relevant to autoimmune disease. In particular, we will test mercury's ability to interfere with antigen receptor mediated and P1K-dependent signal transduction and proliferative control in established T and B cell lines, as well as in freshly isolated human peripheral blood lymphocytes. We will also examine the effect that low concentrations of mercury have on antigen receptor mediated apoptosis in lymphocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS RELATED BIOMAKERS OF TOXIC EXPOSURES Principal Investigator & Institution: Checkoway, Harvey L.; Professor; Environmental and Occupational Health Studies; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-MAR-2005 Summary: This proposal is for a 5-year competing renewal of the UW Superfund Basic Research Program Project. The theme of this Program Project is that biomarkers measured in accessible tissues are predictive of: a) toxicant exposures; b) early indicators of damage; and/or c) unusual susceptibility to toxic agents that commonly occur at hazardous waste sites. The UW Program Project includes 9 research projects (7 biomedical, 2 bioremediation), an administrative core, a service core dedicated to molecular biology assays, a training core and an outreach core. The research projects can
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be divided into four subgroups: 1) laboratory-based development of sensitive biomarkers of adverse effects and disease susceptibility; 2) applications of biomarkers to human populations. 4) biomarker measurements of environmental chemical toxicity in terrestrial and aquatic species and 4) biomarker applications for hazardous waste remediation. Multi-disciplinary cross-project interactions among toxicologists, epidemiologists, molecular biologists and environmental engineers (e.g. measurement of the same biomarkers in various projects to assess a range of effects) have been carefully devised to maximize scientific yield. This project will continue investigations in glutathione biosynthesis biomarker as indicators of oxidative to assess a range of effects) have been carefully devised to maximized scientific yield. This project will continue investigations on glutathione biosynthesis biomarker as indicators of oxidative stress; characterization of novel biomarkers and applications to epidemiologic investigations are newer directions. This project will continue investigations on glutathione biosynthesis biomarker as indicators of oxidative stress; characterization and novel biomarkers and applications to epidemiologic investigations are newer directions. This project will identify genetic polymorphisms of porphyrin synthesis enzymes, and test these as markers of neurobehavioral toxicity in mercury-exposed humans. This project is a new project that will investigate paraoxonase phenotype and genotype inter-relations, with applications to experimental toxicokinetic studies in rats and to an epidemiologic studies of parkinsonism. This project continues to examine epidemiologically the interactions between environmental toxicants and genetic polymorphisms of enzymes involved in xenobiotic activation and detoxification. This project will apply a physiologically-based toxicokinetic model derived from controlled human exposures to organic solvents to characterize determinants of uptake, metabolism, and excretion. This project continues to examine biomarkers of exposure and effect in wildlife residing near or in hazardous waste sites. This project is a continuing study of DNA oxidative damage in fish from polluted and reference water sites. This project will continue to evaluate the effectiveness of genetically- engineered trees for bioremediation of toxic chemicals (e.g., trichloroethylene). This project will involve laboratory and field genetically-engineered trees for bioremediation of toxic chemicals (e.g., trichloroethylene). This project will involve laboratory and field experiments of in situ engineering methods for bioremediation of chlorinated aliphatic toxicants. The Administrative Core, directed by the Program Director, will oversee all major budgetary and personnel aspects of the program project, will coordinate multidisciplinary interactions among research projects and cores, and will assume responsibility for information dissemination and technology transfer. The Program Director will be advised by the Deputy Director, an Internal Executive Committee comprised of research and core directors, and an External Science Advisory Board that includes distinguished environmental scientists from academia and governmental agencies. The Bioanalytical Core will offer genotyping and/or DNA sequencing services to the research projects. The Training Core will ensure that doctoral students and postdoctoral fellows in Environmental Health and Civil Engineering receive crossdisciplinary classroom and research experience. The Outreach Core, which is a new intuitive for this Program Project, will be dedicated to the development of instructional materials relevant to hazardous waste contaminant issues, with an emphasis on biomarker applications for toxicity assessment and bioremediation. The principal audiences for outreach will be K-12 school teachers, health and engineering professionals, and interested community residents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENHANCED DENTAL AMALGAM TRAP Principal Investigator & Institution: Turchi, Craig S.; Ada Technologies, Inc. 8100 Shaffer Pky, Ste 130 Littleton, Co 801274124 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: (provided by the applicant) Surveys conducted by municipal wastewater treatment plants across the country have concluded that 10 percent to over 70 percent of the mercury reaching the plants comes from dental offices. These findings, combined with increasingly stringent regulations on mercury discharges, have placed pressure on the dental profession to reduce their discharges of mercury-bearing amalgam. The objective of this project is to enhance the performance of sedimentation-type amalgam separators by controlling the water chemistry within the separator. Dental wastewater contains mercury in three general forms: large particles of amalgam, fine particles of amalgam, and dissolved mercury. Simple sedimentation traps can capture the large particles and many of the fine particles. However, colloidal particles and dissolved mercury can still exceed discharge limits. At present, expensive and maintenanceintensive adsorbents are needed to achieve discharge concentrations in the low-ppb range. During Phase I ADA Technologies showed that safe, inexpensive additives could be used within a sedimentation device to minimize the release of dissolved mercury. In Phase II, we intend to document the effective use of optimized versions of these additives at several dental clinics, demonstrating ppb-level mercury concentrations at costs significantly below those for adsorbent-based processes. PROPOSED COMMERCIAL APPLICATION: US dentists use some 45 tons of mercury per year for new amalgam fillings. European, Canadian, and some US municipalities limit dental office discharges of mercury. New regulations are pending across North America. Successful completion of this project would yield a low-cost, field-proven amalgam trap, capable of reducing mercury in dental wastewater to the low parts-per-billion range. ADA Technologies will utilize its network of partners and experience in dental waste treatment and equipment manufacturing to bring this enhanced trap rapidly to the marketplace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENVIRONMENTAL IMPACT ON THE EMBRYONIC MTDNA GENOME Principal Investigator & Institution: Knudsen, Thomas B.; Professor; Pathology, Anat/Cell Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-MAY-2005 Summary: (Applicant's Abstract): The long-term goal is to understand teratogenic mechanisms at the molecular level. Microphthalmia is a low level effect of methylmercury exposure and can be induced in early mouse embryos to reflect clinical disorders seen in exposed children. Gene expression arrays will be used to recognize fundamental biomolecular parameters that describe critical events leading to this malformation. Preliminary studies identified a critical response involving p53 tumor suppressor (Trp53) and peripheral-type benzodiazepine receptor (Bzrp), leading to the proposed focus on metabolic and regulatory pathways controlling mitochondrial DNA (mtDNA) genome expression. During neurulation, the embryo shifts from an anaerobic (glycolytic) to aerobic (oxidative) metabolism. This diauxic shift requires mtDNA genome expression and, consequently, a tight link between morphogenetic and metabolic differentiation. The investigators hypothesize control by retrograde regulation
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whereby a signal started in the mitochondrion leads to an adaptive response in the nucleus to culminate in mtDNA biogenesis. Four specific aims will begin to trace this pathway at the molecular level. Specific Aim 1, a teratological study, will determine exposure-disease relationships for methylmercury-induced microphthalmia with respect to dose response, genetic susceptibility (Trp53), and therapeutic intervention (Bzrp). Specific Aim 2 will use expression microarrays to profile gene expression for developing eye across the critical period of vulnerability (days 8-10 of gestation). Specific Aim 3 will profile exposure-disease pathways for methylmercury-induced microphthalmia with respect to dose-response, genetic susceptibility, and therapeutic intervention. Specific Aim 4 entails pathway integration to confirm cellular activities as they change over time. At ends we expect to build a searchable transcriptome database for the developing eye and a platform with which to discover the cellular pathways that hypothetically define a temporal sequence in dysmorphogenesis induced with methylmercury and other environmental toxicants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMALGAMS
EVALUATION
OF
MERCURY
RELEASE
FROM
DENTAL
Principal Investigator & Institution: Okabe, Toru; Regents Professor & Chair; Biomaterials Science; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2004 Summary: (adapted from the Investigator's abstract): The primary goal of this application is to determine the mechanism by which changes in the formulation of the alloy reduce mercury (Hg) release from dental amalgam. A series of alloys will be prepared to test specific hypotheses about the effect of palladium (Pd) additions, silver (Ag) and tin (Sn) ratio, and copper (Cu) content. The composition of the pre-trituration alloys and the resulting amalgams will be evaluated by scanning electron microprobe and scanning transmission electron microscopy with micro-diffraction and XEDA to correlate changes in Hg release with microstructure. In addition, amalgams will be prepared from alloys mixed with pure Hg and indium (In)-Hg alloys to further understand the effect of indium on reducing Hg release, and to produce minimal Hgreleasing formulations. The investigators expect to identify commercially viable amalgams with reduced Hg vaporization during setting and after abrasion, and reduced Hg dissolution. The physical properties of these amalgams will be evaluated to verify that they are adequate for clinical use and to further describe the effect of composition on properties. Dynamic dissolution into both neutral saline and acidic solutions, as well as thermal properties, will be assessed to correlate the stability of the amalgams with composition. Finally, Hg release from aged amalgams will be correlated with changes in their microstructure. The primary hypothesis is that Hg release will be minimized when the Ag-Hg matrix phase of amalgam is most effectively stabilized and its surface oxidized and that this is accomplished by maximizing the amount of Sn present in the gamma one matrix. There are four aims: to identify the mechanism by which additions of Pd, changes in the Cu content, and alterations in the Ag and Sn concentrations in dental amalgam alloy affect the vaporization of Hg; to identify the mechanism by which those variables affect the dissolution of Hg from dental amalgam; to verify that the new alloys produce amalgams with acceptable physical properties; and to verify that the amalgams are stable over a two year period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EVOLUTION OF ANTIBIOTIC RESISTANCE PLASMIDS Principal Investigator & Institution: Top, Eva M.; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2002; Project Start 23-FEB-2002; Project End 31-JAN-2007 Summary: Plasmids play a central role in the spread of resistance among bacterial species thereby decreasing the effectiveness of various chemotherapeutic agents for the treatment of infectious diseases. They carry genes that encode essential functions, such as replication, maintenance and transfer, as well as a variety of accessory functions, such as antibiotic resistance determinants. The objective of the proposed research is to obtain a more systematic and comprehensive understanding of plasmid evolution through experimental evolution studies. The specific aims are 1) To assess the tempo and mechanisms of plasmid evolution during vertical transmission in a single host as compared to vertical and horizontal transmission among phylogenetically distinct hosts, in the presence of selective pressure; 2) To characterize and compare the genetic and phenotypic changes that occur during such experimental plasmid evolution; 3) To test the ability of various algorithms to accurately reconstruct the true phylogenies of independently evolved plasmids and specific genes. The broad host range Inc-1beta plasmid pB10, which encodes resistance to four antibiotics and mercury, will be experimentally evolved in replicate cultures of three genetically distinct hosts (Escherichia coli, Pseudomonas aeruginosa, Burkholderia cepacia) as previously described in studies of microbial evolution. Plasmid evolution in one single host will be compared with evolution in alternating hosts, and in each case plasmids evolved for differing periods of time will be characterized. Phenotypic changes will be characterized by examining the effect of the evolved plasmid on host fitness and by assessing differences in the stability and broad host range characteristics of the evolved and ancestral plasmids. Genetic changes that may account for the observed phenotypic differences will be identified by characterizing macroscale and microscale variations in the evolved replicons. Possible correlations between phenotypic changes and genotypic variations will be examined. In addition an experimental plasmid phlogeny will be constructed that has the same topology as described in Project 1 (Experimental Evolution of Viruses), and which will permit us to test the ability of currently available algorithms and those developed in Project 4 to accurately reconstruct the phylogeny of a BHR plasmid that evolves in more than one genetic background. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FETAL EXPOSURE TO ENVIRONMENTAL TOXINS & INFANT OUTCOME Principal Investigator & Institution: Ostrea, Enrique M.; Pediatrics; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The exposure of pregnant women to environmental toxins is of major concern because of their potential harm on the fetus. However, the detection of fetal exposure to environmental toxins still remains a major challenge. We propose that meconium analysis is a promising tool to meet this challenge. Aims: (1) To compare the prevalence and amount of fetal exposure to environmental toxins through the analysis of meconium, cord blood and neonatal hair and to determine the degree of agreement among these three methods, (2) to determine the relationship between the prevalence and amount of maternal exposure to environmental toxins during pregnancy, as determined by serial analyses of maternal hair and blood, to the
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prevalence and amount of fetal exposure to environmental toxins as determined by meconium, cord blood and neonatal hair analyses, and (3) to compare adverse immediate (birth weight, length, head circumference, gestational age) and long term (postnatal growth and neurobehavioral development up to 2 yrs from enrollment) outcomes that are associated with antenatal exposure to environmental toxins as determined by maternal blood, maternal hair, meconium, cord blood and neonatal hair analyses. Study design: Pregnant women (n=750) will be recruited, at midgestation, from the Outpatient Clinic of the Bulacan Provincial Hospital, Philippines and their blood and hair will be obtained at the time of recruitment and at delivery. Umbilical cord blood, meconium and neonatal hair will also be obtained. The samples will be analyzed, by atomic absorption spectrometry, for lead, mercury and cadmium and by gas chromatography/mass spectrometry for the following pesticides and their metabolites: propoxur, transfluthrin, Malathion, DDT, chlorpyrifos, bioallethrin, pretilachlor, lindane, cyfluthrin and cypermethrin. Pertinent maternal and infant data will be obtained after birth. The infants will be subsequently followed up at scheduled intervals for 2 years, to study their physical growth and neurobehavioral development using a battery of tests. Data analysis: The relationship between the presence/amount of environmental toxins in meconium, maternal blood, maternal hair, cord blood or neonatal hair to the immediate and two year outcome in the infants will be studied, while controlling for potential confounders. The presence/amount of environmental toxins in maternal blood, hair, cord blood, meconium and neonatal hair will be also evaluated to determine which substrate (s) provide(s) the best index of exposure for a given toxin. Expected benefits: Meconium analysis may provide a powerful tool to study the prevalence and degree of fetal exposure to environmental toxins and its associated adverse effects. This project can also serve as a model for the study of environmental pollutant problems during pregnancy at a local, national or global level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENERAL CLINICAL RESEARCH CENTER-FORSYTH DENTAL INSTIT Principal Investigator & Institution: Flier, Jeffrey S.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-DEC-1977; Project End 30-NOV-2004 Summary: (provided by applicant): The BIDMC's GCRC proposes to form a satellite with the Forsyth Dental Institute (FDI), a world class center for clinical investigation of oral disease. This proposal describes a spectrum of investigations involving treatment of periodontal diseases, development of a vaccine for dental caries, testing of mercury amalgam toxicity and investigation of oral cancer. Sixteen projects are described that will be conducted at the Satellite Center that include microbiology, microbial genomics, microbial taxonomy, immunology and toxicology as these studies relate to conditions of oral health and disease and microbial biofilms. The proposed Satellite Center will include a Dental Clinic Core, a Laboratory Core and Biostatistics/Informatics support. Specific areas of investigation in this application include: 1) comparison of conventional and antibacterial_supplemented treatments of periodontal disease; 2) investigation of means to prevent periodontal disease; 3) studies on familial distribution of oral bacteria; 4) studies of oral bacteria as examples of naturally occurring biofilms; 5) studies of oral bacteria that penetrate cells; 6) studies of the ways in which early lesions of periodontal disease are initiated; 7) investigation of the microbiology associated with oral cancer; 8) studies that contribute to the development of a dental caries vaccine; 9) investigation of the potential toxicity of mercury amalgams; and 10) studies of the uncultivable bacteria
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of the oral cavity with planned development of a microbial microarray for oral bacteria identification. In addition to the planned studies as outlined above, a strategy to create bi_directional linkage between parent and satellite GCRC's is described in which a dental facility will be established at the BIDMC GCRC to be staffed by Forsyth personnel. Through this facility, it is envisioned that future studies on the oral health effects of systemic disease, and the converse, effects of systemic disease on oral health will be investigated. It is also stressed that this facility will encourage closer affiliation between the Joslin Diabetes Center (JDC) Satellite and the Forsyth Satellite. It is envisioned that this proposal will expand the research horizon of the FDI and contribute new technology to the research of the parent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC /ENVIRONMENTAL INFLUENCES ON SLE NEPHRITIS Principal Investigator & Institution: Gilkeson, Gary S.; Professor; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies and immune complex mediated glomerulonephritis. African- Americans have a three-fold increased incidence of SLE, more frequently develop nephritis, more frequently progress to renal failure and have increased mortality compared to whites. The worse prognosis in African-Americans may represent a generalized predisposition towards renal failure following any renal injury rather than being lupus specific. Environmental exposures such as smoking and exposure to occupational or environmental agents (i.e., lead, mercury, silica) may affect the development and progression of lupus nephritis. Our central hypothesis is that there are specific genetic factors that interact with environmental exposures leading to progressive renal disease in African-Americans with lupus. The Carolina Lupus Study includes 265 SLE patients who were diagnosed between January 1, 1995 and July 31, 1999. This cohort of patients provides an opportunity to examine renal disease and its progression in African- American SLE patients matched with appropriate population based controls. The Gullah population lives on the sea islands of South Carolina. They are unique in their genetic homogeneity with minimal Caucasian admixture (<5%). A large ongoing study of diabetes (Sea Island Project) in this population has established a working framework onto which we propose to piggyback studies of SLE. Using these unique cohorts of patients and controls, we propose the following specific aims to address our hypothesis: 1) Determine the development and progression of renal disease in CLU patients in relation to specific genetic factors. We will assess if genes linked with renal disease in hypertension and diabetes in African-Americans are associated with development and/or progression of renal disease in lupus. 2) Determine the risk of development and progression of lupus nephritis in CLU patients in relation to comorbid conditions (hypertension, diabetes), measures of socioeconomic status and/or modifiable environmental factors that have been associated with other forms of renal disease. 3) Perform pilot studies in the unique genetically homogenous Sea Island African-American Gullah population to assess the presence of lupus multiplex families, the prevalence of the genetic polymorphisms being assayed in Aim 1 and determine the prevalence of ANA positivity compared to control African- American cohorts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEALTH EFFECTS OF DENTAL AMALGAMS IN CHILDREN Principal Investigator & Institution: Mckinlay, Sonja M.; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: The safety of silver amalgam as a dental restorative material has been controversial since its introduction 150 years ago, but-until recently it has been generally assumed that the exposure to mercury from dental amalgam is limited to the acute placement phase. Some recent studies (mostly observational and primarily of adults) have demonstrated chronic release of mercury vapor from amalgam fillings during chewing and brushing, raising new safety concerns. The randomized trial, Children's Amalgam Trial (CAT) is designed as a comprehensive assessment of the relative safety of silver amalgam, compared to the alternate, mercury-free materials, demonstrating equivalence of cognitive and renal outcomes. Children aged 6-10 at last birthday with no prior dental restoration (to minimize prior mercury exposure) and mixed (primary and permanent) dentition were recruited from two New England communities (rural Main and inner city Boston/Cambridge, Massachusetts) to represent, to the extent feasible, the likely effects in children in the US. Children were chosen for this trial as they are most likely to be amalgam-free at randomization and, given their smaller body mass and developmental stage, more likely to demonstrate adverse effects (if any) of increased body mercury burden. This 5-year competing continuation will enable completion of 6 years of observation of the trial subjects/randomized from August 1997 to September 1999). Current funding, through July 2001, will include two years of observation only. Given the obvious public health significance of the potential long range impact of mercury on cognitive function, the primary endpoint measure is the full scale IQ score of the Wechsler Intelligence Scale for Children: Third Edition (WISC III) and the primary outcome is the estimated change in the score between Baseline and 6 years post randomization, adjusted for the baseline IQ score. Secondary outcomes include more immediately measured safety endpoints that will be monitored annually, including: urine mercury levels; a dip-stick screening test for urinary protein (confirmed by albumin level); and gamma-glutamyl transpeptidase (gamma-GTP). Other endpoints include other aspects of cognitive function from an extensive neuropsychological test battery, while key covariates include a measure of dietary mercury (hair levels) and the dose of amalgam summarized in "surface-years" of exposure. To date, 534 subjects have been randomized (107%) and follow-up through the 12 month visit, although not yet complete, indicates that the initial (12 month) response rate should be at least 92%. Subsequent losses are expected to be negligible (about 2% per year). A non- orthogonal analysis of covariance will test for equivalence on IQ scores between treatments arms similar modeling will be used to address secondary aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEAVY METAL-INDUCED AUTOIMMUNITY Principal Investigator & Institution: Kono, Dwight H.; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 30-APR-2006 Summary: (Applicant's Abstract): Although evidence indicates that environmental factors play a major role in precipitating systemic in genetically susceptible individuals, little is known about the mechanisms involved. Certain heavy metals, such as mercury, are potent environmental immunostimulants that produce a number of immunopathologic sequelae including lymphoproliferation, hypergammaglobulinemia
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and overt systemic autoimmunity. Predisposition to such metal-induced immunopathology has been shown, in mice and other experimental animals, to be influenced by both MHC and non-MHC genes, as well susceptibility to spontaneous lupus. Among the various mouse strains examined thus far, the DBA/2 appears to be the only background that is not susceptible to mercury-induced autoimmunity (HgIA) despite expressing a susceptible H-2 haplotype (H-2d). To define the genetic basis for this trait, two genome-wide scans were conducted in F2 intercrosses of the DBA/2 strain with either the SJL or NZB strains, both of which are susceptible to HgIA. A single major quantitative trait locus (QTL) on chromosome 1, designated Hmr1, was the only region identified in common in both crosses. The aims of this proposal are to define the role of Hmr1 in heavy metal-induced and spontaneous autoimmunity using reciprocal intervalspecific congenic strains and to dissect the Hmr1 interval by more precisely mapping linked traits. Mapping studies will determine whether Hmr1 represents one or more genetic alterations, examine the relationship of Hmr1 to a previously defined NZB QTL on chromosome I (Lbw7) and reduce the interval containing Hmr1 to less than one centimorgan (cM). Identification and characterization of susceptibility/resistance genes and mechanisms relevant to the immunopathogenesis of mercury induced autoimmunity should provide important insights on the pathogenesis of autoimmunity and may reveal novel targets for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH RESOLUTION MAMMOGRAPHY SENSOR Principal Investigator & Institution: Squillante, Michael R.; Vice President of Research; Radiation Monitoring Devices, Inc. 44 Hunt St Watertown, Ma 02472 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Breast carcinoma is the leading cause of cancer in women in the U.S. It is well known that if breast cancer is detected when the tumor is small and axillary nodes are not involved, the survival rate is very high. However, if the cancer has spread with time, the survival rate drops significantly. Early detection of breast tumors is therefore critical to the successful treatment of breast cancer and significant reduction in the breast mammography (ACS, Shapiro, Tabar). X-ray mammography is currently performed using a film-screen system and while it has shown good success in detecting early stage, clinically occult breast cancer (ACS, Kopans), the film-screen detector has limited latitude and dynamic range (Nishikawa.) Its performance is also affected by trade-off between detection efficiency and spatial resolution due to increased light spreading in thicker screens which are more efficient in stopping X-rays. In view of these limitations, we plan to explore a novel digital imaging detector for mammography. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGH SPEED PLANAR ARRAY INFRARED PA-IR SPECTROGRAPH Principal Investigator & Institution: Rabolt, John F.; Materials Science and Engineering; University of Delaware Newark, De 19716 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Recently a new paradigm for doing infrared (IR) spectroscopy was developed in the Principal Investigator's (Pl's) laboratory. PA-IR uses a focal plane array (FPA) detector onto which a beam of light dispersed by a prism or grating is focused. The broad range of frequencies displayed on the pixel array simultaneously make this a multiplex technique without using the complex scanning
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mechanism or computational requirements (for Fourier transformation of the data) used in FT-IR interferometry. Thus the no-moving parts configuration of the PA-IR instrument provides the ruggedness required to make the instrument the size of a "shoebox" and hence portable. In addition the increased sensitivity (100-1000X over single element FT-IR detectors) of the FPA can provide an IR spectrum to be accumulated in as little as 10 microseconds. The only current limitation comes from the frequency range available (3400-2000 cm[-1]) due to the initial availability of only indium-antimonide FPAs during the development of the prototype. This proposal is to design and construct a portable "broad band" PA-IR instrument that works in the more traditional IR "fingerprint" region (2000-800 cm [-1]) now that Mercury-Cadmium-Telluride FPAs are commercially available and show that it has the sensitivity and speed for in vivo disease prediction/diagnosis. If the PA-IR instrument is coupled with an IR fiber optic sampling probe, it should be possible to characterize ocular tissues in the lens. The advantage of this fiber optic PA-IR technique over conventional dynamic light scattering (DLS) systems currently in use for eye diagnostics is that PA-IR will provide a chemical signature of the various components (collagen IV, gamma-crystallin, etc.) present simultaneously in the "real-time" domain potentially allowing both qualitative and quantitative analysis of the components. For example, PA-IR would allow the detection of protein aggregation (dimers, oligomers) and be able to detect changes in the amount of alpha-helical, beta-sheet or disordered conformation in a protein thereby detecting the onset of cataracts at a very early stage before protein particles become large enough to be detected by DLS. Once this "broad Band" PA-IR is shown to have high sensitivity then other applications such as monitoring the presence of airborne bacteria and viruses in hospital environments becomes feasible as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOUSEHOLD ENVIRONMENTAL RISK REDUCTION IN RURAL CHILDREN Principal Investigator & Institution: Butterfield, Patricia G.; Associate Professor; University of Montana University Hall 202 Missoula, Mt 598124104 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: More than seven million families participate in Women, Infants, and Children (WIC) and other pediatric public health programs. Providing environmental health information to these families is a common-sense way of integrating risk reduction efforts into existing public health programs. However, the success of such efforts will be predicated on testing interventions that can be easily delivered in home and clinic settings. The proposed study will yield evidence addressing: 1) baseline estimates of rural children's exposure to multiple agents in the home setting, and 2) the effectiveness of a risk reduction intervention delivered by public health nurses. Subjects will include child-parent dyads residing in rural Montana; there is preliminary evidence that exposures to children living in the rural West may differ significantly from those living in other parts of the country. The research involves four phases. In Phase 1, biomonitoring (i.e., children's blood lead, urinary cotinine), household (i.e., analysis of water for total coliforms, E-coli, lead, nitrate/nitrite, arsenic, mercury, and a pesticide and petroleum screen; air monitoring for radon and carbon monoxide), and parents' knowledge / attitude / behavior data will be collected from 50 families. In Phase 2, these data will be reviewed by an expert panel to identify priority agents--there is preliminary evidence that these will include radon, lead, arsenic, and nitrate/nitrite. Phase 3 will focus on finalizing agent-specific and general risk reduction interventions. General risk reduction actions will be based on national pediatric health
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recommendations. During Phase 4, the intervention will be tested with a sample of 150 families using private wells; 75 treatment families will receive the home visit intervention and 75 control families will receive an alternate (addressing a nonenvironmental health topic) intervention. The intervention will be delivered by local public health nurses who are already making home visits to families participating in child health programs for lower-income families. Outcome measures of interest include: 1) estimates of exposure (biomarkers and household monitoring), and 2) parents' knowledge and attitudes toward reduction actions on behalf of their children. The proposed research is consistent with recommendations that communitybased environmental health programs be framed and delivered in a manner that is meaningful to families and high-risk subgroups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IL-1 BETA INFLUENCES ON NGF IN NEURAL DEVELOPMENT Principal Investigator & Institution: Jelaso, Anna M.; Environmental Institute; Western Michigan University 1903 W Michigan Ave Kalamazoo, Mi 49008 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 30-JUN-2005 Summary: (provided by applicant): An intriguing problem in developmental neurobiology is how cytokines and growth factors interact to shape the differentiation, survival or plasticity of specific neural circuits during development. The cytokine, interleukin-1beta is expressed in the developing nervous system, independent of neuroimmune or neuroendocrine function, indicating that it may play an important role in neural development. However, its role is not yet completely understood. In mammalian glial cells, IL-1beta induces the neurotrophin, nerve growth factor (NGF), through an NF-KB mediated signal transduction mechanism during neural development. My previous work in the developing frog, has shown that IL-1beta and the interleukin-1 type I receptor (IL-1RI) are expressed in identifiable neurons and other neural cell types that comprise functional, sensory motor locomotor circuits. Pilot studies demonstrated that the interleukin-1 receptor antagonist protein (IL-1ra) and NGF are co-expressed with IL-1beta and IL-1RI. The work in this proposal tests the idea that IL-1beta regulates NGF expression in developing neural circuits of the frog, Xenopus laevis, through an NF-KB signal transduction mechanism. The proposed work will complete pilot studies defining IL-1ra and NGF protein expression in developing neural circuits. Additional experiments will inhibit neural IL-1beta by microinjection of IL-1ra or by exposure to the environmental contaminant, methyl mercury. The effects of IL-1beta inhibition on IL-1beta, XrelA (NF-KB homolog) and NGF gene expression will be analyzed using real-time PCR. This work will establish a system for understanding how cytokines and neurotrophins interact during neural development to influence the development and/or maintenance of functional neural circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNOTOXIC PROPERTIES OF MERCURIC COMPOUNDS Principal Investigator & Institution: Shenker, Bruce J.; Professor and Chair; Pathology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-1994; Project End 31-MAR-2004 Summary: (adapted from the Investigator's abstract): Mercury and its congeners are extremely toxic substances which exist as inorganic mercury (Hg++), organic mercury, and mercury vapor (Hg0). Sources of human exposure to mercury include seafood, seeds, foodstuffs, water, and dental amalgam. In previous studies, the Principal
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Investigator has shown that mercury, at low concentrations, kills human lymphoid cells in a manner consistent with apoptosis. The mitochondrion is the target organelle resulting in development of the permeability transition state and oxidative stress. The hypothesis to be tested in these studies is that exposure to mercury may cause health deficits by impairing host defense mechanisms. In addition, perturbed mitochondrial function provides a major cytotoxic pathway for mercurial compounds. In this proposal, the cascade of events responsible for mercury-induced apoptosis in humans will be further defined. The immunotoxic effects of Hg0 will be characterized to determine if it kills human T cells via apoptosis as a consequence of oxidative stress. The study is divided into four specific aims. The first is to determine if mercury-induced mitochondrial dysfunction is due to direct effects of the toxicant on the expression or function of Bcl-2 protein family members of apoptotic regulatory proteins. The second specific aim is to ascertain if mercury- dependent changes in mitochondrial function promote caspase activity and induce T cell apoptosis. It is proposed that activation of the caspase cascade is a result of mercury-induced mitochondrial permeability transition. The third specific aim is to measure the effect of mercury on (a) the expression and activity of the redox sensitivity transcription factors NF-kB and AP-1, and (b) the expression of novel genes associated with oxidative stress. The fourth specific aim is to determine if Hg0-induces T cell apoptosis and learn if cell death is linked to mitochondrial dysfunction. It is proposed that exposure to Hg0 leads to rapid T cell apoptosis due to physical characteristics of the uncharged species. The goal of this application is to better understand the pathways responsible for mercury toxicity, as well as health implications associated with exposure to mercury-containing compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOTOXICOLOGIC EFFECTS OF MERCURY ON B CELLS Principal Investigator & Institution: Monestier, Marc; Professor; Microbiology and Immunology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2003; Project Start 18-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Human exposure to various chemical or pollutants is associated with an increased incidence of autoimmune diseases. Nevertheless, there are only a few useful animal models to study the mechanisms of chemically induced autoimmunity. In genetically susceptible mice, subtoxic doses of mercury elicit a complex autoimmune syndrome with production of highly specific IgG antinucleolar antibodies and a polyclonal increase in serum IgG1 and IgE. Mercury exposure affects various components of the immune system and, in this proposal; we plan to characterize the effects of mercury on B cells. Our preliminary data lead us to propose the hypothesis that mercury accelerates B cell maturation in the periphery and that mercury triggers secondary immunoglobulin gene rearrangements. In Specific Aim 1, we will assess how mercury influences the development of peripheral B cell subsets. We are particularly interested in determining whether mercury administration results in the upregulation of RAG proteins and in secondary immunoglobulin rearrangements. In Specific Aim 2, we will examine how mercury affects the expression and regulation of an anti-DNA transgene that has been bred onto a mercury susceptible genetic background. In Specific Aim 3, we will generate mice that possess a site directed transgene for an antinucleolar antibody. We will characterize the regulation of these B cells and evaluate their responses to mercury exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNOTOXICOLOGY OF A HEAVY METAL Principal Investigator & Institution: Pollard, Kenneth Michael.; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAR-2005 Summary: (Applicant's Abstract): Exposure to toxins and chemicals can produce aberrant immune reactions that may include autoimmunity. The observation that eludes explanation is the restriction of the autoantibody response to a single, or a limited number of intracellular antigens the specificity of which appears dependent in part upon the toxin or chemical involved. We have shown that the heavy metal mercury induces a genetically restricted autoantibody response in mice that targets the nucleolar protein fibrillarin. Mercury-induced cell death results in modification of the molecular properties of fibrillarin, however mercury-modified fibrillarin is a poor antigen for HgCI2-induced antifibrillarin autoantibodies. These observations suggest that mercurymodified fibrillarin might be a source of (cryptic) T cell determinants. Immunization studies with bacterial recombinant fibrillarin, modified by mercury, where not successful in eliciting the same spectrum of antifibrillarin antibodies as HgC12treatment. Alternative antigen sources appear more promising, including fragments of fibrillarin produced following cell death associated proteolysis, and eukaryotic cellular material resulting from HgCI2-induced cell death. The investigators propose to continue to examine the immunogenicity of fibrillarin by using eukaryotic expression systems to determine if the nature of the antigen is a limiting factor in autoantibody production. This will be achieved by examination of the fine specificity of anti-fibrillarin antibodies produced by immunization, or HgCI2-treatment. Additional studies will examine the fine specificity of fibrillarin specific T cells, to determine if cryptic epitopes are important in the autoantibody response and whether immunization elicits cryptic epitope specific T cells. The importance of T cell specificity in the anti-fibrillarin autoantibody response will be determined by examining the ability of antigen specific T cells to drive B cells to produce antibody. Analysis of the interaction between fibrillarin, mercury and cells of the lymphoid system may lead to insights into how an imunotoxin renders self-antigen immunogenic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INFANT AND CHILD NEUROTOXICITY STUDIES: Principal Investigator & Institution: Cranmer, Joan M.; Associate Professor; Pediatrics; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2005 Summary: (provided by applicant) The 21st International Neurotoxicology Conference (NTX XXI) will be held Feb. 10-14, 2004 at the Ala Moana hotel in Honolulu, Hawaii. NTX XXI will address the theme Infant and Child Neurotoxicity Studies: Subtle and Long-Term Effects. Studies will focus on methylmercury (MeHg), PCBs, heptachlor, other persistent pollutants and mixtures. The highlight of this conference is that all the major longitudinal children's studies addressing these important pollutants will be presented together for the first time! This will allow a unique opportunity to make significant advances in our understanding of the subtle and latent effects that these chemicals -alone or in combination-may be posing to our children. Justification for Hawaii Venue: Results of two major research efforts involving Hawaiians and others from the Pacific Rim will be presented for the first time at this conference. These two major themes require the meeting to be held on Oahu. The two areas are: (1) The Hawaii Heptachlor Study (20-yr study results) and (2) Persistent Pesticides and the Honolulu-
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Mercury
Hawaii-Asia Aging Cohort. The Hawaii Heptachlor Research and Education Foundation promised Hawaiian citizens that the results of the Heptachlor Children's Study first would be reported to the Hawaiian community. The last day of the conference will be a "Report Back to the Community" in a Public Session devoted to the Hawaii Heptachlor Study 20 years after the initial pollution. Specific Aims: (1) To provide an internationally recognized, interdisciplinary scientific forum for presentation of the major longitudinal children's studies investigating the low-level, long-term effects of MeHg, PCBs, lead, heptachlor, other pesticides and mixtures. (2) To conduct an Open Public Forum/Town Meeting for clinical and basic scientists, clinicians and the citizens of Hawaii who were involved in the 20-year Heptachlor studies. To facilitate communication between the researchers, and the parents & children from Hawaii who were exposed to Heptachlor to discuss the implications of study results. (3) To convene scientists from different sectors to exchange data and theories regarding the etiology, mechanisms, diagnosis, treatment and prevention of environmentally-induced diseases or disorders of the nervous system in the fetus, infant, child, adolescent, and latent effects in the adult. To provide an established venue and ample time for informal scientific exchange to establish and promote collaborations and networking worldwide. (4) To encourage, mentor and recognize student researchers and young neurotoxicologists by offering predoctoral and post-doctoral awards (cash and plaques, travel scholarships, mentoring and networking opportunities. (5) To organize the keynote presentations, tutorials, invited and free presentations, discussions, demonstrations and interactions to document, major new research advances, facilitate identification of specific research gaps and potential experimental designs to answer questions. (6) To rapidly peer review and disseminate findings to the scientific community. The overall goal will be accomplished by organizing and conducting a five-day widely-advertised and wellorganized conference according to the format of previous conferences in this wellestablished Neurotoxicology Conference series which has proven to be very successful. All presenters are invited to submit original research papers of new data presented and/or summaries of recent findings related to the specific topics in the Program. Papers will be peer-reviewed and rapidly published (less than one year) in Neurotoxicology, an international scientific journal that is widely disseminated, indexed, abstracted and available online. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERMEMBRANE HYDROPEROXIDES
TRANSFER
OF
CHOLESTEROL
Principal Investigator & Institution: Girotti, Albert W.; Professor; Biochemistry; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 05-MAY-2001; Project End 30-APR-2004 Summary: Cholesterol (Ch), the most prominent sterol of mammalian cells, is located predominantly in the plasma membrane, where it comprises 40-45 mol percent of the total lipid. Like other unsaturated lipids, Ch can be oxidized under conditions of cytotoxic oxidative stress. Among the oxidation products, cholesterol hydroperoxides (ChOOHs) are highly important because they can undergo iron-catalyzed 1-electron reduction, thereby triggering chain peroxidation reactions which expand the boundaries of membrane oxidative damage. Alternatively, ChOOHs may undergo glutathionedependent 2-electron reductive detoxification if a selenoperoxidase (SePX) is encountered. Superimposed on these alternate fates (which are under study in the parent project) is the possibility that ChOOHs can move (or be transferred) from one membrane to another, either within or between cells. Little is known about this
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prospect. In this proposal to investigate ChOOH transfer, two hypotheses will be tested: (i) ChOOHs, being more polar than Ch, will translocate relatively rapidly from donor to acceptor membranes, and this can be enhanced by a sterol carrier protein; (ii) ChOOH transfer can be hazardous to an acceptor if its antioxidant capabilities are overwhelmed. The specific aims of the project are to examine: (i) spontaneous intermembrane transfer of ChOOHs (ii) sterol carrier protein-mediated intermembrane transfer of ChOOHs, and (iii) spontaneous vs. protein-facilitated transfer to mammalian cells and its cytotoxic consequences. The studies will involve, liposomal membranes, erythrocyte membranes, aortic endothelial cells, selenium and iron manipulation, and two unique analytical techniques developed during past interactions between the Principal Investigator and Co-investigator: high performance liquid chromatography with mercury cathode electrochemical detection, and high performance thin layer chromatography with radioimaging detection. In addition to strengthening collaborative ties between the host and foreign laboratories, these studies will provide insights into previously unrecognized ways by which cells might be exposed to the prooxidant/cytotoxic effects of ChOOHs. The work is biomedically significant because disorders such as atherogenesis and neurodegeneration are associated with lipid peroxidation, and ChOOH transfer may promote this process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LOW COST, ACCURATE, PORTABLE BLOOD LEAD ANALYZER Principal Investigator & Institution: Lewandowski, Jan J.; Director of Res. & Development; Biomec, Inc. 1771 E 30Th St Cleveland, Oh 44114 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-MAY-2003 Summary: We will develop a low cost, accurate, portable blood lead analyzer. The device will utilize a unique miniature rotating microsample system, which can be incorporated into a fluidic chip. The electrochemistry of the system is equivalent to the performance of a typical rotating electrode but no moving mechanical parts are required. Anodic Stripping Voltammetry and Potential Stripping Analysis techniques will be evaluated. Based on preliminary data, it is expected that the device will be capable of providing blood lead determinations with the accuracy and sensitivity required by the CDC. Lead poisoning is the most common environmental health problem affecting children. The irreversible neurotoxic effects of childhood blood-lead at low concentrations, that do not cause immediate clinical symptoms, are now well documented. The present lack of inexpensive but accurate blood determination techniques prevents necessary widespread screening programs. Our device will be an order of magnitude cheaper than Atomic Absorption Spectroscopy systems and the blood lead analyses will be so inexpensive that widespread screening will be feasible. The proposed device can be easily adapted for determination of other toxic heavy metals such as mercury or cadmium. PROPOSED COMMERCIAL APPLICATIONS: The results of a cost-to-benefit analysis of blood level screening programs was presented in the CDC's report "Costs and benefits of Universal Screening Program for Elevated Lead Levels in 1 year old children". According to this document, the current average cost of blood lead screening is $60 per child. At this price the economic benefits of screening program exceed the costs of screening when the prevalence of the elevated blood level in the child population is 14% or greater. Our estimate is that the proposed device will reduce cost per assay to $10 or less. This will be accomplished by lowering of the direct cost of the assay and reducing the cost of sample withdrawal (finger piercing vs. venipuncture). Additionally the device will not require expensive, highly trained lab personnel to operate it.
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Mercury
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LSM SCANDHEAD W META DETECTOR & 405 NM LASER Principal Investigator & Institution: Wandinger-Ness, Angela U.; Associate Professor; Pathology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2005 Summary: (provided by applicant): New instrumentation and probes offer unparalleled opportunities for molecular imaging. By applying these technologies it is now possible to monitor the proximities of molecules and trace their movements and interactions in real time using multiple fluorophore combinations. At the University of New Mexico, eight NIH-funded investigators mapping brain gene expression or defining membrane trafficking, signal transduction and adhesion mechanisms form a core user group whose research depends heavily on the application of such sophisticated biological imaging technologies. A Center for Spatiotemporal Imaging has been established to develop new algorithms for three-dimensional modeling and image qunatification. Three of the investigators participating in the center and five others constitute major users of a Zeiss LSM 510 and a recently installed BioRad Radiance both located in our Shared Cancer Center Microscopy Facility. In this application we are requesting funds for the purchase of a new Zeiss scanhead equipped with META detector and 405 nm laser to be mounted on an existing Axiovert microscope. The requested insmnnentation is necessary to enable simultaneous imaging of larger numbers of fluorophores including those in the UV range. In addition, several users have secured the photoactivable GFP isoform and demonstrated the utility of this new probe for their experiments. Although the probe can be activated by a mercury lamp, as shown by our proof of principle experiments, a 405 nm laser with AOTF is essential for these applications to take advantage of the spatial and temporal imaging capabilities afforded by this probe. Half of the users routinely conduct FRET experiments and are in need of the META detector's linear spectral unmixing functions to obtain quantitative and spatial information. Close interactions with investigators at Sandia National Laboratories will allow the immediate application of new multivariate curve resolution algorithms for the quantification and analysis of the multispectral data obtained with the META detector. Thus, the user group is uniquely poised to exploit new imaging probes and technologies with the proposed instrumentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MANIPULATION OF THE NOS PATHWAY IN ARTERIAL DISEASE Principal Investigator & Institution: Cooke, John P.; Associate Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Under certain conditions, NO synthesis is disturbed, and this may contribute to the progression of atherosclerosis, and impair angiogenic response. The impairment of the NO synthase pathway may be due in part to an endogenous NOS inhibitor ADMA (asymmetric dimethylarginine). In patients with peripheral arterial disease (PAD), ADMA levels are elevated. In these individuals L-arginine enhances NO synthesis and improves limb blood flow. Our proposal is designed to determine if chronic administration of L-arginine will cause a sustained enhancement of limb blood flow, and will reduce symptoms in individuals with PAD. We will also determine if these effects are accompanied by anti- atherogenic and/or pro-angiogenic effects of NO
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biosynthesis. Patients with PAD will be entered into a randomized placebo-controlled clinical trial to assess the effects of L-arginine upon functional status (treadmill exercise testing; quality of life) and limb blood (by mercury strain gauge plethysmography). We will determine if NO biosynthesis is involved in the effects of L-arginine by: function of duplex ultrasonography of flow-mediated vasodilation. We will assess limb hemodynamics (by Doppler-derived pressures, plethysmography, and by MR perfusion imaging), conduit vessel structure (using magnetic resonance angiography); and evidence of angiogenesis using novel MR algorithms (to include flow-independent imaging, manipulation, manipulation of 3-dimensional data sets, and use of oxygen saturation effects on T2 relaxation time). These studies will determine if prolonged Larginine treatment may have effects upon vascular structure, lesion size and/or angiogenesis. These studies may lead to a novel and cost-effective strategy for treatment of peripheral arterial disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF THIMEROSAL INDUCED NEUROTOXICITY Principal Investigator & Institution: Kiningham, Kinsley K.; Pharmacology; Marshall University Huntington, Wv 25701 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): Mercurials are potent neurotoxins, which localize to both neurons and glia within the central nervous system and elicit a range of deleterious actions. Sodium ethylmercurithiosalicylate (thimerosal) is a widely used ethyl mercury containing preservative used in over-the-counter medications, cleaners and cosmetics. Recent concern has been raised on the use of thimerosal in over 30 vaccines licensed in the United States. With the addition of several important vaccines over the last few years, exposure to mercury has increased among infants, leading some investigators to suggest an association between thimerosal exposure and autism. There is limited toxicological information regarding ethyl mercury; therefore, estimates of health risks from thimerosal exposure have been based on mechanistic studies of methyl mercury, a close chemical relative about which much is known. These estimates may actually underestimate the toxicity of ethyl mercury containing agents. The wide use of thimerosal makes understanding the mechanism(s) of its toxicity a significant human health issue. The overall goal of this project is to investigate the mechanism by which thimerosal causes neuronal cell death. The hypothesis to be tested is that thimerosal results in dose-dependent activation of specific signaling molecules and redox-sensitive transcription factors known to activate pro-death genes in neurons. If this hypothesis is correct then pharmacological intervention should attenuate toxicity as a result of thimerosal exposure. Using a human neuroblastoma cell line, SK-N-SH, this project will test the hypothesis in four specific aims. Aim 1 will identify in a dose-dependent manner the predominant cell death pathway (apoptotic versus necrotic) associated with thimerosal exposure and to determine if it is associated with an increase in reactive oxygen species and caspase-3 dependent. Aim 2 will determine if cell death is mediated through an AP-1-dependent pathway. In addition, this specific aim will establish the role of c-Jun-N-terminal kinase; an enzyme, which phosphorylates and activates AP-1, in thimerosal-mediated neuronal death. Aim 3 will determine if the cell death pathway is mediated through an NFkappaB-dependent mechanism. Aim 4 will determine if thimerosal toxicity can be attenuated by the administration of S-adenosylmethionine, an enzyme which increases endogenous levels of glutathione. This project will generate mechanistic data on thimerosal neurotoxicity and potentially identify specific targets for pharmacological intervention.
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Mercury
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS FOR RENAL UPTAKE OF MERCURY Principal Investigator & Institution: Bridges, Christy C.; Basic Medical Sciences; Mercer University Macon Macon, Ga 312070001 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Mercury is a significant environmental and occupational health hazard in many countries, including the United States. The primary site of mercury toxicity is the kidney, specifically the pars recta of the proximal tubule. Based on current data, we have formulated the following hypothesis: Inorganic mercury is taken up at the luminal and basolateral plasma membranes of the proximal tubular epithelium as a conjugate of thiol-containing biomolecules and this uptake occurs via known transporters, such as amino acid- and organic anion- transporters, through a mechanism involving molecular mimicry. The luminal uptake of mercuric ions is thought to involve amino acid transporters such as systems b0,+ , B0,+, or system ASC, while the basolateral uptake of mercury is thought to involve the organic anion transporters 1 and 3. To study the role of various transporters in the uptake of mercury, isolated perfused tubules will be used. In order to study the role of individual transporters, Xenopus oocytes will be injected with individual transporter RNA and Madin-Darby Canine Kidney and NRK- 52E cells will be stably transfected with individual amino acid- and organic anion- transport proteins. The role of each carrier in the transport of mercuric ions will be tested using functional biochemical assays. These experiments will also determine the specific species of mercury that is taken up at the plasma membrane. These studies are important in that they will determine the exact mechanisms that participate in the transport of mercury across the plasma membranes of the proximal tubular cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF METHYLMERCURY INDUCED NEURONAL TOXICITY Principal Investigator & Institution: Aschner, Michael; Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Methylmercury (MeHg) is a significant environmental contaminant that continues to pose a great risk to human health. Considerable attention in the scientific and health policy fora is focused on the question of whether MeHg intake from a diet high in fish is associated with aberrant CNS function. A number of recent studies (Kjellstrom et al., 1986, 1989; McKeon-Eyssen et al., 1983; Grandjean et al., 1997) suggest that fetal exposure at levels attained by mothers eating fish regularly during pregnancy are associated with neurological deficits in their offspring. Astrocytes play a key role in MeHg-induced excitotoxicity. [1] MeHg preferentially accumulates in astrocytes. [2] MeHg potently and specifically inhibits glutamate uptake in astrocytes. [3] Neuronal function is secondary to disturbances in astrocytes. [4] co-application of nontoxic concentrations of mercury and glutamate leads to the typical appearance of neuronal lesions associated with excitotoxic stimulation. [5] MeHg induces swelling in astrocytes. These observations are fully consistent with MeHg-induced dysregulation of excitatory amino acid homeostasis, and indicate that a glutamate-mediated excitotoxic mechanism is involved. The working hypotheses of the proposal outline a number of critical target sites for MeHg-induced neurotoxicity. In
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Specific Aim 1.0 we will test the hypothesis that activation of the astrocyte-specific enzyme, cytosolic phospholipase A2 (cPLA2) and the ensuing hydrolysis and release of arachidonic acid (AA) are mediators of glutamate release upon exposure to MeHg. We will investigate the lipase(s) involved, and determine the relationship between cPLA2 activation, regulatory volume decrease (RVD), and glutamate release. In specific Aim 2.0, we will test the hypothesis that MeHg-induced increased extracellular glutamate concentrations will competitively inhibit cystine transport into astrocytes, leading to diminished supply of cysteine for neuronal glutathione (GSH) synthesis. In Specific Aim 3.0, we will test the hypothesis that modification of cysteine residues by MeHg is associated with altered glutamate transport, and that it is regulated by the chemical redox-state of reactive cysteine residues in the astrocyte-specific glutamate transporters, GLAST and GLT1. The studies will be carried out in rat primary cultures of neurons and astrocytes, as well as Chinese hamster ovary (CHO-K1) cells (where transporters can be over expressed in cells that lack the endogenous glutamate transporter). Our approach will encompass a broad array of methods, including molecular biology, electrophysiology, radiolabel trans-membrane fluxes, and electrical impedance measurements of cell volume. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MERCURY ASSOCIATED NEUROBEHAVIORAL DEFICIT IN CHILDREN Principal Investigator & Institution: Grandjean, Philippe A.; Professor; Environmental Health; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-DEC-2002 Summary: Methylmercury is an important contaminant of seafood and freshwater fish worldwide. Although tragic pollution episodes have demonstrated that the fetal brain is particularly susceptible to methylmercury toxicity, the upper limit for safe mercury exposure is unknown. A birth cohort of 1,000 children was formed during 1986 to 87 at the Faroe Islands, where increase exposure to methylmercury is mainly due to consumption of pilot whale meat. The fishing community is unique and highly suitable for population-based studies or prenatal methylmercury neurotoxicity: Average mercury exposures vary more than a 100-fold within the population, and socioeconomic factors and other confounding variables are of only limited concern. Ninety percent of the children from the cohort went through extensive neurobehavioral examinations at age 7 years, and the results showed mild deficits associated with prenatal exposures that were previously thought to be safe. These data will be scrutinized further statistically and neuropsychologically. In addition, to determine the long-term implications and the potential reversibility of mercury-associated deficits, follow-up of the cohort at age 14 years will be carried out. Neurobehavioral performance will be related to several mercury exposure biomarkers that reflect both prenatal and postnatal exposures. Exposures to polychlorinated biphenyls (PCBs) will also be assessed and analyzed for their possible neurobehavioral effects. Advanced statistical methods will be applied to provide documentation that can be used directly in risk assessment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METALLOREGULATION BY MERR AND FUR PROTEIN FAMILIES Principal Investigator & Institution: O'halloran, Thomas V.; Professor; Chemistry; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 28-FEB-2006
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Mercury
Summary: (applicant's description): Metal ion sensory mechanisms are critical for cellular responses to essential and toxic metals alike. Emerging from studies of microbial metalloregulatory systems are general models that serve as starting points for understanding the cell biology of metals in humans. The MerR and Fur families of metalloregulatory proteins control the expression of an array of genes that protect the eubacterial cell from physical and chemical stresses including antibiotic treatments. In a variety of virulent microbes, Fur or a closely related iron-sensor protein controls toxin expression. A general but controversial mechanism for iron-responsive derepression has been proposed but is as of yet unresolved. Mechanistic studies of these mercury and iron sensor proteins are now beginning to provide insights into zinc and copperresponsive metalloregulation. The E. coli ZntR protein, a recently discovered member of the MerR family, is a zinc-specific metalloregulatory protein that controls expression of zinc export machinery. Its counterpart, the Zur protein, is a member of the Fur family that exerts zinc-responsive control over the expression of zinc uptake machinery. Together these genes govern zinc uptake and export, ensuring that cells experience neither zinc starvation nor toxicity. In both cases the mechanisms of transcriptional control or the molecular basis of metal recognition are not yet established. This proposal focuses on energetic and structural aspects of metal recognition and metal-induced conformation changes in the allosteric switching mechanism. MerR controls transcription in an unprecedented manner: metal-protein interactions induce distortions in DNA structure that make the DNA a better template for the transcription machinery. By comparing the positive control mechanism for other family members such as ZntR, a comprehensive test of this DNA distortion mechanism is possible. Positive control mechanisms are poorly understood and yet are of fundamental importance in understanding the molecular basis of genetic regulation. The molecular basis of heavy metal recognition in the ZntR, Zur, and Fur systems will be probed at the biopolymer and coordination chemistry levels. The structure, function, and energetic insights of these new stress-responsive transcription factors will provide a deeper understanding of molecular mechanisms and transition metal cell biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHYL MERCURY EVALUATION IN DENTAL WASTE WATER Principal Investigator & Institution: Drummond, James L.; Professor; Restorative Dentistry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Quantifiable particulate, soluble and even methylmercury concentrations are detectable in the Dental waste water (DWW) stream during the removal of amalgam from the oral cavity through aspiration with high vacuum suction. These toxic compounds are discharged into the sanitary sewer system and eventually into the environment, to be taken up by microbes, plants and animals and through the food chain to impact on human mercury consumption. The objectives of this project are to quantify the inorganic and organic concentrations in Dental wastewater, to identify the bacteria in biofilms of the discharge environment and to specifically identify the microbial activities involved in oxidation from metallic Hg(O) to ionic Hg(ll). In addition, other objectives are to determine the reverse reduction enzymatic reaction, the methylation of Hg(lI) to monomethyl-mercury, and finally to specify bacteria responsible for mercury metabolism in DWW biofilms. Specific Aim 1: Analyze mercury concentrations both inorganic and organic in DWW. Hypothesis:Amalgam waste loads correlate to methyl-mercury yields. Specific Aim 2: Classify bacterial species in Dental wastewater lines. Hypothesis: Bacterial species in the
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Dental sewage pipe biofilms include those from the oral biofilms (e.g. plaque), but more likely are the normal environmental bacteria found growing in other piped water biofilms, from sources not involved with Dental water units. Specific Aim 3: Identify specific bacterial species involved in mercury conversion. Hypothesis: Element mercury released in DWW is converted to Hg(lI) and then in more limited amounts to methylmercury by specific biofilm bacterial species in the Dental sewage pipes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHYLMERCURY TRANSPORT ACROSS CELL MEMBRANES Principal Investigator & Institution: Ballatori, Nazzareno A.; Associate Professor of Environmental Med; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-SEP-1993; Project End 31-AUG-2006 Summary: The overall objective of this laboratory is to identify those factors that underlie human susceptibility to methylmercury (MeHg) poisoning. MeHg is a highly toxic environmental pollutant: clinical and experimental studies demonstrate that exposure to MeHg results in neurologic damage characterized by ataxia, sensory disturbances and changes in mental state. The only way to prevent or ameliorate toxicity once MeHg has been ingested is to accelerate its removal from the body. Our goal is to identify and characterize the mechanisms by which MeHg crosses cell membranes to reach its target sites, or conversely, to be eliminated from the cell. This information is critical both for defining mechanisms of toxicity, and for developing effective biomarkers of exposure and therapeutic strategies. Our previous work provided the first direct demonstration of the mechanism by which MeHg crosses the blood-brain barrier to reach its target tissue, and of the mechanism by which MeHg is transported across the liver cell canalicular membrane into bile, a major route for its excretion. Recent studies have also identified a novel antidote for MeHg, namely N-acetylcysteine (NAC). Our working hypothesis is that NAC enhances urinary MeHg excretion because it leads to the formation of the anionic MeHg-NAC complex, which is a substrate for the renal organic anion transporters. The proposed studies aim to characterize these MeHg transport mechanisms at the molecular and cellular level. Our Specific Aims are: I. Examine the mechanism by which the MeHg-L-cysteine complex is transported on the L-type amino acid transporters LAT1 and LAT2. II. Test whether the MeHg-glutathione complex (MeHg-SG) is a substrate for some members of the MRP family of transporters. III. Evaluate the molecular mechanism by which NAC stimulates renal excretion of MeHg. IV. Test the hypothesis that urinary excretion of MeHg following an NAC oral challenge may be used as a new biomarker of MeHg exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR IMMUNOTOXICITY
MECHANISMS
OF
MERCURY-INDUCED
Principal Investigator & Institution: Reddy, P Gopal.; Tuskegee University Tuskegee Institute, Al 36088 Timing: Fiscal Year 2002; Project Start 01-JUN-1978; Project End 30-JUN-2006 Summary: (provided by applicant): The main goal of the proposed project is to further delineate the molecular mechanisms involved in mercury-induced immunotoxicity. Exposure to mercury at low levels may alter immune parameters before it causes any clinically apparent manifestations. Even subtle immune system alterations may indirectly affect ability to resist microbial infections or development of cancers. Previous
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studies have shown that Brown Norway (BN) rats are highly susceptible for the development of autoimmune disease conditions but the molecular mechanisms including the involvement of Th1 and Th2 responses are not fully delineated. In a preliminary study, we have shown predominance of Th2 type responses in Sprague Dawley (SD) rats given oral gavage of mercuric chloride. We propose to develop a comprehensive data base that is needed to clarify the Th1/Th2 cell responses in the development of mercury-induced immunotoxicity. In the proposed project, we will study the effects of methyl-mercury using an in vivo protocol with both BN and SD rats and an in vitro protocol using human peripheral blood lymphocytes. We will study the status of Th1 cytokines, interferon-gamma, Interleukin-2 (IL-2) and Th2 cytokines, IL-4 and IL-10. We will employ several different assays including: real-time quantitative RTPCR, ribonuclease protection assay (RPM, ELISA, and ELISPOT. These different assays targeting the Th1/Th2 cell responses are expected to give us detailed information on the expression of the cytokines at the level of both transcription and protein production. It will also give us some information on the status of cells involved in the secretion of these cytokines. We will compare the immune cells of BN and SD rats as well as human cells for activation markers CD25 (Il-2R alpha) and MHC class II antigens, and for various apoptosis markers, FAS, FASL, bcl-x (L), bcl-x (5), bax, bcl-2, and caspases 1, 2, 3. We will compare serum samples of BN and SD rats for immune-mediated disease markers including anti-nuclear antibody (ANA), circulating immune complexes, and Creactive protein. To study whether mercury-induced alterations of the immune responses adversely affect host disease resistance mechanisms, we will experimentally infect the rats with Pseudomonas aeruginosa and study the morbidity and mortality. These in vitro and in vivo data will help us further delineate the molecular mechanisms involved in mercury-induced immunotoxicity which may be useful for planning immunomodulatory and immunotherapeutic measures in subjects exposed to mercury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROTOXICITY OF METHYLMERCURY ACROSS THE LIFESPAN Principal Investigator & Institution: Newland, M. Christopher.; Professor; Psychology; Auburn University at Auburn Auburn University, Al 36849 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (ADAPTED FROM APPLICANT'S ABSTRACT) Fetal exposure to methylmercury (MeHg) has long-lasting effects on sensory-motor function, schedulecontrolled behavior, learning (not memory) and sensitivity to certain behaviorally active drugs. Human and animal studies now associate developmental or adult MeHg exposure with age-related declines in certain behavioral functions. Nutritional influences also modify mercury's neurotoxicity, although how these interact through the lifespan is not well understood. This is important both mechanistically and because of concerns that a low RfD for MeHg would decrease consumption of fish, a source of selenium and n-3 fatty acids, especially docosahexanoic acid (DHA). In previous work, rats on a chow diet consuming 40 or 500 mg/kg/day Hg (as MeHg) showed age- and dose-related decrements on high-rate operant behavior, retarded learning, and altered sensitivity to amphetamine and pentobarbital. Proposed studies extend these observations by examining age and diet as modifiers of MeHg's neurobehavioral toxicity. High-rate operant behavior will be examined using a refined procedure (targeted percentile schedule) that maintains high response rates but without lowering reinforcement rates if behavior deteriorates. Concurrent schedule performance in transition, which now can be conducted in single sessions, will be the measure of learning. Fixed-interval (FI) schedule performance will be examined per se and as a
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baseline for drug challenges. Female rats will start one of three diets (modified semipurified, DHA-enriched, Se-enriched) for two weeks, then MeHg exposure (0. 0.5, or 5 ppm in drinking water) for two weeks, then they will be mated. Maternal rats will continue the diets and mercury exposure to 30 months of age, and their behavior examined under a targeted percentile schedule of reinforcement. During this time they will receive selected drug challenges. At death mercury levels in blood and brain, Se (in the Se cohort) and DHA in the DHA cohort) will be examined. Offspring will be maintained on the different diets and used as follows: 1) Hg and Se or FA profile determination PN1; 2) FI schedule performance in transition with drug challenges: 3) Targeted percentile schdule performance, and 4) Concurrent schedule performance in transition with drug challenges. Items 2-4 will be conducted as adults and 3-4 to 30 months of age. At death Hg and either Se or FA profiles will be determined, depending on the cohort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL 199HG NMR METHODS FOR MONITORING PROTEIN FOLDING Principal Investigator & Institution: Bebout, Deborah C.; Chemistry; College of William and Mary Williamsburg, Va 23187 Timing: Fiscal Year 1999; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (Adapted from the applicant's abstract) Abnormalities in protein folding are associated with a growing list of human diseases. Characterization of the origin of these abnormalities at the atomic level is hindered by difficulties in monitoring specific interactions during the folding process. Nuclear magnetic resonance (NMR) spectroscopy is one of the few techniques employed for the study of protein folding that can provide information at the atomic level. Because proteins are very rich in NMRactive protons, the resulting proton-based NMR spectra are rarely fully resolvable. The class of proteins that require cofactors for folding provide an opportunity to study the folding process by monitoring the NMR signal of the cofactor. The proposed work will focus on the use of 199Hg as a probe of metalloprotein folding. Two-dimensional {1H199Hg} NMR methods will be developed to highlight the biomolecular interactions during the folding process. These studies will also provide a new tool for investigating the pathology of environmental exposure to mercury and certain other metals. X-ray crystallographic methods will be employed to determine the structures of a diverse library of Hg(II) coordination compounds using synthetic ligand models of protein metal-binding sites. This library will extend our knowledge of biologically relevant structure-spectroscopy relationships for 199Hg chemical shifts and coupling constants between 199Hg and 1H in solution and the solid state. Isostructural complexes of other transition metals with favorable NMR properties will be prepared to initiate a systematic comparison of their relative merits as metallobioprobes. Finally, the Hg(II) coordination chemistry of a variety of potentially metal-coordinating cyclic dipeptides will be examined using X-ray crystallography and NMR as a prelude to the application of these new techniques to metalloproteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NUCLEAR RECEPTOR COACTIVATORS AND BREAST CANCER Principal Investigator & Institution: Zhu, Yijun; Pathology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 15-JUN-2000; Project End 31-MAY-2005
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Summary: The investigator is a senior resident in Clinical Pathology Training at Northwestern University Medical School, who will be board-eligible in the spring of year 2000. He will join the Department of Pathology as Assistant Professor, tenureeligible Investigator-Clinician track, beginning April 1, 2000, to develop an independent hypothesis driven basic research program focusing on the role of nuclear receptor coactivators in development, differentiation and neoplastic conversion in breast induced by natural and synthetic ligands of nuclear receptors. Northwestern University provides an excellent environment for research dealing with nuclear receptors, transcription factors, and nuclear receptor coactivators on the responses of genes, cells, tissues, and species to the influence of natural and synthetic agonists and antagonists. Strong programs in molecular mechanisms of xenobiotic mediated transcriptional activation of genes exist with nationally recognized leaders dealing with: peroxisome proliferators (Drs. J. K. Reddy, T. Hashimoto, and M. S. Rao), responses of cells to environmental stress and altered gene products (Dr. R. Morimoto), molecular mechanisms of copper, mercury and other trace metal toxicity and the role of metallochaperones (Dr. T. O'Halloran), transcriptional corepressors and coactivators (thyroid and estrogen receptor action, Dr. L. Jameson; mitochondrial gene regulation, Dr. R. Scarpulla; and coactivators in cell cycle regulation Dr. B. Thimmapaya), and prevention of breast cancer using antiestrogens tamoxifen and raloxifene (Dr. C. Jordan). Some of these individuals also serve as preceptors on the pre- and postdoctoral Molecular Toxicology Training Program (NIEHS) at Northwestern University. The goal of the mentored Clinical Scientist Development Program is to fully train Dr. Yijun Zhu in an integrated and highly interactive atmosphere in the area of molecular mechanisms responsible for gene expression and in exploring the relevance of single and multiple gene defects in the overall phenotypic outcome by developing transgenic and gene knockout mice. The proposed training program will enable the candidate to enhance his scientific foundation of critical thinking and experimentation. He will also acquire the skills necessary to effectively and intensely interface in the clinical pathology laboratories, in a subspecialty diagnostics area in a major academic medical center. The proposed research focuses on the role of PBP, a peroxisome proliferator activated receptor-binding protein, in breast development and neoplastic conversion. Dr. Zhu cloned PBP, identified it as a nuclear receptor coactivator and found that it is amplified and overexpressed in some human breast cancers. Since a variety of phytoestrogens and environmental endocrine disrupting chemicals possess estrogen receptor activity, exploration of interactions of PBP with estrogen receptor and p53 and the development of transgenic models of overexpression of PBP and the gene disruption model of PBP deficiency will provide fundamental clues as to the role of coactivators in development, differentiation and neoplastic conversion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ON-SITE TRACE METALS TEST FOR MEDICAL AND OTHER SAMPLES Principal Investigator & Institution: Dietze, William T.; Tracedetect, Inc. 180 N Canal St Seattle, Wa 98103 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2004 Summary: (Applicant's abstract) OC Technologies, LLC (d.b.a. TraceDetect) is dedicated to the development and commercialization of a suite of trace-metal monitors based on a new, patented technology. The work detailed in this proposal will commercialize this technology for point-of-care use in a clinical setting. The goal of this research is to move metals monitoring out of the analytical labs and to the point-of-interest/care. The sensor
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detects metals at trace and ultra-trace levels: the detection limit is in the low parts-perbillion (0.1 micrograms per deciliter) range. Coupled with instantaneous results and superior accuracy, these detection limits will provide with accurate and point-of-care screening for toxic metals in children, adults, and their environment. To support in costeffective screening we will develop reliable and inexpensive disposable sensors and identify simple sample preparation techniques for blood, saliva, soil, and dust. This monitor will measure lead, mercury, and cadmium in biological fluids at parts per billion (ppb) and sub-ppb levels. It will also measure these contaminants in water and other aqueous solutions at the same detection levels, making it suitable for many applications, from municipal water and industrial process control to the environmental, analytical, and work place safety markets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORGANOCHLORINES AND METALS IN NEW YORK AND THE HUDSON Principal Investigator & Institution: Landrigan, Philip J.; Professor of Environmental Medicine; Community and Preventive Med; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-MAY-1995; Project End 31-MAR-2005 Summary: (Taken from application) The Mount Sinai Superfund Basic Research Program is a coordinated, interdisciplinary program of research, training, community outreach and public health intervention. The program?s goal is to prevent disease, developmental dysfunction and environmental degradation associated with organochlorines and heavy metals. Biomedical studies in the program focus on neurobiological, endocrine and reproductive outcomes. The geographic focus is the watershed of the lower Hudson River and New York City, a 300-km long, densely populated, heavily industrialized region that is contaminated by a complex mix of organochlorines - PCBs, DDT, chlordane, dieldrin, and dioxins - as well as by heavy metals, especially lead and mercury. EPA has declared the lower Hudson River the nation s longest Superfund site. Research projects in this program will examine: 1) environmental sources, distribution and fate of organochlorines in the lower Hudson River and New York Harbor; 2) inhibition of cell membrane efflux pumps by organochlorines, a possible novel mechanism of estrogenic action; 3) disruption by organochlorines of the Wnt gene pathway in the female reproductive tract, a possible molecular genetic mechanism of developmental toxicity; 4) interactions of organochlorine exposures and genetic polymorphisms in the genesis of Parkinson's Disease; 5) cumulative exposures to organochlorines and heavy metals in urban anglers who eat fish and shellfish from the lower Hudson River and New York Harbor; 6) Environmental sources, distribution and fate of heavy metals; 7) mobilization of stored lead from bone during pregnancy and lactation, a possible risk factor for neurodevelopmental toxicity. The program includes a Community-Based Prevention/Intervention Research Project, "Preventing Fetal Neurotoxicity by Reducing Local Fish Consumption: An Education Intervention among Women in New York City." It contains support cores in Biostatistics and Data Management, Exposure Assessment, Stable Lead Isotope Analysis and Genetic Analysis. The Outreach Core seeks to empower urban communities affected by hazardous wastes through partnerships in environmental education. The multi-tiered Training Core offers a range of programs in environmental education that extends from high school through the graduate level. The Administrative Core integrates the work of the entire program and translates the results
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of research into prevention-centered public policy through coordinating our efforts in communications, technology transfer and government liaison. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT -- EFFECTS OF MERCURIC CHLORIDE ON MALE REPRODUCTION Principal Investigator & Institution: Atkinson, Alfonza W.; Tuskegee University Tuskegee Institute, Al 36088 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-MAY-2008 Summary: Abstract: Effects of mercuric chloride (MC) on the reproductive performance of two successive generations of rats were evaluated in our laboratory. Significant differences resulting from exposure of the F0 generations to MC were found in implantation efficiency, fertility, live births, day 4 survival indices, litter size, and body weights of F1 pups. Limitations of this study design were its inability to determine which sex, male, female or both, may have contributed most to the reproductive and fertility effects, and the lack of a detailed semen evaluation that is critical in the assessment of the male reproductive system after exposure to environmental toxicants. In order to determine which sex was responsible for adverse effects on reproduction, a crossover mating trial is planned with the control and high dose groups. The long-term goals of the research proposed here are to 1. Test the hypothesis that reduced fertility seen in the F0 generation of the study by Atkinson et al 2001 results from exposure of male rats to MC. 2. Test the hypothesis that MC-induced reduced fertility may have resulted from deficits in epididymal sperm function (number, morphology and motility) and/or lower testosterone. 3. Test the hypothesis that MC-induced decreased testicular weights and serum testosterone levels may have resulted from increased apoptosis in germ and/or somatic cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT -- MOLECULAR MECHANISMS OF MERCURY INDUCED IMMUNOTOXICITY Principal Investigator & Institution: Reddy, Gopal; Tuskegee University Tuskegee Institute, Al 36088 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-MAY-2008 Summary: Deleterious effects of environmental toxicants such as mercury affect the poor and minorities first and most dramatically. Mercury levels in the environment have been rising 2-5 fold over the last century and 1.5% per year since 1970. Environmental Protection Agency (EPA) lists mercury as a hazardous air pollutant under Title Ill of the federal Clean Air Act. The main goal of the proposed five year project is to further delineate the molecular mechanisms involved in mercury-induced immunotoxicity. Exposure to mercury even at low levels may cause subtle immune system alterations which may indirectly affect ability to resist microbial infections or development of cancers. Mercury may have a devastating effect on the immune system of the neonatal child, but this aspect has not been well studied. Previous studies have shown that mercury may induce autoimmunity, especially in Brown-Norway (BN) rats or in some cases immunosuppression. In the proposed project, we will study the effects of methylmercury chloride (CH3HgCI) using both BN and Sprague-Dawley (SD) rats. We will also study the effects of CH3HgCI on the neonatal immune system in weanling pups by exposing pregnant and lactating rats of both BN and SD strains. Using DNA microarray technology, we will study the changes in cytokine gene expression in
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lymphoid cells exposed to CH3HgCI in vitro or in vivo as compared to control cells. Based on the results, we will study in-depth, the status of some important Th1 and Th2 cytokines. We will employ both realtime quantitative RT-PCR, ribonuclease protection assay (RPA) and ELISA. These different assays targeting the Th1/Th2 cell responses are expected to give us detailed information on the expression of the cytokines at the level of both transcription and protein production. We will study the control and mercuryexposed immune cells of adult and neonatal rats for activation markers, CD25 (IL-2R alpha) and MHC class II antigens and serum samples for antinuclear antibody, Creactive protein and circulating immune complexes. To study whether mercury-induced alterations of the immune responses adversely affect host disease resistance mechanisms in vivo, we will experimentally infect the weanling rats with Pseudomonas aeruginosa and study the morbidity and mortality. Comparison of the data obtained using adult and neonatal BN rats which are susceptible to mercury-induced autoimmune-like disease with that of SD rats and correlation of cytokine profiles with the expression of markers for activation and autoimmune disease as well as resistance to infection, will help us further delineate the molecular mechanisms involved in mercury-induced immunotoxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYAMINE-MODULATED TUMORIGENESIS
HISTONE
ACETYLATION
IN
Principal Investigator & Institution: Gilmour, Susan K.; Investigator; Lankenau Institute for Medical Research Wynnewood, Pa 19096 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Omithine decarboxylase (ODC) is a key regulatory enzyme in the biosynthesis of polyamines which are essential for normal cell growth and differentiation. Although ODC overexpression is not sufficient to induce tumors in normal cells, we have demonstrated that elevated levels of ODC and polyamines cooperate with activated Ha-ras to promote epithelial tumor formation and invasion. Due to their cationic nature, polyamines have been suspected to affect overall chromosome conformation, thereby contributing to transcriptional regulation. Recently it has been shown that histone acetyltransferase (HAT) and deacetylase (HDAC) activities intrinsic to some transcriptional control proteins are targeted to various gene promoters causing dynamic remodeling of chromatin and leading to the activation or repression of transcription. Elevated levels of ODC and polyamines alter the expression of a number of genes that are associated with proliferation and differentiation. Significantly, we have found that they also promote changes in histone acetylation which can be reversed with the specific ODC inhibitor, alpha-difluoromethylomithine. The overall goal of this project is to determine how polyamines mediate changes in the chromatin environment, and the consequences for gene expression in the context of epithelial tumorgenesis. Thus, we propose the following specific aims: 1. To establish a link between polyamine induced alterations in histone acetylation and transcriptional activity of impacted genes which are key to malignant transformation of epidermal cells by: a. identifying specific genes that are transcriptionally regulated by polyamines using representative difference analysis (RDA) of transcriptionally competent genomic DNA purified by chromatin immunoprecipitation (ChIP) or mercury affinity chromatography, and b. verifying altered acetylation of nucleosomes associated with promoters of genes transcriptionally regulated by polyamines in cells or tissue expressing high versus normal levels of ODC. 2. To identify the mechanism(s) by which polyamines modulate the function of HATs and HDACs in the skin. Using reporter
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gene-based strategies, we will: 1) determine the role of HAT/HDAC enzymatic activities in mediating polyamine effects on reporter gene transactivation or repression, and 2) examine the effect of elevated levels of polyamines on the interactions between various protein components of chromatin remodeling complexes that are involved in targeting HATs and HDACs to specific gene promoters. We will also begin to characterize/identify the HAT(s) responsible for the aberrantly high HAT activity observed in tumors from ODC/Ras double transgenic mice. 3.To elucidate the individual mechanism(s) by which polyamines modulate the remodeling of chromatin at promoters of specific genes that are differentially acetylated and whose expression is correspondingly altered in response to ODC overexpression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PORTABLE ARSENIC MONITOR FOR DRINKING WATER Principal Investigator & Institution: Cepak, Veronica M.; Eltron Research, Inc. 4600 Nautilus Ct S Boulder, Co 803013241 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2005 Summary: (provided by applicant): This proposal describes a program to develop a small, portable, low-power electrochemical monitor to detect dissolved arsenic in drinking water. A non-toxic, renewable, microfabricated sensor chip integrated into a compact rnicrofluidic flow system is proposed and will be designed to detect both arsenate and arsenite in water based on a sensitive voltammetric method. This method will allow analysis of arsenic without significant dilution or reduction in the sensitivity of the detected analyte. The flow-cell sensor will use non-mercury microelectrodes which will enhance the sensitivity and limit of detection compared to conventional sized electrodes of millimeter dimensions. The device will also use a simple pump and valve system for both electrolyte and analyte introduction into the sensor and simple, proven electrochemical instrumentation for arsenic detection. Electrochemical detection of arsenic in aqueous samples is cost-effective and will find use for in situ monitoring of drinking water and surface waters. Our proposed monitor will eliminate the need to collect samples in the field for subsequent analysis and will be more sensitive than currently available colorimetric field kits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRENATAL AND NEONATAL BIOLOGIC MARKERS FOR AUTISM Principal Investigator & Institution: Croen, Lisa A.; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): Autism is a serious behaviorally defined disorder whose prevalence appears to be increasing dramatically. In response to Program Announcement PA-01-051, we propose a nested case control study to evaluate the association between the risk of autism and several biologic markers with the potential to impact neurodevelopment that can be measured in archived maternal sera specimens collected in early pregnancy and neonatal blood specimens collected in the first few days of life. The study population will be drawn from the cohort of women who were pregnant in Orange county, California, who participated in the state-mandated prenatal expanded alpha-fetoprotein screening program (XAFP), and who delivered a live born infant between July 2000 - September 2001. Three groups of children born to women in the cohort will be identified. Cases (n=100) will be children enrolled in the Regional Center of Orange County (RCOC) with a diagnosis of autism with or without mental
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retardation (MR). One set of controls will be children with MR but not autism (n=100), also identified from RCOC. The second set of controls will be general population controls (n=100), randomly sampled from the population of live births in Orange and surrounding counties, frequency matched to the cases on birth year, county of residence at birth, and gender. Verification of autism and MR diagnoses will be based on thorough abstraction of diagnostic and clinical information contained in the RCOC medical records followed by expert clinical review. Maternal early pregnancy blood specimens will be obtained from the Project Baby's Breath maternal XAFP specimen bank. This unique resource will allow us to conduct a retrospective nested case-control study using prospectively collected biologic specimens from a time period critical to fetal neurodevelopment. Several analytes that are known or suspected to play a key role in early brain development will be examined, including antibodies to viral infections, cytokines, autoantibodies to neural tissue and thyroid peroxidase, free thyroxine, TSH, testosterone, estradiol, selected neuropeptides and neurotrophins, and selected metals. We will also incorporate results from routine neonatal screening, and demographic and perinatal data routinely recorded on the birth certificate. Results from this study will provide direction for future investigations of prenatal and neonatal specimens already archived in California and investigations of specimen banks now being created in Norway and other countries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRENATAL PCB EXPOSURE AND ACUTE STRESS REACTIVITY Principal Investigator & Institution: Gump, Brooks B.; Assistant Professor; Psychology; College at Oswego Oswego, Ny 13126 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: This application proposes to test the hypothesis that young children (10 years of age) with gestational exposure to the environmental toxicants found in Lake Ontario fish (e.g., PCBs, mercury, cadmium) will exhibit exaggerated responses to acute stress. Preliminary evidence suggests that a) newborns with highest gestational exposure to contaminants found in Lake Ontario fish have significantly poorer habituation recoveries and appear to overreact to stimulation, and b) at 6 months, 4 years, and 6 years of age these children show emotional dysregulation. Emotional dysregulation is frequently associated with corresponding increases in cardiovascular and cortisol reactivity to acute stress, however, psychophysiological reactivity has not yet been investigated in humans with gestational exposure to environmental toxicants. Determining the effects of these environmental toxicants on psychophysiological reactivity to acute stress is important given evidence that a) heightened or prolonged cardiovascular reactivity is associated with pathophysiological processes (e.g., vascular changes, lipid mobilization), and b) heightened cortisol reactivity is associated with psychopathological processes (e.g., social withdrawal, anxiety). The proposed study examines reactivity to acute stress in children currently participating in the Oswego Newborn and Infant Development Project, an ongoing longitudinal study of 224 children born to women interviewed between 1991 and 1994. Extensive data currently exists for these children, including background sociodemographic characteristics (e.g., socioeconomic status, maternal health behaviors) and gestational toxicant exposure levels determined by maternal dietary recall and cord blood levels. The proposed laboratory protocol will provide a) assessment of emotional, cardiovascular, and cortisol reactivity to mildly stressful events, and b) assessment of a number of psychosocial variables (e.g., anxiety, depression). Important features of this proposed study include a) the participation of children currently involved in a longitudinal study and, therefore,
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no new recruitment, b) an assessment of a full range of possible consequences of gestational exposure to environmental toxicants, including emotional, cardiovascular, and cortisol reactivity, and c) the ability to relate these emotional and psychophysiological outcomes to the large set of existing data for these children (e.g., cognitive functioning). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRENATAL PCB EXPOSURE AND COGNITIVE DEVELOPMENT Principal Investigator & Institution: Stewart, Paul W.; Psychology; College at Oswego Oswego, Ny 13126 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The current project investigates the effects of prenatal exposure to polychlorinated biphenyls (PCBs) n cognitive development in school-age children. The Oswego Newborn and Infant Development Project tracks the development of 224 children born to women who did or did not consume Great Lakes fish during pregnancy. An established database of umbilical cord levels of PCBs, DDE, Mirex, HCB, lead, EP and hair mercury are on file for every child in the project. In addition, an extensive database of demographic, substance use, and labor/delivery variables containing well over 100 potentially confounding or mediating variables is interleaved with the cord blood database. These data, combined with extremely low project attrition over the past 6 years, provides the opportunity to assess the impact of PCBs and related contaminants on cognitive development. Recent data from the Oswego Newborn and Infant Development Project indicates that prenatal exposure to PCBs impairs cognitive functioning in children as early as 1 and 3 years of age. The project will now track their progress into the early school-age years. This will be accomplished through the use of domain-specific and global cognitive assessment batteries including the Sternberg test of cognitive processing efficiency, The Wechsler Intelligence Scale for Children (WISC III), and the Woodcock-Johnson Psychoeducational Battery. In addition, behavioral functions shown to be repeatedly affected by PCBs and lead in animal models, specifically fixed-interval performance, will be assessed in the children. All outcome measures will be related to the cord blood database of PCBs, lead, DDE, HCB, Mirex, and mercury levels. Further, analysis of tissue-banked Placenta indicate that the PCB concentration exceeds cord-blood levels by 3-4 orders of magnitude. Analysis of the placenta will dramatically enhance exposure assessment through the virtual absence of any placenta PCB data below the detection limit. Control of over 100 potentially confounding variables will be assessed in a multivariate model. The current project will provide critically needed answers to questions surrounding the putative effects of low level PCB exposure on cognitive and behavioral development, and whether the effects of PCBs and related contaminants on standard psychometric batteries translate into functional deficits in school-related performance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROXIMITRY SURGICAL PROBE Principal Investigator & Institution: Devito, Raymond P.; Constellation Technology Corporation 7887 Bryan Diary Rd, Ste 100 Largo, Fl 33777 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2004 Summary: (provided by applicant): An intraoperative surgical probe using a mercuric iodide radiation detector is proposed. The probe will have the ability to simultaneously measure the 140 keV gamma-ray emission and the 18 keV x-ray emission from Tc-99m.
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Good energy resolution is necessary for the lower energy x-rays to separate them from the potentially large scatter background. Comparison of the measured strength of the xray and gamma ray transitions provides a sensitive indicator of the depth in soft tissue of the radioactive source. This adds to the capability of surgical probes by providing a third dimension of position sensitivity. Current state-of-the art probes do not provide accurate, if any source depth information. The surgeon can use this depth information to more accurately locate margins and metastases. An experimental evaluation of the detectors is proposed, leading to specification of how to configure detectors for this application and verification that the method is feasible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RED CELL AQUAPORIN-1 WATER TRANSPORT PROTEIN Principal Investigator & Institution: Agre, Peter C.; Professor; Biological Chemistry; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-1985; Project End 31-MAR-2005 Summary: The human red cell membrane is the model upon which our general understanding of plasma membranes is based. Several membrane transport proteins have first been identified in red cells, and during previous years of this project, a 28kDa protein was discovered, purified, cloned, expressed and functionally defined in Dr. Agre's laboratory. Now designated AQP1, this protein is the first recognized membrane water transport molecule. While multiple homologous aquaporins are now becoming recognized in other tissues, physical studies of human red cell AQP1 are revealing its structure at subnanometer resolution and are providing advanced insight into the biophysical transport function of the molecule. Here Dr. Agre proposes studies to establish the molecular structure of AQP1 at near-atomic resolution and to define the behavior of AQP1 in membranes. Aim I. Structure and function of purified AQP1 protein. High resolution cryoelectron microscopic analysis of membrane crystals containing red cell AQP1 will be undertaken to elucidate the 3D structure of AQP1 at better than 3 resolution. Yeast and other heterologous systems will be developed to express mutagenized AQP1 molecules with specific epitopes for affinity-purifications, metal binding, definition of the aqueous pore, identification of the sites of ion repulsion and assembly of individual subunits into tetramers. Functional analysis of mutagenized forms of AQP1 will be determined by direct measurement of the water permeability of AQP1 proteins in yeast microsomal vesicles and in reconstituted proteoliposomes. Aim II. AQP1 protein in cell membranes. The Colton blood group antigens result from a polymorphism in the first extracellular loop of the AQP1 protein. Using fluorescently labeled-anti-Co, Dr. Agre plans to characterize the surface equilibrium distributions of AQP1 on normal red cells by immunofluorescence, immunoprecipitations, and flow sorting. Kinetic distributions of AQP1 in red cell membranes will be undertaken with anti-Co by measurement of fluorescence recovery after photobleaching. Similar studies will be performed on enzymatically modified red cells and red cells from patients with sickle cell anemia and other congenital hemolytic states. These abnormal red cells and AQP1 deficient red cells will also be examined for membrane water permeabilities. To fully define the molecular determinants of the Co antigen, nonerythroid cells will be studied for Co expression by transfection with mutagenized forms of AQP1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RENAL TRANSPORT OF ORGANIC CHELATORS OF HEAVY METALS Principal Investigator & Institution: Wright, Stephen H.; Professor; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Adapted from the Applicant's Abstract): The long term goal of the proposed program of research is to understand the cellular mechanisms associated with the entrance and exit from renal cells of organic conjugates and chelates of heavy metals. Because these complexes carry a net negative charge, it has been assumed that the classical 'renal organic anion secretory pathway' plays a central role in the renal elimination of these compounds. While this may be true, there is no direct evidence that uptake or elimination of metal-containing complexes involves this process. Indeed, the cellular basis for clearance of anionic metal chelates from intoxicated cells is unknown. The mechanism by which the kidney secretes organic anions (OAs) has, in fact, received considerable attention, and a cellular model of OA secretion, for which paminohippurate (PAH) is considered the prototypic substrate, has been widely accepted. New evidence, however, suggests that renal OA secretion involves several distinct transporters with overlapping selectivity. Consequently, the overarching goal of the this study, i.e., establishing the mechanism of renal transport of anionic metal complexes, must be placed into the following context: the several, distinct mechanisms involved in renal transport of organic anions (OAs) have only recently begun to be identified, and the relative role played by each in renal secretion is largely unknown. We outline here, in two Specific Aims, experiments that examine characteristics of individual OA transporters, and their integrated behavior when working in concert with multiple processes in native renal tubules. We focus on several transporters: OAT1 (renal organic anion transporter); OAT-K2 (a renal homologue of the organic anion transporting polypeptide); and Mrp2 (the apical membrane homologue of the family of multidrug resistance-associated transport proteins). These transporters were selected because current evidence on their substrate specificity and their distribution within renal proximal tubules suggests that they can interact with anionic chelators and/or their heavy metal chelates. In Aim 1, we will determine, using heterologous expression systems, the extent to which these OA transporters interact with a common set of test substrates and inhibitors (including the anionic chelator 2,3-dimercapto-lpropanesulfonate [DMSP] and its mercury and arsenic-containing chelates). The information obtained in these experiments will be applied in Aim 2, which will examine the integrated behavior of these processes in (i) a model cell culture system containing selected combinations of these processes; and (ii) intact proximal tubules in which OA secretion is the product of a suite of transporters working in the physiological contex of the intact cell. The studies with intact tubules will include direct tests of the hypothesis that DMPS-metal chelates are exported from renal cells through interaction with Mrp2 and OAT-K2. The proposed studies will result in a new, general model of the cellular strategy for secretion of a diverse array of xenobiotic OAs, and a more specific understanding of the action of heavy metal chelators on renal cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SOUTH BRONX EJ PARTNERSHIP AND ETHICAL ISSUES IN EH Principal Investigator & Institution: Strelnick, a H.; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007
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Summary: (provided by applicant) The mission of the South Bronx Environmental Justice Partnership (SBEJP) is to improve the health of the people who live and work in the South Bronx, beginning with children and pregnant women, and expanding to include other adults. SBEJP is a partnership between the Montefiore Medical Center (MMC), Albert Einstein College of Medicine (AECOM), and South Bronx Clean Air Coalition (SBCAC). The SBEJP Advisory Board will include representatives of other community organizations. In this proposal, the SBEJP proposes to explore the most appropriate methods for addressing the social, ethical, and legal challenges arising from non-therapeutic, epidemiological research on the prevalence of elevated mercury levels in urine of children living in the South Bronx and its possible sources. The specific aims of the SBEJP are as follows: 1) To assess the South Bronx community's level of knowledge regarding the health impacts of environmental mercury and its sources in the local environment. 2) To develop, implement, and evaluate educational materials and programs that enhance the South Bronx's community awareness of the ethical issues and challenges related to conducting environmental health research on mercury. 3) To develop a community-driven educational intervention to reduce childhood exposure to mercury in the South Bronx for both community residents and health professionals informed by on-going dialogue with its community and spiritual leaders, clergy, bioethicists, and scientific and clinical experts. 4) Establish an on-going and long-term dialogue between SBEJP environmental health scientists, clinicians, bioethicists, community members, clergy, and spiritual leaders on ethical issues related to environmental health research on the ritual use of elemental mercury as a case study or model. Formal evaluation will be conducted of all specific activities, including formative, process, and outcome evaluations, and will be the responsibility of the principal investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL INVESTIGATIONS OF METALLOPROTEIN METAL SITES Principal Investigator & Institution: Penner-Hahn, James E.; Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 30-NOV-2004 Summary: (Adapted from applicant's abstract) The long term objective of this proposal is to characterize in detail the structural and functional properties of Zn(II) in biological systems. Zinc is the most common metal found in metalloproteins and is the only metal that is known to be required for every major class of enzyme catalysis. Hundreds of zinc proteins have been isolated and thousands of potential zinc binding sites have been identified in protein sequences. Imbalances in the levels of Zn, or errors in its transport or regulation can have profound health consequence. Despite its importance, there is relatively little information available about biological Zn(II) sites due to the difficulty of studying this spectroscopically "silent" metal. X-ray absorption spectroscopy, one of the few methods able to provide structural information for non-crystalline materials, will be used to determine their structures. Three major, inter-related objectives are proposed: X-ray absorption spectroscopy will be used to characterize the Zn binding sites in a series of important proteins, with particular emphasis on a novel class of Zn-alkyl transfer enzymes. -Detailed comparisons will be made of the metal binding sites in a series of structurally defined peptides. The objective of this second set of experiments is to determine the relative importance of metal stereochemical preference and protein structure in defining the structure of a metal binding site. For this work, structures will
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be compared for a series of spectroscopically silent d10 metal ions (Cu(I), (Ag(I), Cd(II), Hg(II)) and metalloids As(III). -X-ray absorption spectroscopy, x-ray microprobe imaging, microprobe spectroscopy, and x-ray microtomography will be used to characterize the role(s) of Zn in embryo development in zebra fish and Xenopus laevis. Spatially and temporally-resolved spectroscopy will be used to determine the Zn speciation in developing embryos. Coupled capillary-electrophoresis/x-ray fluorescence will be used to resolve and characterize Zn containing proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE/FUNCTION OF MEMBRANE PROTEIN CHANNELS Principal Investigator & Institution: Mitra, Alok K.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-MAY-1995; Project End 31-JUL-2002 Summary: The objective of this proposal is to understand structural details in the bilayer that relate to transport properties of membrane protein channels. Specifically, we wish to understand the structure/function relationships for the mammalian water channels AQP1 and AQP4 and the pore-forming anthrax toxin protective antigen by highresolution electron crystallography. Our specific aims are listed below. AIM I. Examine at the structural level the inhibition of water transport in AQP1 by mercurial compounds. We will apply electron diffraction to quantitate in 3-dimensions structural changes in AQP1 upon mercurial binding. This will allow us to understand AQP1 function based on its modulation by the pharmacological inhibitor. AIM II. Examine the structural/functional roles of residues involved in the selective water transport in AQP1. We will examine the functional roles of polar and charged amino acids in the putative membrane-spanning region of AQP1 using a combined functional and structural approach. Amino-acid substitutions that lead to altered function without structural perturbation will allow us to identify residues critical for water transport. AIM III. Structural studies on the AQP4 water channel. The AQP4 water channel expressed primarily in brain elicits highest osmotic water permeability. We will crystallize AQP4 in the lipid bilayer and use it as a model to understand and identify at the structural level factors responsible for diversity in solute transport mediated by aquaporins. AIM IV. Structural studies on anthrax toxin protective antigen. The structure of the soluble and membrane-integrated complex of protective antigen (PA63) heptamers with and without bound lethal factor (LF) will be studied using single particle image analysis and conical-tilt reconstructions. This will allow us to understand the binding of LF and test the proposed porin-like model for the membrane-embedded domain of PA63. The selective expression of AQP1 and homologous water channels believed to be involved in fluid absorption and/or secretion makes them an important pharmacological target. The pore-forming anthrax toxin has been shown to have a potential for delivery of macromolecules across the bilayer. Thus structural studies on these systems will potentially have impact on structure-based drug design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STUDY OF PREVALENT NEUROTOXICANTS IN CHILDREN Principal Investigator & Institution: Lanphear, Bruce P.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 29-SEP-2006 Summary: (provided by applicant) Exposure to numerous environmental agents, including lead, mercury, PCBs, and environmental tobacco smoke, has been linked with
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adverse neurobehavioral effects. Still, the ideal biomarker fof measuring in utero exposure to specific toxicants has not been established and the adverse effects of many potential neurotoxicants have not been rigorously tested. Fetal exposure is typically measured with self-reported surveys, maternal blood and urine, or cord blood. In contrast, meconium as a biomarker is a non-invasive method to simultaneously test for cumulative exposures to numerous toxicants. But it is unclear whether conventional biomarkers or meconium levels are more predictive of the adverse effects linked with specific toxicants. For lead exposure, emerging data indicate that our efforts should emphasize primary prevention, but the efficacy of lead hazard controls are uncertain, especially for children with low blood lead concentrations. The investigators propose to conduct a cohort study of 400 children, followed from less than 16 weeks gestation to 36 months if age, to examine the effect of low-level exposures to prevalent neurotoxicants. Endpoints include behavioral problems, such as conduct disorder and features consistent with ADHD, cognitive deficits, and hearing loss. The investigators will also conduct a nested, randomized controlled trial to test the efficacy of lead hazard controls on the development of adverse neurobehavioral effects. They will test the following hypotheses: 1) Children in the Lead Reduction Group will have blood lead levels that are 2.7 ug/dL (30%) or lower, significantly higher cognitive scores, less hearing loss, and fewer behavioral problems than one Control group at 36 months of age. 2) Fetal and postnatal exposures to pesticides, ETS and lead (at blood levels below 10 ug/dL) are associated with adverse neurobehavioral effects, growth delay and hearing loss in early childhood. 3) Fetal exposures, as measured by survey (ETS), maternal and cord blood (lead, methyl mercury, pesticides and ETS), and urine (pesticides), are less predictive of the adverse effects of toxicants on cognition, behavioral problems and hearing, compared with the same toxicants in meconium. This project, in combination with the research described in Project 2, will test the efficacy of an intervention for the primary prevention of lead toxicity, as measured by lead concentration and neurobehavioral functioning at 36 months of age, serve as a model to evaluate the adverse effects of exposures to multiple prevalent toxicants among fetuses and children test meconium levels as a biomarker of fetal exposure to numerous toxicants, and provide exposure and risk assessment data for residential pesticides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUPERFUND TOXIC SUBSTANCES--EXPOSURE AND DISEASE Principal Investigator & Institution: Kelsey, Karl T.; Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-APR-1992; Project End 31-MAR-2005 Summary: Our theme is the understanding and assessment of risk to human health from exposure to hazardous substances. We approach this theme from the perspective of an interdisciplinary team that integrates exposure assessment, biologic pathogenesis, and epidemiologic studies. Our biomedical studies revolve around three classes of illness: reproductive health, cardio-respiratory health, and cancer. Our non-biomedical studies relate to health of the ecosystem and to factors that affect aquatic organisms. These studies encompass specific exposures to metals and to organo-chlorine compounds. Reproductive health is being evaluated in relation to environmental exposure to lead, mercury, polychlorinated biphenyls (PCBs) and related compounds; cardio-respiratory health is being evaluated in relation to occupational exposure to fuel oil ash, which contains a high level of vanadium and other metals; the occurrence of cancer and its precursors are being evaluated in relation to arsenic in drinking water supplies; the health of the ecosystem, specifically of aquatic organisms, is being evaluated in relation
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to the presence of metals, PCBs, and polyaromatic hydrocarbons (PAHs). Our general goal is to evaluate the relation between chemicals in the environment and their relation to human ill health. Our objectives include the following: - to assess the use of calcium supplements to minimize the adverse effects of lead on the fetus - to assess uncertainties in development effects in children related to multiple environmental exposure to metals and organic compounds - to evaluate the effects of in utero exposure to ambient levels of PCBs on growth and development of the child and on female reproductive health. - to evaluate the cardiac and respiratory effects of fuel-ash oil on the human lung and to determine the mechanism through which vanadium and other metallic components of fuel-ash adversely effect the heart and the lung - to evaluate the nature of the association between arsenic and skin and skin bladder cancers and their precursors and to assess the epigenetic mechanisms through which arsenic may affect human health - to evaluate the effects of these and related chemicals on the aquatic ecosystem so that a comprehensive approach can be developed to assess the health of the ecosystem - to develop an approach for exposure assessment and health evaluation in the community that will enable enlightened interaction between scientists and the community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNTHESIS OF NUCLEIC ACID AND NUCLEOTIDE METAL COMPLEXES Principal Investigator & Institution: Marzilli, Luigi G.; Professor and Chairman; Chemistry; Louisiana State Univ A&M Col Baton Rouge Office of Sponsored Programs Baton Rouge, La 70803 Timing: Fiscal Year 2002; Project Start 01-SEP-1980; Project End 30-JUN-2004 Summary: (verbatim from applicant's abstract) My aim is to define the fundamental chemical principles of metal interactions with nucleic acids and nucleotides. Recently we have made observations that greatly alter important concepts about cisplatin-DNA adducts with guanines cross-linked by an N7-Pt-N7 motif. This valuable anticancer therapeutic agent, used clinically for treating cancers with growing incidence, is predicted to have continued importance well into the future. In the generally accepted hypothesis, interaction of proteins (including enzymes) with the distorted PtDNA initiates the stream of biological events causing cancer cell death. The large number of proteins found to interact with the lesion has created a lack of consensus on the biological mechanism that plagues this crucial field. Also, the world-wide effort to find a superior drug has failed, despite the testing of over 3,000 analogues differing in the carrier ligands. I hypothesize that both serious biomedical problems result from an inadequate understanding of the cisplatin adduct chemistry; this chemistry is intractable because the drug's simplicity affords few handles for elucidating the chemistry. I also hypothesize that very large and rapid dynamic motions centered at the Pt of DNA GN7Pt-GN7 cross-link lesions occur but have not been appreciated fully by investigators. We test these hypotheses through a deliberate unique retro-modeling strategy using isomerically pure complexes with carrier ligands designed to provide the needed handles and to decrease adduct motion. We have slowed the dynamic processes by a billion-fold, thereby uncovering numerous novel N7-Pt-N7 cross-link properties undetectable by traditional approaches to Pt drug chemistry. Many of these properties could not have been foreseen, and they raise hypotheses about the PtDNA chemistry that might bestow on cisplatin its remarkable activity. I propose to advance this retromodeling chemistry to test several new hypotheses relating to DNA duplex adducts, including (a) the existence and possible importance of single-stranded regions and novel lesion conformers, (b) the formation of cross-links, and (c) the influence of carrier ligand
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NH groups on structure and dynamics. Our approach will yield a new class of synthetic cisplatin analogs acting as biosensors; these biosensors will bear an identifiable imprint of adduct conformation in DNA polymers and have advantages in spectroscopic studies. Also, we will construct stable less fluxional Pt-oligonucleotide duplexes, which will be available as tools for probing biological mechanisms. Our unprecedented findings have significance beyond the field of anticancer drugs since we are identifying novel nucleic acid structures and the spectroscopic signatures such unusual structures possess. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF METALS IN OSTEOARTHRITIS Principal Investigator & Institution: Jordan, Joanne M.; Associate Professor; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: Symptomatic osteoarthritis (OA) of the knee and hip is common, the leading cause of disability and diminished quality of life among those 65 years of age and older, and responsible for a large proportion of the costs associated with joint replacement surgery and other direct and indirect health costs(I-10). As the population in the United States ages, this problem can only be expected to increase(9). Despite the high personal and societal costs of knee and hip OA, few modifiable risk factors for its occurrence or progression have been identified (11; 12). Heavy metals are ubiquitous, and exposure through drinking water, contaminated food, pesticides, and other means, is widespread in our society(13-18). This proposal introduces chronic metal exposures as novel, potentially modifiable risk factors for thc incidence and progression of knee and hip OA and its consequences. The study population is the Johnston County Osteoarthritis Project, an ongoing longitudinal study of OA in African-Americans and Caucasians in a rural county of North Carolina. The research plan adds the collection of additional biological specimens, namely whole blood and toenails, to the already funded examinations of the cohort to establish a resource for current and future examinations of multiple metals in OA and OA-related outcomes. Whole blood will be analyzed for lead at the Centers for Disease Control and Prevention, and toenails will be analyzed for mercury and selenium by instrtmaental neutron activation analysis at the University of Missouri-Columbia Research Reactor Center. Multiple logistic regression will be used to test associations between these metals and incidence and progression of radiographic knee and hip OA, knee and hip symptoms, and disability. By dovetailing this proposal with the funded cohort, costs are minimized, and efficiency and utility maximized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THERMALLY INDUCED CHANGES IN DENTAL PORCELAIN EXPANSION Principal Investigator & Institution: Mackert, Rodway J.; Professor; Oral Surgery; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2002; Project Start 01-SEP-1986; Project End 31-JUL-2004 Summary: Despite the weight of scientific evidence, as well as assurances from international health advisory groups, that mercury release from dental amalgam poses no health threat to the general population (Mackert and Berglund, 1997a, b), a number of countries have already placed restrictions on the use of dental amalgam. There is, therefore, a need to perfect biocompatible dental materials such as ceramics so that they can serve as amalgam substitutes in the event of further restriction, or an outright ban,
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on dental amalgam. The research proposed in this application is directed toward developing stronger, less abrasive, and more thermally stable dental ceramics for use in porcelain-fused-to- metal (PFM) and all-ceramic restorations. Ceramics have many desirable properties that make them useful for dental restorations - translucency, chemical durability, and biocompatibility. However, two major problems arise in their use as replacements for tooth structure lost to disease or trauma: their potential for brittle fracture and their capacity to cause abrasive wear of opposing tooth structure (Rosenblum and Schulman, 1997). When porcelains are fused to metal or to a highstrength ceramic core as a means of obviating their shortcomings in the area of strength, the potential for a third problem is introduced - porcelain thermal expansion instability and the resulting thermal incompatibility between the porcelain and the metal or ceramic core. Five specific aims are proposed: 1. To develop firing schedules for various porcelain metal systems to minimize the thermally induced changes in leucite content that lead to thermal expansion changes; 2. To continue modification of porcelains to render them more resistant to thermal expansion changes; 3. To develop a leucitereinforced machinable ceramic that can be strengthened via heat treatment following machining in the CEREC 2 CAD/CIM machine; 4. To develop experimental porcelain with a leucite particle size of less than 4 um as a means of minimizing microcracking, increasing strength, and reducing wear of opposing enamel; and 5. To evaluate the release of Al, Si, and other elements from the experimental ceramics to be developed in the proposed research, compare these release value to those of existing ceramics, and relate them to dietary and other sources of intake of these elements. New ceramic formulations and combinations of nucleating agents will be investigated to reduce the leucite particle size as means to effect these physical properties improvements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOXIC METAL COMPLEXATION BY DE NOVO DESIGNED PEPTIDES Principal Investigator & Institution: Pecoraro, Vincent L.; Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 09-JUN-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Heavy metal poisoning by elements such as mercury, lead, cadmium, and arsenic is a significant human health problem. Understanding the interaction of heavy metals with proteins is essential for defining the mechanism of toxicity, developing ways to minimize human exposure and to provide therapeutic regimens for removal of toxic ions. Our goals are (1) to develop peptide systems that provide a groundwork for the understanding of metalloregulatory proteins and metallochaperones, (2) to develop peptidic systems that can efficiently and selectively sequester heavy metal ions from aqueous solutions, and (3) to understand the thermodynamics and kinetics of metal binding to these designed peptides. To achieve these goals we will use a de novo peptide system based on the three-stranded coiled coil peptide aggregate motif that encapsulates with high affinity single heavy metal ions and provides spectroscopic models of mercury, cadmium and arsenic binding sites in biological systems. We will generate high resolution structures of this peptide system in the presence and absence of these heavy metals, elucidate the kinetic and thermodynamic mechanisms of heavy metal encapsulation, and expand the array of characterized systems to transition metal ions Fe(II), Cu(I), Ni(II), Co(II) and Zn(II). We will also extend the original design to include single chain peptides that encapsulate heavy metals and coiled coils that provide different coordination environments than the
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original design and those that encapsulate more than one heavy metal ion. These studies will expand the foundation of knowledge that has been laid by the scientific community investigating metallopeptide design, metalloregulatory proteins and heavy metal detoxification. These objectives will develop insight into the interplay between metal coordination and apopeptide structure in defining the overall metallopeptide fold, an important aspect of metallopeptide design. Also, development of highly efficient and specific heavy metal sequestering peptides could, ultimately, provide a viable and biodegradable means of removing heavy metals from contaminated water. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOXIC METALS IN THE NORTHEAST: FROM BIOLOGICAL TO ENVIRO Principal Investigator & Institution: Hamilton, Joshua W.; Associate Professor; Pharmacology and Toxicology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-MAY-1995; Project End 31-MAR-2005 Summary: The overall goal of the Dartmouth SBRP Program Project, Toxic Metals in the Northeast: From Biological to Environmental Implications, is to determine the impact of toxic metals found at Superfund sites, at other waste sites, and in the environment on adverse effects on human health and the environment. Eight of the twenty-two agents on the ATSDR priority list. Over 60% of all Superfund sites contain significant toxic metal contamination, and more than 70% of these contain arsenic, which is the top ATSDR agent of concern. The distinct and program-wide focus of this research program is on toxic metals, and particularly on arsenic, which is being examined in all their goals and scientific focus, including chromium, nickel, cadmium, mercury, cobalt and lead. This program consists of five biomedical projects (Projects 1-5), two non-biomedical projects (Projects 6, 7), and three program support cores (Molecular Biology, Trace Metals Analysis and Biostatistics), plus an Administrative core, Training laboratory investigations on the cellular and molecular mechanisms of toxic metal actions in humans and include Project 1 (arsenic-induced vascular disease), Project 2 (arsenic- and chromium- induced cancer), Project 3 (arsenic effects on xenobiotic metabolism) and Project 5 (interactions of toxic metals with cellular proteins). The second includes Project 4 (human epidemiology of arsenic and skin and bladder cancer), Project 6 (sources, fate and third area involves development and implementation of molecular biomarkers of toxic metal exposure and health elucidate the sub-set of genes, mRNAs and proteins whose expression is specifically modified by toxic metal mechanistic laboratory studies and in the ecology and epidemiology projects. The multi- disciplinary nature of this program, combined with its unique program- wide focus on arsenic and other toxic metals, is designed to create and foster an environment for truly inter-disciplinary yet focused research, training and outreach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TOXICITY POPULATION
OF
METHYL
MERCURY
IN
A
FISH
EATING
Principal Investigator & Institution: Clarkson, Thomas W.; Associate Professor; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 21-JUL-2000; Project End 30-JUN-2005
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Summary: Methyl mercury is considered to be a developmental neurotoxicant. However, contrary to expected findings, a longitudinal study in the Seychelles has revealed a positive association between increasing mercury levels, measured in maternal hair prenatally and in infant hair, and enhanced child development. Given that fish consumption the Seychelles is high, and that fish intakes correlate with hair mercury levels, we hypothesize that certain micronutrients in fish may be (a) beneficial the child development and (b) protective against the neurotoxic effects of methyl mercury. We propose to test this hypothesis in a new study of 250 mother-infant pairs recruited in the Seychelles during the first trimester and followed longitudinally until the infants reach 29 months of age using the most sensitive developmental endpoints available. The four likely micronutrients, based on their levels in fish and their documented roles in brain development and prioritized in terms of biological plausibility, are the long chain polyunsaturated fatty acids principally docosahexaenoic acid, iodine, iron and the amino acid taurine. Also, selenium may play a role as a modifier of the toxic action of methyl mercury and, as such, will be included with mercury as an independent variable. Mercury in maternal and infant hair will continue to be used as our primary measure of prenatal and post natal exposures. In addition to direct measures of mercury, micronutrient status and selenium levels in biological samples from mother and infant, a diet survey including fish consumption will be made at selected pre- and postnatal stages of this study. These data will allow us to characterize metabolic interrelationship between fish intake and levels of mercury and micronutrients that should further test the plausibility of our hypothesis. This proposed study should break new scientific grounds on the interrelationship between nutrition and toxicology. Specifically, we expect that data emanating from the project to indicate that nutritional variables must be taken into account in any evaluation of the neurotoxicity of methyl mercury when fish is the principal source of human exposure to mercury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOXICOGENOMICS OF LEAD, MERCURY, AND CADMIUM Principal Investigator & Institution: Ruden, Douglas M.; Environmental Health Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-JAN-2004 Summary: Human activity has resulted in the environmental distribution of many toxic substances, among them the heavy metals that are spread throughout our biosphere. In addition to acute toxic effects in the humans exposed to heavy metals there are more insidious effects of chronic exposure on the development of all organisms. The resulting altered developmental processes produce in human children symptoms such as hyperactivity, changes in sensory function, and changes in cognitive abilities (IQ). Drosophila is a promising model organism to study the effects of heavy metal exposure during development because of (1) the sophisticated understanding of its genetics, and the ease of manipulating its genome; (2) availability of behavioral and morphological assays sensitive to small doses of toxins. Both human and Drosophila cells are thought to induce expression of protective genes upon exposure to certain toxicants. The hypothesis of this proposal is that over-expressing some of the "protective genes" induced by heavy metals will make flies resistant to the behavioral and developmental alterations caused by heavy metal exposure, and conversely, that knocking out some of these genes might make flies more sensitive to heavy metal exposure. To test this hypothesis, Aim 1 is to expose the larvae to environmentally relevant doses of lead, mercury, and cadmium, and to provide data on their effects on cognition, locomotion
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and synaptic function. Aim 2 is to perform DNA microarray analysis heavy metalexposed larvae (exposure will be to NOAEL, LOAEL, and LD50, as determined in the Aim 1, and determine what subsets of genes are most affected, either positively or negatively. Aim 3 is to upregulate, by conditional overexpression, or down regulate, by using existing mutations, the genes with the most significant changes in expression and to determine the effects of the test chemicals on cognition, locomotion, and synaptic function of these genetically altered flies. Results of these studies will identify candidates for the most important genes that are altered during heavy metal exposure in humans, and could well lead to bioassays or treatments for heavy metal exposure at or below NOAEL and LOAEL values. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSPORT AND TOXICITY OF MERCURY IN THE NEPHRON Principal Investigator & Institution: Zalups, Rudolfs K.; Professor; Basic Medical Sciences; Mercer University Macon Macon, Ga 312070001 Timing: Fiscal Year 2002; Project Start 01-JUN-1993; Project End 31-MAY-2007 Summary: (provided by applicant): Mercury is a group IIB transition metal that is a significant environmental and occupational contaminant and hazard in the United States (and other countries). One of the primary target sites where mercuric ions accumulate and induce significant toxic effects is in the kidney. Within the kidneys, mercuric ions accumulate mainly along the three segments of the proximal tubule, although distal segments of the nephron have not been excluded as secondary targets where mercuric ions may be handled. Inorganic mercury appears to be taken up along the three segments of the proximal tubule in a heterogeneous manner. Moreover, at least two distinct sets of mechanisms are involved in the uptake of mercury along the proximal tubule. One of these sets of mechanisms is localized on the luminal membrane and the other is localized on the basolateral membrane. Based on the research we have carried out to date, we have come up with the following central hypothesis: Mercuric conjugates of biologically relevant endogenous thiol-containing molecules (or their metabolites), are 1) the primary transportable species of inorganic mercury in the kidneys, and 2) are taken up by proximal tubular epithelial cells at both the luminal and basolateral membranes by known transporters of other molecules, such as those involved in the transport of amino acids and organic anions, presumably through mechanisms involving molecular homology or "mimicry' One technology we will use to test this hypothesis will include the in vitro stable transfection of a distal-tubular, renalepithelial, cell-line with the genetic code(s) for specific luminal and basolateral transporters presumed to be involved in the transport of mercury. Expression of a transporter in a cell that normally does contain it will permit us to determine if there is a gain of function. More specifically, we will be able to document if transport (and inhibition of transport) of specific mercuric conjugates occurs. The other technology we propose to use is the isolated perfused tubule, which is the only in vitro technique that allows one to access, perfuse, and bathe virtually any intact segment of the nephron to study the characteristics of particular transport systems under biophysical conditions similar to those found in vivo. With these techniques, we will be able to provide the most detailed and comprehensive assessment, to date, of the mechanisms involved in the uptake of inorganic mercuric ions along pars recta segments of the proximal tubule, which are the segments of the nephron most vulnerable to the nephrotoxic effects of mercury Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Mercury
Project Title: X RAY ABSORPTION SPECTROSCOPY OF METALLOENZYMES Principal Investigator & Institution: Scott, Robert A.; Professor and Head; Chemistry; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 30-NOV-2002 Summary: X-ray absorption spectroscopy (XAS) will be used, as a component of multidisciplinary biochemical and biophysical structure/function studies, to provide high-resolution local structural information about metal sites in a number of metallobiochemical systems. Proposed studies focus on the unique contribution to be made by XAS in studying "spectroscopically difficult" metals, including Zn, Cd, Hg, As, Sb. Many of the proposed experiments involve the role of metals in the important biological processes of transcription and its metalloregulation, heavy metal toxicity and resistance, and metal homeostasis. In particular, presumptive metal-binding motifs in basal eucaryal and archaeal transcription factors will be examined for metal binding, specificity, and requirement. The initial target for this effort is TFIIB. Other experiments will characterize the metal-binding residues and coordination environments of the metalloregulatory proteins MerR, ArsR, ArsD, and CadC. The correlation of metal coordination changes and allosteric regulation associated with protein conformational changes will be studied. Site-directed mutagenesis designed to alter the specificity for metal inducers, creating a Cd(II)-sensitive ArsR, for example, will require XAS for metal site characterization. Biophysical characterization of metal-binding affinity and specificity of MerP, a prototypical example of a widely distributed ca. 40-residue sequence motif containing a GmtCxxC sequence (Met2 and Thr3 are nearly conserved) will be carried out. The occurrence of variants of this "heavy metal associated" (HMA) motif in a family of CPx-type ATPases, all of which are involved in heavy metal efflux or homeostasis for mercury, cadmium, and copper (at least), makes a characterization of their specificity particularly attractive. Six copies of these HMA motifs occur near the Ntermini of the products of the MNK and WND genes, which have been associated with the copper-based Menkes and Wilson's diseases, respectively. The use of directed evolution to develop the MerP HMA motif into a specific recognition domain for any given metal ion will require XAS to characterize the metal coordination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “mercury” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for mercury in the PubMed Central database:
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A mercury-thiol affinity system for rapid generation of overlapping labeled DNA fragments for DNA sequencing. by Hartley JL, Chen KK, Donelson JE.; 1982 Jul 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320774
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A new mercury-penicillin V derivative as a probe for ultrastructural localization of penicillin-binding proteins in Escherichia coli. by Paul TR, Halligan NG, Blaszczak LC, Parr TR Jr, Beveridge TJ.; 1992 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206265
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Algal blooms reduce the uptake of toxic methylmercury in freshwater food webs. by Pickhardt PC, Folt CL, Chen CY, Klaue B, Blum JD.; 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123663
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Antimicrobial and mercury resistance in aerobic gram-negative bacilli in fecal flora among persons with and without dental amalgam fillings. by Osterblad M, Leistevuo J, Leistevuo T, Jarvinen H, Pyy L, Tenovuo J, Huovinen P.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162972
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Aspects of Bioavailability of Mercury for Methylation in Pure Cultures of Desulfobulbus propionicus (1pr3). by Benoit JM, Gilmour CC, Mason RP.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92513
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Association of mercury resistance with antibiotic resistance in the gram-negative fecal bacteria of primates. by Wireman J, Liebert CA, Smith T, Summers AO.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168768
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Bacterial Oxidation of Mercury Metal Vapor, Hg(0). by Smith T, Pitts K, McGarvey JA, Summers AO.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106150
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Biodegradation of Phenylmercuric Acetate by Mercury-Resistant Bacteria. by Nelson JD, Blair W, Brinckman FE, Colwell RR, Iverson WP.; 1973 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=379783
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Biotoxicity of mercury as influenced by mercury(II) speciation. by Farrell RE, Germida JJ, Huang PM.; 1990 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184891
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Cadmium- and mercury-resistant Bacillus strains from a salt marsh and from Boston Harbor. by Mahler I, Levinson HS, Wang Y, Halvorson HO.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239224
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Carbon Flow in Mercury Biomethylation by Desulfovibrio desulfuricans. by Berman M, Chase T Jr, Bartha R.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183328
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Cell-free mercury volatilization activity from three marine caulobacter strains. by Ji GY, Salzberg SP, Silver S.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184146
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Cell-Free Mercury(II)-Reducing Activity in a Plasmid-Bearing Strain of Escherichia coli. by Summers AO, Sugarman LI.; 1974 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245595
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Characteristics and Relationships of Mercury-Resistant Mutants and Methionine Auxotrophs of Yeast. by Singh A, Sherman F.; 1974 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246839
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Characterization of a new vacuolar membrane aquaporin sensitive to mercury at a unique site. by Daniels MJ, Chaumont F, Mirkov TE, Chrispeels MJ.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=161122
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Characterization of the OCT plasmid encoding alkane oxidation and mercury resistance in Pseudomonas putida. by Harder PA, Kunz DA.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214470
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Chemical composition of Earth, Venus, and Mercury. by Morgan JW, Anders E.; 1980 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350422
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City bans medical devices that contain mercury. by Sibbald B.; 2003 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139331
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Cloning and expression in Escherichia coli of chromosomal mercury resistance genes from a Bacillus sp. by Wang Y, Mahler I, Levinson HS, Halvorson HO.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213867
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Cloning and expression of Thiobacillus ferrooxidans mercury ion resistance genes in Escherichia coli. by Shiratori T, Inoue C, Sugawara K, Kusano T, Kitagawa Y.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210071
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Cloning and Sequence Analysis of the Mercury Resistance Operon of Streptomyces sp. Strain CHR28 Reveals a Novel Putative Second Regulatory Gene. by Ravel J, DiRuggiero J, Robb FT, Hill RT.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111291
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Cobalamin-mediated mercury methylation by Desulfovibrio desulfuricans LS. by Choi SC, Bartha R.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202093
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Degradation of Methylmercury by Bacteria Isolated from Environmental Samples. by Spangler WJ, Spigarelli JL, Rose JM, Flippin RS, Miller HH.; 1973 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=380848
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Deletions in the r-determinant mer region of plasmid R100-1 selected for loss of mercury hypersensitivy. by Foster TJ, Nakahara H.; 1979 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216811
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Detoxification of mercury, cadmium, and lead in Klebsiella aerogenes NCTC 418 growing in continuous culture. by Aiking H, Govers H, van 't Riet J.; 1985 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238736
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Development of Bacterium-Based Heavy Metal Biosorbents: Enhanced Uptake of Cadmium and Mercury by Escherichia coli Expressing a Metal Binding Motif. by Pazirandeh M, Wells BM, Ryan RL.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106604
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Distribution of DNA Sequences Encoding Narrow- and Broad-Spectrum Mercury Resistance. by Rochelle PA, Wetherbee MK, Olson BH.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183436
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Do recent data from the Seychelles Islands alter the conclusions of the NRC Report on the toxicological effects of methylmercury? by Stern AH, Jacobson JL, Ryan L, Burke TA.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=365028
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Effect of Salinity on Mercury-Methylating Activity of Sulfate-Reducing Bacteria in Estuarine Sediments. by Compeau GC, Bartha R.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203648
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Effects of acidification on mercury methylation, demethylation, and volatilization in sediments from an acid-susceptible lake. by Steffan RJ, Korthals ET, Winfrey MR.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202793
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Effects of chemical speciation in growth media on the toxicity of mercury(II). by Farrell RE, Germida JJ, Huang PM.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182111
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Effects of Cinnabar on Pyrite Oxidation by Thiobacillus ferrooxidans and Cinnabar Mobilization by a Mercury-Resistant Strain. by Baldi F, Olson GJ.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203754
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Effects of dissolved organic carbon and salinity on bioavailability of mercury. by Barkay T, Gillman M, Turner RR.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168746
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Effects of FP2 and a mercury resistance plasmid from Pseudomonas aeruginosa PA103 on exoenzyme production. by Johnson J, Warren RL, Branstrom AA.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269912
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Effects of Glucose Concentrations on Cadmium, Copper, Mercury, and Zinc Toxicity to a Klebsiella sp. by Brynhildsen L, Lundgren BV, Allard B, Rosswall T.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202729
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Effects of Hg2+, CH3-Hg+, and Temperature on the Expression of Mercury Resistance Genes in Environmental Bacteria. by Tsai YL, Olson BH.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184940
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Effects of mercuric chloride on growth and morphology of selected strains of mercury-resistant bacteria. by Vaituzis Z, Nelson JD Jr, Wan LW, Colwell RR.; 1975 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186958
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Enhanced Mercury Biosorption by Bacterial Cells with Surface-Displayed MerR. by Bae W, Wu CH, Kostal J, Mulchandani A, Chen W.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161548
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Enzymatic catalysis of mercury methylation by Desulfovibrio desulfuricans LS. by Choi SC, Chase T Jr, Bartha R.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201479
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Estimation of health effects of prenatal methylmercury exposure using structural equation models. by Budtz-Jorgensen E, Keiding N, Grandjean P, Weihe P.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149391
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Evidence for a staphylococcal-like mercury resistance gene in Enterococcus faecalis. by Zscheck KK, Murray BE.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171805
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Evolution of complex resistance transposons from an ancestral mercury transposon. by Tanaka M, Yamamoto T, Sawai T.; 1983 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221794
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Ferrous Iron-Dependent Volatilization of Mercury by the Plasma Membrane of Thiobacillus ferrooxidans. by Iwahori K, Takeuchi F, Kamimura K, Sugio T.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92226
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Formation of methyl mercury by bacteria. by Hamdy MK, Noyes OR.; 1975 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187198
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Genetic Engineering of Escherichia coli for Enhanced Uptake and Bioaccumulation of Mercury. by Bae W, Mehra RK, Mulchandani A, Chen W.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93311
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High-frequency chromosome transfer in Rhodopseudomonas sphaeroides promoted by broad-host-range plasmid RP1 carrying mercury transposon Tn501. by Pemberton JM, Bowen AR.; 1981 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216014
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Homologous metalloregulatory proteins from both gram-positive and gram-negative bacteria control transcription of mercury resistance operons. by Helmann JD, Wang Y, Mahler I, Walsh CT.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209576
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Hydraulic Conductance and Mercury-Sensitive Water Transport for Roots of Opuntia acanthocarpa in Relation to Soil Drying and Rewetting. by Martre P, North GB, Nobel PS.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102309
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Influence of Cadmium and Mercury on Activities of Ligninolytic Enzymes and Degradation of Polycyclic Aromatic Hydrocarbons by Pleurotus ostreatus in Soil. by Baldrian P, in der Wiesche C, Gabriel J, Nerud F, Zadrazil F.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110561
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Influence of salts and temperature on the transfer of mercury resistance from a marine pseudomonad to Escherichia coli. by Gauthier MJ, Cauvin F, Breittmayer JP.; 1985 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238569
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Intracellular inducer Hg2+ concentration is rate determining for the expression of the mercury-resistance operon in cells. by Yu H, Chu L, Misra TK.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178000
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Laboratory Study of Chemical Speciation of Mercury in Lake Sediment and Water under Aerobic and Anaerobic Conditions. by Regnell O, Tunlid A.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182796
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Linkage of Mercury, Cadmium, and Arsenate and Drug Resistance in Clinical Isolates of Pseudomonas aeruginosa. by Nakahara H, Ishikawa T, Sarai Y, Kondo I, Kozukue H, Silver S.; 1977 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=170800
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Localization of penicillin-binding proteins to the splitting system of Staphylococcus aureus septa by using a mercury-penicillin V derivative. by Paul TR, Venter A, Blaszczak LC, Parr TR Jr, Labischinski H, Beveridge TJ.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177077
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Low level methylmercury exposure affects neuropsychological function in adults. by Yokoo EM, Valente JG, Grattan L, Schmidt SL, Platt I, Silbergeld EK.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165591
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Measurement of Mercury Methylation in Lake Water and Sediment Samples. by Furutani A, Rudd JW.; 1980 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291658
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Mechanism of mercury(II) reductase and influence of ligation on the reduction of mercury(II) by a water soluble 1,5-dihydroflavin. by Gopinath E, Kaaret TW, Bruice TC.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287060
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Mechanisms of microbial resistance and detoxification of mercury and organomercury compounds: physiological, biochemical, and genetic analyses. by Robinson JB, Tuovinen OH.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=373215
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Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria. by Steingrube VA, Wallace RJ Jr, Steele LC, Pang YJ.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245113
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Mercuric reductase enzyme from a mercury-volatilizing strain of Thiobacillus ferrooxidans. by Olson GJ, Porter FD, Rubinstein J, Silver S.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=220400
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Mercury and Cadmium Resistances Mediated by the Penicillinase Plasmid in Staphylococcus aureus. by Kondo I, Ishikawa T, Nakahara H.; 1974 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246517
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Mercury and Organomercurial Resistances Determined by Plasmids in Pseudomonas. by Clark DL, Weiss AA, Silver S.; 1977 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221844
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Mercury and Organomercurial Resistances Determined by Plasmids in Staphylococcus aureus. by Weiss AA, Murphy SD, Silver S.; 1977 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221845
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Mercury in seafood. by Sehmer J.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117079
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Mercury Methylation and Demethylation in Anoxic Lake Sediments and by Strictly Anaerobic Bacteria. by Pak KR, Bartha R.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106359
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Mercury Methylation by Desulfovibrio desulfuricans ND132 in the Presence of Polysulfides. by Jay JA, Murray KJ, Gilmour CC, Mason RP, Morel FM, Roberts AL, Hemond HF.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129902
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Mercury methylation by fish intestinal contents. by Rudd JW, Furutani A, Turner MA.; 1980 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291659
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Mercury Methylation by Interspecies Hydrogen and Acetate Transfer between Sulfidogens and Methanogens. by Pak KR, Bartha R.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106268
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Mercury Methylation Independent of the Acetyl-Coenzyme A Pathway in SulfateReducing Bacteria. by Ekstrom EB, Morel FM, Benoit JM.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194973
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Mercury operon regulation by the merR gene of the organomercurial resistance system of plasmid pDU1358. by Nucifora G, Chu L, Silver S, Misra TK.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210196
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Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates. by Summers AO, Wireman J, Vimy MJ, Lorscheider FL, Marshall B, Levy SB, Bennett S, Billard L.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187773
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Mercury Resistance Determinants Related to Tn21, Tn1696, and Tn5053 in Enterobacteria from the Preantibiotic Era. by Essa AM, Julian DJ, Kidd SP, Brown NL, Hobman JL.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149298
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Mercury Resistance in a Plasmid-Bearing Strain of Escherichia coli. by Summers AO, Silver S.; 1972 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251553
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Mercury Resistance in Bacillus cereus RC607: Transcriptional Organization and Two New Open Reading Frames. by Gupta A, Phung LT, Chakravarty L, Silver S.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94184
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Mercury Resistance Is Encoded by Transferable Giant Linear Plasmids in Two Chesapeake Bay Streptomyces Strains. by Ravel J, Schrempf H, Hill RT.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106736
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Mercury selection of allozymes in marine organisms: Prediction and verification in nature. by Nevo E, Ben-Shlomo R, Lavie B.; 1984 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=344806
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Mercury(II) binding to s4U in E.coli tRNAVal. by Sunshine HR, Lippard SJ.; 1974 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=343368
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Mercury-induced transitions between right-handed and putative left-handed forms of poly[d(A-T).d(A-T)] and poly[d(G-C).d(G-C)]. by Gruenwedel DW, Cruikshank MK.; 1989 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=335115
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Mercury-Resistant Bacteria and Petroleum Degradation. by Walker JD, Colwell RR.; 1974 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=380012
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Metabolic Pathways Leading to Mercury Methylation in Desulfovibrio desulfuricans LS. by Choi SC, Chase T Jr, Bartha R.; 1994 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201938
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Methods for Measuring Specific Rates of Mercury Methylation and Degradation and Their Use in Determining Factors Controlling Net Rates of Mercury Methylation. by Ramlal PS, Rudd JW, Hecky RE.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238825
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Methylation and demethylation of mercury under controlled redox, pH and salinity conditions. by Compeau G, Bartha R.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=241710
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Methylmercury Decomposition in Sediments and Bacterial Cultures: Involvement of Methanogens and Sulfate Reducers in Oxidative Demethylation. by Oremland RS, Culbertson CW, Winfrey MR.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182673
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Methylmercury exposure: fishing for answers. by Weir E.; 2001 Jul 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81308
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Methylmercury Resistance in Desulfovibrio desulfuricans Strains in Relation to Methylmercury Degradation. by Baldi F, Pepi M, Filippelli M.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182309
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Molecular analysis of mercury-resistant Bacillus isolates from sediment of Minamata Bay, Japan. by Nakamura K, Silver S.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202026
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Nucleotide sequence of a chromosomal mercury resistance determinant from a Bacillus sp. with broad-spectrum mercury resistance. by Wang Y, Moore M, Levinson HS, Silver S, Walsh C, Mahler I.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209558
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Nucleotide sequences at the ends of the mercury resistance transposon, Tn501. by Brown NL, Choi CL, Grinsted J, Richmond MH, Whitehead PR.; 1980 May 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324048
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Ordering of the flagellar genes in Pseudomonas aeruginosa by insertions of mercury transposon Tn501. by Tsuda M, Iino T.; 1983 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221725
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Organomercurial-volatilizing bacteria in the mercury-polluted sediment of Minamata Bay, Japan. by Nakamura K, Sakamoto M, Uchiyama H, Yagi O.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183330
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Phenotypic and genotypic adaptation of aerobic heterotrophic sediment bacterial communities to mercury stress. by Barkay T, Olson BH.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203542
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Phylogeny of mercury resistance (mer) operons of gram-negative bacteria isolated from the fecal flora of primates. by Liebert CA, Wireman J, Smith T, Summers AO.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168397
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Phytoremediation of methylmercury pollution: merB expression in Arabidopsis thaliana confers resistance to organomercurials. by Bizily SP, Rugh CL, Summers AO, Meagher RB.; 1999 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21997
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Pink ladies: mercury poisoning in twin girls. by Weinstein M, Bernstein S.; 2003 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140434
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Plasmid-controlled mercury biotransformation by Clostridium cochlearium T-2. by Pan-Hou HS, Hosono M, Imura N.; 1980 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291712
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Preparation of a DNA gene probe for detection of mercury resistance genes in gramnegative bacterial communities. by Barkay T, Fouts DL, Olson BH.; 1985 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=373572
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Properties of lambda transducing bacteriophages carrying R100 plasmid DNA: mercury resistance genes. by Dempsey WB, McIntire SA, Willetts N, Schottel J, Kinscherf TG, Silver S, Shannon WA Jr.; 1978 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218544
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Pseudomonas putida Strains Which Constitutively Overexpress Mercury Resistance for Biodetoxification of Organomercurial Pollutants. by Horn JM, Brunke M, Deckwer WD, Timmis KN.; 1994 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201314
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Purification and properties of a second enzyme catalyzing the splitting of carbonmercury linkages from mercury-resistant Pseudomonas K-62. by Tezuka T, Tonomura K.; 1978 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=224790
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Reduction of Mercury to the Elemental State by a Yeast. by Brunker RL, Bott TL.; 1974 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=380168
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Regulation of the Staphylococcus aureus plasmid pI258 mercury resistance operon. by Chu L, Mukhopadhyay D, Yu H, Kim KS, Misra TK.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207386
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Removal of Mercury from Chloralkali Electrolysis Wastewater by a MercuryResistant Pseudomonas putida Strain. by von Canstein H, Li Y, Timmis KN, Deckwer WD, Wagner-Dobler I.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91717
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Renal Handling of Phosphorus in Oliguric and Nonoliguric Mercury-Induced Acute Renal Failure in Rats. by Popovtzer MM, Massry SG, Villamil M, Kleeman CR.; 1971 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292177
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Resistance to Mercury and Antimicrobial Agents in Streptococcus mutans Isolates from Human Subjects in Relation to Exposure to Dental Amalgam Fillings. by Leistevuo J, Jarvinen H, Osterblad M, Leistevuo T, Huovinen P, Tenovuo J.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89706
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Resistance to mercury and to cadmium in chromosomally resistant Staphylococcus aureus. by Witte W, Green L, Misra TK, Silver S.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180463
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RNA synthesis in isolated nuclei of lactating mammary cells in presence of unmodified and mercury-labeled CTP. by Ganguly R, Banerjee MR.; 1978 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342762
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Role of bacteria in bioaccumulation of mercury in the oyster Crassostrea virginica. by Sayler GS, Nelson JD Jr, Colwell RR.; 1975 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187121
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Role of plasmids in mercury transformation by bacteria isolated from the aquatic environment. by Olson BH, Barkay T, Colwell RR.; 1979 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=243520
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Roles of the Tn21 merT, merP, and merC gene products in mercury resistance and mercury binding. by Hamlett NV, Landale EC, Davis BH, Summers AO.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207586
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Seasonal and Spatial Variations in Mercury Methylation and Demethylation in an Oligotrophic Lake. by Korthals ET, Winfrey MR.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204120
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Sediment Microbial Community Structure and Mercury Methylation in MercuryPolluted Clear Lake, California. by Macalady JL, Mack EE, Nelson DC, Scow KM.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92011
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Self-assembly of a metal-ion-bound monolayer of trigonal connectors on mercury: An electrochemical Langmuir trough. by Varaksa N, Pospisil L, Magnera TF, Michl J.; 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122713
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Self-Transmissible Mercury Resistance Plasmids with Gene-Mobilizing Capacity in Soil Bacterial Populations: Influence of Wheat Roots and Mercury Addition. by Smit E, Wolters A, van Elsas JD.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106131
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Sequencing Bands of Ribosomal Intergenic Spacer Analysis Fingerprints for Characterization and Microscale Distribution of Soil Bacterium Populations Responding to Mercury Spiking. by Ranjard L, Brothier E, Nazaret S.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92465
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Simple Method for Introducing Elemental Mercury into Biological Growth Systems. by Holm HW, Cox MF.; 1974 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=380100
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Simplified X-ray film method for detection of bacterial volatilization of mercury chloride by Escherichia coli. by Nakamura K, Nakahara H.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204390
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Spatially Oscillating Activity and Microbial Succession of Mercury-Reducing Biofilms in a Technical-Scale Bioremediation System. by von Canstein H, Li Y, Leonhauser J, Haase E, Felske A, Deckwer WD, Wagner-Dobler I.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123881
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Species Diversity Improves the Efficiency of Mercury-Reducing Biofilms under Changing Environmental Conditions. by von Canstein H, Kelly S, Li Y, Wagner-Dobler I.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123942
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Structure and Species Composition of Mercury-Reducing Biofilms. by Wagner-Dobler I, Lunsdorf H, Lubbehusen T, von Canstein HF, Li Y.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92343
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Subcellular Targeting of Methylmercury Lyase Enhances Its Specific Activity for Organic Mercury Detoxification in Plants. by Bizily SP, Kim T, Kandasamy MK, Meagher RB.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166823
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Sulfate-Reducing Bacteria Methylate Mercury at Variable Rates in Pure Culture and in Marine Sediments. by King JK, Kostka JE, Frischer ME, Saunders FM.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110551
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The effects of mercury-substitution on the hybridisation characteristics of nucleic acids. by Brown TD, Balmain A.; 1979 Dec 20; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342389
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The genetic organization and evolution of the broad host range mercury resistance plasmid pSB102 isolated from a microbial population residing in the rhizosphere of alfalfa. by Schneiker S, Keller M, Droge M, Lanka E, Puhler A, Selbitschka W.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97592
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THE MANGANESE MERCURY STAR [pi]1 BOOTIS. by Montgomery JW, Aller LH.; 1969 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=223423
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The merG Gene Product Is Involved in Phenylmercury Resistance in Pseudomonas Strain K-62. by Kiyono M, Pan-Hou H.; 1999 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93436
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The plasma membrane of Arabidopsis thaliana contains a mercury-insensitive aquaporin that is a homolog of the tonoplast water channel protein TIP. by Daniels MJ, Mirkov TE, Chrispeels MJ.; 1994 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=159670
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The Role of "Leakage" of Tubular Fluid in Anuria Due to Mercury Poisoning. by Bank N, Mutz BF, Aynedjian HS.; 1967 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297072
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Transcellular Water Transport in Lung Alveolar Epithelium Through MercurySensitive Water Channels. by Folkesson HG, Matthay MA, Hasegawa H, Kheradmand F, Verkman AS.; 1994 May 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43911
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Transcriptional analysis of the Staphylococcus aureus plasmid pI258 mercury resistance determinant. by Skinner JS, Ribot E, Laddaga RA.; 1991 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208219
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Transfer and Occurrence of Large Mercury Resistance Plasmids in River Epilithon. by Bale MJ, Fry JC, Day MJ.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202582
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Transformation of elemental mercury by bacteria. by Holm HW, Cox MF.; 1975 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187012
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Transformation of mercuric chloride and methylmercury by the rumen microflora. by Kozak S, Forsberg CW.; 1979 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=243551
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Transformations of inorganic mercury by Candida albicans and Saccharomyces cerevisiae. by Yannai S, Berdicevsky I, Duek L.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182692
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Volatilization of Mercuric Chloride by Mercury-Resistant Plasmid-Bearing Strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. by Summers AO, Lewis E.; 1973 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285330
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Water Stress Inhibits Hydraulic Conductance and Leaf Growth in Rice Seedlings but Not the Transport of Water via Mercury-Sensitive Water Channels in the Root. by Lu Z, Neumann PM.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59246
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with mercury, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “mercury” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for mercury (hyperlinks lead to article summaries): •
A basin-specific aquatic food web biomagnification model for estimation of mercury target levels. Author(s): Hope B. Source: Environmental Toxicology and Chemistry / Setac. 2003 October; 22(10): 2525-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552019
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A case of lichen planus caused by mercury allergy. Author(s): Kato Y, Hayakawa R, Shiraki R, Ozeki K. Source: The British Journal of Dermatology. 2003 June; 148(6): 1268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828762
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A compartmental model for the kinetics of mercury vapor in humans. Author(s): Jonsson F, Sandborgh-Englund G, Johanson G. Source: Toxicology and Applied Pharmacology. 1999 March 1; 155(2): 161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10053170
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A contribution to the establishment of reference values for total mercury levels in hair and fish in amazonia. Author(s): Santos EC, Camara VM, Jesus IM, Brabo ES, Loureiro EC, Mascarenhas AF, Fayal KF, Sa Filho GC, Sagica FE, Lima MO, Higuchi H, Silveira IM. Source: Environmental Research. 2002 September; 90(1): 6-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359185
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A diet rich in fish. High-end consumers face more mercury risks. Author(s): Hood E. Source: Environmental Health Perspectives. 2003 April; 111(4): A233. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12718314
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A low-cost thermochromic thermometer to replace glass and mercury thermometers. Author(s): Bell E, Bell H, Socrates C, Morley D, Barsby K, Boon G. Source: Trop Doct. 2002 July; 32(3): 168-71. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139163
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A multidisciplinary clinical study of patients suffering from illness associated with release of mercury from dental restorations. Medical and odontological aspects. Author(s): Furhoff AK, Tomson Y, Ilie M, Bagedahl-Strindlund M, Larsson KS, Sandborgh-Englund G, Torstenson B, Wretlind K. Source: Scandinavian Journal of Primary Health Care. 1998 December; 16(4): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9932320
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A new cutaneous sign of mercury poisoning. Author(s): Dantzig PI. Source: Annals of Internal Medicine. 2003 July 1; 139(1): 78-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834329
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A new cutaneous sign of mercury poisoning? Author(s): Dantzig PI. Source: Journal of the American Academy of Dermatology. 2003 December; 49(6): 110911. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639393
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A patient with postoperative mercury contamination of the peritoneum. Author(s): Haas NS, Shih R, Gochfeld M. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(2): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733856
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A review of mercury in Lake Victoria, East Africa: implications for human and ecosystem health. Author(s): Campbell L, Dixon DG, Hecky RE. Source: Journal of Toxicology and Environmental Health. Part B, Critical Reviews. 2003 July-August; 6(4): 325-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775518
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A review of the ADA mercury hygiene recommendations. Author(s): Davis MW; American Dental Association. Source: Dent Today. 2003 January; 22(1): 86-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616896
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Accuracy of aneroid sphygmomanometer blood pressure recording compared with digital and mercury measurements in Brazil. Author(s): Gill G, Ala L, Gurgel R, Cuevas L. Source: Trop Doct. 2004 January; 34(1): 26-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14959969
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Adsorptive stripping voltammetric determination of cefepime at the mercury electrode in human urine and cerebrospinal fluid, and differential pulse polarographic determination in serum. Author(s): Palacios FJ, Mochon MC, Sanchez JC, Carranza JH. Source: Journal of Pharmaceutical Sciences. 2003 September; 92(9): 1854-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950003
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Alzheimer's disease, dental amalgam and mercury. Author(s): Saxe SR, Wekstein MW, Kryscio RJ, Henry RG, Cornett CR, Snowdon DA, Grant FT, Schmitt FA, Donegan SJ, Wekstein DR, Ehmann WD, Markesbery WR. Source: The Journal of the American Dental Association. 1999 February; 130(2): 191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10036842
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American Society for Circumpolar Health. Comparison of mercury in selected subsistence foods from western Alaska. Author(s): Rothschild RF. Source: Int J Circumpolar Health. 2003 December; 62(4): 448. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964773
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Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity. Author(s): Godfrey ME, Wojcik DP, Krone CA. Source: Journal of Alzheimer's Disease : Jad. 2003 June; 5(3): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897404
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Application of a latent variable model for a multicenter study on early effects due to mercury exposure. Author(s): Lucchini R, Calza S, Camerino D, Carta P, Decarli A, Parrinello G, Soleo L, Zefferino R, Alessio L. Source: Neurotoxicology. 2003 August; 24(4-5): 605-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900073
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Application of ferric sludge to immobilize leachable mercury in soils and concrete. Author(s): Zhuang JM, Walsh T, Lam T, Boulter D. Source: Environmental Technology. 2003 November; 24(11): 1445-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14733397
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Assessment of mercury exposure and malaria in a Brazilian Amazon riverine community. Author(s): Crompton P, Ventura AM, de Souza JM, Santos E, Strickland GT, Silbergeld E. Source: Environmental Research. 2002 October; 90(2): 69-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483796
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Ban or regulate? Costs of dental occupational safety from mercury. Author(s): Eid F, Harakeh S. Source: Journal of Health Care Finance. 2003 Winter; 30(2): 65-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977038
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Banned in Boston. Medical mercury is on the way out. Author(s): Perry PA. Source: Materials Management in Health Care. 2001 March; 10(3): 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11299940
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Battlefield: mercury--the element, not the planet. Author(s): Anderson CF. Source: Tex Dent J. 2000 December; 117(12): 8-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858076
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Becoming a mercury free facility: a priority to be achieved by the year 2000. Author(s): Shaner H. Source: Prof Dev Ser (Chic Ill). 1997 November; : 1-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10569812
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Biological mercury measurements before and after administration of a chelator (DMPS) and subjective symptoms allegedly due to amalgam. Author(s): Schuurs A, Exterkate R, ten Cate JM, ten Cate B. Source: European Journal of Oral Sciences. 2000 December; 108(6): 511-22. Erratum In: Eur J Oral Sci 2001 October; 109(5): 368. Ten Cate B [corrected to Ten Cate Jm]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11153926
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Biological monitoring and exposure to mercury. Author(s): Mason HJ, Hindell P, Williams NR. Source: Occupational Medicine (Oxford, England). 2001 February; 51(1): 2-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11235823
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Biological monitoring of environmental and occupational exposure to mercury. Author(s): Langworth S, Elinder CG, Gothe CJ, Vesterberg O. Source: International Archives of Occupational and Environmental Health. 1991; 63(3): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1917065
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Biomonitoring of mercury in the Kastela Bay using transplanted mussels. Author(s): Odzak N, Zvonaric T, Gaspic ZK, Horvat M, Baric A. Source: The Science of the Total Environment. 2000 October 16; 261(1-3): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11036977
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Block of sodium channels by divalent mercury: role of specific cysteinyl residues in the P-loop region. Author(s): Hisatome I, Kurata Y, Sasaki N, Morisaki T, Morisaki H, Tanaka Y, Urashima T, Yatsuhashi T, Tsuboi M, Kitamura F, Miake J, Takeda S, Taniguchi S, Ogino K, Igawa O, Yoshida A, Sato R, Makita N, Shigemasa C. Source: Biophysical Journal. 2000 September; 79(3): 1336-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968996
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Blood levels of total and organic mercury in residents of the upper St. Lawrence River basin, Quebec: association with age, gender, and fish consumption. Author(s): Mahaffey KR, Mergler D. Source: Environmental Research. 1998 May; 77(2): 104-14. Erratum In: Environ Res 1998 November; 79(2): 156. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600803
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Blood mercury and auditory neuro-sensory responses in children and adults in the Nambija gold mining area of Ecuador. Author(s): Counter SA, Buchanan LH, Laurell G, Ortega F. Source: Neurotoxicology. 1998 April; 19(2): 185-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9553955
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Blood mercury concentrations in the population of Rabat area, Morocco. Author(s): Khassouani CD, Soulaymani R, Jana M, Mauras Y, Allain P. Source: Bulletin of Environmental Contamination and Toxicology. 2001 April; 66(4): 43942. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443304
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Blood mercury following DMPS administration to subjects with and without dental amalgam. Author(s): Vamnes JS, Eide R, Isrenn R, Hol PJ, Gjerdet NR. Source: The Science of the Total Environment. 2003 June 1; 308(1-3): 63-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738201
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Blood mercury levels and fish consumption in Louisiana. Author(s): Bellanger TM, Caesar EM, Trachtman L. Source: J La State Med Soc. 2000 February; 152(2): 64-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10745634
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Blood mercury levels in US children and women of childbearing age, 1999-2000. Author(s): Schober SE, Sinks TH, Jones RL, Bolger PM, McDowell M, Osterloh J, Garrett ES, Canady RA, Dillon CF, Sun Y, Joseph CB, Mahaffey KR. Source: Jama : the Journal of the American Medical Association. 2003 April 2; 289(13): 1667-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672735
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Blood mercury levels of dental students and dentists at a dental school. Author(s): Tezel H, Ertas OS, Erakin C, Kayali A. Source: British Dental Journal. 2001 October 27; 191(8): 449-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720018
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Blood mercury levels with amalgam retroseals: a longitudinal study. Author(s): Skoner JR, Wallace JA, Fochtman F, Moore PA, Zullo T, Hoffman D. Source: Journal of Endodontics. 1996 March; 22(3): 140-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8618096
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Blood pressure monitoring with home monitors versus mercury sphygmomanometer. Author(s): Rotch AL, Dean JO, Kendrach MG, Wright SG, Woolley TW. Source: The Annals of Pharmacotherapy. 2001 July-August; 35(7-8): 817-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11485126
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Broadsheet number 48: Mercury, cadmium and arsenic: toxicology and laboratory investigation. Author(s): Campbell BG. Source: Pathology. 1999 February; 31(1): 17-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10212916
Studies
79
•
Broken glass mercury thermometer: a difficult airway foreign body. Author(s): Moxham JP, Lee PK. Source: Otolaryngology and Head and Neck Surgery. 2002 October; 127(4): 339-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402014
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Can environmental purchasing reduce mercury in U.S. health care? Author(s): Eagan PD, Kaiser B. Source: Environmental Health Perspectives. 2002 September; 110(9): 847-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204816
•
Cases of mercury exposure, bioavailability, and absorption. Author(s): Gochfeld M. Source: Ecotoxicology and Environmental Safety. 2003 September; 56(1): 174-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915150
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Change in the iso-enzyme profiles of urinary N-acetyl-beta-D-glucosoaminidase in workers exposed to mercury. Author(s): Mandic L, Radmila M, Jelena A, Dubravka D. Source: Toxicology and Industrial Health. 2002 June; 18(5): 207-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653309
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Chronic mercury intoxication simulating pheochromocytoma: effect of captopril on urinary mercury excretion. Author(s): Kosan C, Topaloglu AK, Ozkan B. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 August; 43(4): 429-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472594
•
Chronic psychological effects of exposure to mercury vapour among chlorine-alkali plant workers. Author(s): Pranjic N, Sinanovic O, Jakubovic R. Source: Med Lav. 2003 November-December; 94(6): 531-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768245
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City bans medical devices that contain mercury. Author(s): Sibbald B. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 January 7; 168(1): 78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12515799
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Color discrimination impairment in workers exposed to mercury vapor. Author(s): Urban P, Gobba F, Nerudova J, Lukas E, Cabelkova Z, Cikrt M. Source: Neurotoxicology. 2003 August; 24(4-5): 711-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900084
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Combining food frequency and survey data to quantify long-term dietary exposure: a methyl mercury case study. Author(s): Tran NL, Barraj L, Smith K, Javier A, Burke TA. Source: Risk Analysis : an Official Publication of the Society for Risk Analysis. 2004 February; 24(1): 19-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027997
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Commentary: Mercury, PCB, and now eicosapentaenoic acid: still another reason why pregnant women should be concerned about eating seafood? Author(s): Olsen SF. Source: International Journal of Epidemiology. 2001 December; 30(6): 1279-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821328
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Comparison of rectal temperature measured by digital vs. mercury glass thermometer in infants under two months old. Author(s): Jones HL, Kleber CB, Eckert GJ, Mahon BE. Source: Clinical Pediatrics. 2003 May; 42(4): 357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800731
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Comparison of the oscillometric blood pressure monitor (BPM-100(Beta) ) with the auscultatory mercury sphygmomanometer. Author(s): Mattu GS, Perry TL Jr, Wright JM. Source: Blood Pressure Monitoring. 2001 June; 6(3): 153-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518839
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Concentrations of arsenic, cadmium, mercury, and lead in common foods and estimated daily intake by children, adolescents, adults, and seniors of Catalonia, Spain. Author(s): Llobet JM, Falco G, Casas C, Teixido A, Domingo JL. Source: Journal of Agricultural and Food Chemistry. 2003 January 29; 51(3): 838-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12537467
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Concentrations of major elements and mercury in unstimulated human saliva. Author(s): Monaci F, Bargagli E, Bravi F, Rottoli P. Source: Biological Trace Element Research. 2002 December; 89(3): 193-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462743
Studies
81
•
Concern over mercury pollution in India. Author(s): Sharma DC. Source: Lancet. 2003 September 27; 362(9389): 1050. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526779
•
Concerns continue over mercury and autism. Author(s): Blaxill MF. Source: American Journal of Preventive Medicine. 2004 January; 26(1): 91; Reply 91-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700719
•
Contact orofacial granulomatosis caused by delayed hypersensitivity to gold and mercury. Author(s): Lazarov A, Kidron D, Tulchinsky Z, Minkow B. Source: Journal of the American Academy of Dermatology. 2003 December; 49(6): 111720. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639396
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Contamination of the environment by the current disposal methods of mercurycontaining lamps in the state of Minas Gerais, Brazil. Author(s): Raposo C, Roeser HM. Source: Waste Management (New York, N.Y.). 2001; 21(7): 661-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530922
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Content and bioconcentration of mercury in mushrooms from northern Poland. Author(s): Falandysz J, Gucia M, Brzostowski A, Kawano M, Bielawski L, Frankowska A, Wyrzykowska B. Source: Food Additives and Contaminants. 2003 March; 20(3): 247-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623649
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Correlation between mercury and selenium concentrations in Indian hair from Rondjnia State, Amazon region, Brazil. Author(s): Soares D, Sarkis J, Muller R, Brabo E, Santos E. Source: The Science of the Total Environment. 2002 March 15; 287(1-2): 155-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11883757
•
Current hair mercury levels in Japanese: survey in five districts. Author(s): Yasutake A, Matsumoto M, Yamaguchi M, Hachiya N. Source: The Tohoku Journal of Experimental Medicine. 2003 March; 199(3): 161-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12703660
82
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Danger: mercury is hazardous to our health. Author(s): Ilardi D. Source: School Nurse News. 2003 September; 20(4): 24-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552261
•
Decline in fish consumption among pregnant women after a national mercury advisory. Author(s): Oken E, Kleinman KP, Berland WE, Simon SR, Rich-Edwards JW, Gillman MW. Source: Obstetrics and Gynecology. 2003 August; 102(2): 346-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907111
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Deliberate, repeated self-administration of metallic mercury injection: case report and review of the literature. Author(s): Givica-Perez A, Santana-Montesdeoca JM, Diaz-Sanchez M, MartinezLagares FJ, Castaneda WR. Source: European Radiology. 2001; 11(8): 1351-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11519542
•
Demise of the mercury sphygmomanometer and the dawning of a new era in blood pressure measurement. Author(s): O'Brien E. Source: Blood Pressure Monitoring. 2003 February; 8(1): 19-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604931
•
Dental mercury hygiene recommendations. Author(s): ADA Council on Scientific Affairs. Source: The Journal of the American Dental Association. 2003 November; 134(11): 14989. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14664270
•
Depression, insomnia, and memory loss in a patient with chronic intoxication by inorganic mercury. Author(s): Cordeiro Q Jr, de Araujo Medrado Faria M, Fraguas R Jr. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Fall; 15(4): 457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627777
Studies
83
•
Detection of mercury and other undetermined materials in skin biopsies of endemic pemphigus foliaceus. Author(s): Abreu Velez AM, Warfvinge G, Herrera WL, Abreu Velez CE, Montoya M F, Hardy DM, Bollag WB, Hashimoto K. Source: The American Journal of Dermatopathology. 2003 October; 25(5): 384-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501287
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Determination of mercury in blood, urine and saliva for the biological monitoring of an exposure from amalgam fillings in a group with self-reported adverse health effects. Author(s): Zimmer H, Ludwig H, Bader M, Bailer J, Eickholz P, Staehle HJ, Triebig G. Source: International Journal of Hygiene and Environmental Health. 2002 April; 205(3): 205-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040918
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Determination of methyl mercury in dental-unit wastewater. Author(s): Stone ME, Cohen ME, Liang L, Pang P. Source: Dental Materials : Official Publication of the Academy of Dental Materials. 2003 November; 19(7): 675-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901994
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Determination of total mercury and methylmercury in human hair by graphitefurnace atomic absorption spectrophotometry using 2,3-dimercaptopropane-1sulfonate as a complexing agent. Author(s): Chen WY, Wang YC, Kuo MS. Source: Anal Sci. 2002 March; 18(3): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918181
•
Determination of total mercury in foods of plant origin in Poland by cold vapour atomic absorption spectrometry. Author(s): Jedrzejczak R. Source: Food Additives and Contaminants. 2002 October; 19(10): 996-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12443563
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Determination of total urinary mercury by on-line sample microwave digestion followed by flow injection cold vapour inductively coupled plasma mass spectrometry or atomic absorption spectrometry. Author(s): Bettinelli M, Spezia S, Ronchi A, Minoia C. Source: Rapid Communications in Mass Spectrometry : Rcm. 2002; 16(15): 1432-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12125019
84
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Development of an in vitro blood-brain barrier model-cytotoxicity of mercury and aluminum. Author(s): Toimela T, Maenpaa H, Mannerstrom M, Tahti H. Source: Toxicology and Applied Pharmacology. 2004 February 15; 195(1): 73-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962507
•
Dietary intake of arsenic, mercury and selenium by children from a German North Sea island using duplicate portion sampling. Author(s): Wilhelm M, Wittsiepe J, Schrey P, Lajoie-Junge L, Busch V. Source: Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (Gms). 2003; 17(2): 123-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531641
•
Different transport mechanisms for cadmium and mercury in Caco-2 cells: inhibition of Cd uptake by Hg without evidence for reciprocal effects. Author(s): Aduayom I, Campbell PG, Denizeau F, Jumarie C. Source: Toxicology and Applied Pharmacology. 2003 May 15; 189(1): 56-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12758060
•
Differential mercury volatilization by tobacco organs expressing a modified bacterial merA gene. Author(s): He YK, Sun JG, Feng XZ, Czako M, Marton L. Source: Cell Research. 2001 September; 11(3): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11642409
•
Direct measurement of the mercury content of exhaled air: a new approach for determination of the mercury dose received. Author(s): Pogarev SE, Ryzhov V, Mashyanov N, Sholupov S, Zharskaya V. Source: Analytical and Bioanalytical Chemistry. 2002 November; 374(6): 1039-44. Epub 2002 October 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458416
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Disputed diagnoses hamper claims of mercury poisoning. Author(s): Cyranoski D. Source: Nature. 2001 November 8; 414(6860): 138. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11700515
•
Does changing from mercury to electronic blood pressure measurement influence recorded blood pressure? An observational study. Author(s): McManus RJ, Mant J, Hull MR, Hobbs FD. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 December; 53(497): 953-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960220
Studies
85
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Does elemental mercury exist in the workplace? Author(s): Potter WE. Source: Health Physics. 2002 August; 83(8 Suppl): S30-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12132725
•
Eating tropical fruit reduces mercury exposure from fish consumption in the Brazilian Amazon. Author(s): Passos CJ, Mergler D, Gaspar E, Morais S, Lucotte M, Larribe F, Davidson R, de Grosbois S. Source: Environmental Research. 2003 October; 93(2): 123-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963396
•
EEG photic driving in workers exposed to mercury vapors. Author(s): Urban P, Nerudova J, Cabelkova Z, Krajca V, Lukas E, Cikrt M. Source: Neurotoxicology. 2003 January; 24(1): 23-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564379
•
Effect of arsenic and mercury speciation on inhibition of respiration rate in activated sludge systems. Author(s): Stasinakis AS, Thomaidis NS, Giannes AS, Lekkas TD. Source: Environ Sci Pollut Res Int. 2003; 10(3): 177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846379
•
Effect of deep-frying fish on risk from mercury. Author(s): Burger J, Dixon C, Boring CS, Gochfeld M. Source: Journal of Toxicology and Environmental Health. Part A. 2003 May 9; 66(9): 81728. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746129
•
Effect of restoration of children's teeth with mercury amalgam on the prevalence of mercury- and antibiotic-resistant oral bacteria. Author(s): Pike R, Lucas V, Petrie A, Roberts G, Stapleton P, Rowbury R, Richards H, Mullany P, Wilson M. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Spring; 9(1): 93-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705688
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Effects of metallic mercury on the perimenstrual symptoms and menstrual outcomes of exposed workers. Author(s): Yang JM, Chen QY, Jiang XZ. Source: American Journal of Industrial Medicine. 2002 November; 42(5): 403-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382253
86
Mercury
•
Electronic versus mercury sphygmomanometers. Author(s): Sharvill J. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2004 February; 54(499): 137-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046060
•
Electronic versus mercury sphygmomanometers. Author(s): Morrison CL. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2004 February; 54(499): 136-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046059
•
Electronic versus mercury sphygmomanometers. Author(s): McAll G. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2004 February; 54(499): 136. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046058
•
Elemental mercury in the appendix: an unusual complication of a Mexican-American folk remedy. Author(s): McKinney PE. Source: Journal of Toxicology. Clinical Toxicology. 1999; 37(1): 103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078167
•
Elemental mercury poisoning in occupational and residential settings. Author(s): Risher JF, Nickle RA, Amler SN. Source: International Journal of Hygiene and Environmental Health. 2003 August; 206(45): 371-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12971692
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Elemental mercury-induced subcutaneous granuloma. A case report and review of the literature. Author(s): Kayias EH, Drosos GI, Hapsas D, Anagnostopoulou GA. Source: Acta Orthop Belg. 2003 June; 69(3): 280-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879712
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Eliminating mercury in health care facilities. Author(s): Gilmore-Hall A. Source: The American Journal of Nursing. 2003 July; 103(7): 120. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865651
Studies
87
•
Environment. Uncertain science underlies new mercury standards. Author(s): Stokstad E. Source: Science. 2004 January 2; 303(5654): 34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14704409
•
Environmental exposure to mercury and its toxicopathologic implications for public health. Author(s): Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D. Source: Environmental Toxicology. 2003 June; 18(3): 149-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740802
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Estimation of daily mercury intake from seafood in Japanese women: Akita crosssectional study. Author(s): Iwasaki Y, Sakamoto M, Nakai K, Oka T, Dakeishi M, Iwata T, Satoh H, Murata K. Source: The Tohoku Journal of Experimental Medicine. 2003 June; 200(2): 67-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962403
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Evaluation of mercury in urine as an indicator of exposure to low levels of mercury vapor. Author(s): Tsuji JS, Williams PR, Edwards MR, Allamneni KP, Kelsh MA, Paustenbach DJ, Sheehan PJ. Source: Environmental Health Perspectives. 2003 April; 111(4): 623-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12676626
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Evaluation of the amalgamation reaction of experimental Ag-Sn-Cu alloys containing Pd using a mercury plating technique. Author(s): Koike M, Ferracane JL, Fujii H, Okabe T. Source: Dent Mater J. 2003 September; 22(3): 280-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628723
•
Exposure or absorption and the crucial question of limits for mercury. Author(s): Jones DW. Source: Journal (Canadian Dental Association). 1999 January; 65(1): 42-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973766
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Exposure to mercury in the urban population of Rio Branco City, state of Acre, Brazil. Author(s): de Oliveira Santos EC, de Jesus IM, Brabo ES, de M Camara V, Loureiro EC, Mascarenhas AF, de F Faial K, da Silva AP, da Silva RU, Luiz RR, Higuchi H. Source: Bulletin of Environmental Contamination and Toxicology. 2002 September; 69(3): 314-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12177749
88
Mercury
•
Facial injury by mercury from a broken thermometer. Author(s): Yotsuyanagi T, Yokoi K, Sawada Y. Source: The Journal of Trauma. 1996 May; 40(5): 847-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8614096
•
Factors affecting internal mercury burdens among eastern German children. Author(s): Trepka MJ, Heinrich J, Krause C, Schulz C, Wjst M, Popescu M, Wichmann HE. Source: Archives of Environmental Health. 1997 March-April; 52(2): 134-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9124874
•
Factors contributing to mercury exposure in dentists. Author(s): Martin MD, Naleway C, Chou HN. Source: The Journal of the American Dental Association. 1995 November; 126(11): 150211. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7499647
•
Factors influencing total mercury levels among Lebanese dentists. Author(s): Harakeh S, Sabra N, Kassak K, Doughan B. Source: The Science of the Total Environment. 2002 October 7; 297(1-3): 153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12389787
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Facts on mercury and fish consumption. Author(s): Wooltorton E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 October 15; 167(8): 897. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406950
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Familial mercury intoxication presenting with cardiovascular abnormalities and acrodynia. Author(s): Laurans M, Brouard J, Arion A, Kauffmann D, Duhamel JF. Source: Acta Paediatrica (Oslo, Norway : 1992). 2001 May; 90(5): 593-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430728
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Family poisoned by mercury vapor inhalation. Author(s): Solis MT, Yuen E, Cortez PS, Goebel PJ. Source: The American Journal of Emergency Medicine. 2000 September; 18(5): 599-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999577
Studies
89
•
FDA warns on mercury in tuna. Author(s): Stephenson J. Source: Jama : the Journal of the American Medical Association. 2004 January 14; 291(2): 171. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722130
•
Fish are central in the diet of Amazonian riparians: should we worry about their mercury concentrations? Author(s): Dorea JG. Source: Environmental Research. 2003 July; 92(3): 232-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804520
•
Fish consumption and exposure to persistent organochlorine compounds, mercury, selenium and methylamines among Swedish fishermen. Author(s): Svensson BG, Nilsson A, Jonsson E, Schutz A, Akesson B, Hagmar L. Source: Scand J Work Environ Health. 1995 April; 21(2): 96-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7618064
•
Fish consumption, fish lore, and mercury pollution--risk communication for the Madeira River people. Author(s): Boischio AA, Henshel D. Source: Environmental Research. 2000 October; 84(2): 108-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11068924
•
Fish contamination and human exposure to mercury in the Tapajos River Basin, Para State, Amazon, Brazil: a screening approach. Author(s): Bidone ED, Castilhos ZC, Cid de Souza TM, Lacerda LD. Source: Bulletin of Environmental Contamination and Toxicology. 1997 August; 59(2): 194-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9211688
•
Fish eating and variations in selenium and mercury levels in plasma and erythrocytes in free-living healthy Japanese men. Author(s): Karita K, Suzuki T. Source: Biological Trace Element Research. 2002 Winter; 90(1-3): 71-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666827
•
Fish mercury concentration in the Alto Pantanal, Brazil: influence of season and water parameters. Author(s): Hylander LD, Pinto FN, Guimaraes JR, Meili M, Oliveira LJ, de Castro e Silva E. Source: The Science of the Total Environment. 2000 October 16; 261(1-3): 9-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11036973
90
Mercury
•
Five years of follow-up after elemental mercury self-poisoning. Author(s): Deschamps F, Strady C, Deslee G, Menciere-Faroy B, Deschamps S. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2002 June; 23(2): 170-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040263
•
Floor of mouth injury by mercury from a broken thermometer. Author(s): Shimoyama T, Kaneko T, Horie N. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1998 January; 56(1): 96-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437990
•
Folk use of elemental mercury: a potential hazard for children? Author(s): Ozuah PO. Source: Journal of the National Medical Association. 2001 September; 93(9): 320-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560286
•
Forest fire indicators and mercury deposition in an intense land use change region in the Brazilian Amazon (Alta Floresta, MT). Author(s): Cordeiro RC, Turcq B, Ribeiro MG, Lacerda LD, Capitaneo J, da Silva AO, Sifeddine A, Turcq PM. Source: The Science of the Total Environment. 2002 July 3; 293(1-3): 247-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109477
•
Fractional mercury levels in Brazilian gold refiners and miners. Author(s): Aks SE, Erickson T, Branches FJ, Naleway C, Chou HN, Levy P, Hryhorczuk D. Source: Journal of Toxicology. Clinical Toxicology. 1995; 33(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7837306
•
From mercury to malaria to penicillin: the history of the treatment of syphilis at the Mayo Clinic--1916-1955. Author(s): Sartin JS, Perry HO. Source: Journal of the American Academy of Dermatology. 1995 February; 32(2 Pt 1): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7829712
Studies
91
•
Genetic characterisation of resistance to metal ions in methicillin-resistant Staphylococcus aureus: elimination of resistance to cadmium, mercury and tetracycline with loss of methicillin resistance. Author(s): Poston SM, Li Saw Hee FL. Source: Journal of Medical Microbiology. 1991 April; 34(4): 193-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2020016
•
Genotoxic activity of methyl mercury chloride and dimethyl mercury in human lymphocytes. Author(s): Betti C, Davini T, Barale R. Source: Mutation Research. 1992 April; 281(4): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1373219
•
Genotoxic effects of mercury on in vitro cultures of human cells. Author(s): Bahia Mde O, De Amorim MI, Burbano RR, Vincent S, Dubeau H. Source: Anais Da Academia Brasileira De Ciencias. 1999; 71(3 Pt 1): 437-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10530333
•
Genotoxicity of mercury compounds. A review. Author(s): De Flora S, Bennicelli C, Bagnasco M. Source: Mutation Research. 1994 February; 317(1): 57-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7507573
•
Geographical variation in urinary mercury concentrations among populations living in highland and lowland Bolivia. Author(s): Watanabe C, Imai H, Kashiwazaki H. Source: The Science of the Total Environment. 1994 May 16; 145(3): 267-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8023133
•
Global warming. If the mercury soars, so may health hazards. Author(s): Stone R. Source: Science. 1995 February 17; 267(5200): 957-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7863337
•
Goal for new millennium: mercury-free health facilities. Author(s): Shaner H. Source: Health Facilities Management. 1998 April; 11(4): 42, 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10178581
92
Mercury
•
Gold dermatitis due to ear piercing: correlations between gold and mercury hypersensitivities. Author(s): Osawa J, Kitamura K, Ikezawa Z, Hariya T, Nakajima H. Source: Contact Dermatitis. 1994 August; 31(2): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7750274
•
Gold mining as a source of mercury exposure in the Brazilian Amazon. Author(s): Malm O. Source: Environmental Research. 1998 May; 77(2): 73-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600798
•
Gold-mining activities and mercury contamination of native amerindian communities in French Guiana: key role of fish in dietary uptake. Author(s): Frery N, Maury-Brachet R, Maillot E, Deheeger M, de Merona B, Boudou A. Source: Environmental Health Perspectives. 2001 May; 109(5): 449-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401755
•
Hair mercury speciation as a function of gender, age, and body mass index in inhabitants of the Negro River basin, Amazon, Brazil. Author(s): Barbosa AC, Jardim W, Dorea JG, Fosberg B, Souza J. Source: Archives of Environmental Contamination and Toxicology. 2001 April; 40(3): 439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443378
•
Has conventional sphygmomanometry ended with the banning of mercury? Author(s): O'Brien E. Source: Blood Pressure Monitoring. 2002 February; 7(1): 37-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040241
•
Health and neuropsychological functioning of dentists exposed to mercury. Author(s): Ritchie KA, Gilmour WH, Macdonald EB, Burke FJ, McGowan DA, Dale IM, Hammersley R, Hamilton RM, Binnie V, Collington D. Source: Occupational and Environmental Medicine. 2002 May; 59(5): 287-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983843
•
Health consequences of an intravenous injection of metallic mercury. Author(s): Winker R, Schaffer AW, Konnaris C, Barth A, Giovanoli P, Osterode W, Rudiger HW, Wolf C. Source: International Archives of Occupational and Environmental Health. 2002 October; 75(8): 581-6. Epub 2002 July 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12373321
Studies
93
•
Health effects of long-term mercury exposure among chloralkali plant workers. Author(s): Frumkin H, Letz R, Williams PL, Gerr F, Pierce M, Sanders A, Elon L, Manning CC, Woods JS, Hertzberg VS, Mueller P, Taylor BB. Source: American Journal of Industrial Medicine. 2001 January; 39(1): 1-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11148011
•
Heavy metal fish. New warnings about mercury tell seafood buyers to beware. Author(s): Shute N. Source: U.S. News & World Report. 2003 March 17; 134(8): 42-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645307
•
Heavy metal. Mercury is dropping off the charts--but not fast enough. Author(s): Quayle C. Source: Health Facilities Management. 2000 February; 13(2): 50, 52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11067518
•
Heavy metal. Weighing the mercury-free options. Author(s): Greene J. Source: Materials Management in Health Care. 2002 December; 11(12): 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12506805
•
Heterogeneity in sources of exposure variability among groups of workers exposed to inorganic mercury. Author(s): Symanski E, Sallsten G, Chan W, Barregard L. Source: The Annals of Occupational Hygiene. 2001 November; 45(8): 677-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718663
•
Highlights of FDA food safety efforts: fruit juice, mercury in fish. Author(s): Formanek R Jr. Source: Fda Consumer. 2001 March-April; 35(2): 15-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11444243
•
HLA-association in patients with intolerance to mercury and other metals in dental materials. Author(s): Prochazkova J, Bartova J, Ivaskova E, Kupkova L, Sterzl I, Stejskal VD. Source: Disease Markers. 2000; 16(3-4): 135-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11381194
94
Mercury
•
Horizontal and vertical variabilities of mercury concentration and speciation in sediments of the Gdansk Basin, Southern Baltic Sea. Author(s): Beldowski J, Pempkowiak J. Source: Chemosphere. 2003 July; 52(3): 645-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738302
•
How should a fever mercury thermometer be disposed of ? A survey of those likely to be asked. Author(s): DiCarlo M, Ruck B, Marcus S. Source: Pediatrics. 2002 May; 109(5): E71-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986477
•
HPLC with simultaneous UV and reductive electrochemical detection at the hanging mercury drop electrode: a highly sensitive and selective tool for the determination of benzodiazepines in forensic samples. Author(s): Wilhelm M, Battista HJ, Obendorf D. Source: Journal of Analytical Toxicology. 2001 May-June; 25(4): 250-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386638
•
Human exposure to mercury in San Jorge river basin, Colombia (South America). Author(s): Olivero J, Johnson B, Arguello E. Source: The Science of the Total Environment. 2002 April 22; 289(1-3): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049405
•
Human health significance of organochlorine and mercury contaminants in Japanese whale meat. Author(s): Simmonds MP, Haraguchi K, Endo T, Cipriano F, Palumbi SR, Troisi GM. Source: Journal of Toxicology and Environmental Health. Part A. 2002 September 13; 65(17): 1211-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167206
•
Human mercury toxicity and ice angler fish consumption: are people eating enough to cause health problems? Author(s): Flaherty CM, Sass GG, Stiles KE. Source: Risk Analysis : an Official Publication of the Society for Risk Analysis. 2003 June; 23(3): 497-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12836842
•
Human milk mercury (Hg) and lead (Pb) levels in Vienna. Author(s): Gundacker C, Pietschnig B, Wittmann KJ, Lischka A. Source: Advances in Experimental Medicine and Biology. 2000; 478: 387-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11065095
Studies
95
•
Human variability in mercury toxicokinetics and steady state biomarker ratios. Author(s): Bartell SM, Ponce RA, Sanga RN, Faustman EM. Source: Environmental Research. 2000 October; 84(2): 127-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11068925
•
Hypertensive urgencies: treating the mercury? Author(s): Gallagher EJ. Source: Annals of Emergency Medicine. 2003 April; 41(4): 530-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658253
•
Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. Author(s): Stajich GV, Lopez GP, Harry SW, Sexson WR. Source: The Journal of Pediatrics. 2000 May; 136(5): 679-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10802503
•
Iatrogenic neonatal mercury poisoning from Mercurochrome treatment of a large omphalocele. Author(s): Mullins ME, Horowitz BZ. Source: Clinical Pediatrics. 1999 February; 38(2): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10047945
•
Images in clinical medicine. Elemental mercury embolism to the lung. Author(s): Gutierrez F, Leon L. Source: The New England Journal of Medicine. 2000 June 15; 342(24): 1791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10853002
•
Immunological disorders in men exposed to metallic mercury vapour. A review. Author(s): Moszczynski P. Source: Cent Eur J Public Health. 1999 February; 7(1): 10-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084014
•
Impact of contrast sensitivity performance on visually presented neurobehavioral tests in mercury-exposed children. Author(s): Grandjean P, White RF, Sullivan K, Debes F, Murata K, Otto DA, Weihe P. Source: Neurotoxicology and Teratology. 2001 March-April; 23(2): 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11348831
•
Impact of human variability on the biological monitoring of exposure to toluene, phenol, lead, and mercury: II. Compartmental based toxicokinetic modelling. Author(s): Pierrehumbert G, Droz PO, Tardif R, Charest-Tardif G, Truchon G. Source: Toxicology Letters. 2002 August 5; 134(1-3): 165-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12191875
96
Mercury
•
Improving the in vivo X-ray fluorescence (XRF) measurement of renal mercury. Author(s): O'Meara JM, Borjesson J, Chettle DR. Source: Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine. 2000 October-November; 53(4-5): 639-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11003501
•
In praise of mercury sphygmomanometers. Appropriate sphygmomanometer should be selected. Author(s): Murray A. Source: Bmj (Clinical Research Ed.). 2001 May 19; 322(7296): 1248-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388187
•
In praise of mercury sphygmomanometers. Electronic readings of blood pressure seem to be higher than readings obtained with mercury sphygmomanometers. Author(s): Ireland J. Source: Bmj (Clinical Research Ed.). 2001 May 19; 322(7296): 1249. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388188
•
In vitro activation of cord blood mononuclear cells and cytokine production in a remote coastal population exposed to organochlorines and methyl mercury. Author(s): Bilrha H, Roy R, Moreau B, Belles-Isles M, Dewailly E, Ayotte P. Source: Environmental Health Perspectives. 2003 December; 111(16): 1952-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644672
•
Infertility, blood mercury concentrations and dietary seafood consumption: a casecontrol study. Author(s): Choy CM, Lam CW, Cheung LT, Briton-Jones CM, Cheung LP, Haines CJ. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 October; 109(10): 1121-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387464
•
Influence of illegal gold mining on mercury levels in fish of north Sulawesi's Minahasa Peninsula, (Indonesia). Author(s): Kambey JL, Farrell AP, Bendell-Young LI. Source: Environmental Pollution (Barking, Essex : 1987). 2001; 114(3): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584628
•
Influence of liquid films on mercury vapor loss from dental amalgam. Author(s): Mahler DB, Adey JD, Simms LE, Marek M. Source: Dental Materials : Official Publication of the Academy of Dental Materials. 2002 July; 18(5): 407-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12175580
Studies
97
•
Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Author(s): Crump KS, Kjellstrom T, Shipp AM, Silvers A, Stewart A. Source: Risk Analysis : an Official Publication of the Society for Risk Analysis. 1998 December; 18(6): 701-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9972579
•
Inhibition of luminol-dependent chemiluminescence of human granulocytes by low doses of inorganic mercury. Author(s): al-Hashimi AH, Mohammad FH, al-Krawi EA. Source: East Mediterr Health J. 2000 March-May; 6(2-3): 425-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11556033
•
Inorganic mercury and methylmercury in placentas of Swedish women. Author(s): Ask K, Akesson A, Berglund M, Vahter M. Source: Environmental Health Perspectives. 2002 May; 110(5): 523-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003757
•
Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex. Author(s): McCabe MJ Jr, Whitekus MJ, Hyun J, Eckles KG, McCollum G, Rosenspire AJ. Source: Toxicology and Applied Pharmacology. 2003 July 15; 190(2): 146-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878044
•
Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol. Author(s): Hultberg B, Andersson A, Isaksson A. Source: Toxicology. 2001 January 2; 156(2-3): 93-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11164611
•
Intoxication with 100 grams of mercury: a case report and importance of supportive therapy. Author(s): Satar S, Toprak N, Gokel Y, Sebe A. Source: European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. 2001 September; 8(3): 245-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11587474
•
Intravenous mercury injection and ingestion: clinical manifestations and management. Author(s): McFee RB, Caraccio TR. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(7): 733-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11778672
98
Mercury
•
Kinetics of mercury in blood and urine after brief occupational exposure. Author(s): Barregard L, Sallsten G, Schutz A, Attewell R, Skerfving S, Jarvholm B. Source: Archives of Environmental Health. 1992 May-June; 47(3): 176-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1596100
•
Lack of reproducibility in pregnancy of Korotkoff phase IV as measured by mercury sphygmomanometry. Author(s): Shennan A, Gupta M, Halligan A, Taylor DJ, de Swiet M. Source: Lancet. 1996 January 20; 347(8995): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8544546
•
Launching mercury-reduction efforts. Author(s): Minda J. Source: Health Progress (Saint Louis, Mo.). 2003 November-December; 84(6): 37-8, 53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628691
•
Lead and mercury in breast milk. Author(s): Gundacker C, Pietschnig B, Wittmann KJ, Lischka A, Salzer H, Hohenauer L, Schuster E. Source: Pediatrics. 2002 November; 110(5): 873-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415023
•
Lead and mercury mutagenesis: type of mutation dependent upon metal concentration. Author(s): Ariza ME, Williams MV. Source: Journal of Biochemical and Molecular Toxicology. 1999; 13(2): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890195
•
Lead, cadmium, and mercury dietary intake in Croatia. Author(s): Blanusa M, Juresa D. Source: Arh Hig Rada Toksikol. 2001 June; 52(2): 229-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11370308
•
Lead, cadmium, arsenic, and mercury levels in maternal and fetal cord blood. Author(s): Soong YK, Tseng R, Liu C, Lin PW. Source: J Formos Med Assoc. 1991 January; 90(1): 59-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1679111
Studies
99
•
Lead, cadmium, mercury and selenium intake by Greenlanders from local marine food. Author(s): Johansen P, Pars T, Bjerregaard P. Source: The Science of the Total Environment. 2000 January 17; 245(1-3): 187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10682366
•
Lead, mercury, and organochlorine compound levels in cord blood in Quebec, Canada. Author(s): Rhainds M, Levallois P, Dewailly E, Ayotte P. Source: Archives of Environmental Health. 1999 January-February; 54(1): 40-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10025415
•
Lessons to be learned: a case study approach. An unusual case of alveolar deposition from swallowing metallic mercury in an attempt at self-poisoning. Author(s): Southgate HJ, Ward A, Taylor A, Carr P. Source: J R Soc Health. 1998 October; 118(5): 305-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10076692
•
Levels of cadmium, lead, and mercury in human brain tumors. Author(s): Al-Saleh I, Shinwari N. Source: Biological Trace Element Research. 2001 March; 79(3): 197-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11354345
•
Levels of selenium and antioxidative enzymes following occupational exposure to inorganic mercury. Author(s): Barregard L, Thomassen Y, Schutz A, Marklund SL. Source: The Science of the Total Environment. 1990 December 1; 99(1-2): 37-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2270469
•
Limiting infant exposure to thimerosal in vaccines and other sources of mercury. Author(s): Halsey NA. Source: Jama : the Journal of the American Medical Association. 1999 November 10; 282(18): 1763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10568650
•
Linear regression models of methyl mercury exposure during prenatal and early postnatal life among riverside people along the upper Madeira river, Amazon. Author(s): Boischio AA, Henshel DS. Source: Environmental Research. 2000 June; 83(2): 150-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856188
100
Mercury
•
Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines. Author(s): Hultberg B, Andersson A, Isaksson A. Source: Toxicology. 2002 June 14; 175(1-3): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049840
•
Longitudinal hair mercury concentration in riverside mothers along the Upper Madeira river (Brazil). Author(s): Boischio AA, Cernichiari E. Source: Environmental Research. 1998 May; 77(2): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600799
•
Longitudinal study of methylmercury and inorganic mercury in blood and urine of pregnant and lactating women, as well as in umbilical cord blood. Author(s): Vahter M, Akesson A, Lind B, Bjors U, Schutz A, Berglund M. Source: Environmental Research. 2000 October; 84(2): 186-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11068932
•
Long-term toxicity of intravenous mercury injection. Author(s): dell'Omo M, Muzi G, Bernard A, Lauwerys RR, Abbritti G. Source: Lancet. 1996 July 6; 348(9019): 64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8691958
•
Low concentrations of inorganic mercury inhibit Ras activation during T cell receptor-mediated signal transduction. Author(s): Mattingly RR, Felczak A, Chen CC, McCabe MJ Jr, Rosenspire AJ. Source: Toxicology and Applied Pharmacology. 2001 November 1; 176(3): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11714248
•
Low level mercury exposure in dentists--the tip of the iceberg. Author(s): Sarantos SR. Source: J N J Dent Assoc. 2003 Winter; 74(1): 25-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12723230
•
Luminescence facilitated detection of bioavailable mercury in natural waters. Author(s): Barkay T, Turner RR, Rasmussen LD, Kelly CA, Rudd JW. Source: Methods in Molecular Biology (Clifton, N.J.). 1998; 102: 231-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9680624
Studies
101
•
Maternal mercury transfer. Author(s): Dorea JG, Barbosa AC. Source: Environmental Research. 2003 October; 93(2): 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963394
•
Mercury and dentistry. Author(s): Kostyniak PJ. Source: Alpha Omegan. 2003 December; 96(4): 53-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983731
•
Mercury contamination in the red meat of whales and dolphins marketed for human consumption in Japan. Author(s): Endo T, Hotta Y, Haraguchi K, Sakata M. Source: Environmental Science & Technology. 2003 June 15; 37(12): 2681-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854705
•
Mercury exchange at the air-water-soil interface: an overview of methods. Author(s): Fang F, Wang Q, Liu R. Source: Scientificworldjournal. 2002 June 12; 2: 1597-602. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12806145
•
Mercury generation potential from dental waste amalgam. Author(s): Drummond JL, Cailas MD, Croke K. Source: Journal of Dentistry. 2003 September; 31(7): 493-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927461
•
Mercury hazards from gold mining to humans, plants, and animals. Author(s): Eisler R. Source: Rev Environ Contam Toxicol. 2004; 181: 139-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738199
•
Mercury in fish and its effect on health: German methods of assessment. Author(s): Schweinsberg F. Source: International Journal of Hygiene and Environmental Health. 2003 June; 206(3): 241-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872535
•
Mercury in fish from three rift valley lakes (Turkana, Naivasha and Baringo), Kenya, East Africa. Author(s): Campbell LM, Osano O, Hecky RE, Dixon DG. Source: Environmental Pollution (Barking, Essex : 1987). 2003; 125(2): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810322
102
Mercury
•
Mercury in hair and in fish consumed by Riparian women of the Rio Negro, Amazon, Brazil. Author(s): Dorea J, Barbosa AC, Ferrari I, de Souza JR. Source: International Journal of Environmental Health Research. 2003 September; 13(3): 239-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909555
•
Mercury in hair--but from where? Author(s): Nielsen JB, Grandjean P. Source: Lancet. 1999 February 6; 353(9151): 502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9989752
•
Mercury in Japan's whale meat. Author(s): Tibbetts J. Source: Environmental Health Perspectives. 2003 November; 111(14): A752. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594643
•
Mercury in wild mushrooms and underlying soil substrate from Koszalin, Northcentral Poland. Author(s): Falandysz J, Jedrusiak A, Lipka K, Kannan K, Kawano M, Gucia M, Brzostowski A, Dadej M. Source: Chemosphere. 2004 January; 54(4): 461-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581048
•
Mercury poisoning: prevalence, knowledge and frequency of gold panning and doing retort among alluvial gold panners in Chiweshe and Tafuna communal lands in Zimbabwe. Author(s): Matchaba-Hove RB, Siziya S, Rusakaniko S, Kadenhe RM, Dumbu S, Chirenda J. Source: Cent Afr J Med. 2001 November-December; 47(11-12): 251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808777
•
Mercury pollution in India. Author(s): Rajgopal T. Source: Lancet. 2003 November 29; 362(9398): 1856-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654334
•
Mercury spill control & cleanup. Author(s): Ceaser MA. Source: Occup Health Saf. 2003 July; 72(7): 94-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929219
Studies
103
•
Mercury toxicity due to the smelting of placer gold recovered by mercury amalgam. Author(s): Donoghue AM. Source: Occupational Medicine (Oxford, England). 1998 September; 48(6): 413-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10024739
•
Micronuclei in lymphocyte subsets in relation to plasma mercury, dental amalgam and acrylate-containing tooth fillings. Author(s): Herrstrom P, Bratt I, Holmen A, Hogstedt B. Source: The Science of the Total Environment. 2003 June 20; 309(1-3): 253-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798108
•
More on mercury content in fish. Author(s): Ekino S, Ninomiya T, Susa M. Source: Science. 2004 February 6; 303(5659): 763-6; Author Reply 763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768074
•
More on mercury content in fish. Author(s): Hudson RJ, Shade CW. Source: Science. 2004 February 6; 303(5659): 763-6; Author Reply 763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768073
•
More on mercury content in fish. Author(s): Stern AH. Source: Science. 2004 February 6; 303(5659): 763-6; Author Reply 763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764851
•
Nephrotic syndrome in two members of a family with mercury poisoning. Author(s): Meeks A, Keith PR, Tanner MS. Source: J Trace Elem Electrolytes Health Dis. 1990 December; 4(4): 237-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2136288
•
Neurobehavioral effects of acute exposure to inorganic mercury vapor. Author(s): Haut MW, Morrow LA, Pool D, Callahan TS, Haut JS, Franzen MD. Source: Applied Neuropsychology. 1999; 6(4): 193-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10635433
•
Neurological and electrophysiological examinations on three groups of workers with different levels of exposure to mercury vapors. Author(s): Urban P, Lukas E, Nerudova J, Cabelkova Z, Cikrt M. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 1999 September; 6(5): 571-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10457390
104
Mercury
•
Neurophysiological anomalies in brainstem responses of mercury-exposed children of Andean gold miners. Author(s): Counter SA. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003 January; 45(1): 87-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553183
•
Neuropsychological and stress evaluation of a residential mercury exposure. Author(s): Fiedler N, Udasin I, Gochfeld M, Buckler G, Kelly-McNeil K, Kipen H. Source: Environmental Health Perspectives. 1999 May; 107(5): 343-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210689
•
Neuropsychological effects associated with exposure to mercury vapor among former chloralkali workers. Author(s): Mathiesen T, Ellingsen DG, Kjuus H. Source: Scand J Work Environ Health. 1999 August; 25(4): 342-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10505660
•
Neuropsychological effects of low mercury exposure in dental staff in Erzurum, Turkey. Author(s): Aydin N, Karaoglanoglu S, Yigit A, Keles MS, Kirpinar I, Seven N. Source: Int Dent J. 2003 April; 53(2): 85-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12731695
•
Neuropsychological effects of low mercury vapor exposure in chloralkali workers. Author(s): Ellingsen DG, Bast-Pettersen R, Efskind J, Thomassen Y. Source: Neurotoxicology. 2001 April; 22(2): 249-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11405256
•
Newly enacted legislation addresses proper disposal of elemental mercury. Author(s): Rossi MS. Source: The New York State Dental Journal. 2003 December; 69(10): 8-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14974186
•
Nummular lichenoid dermatitis from mercury dental amalgam. Author(s): Pigatto PD, Guzzi G, Persichini P. Source: Contact Dermatitis. 2002 June; 46(6): 355-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190626
Studies
105
•
Nutritional factors may modify the toxic action of methyl mercury in fish-eating populations. Author(s): Clarkson TW, Strain JJ. Source: The Journal of Nutrition. 2003 May; 133(5 Suppl 1): 1539S-43S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730461
•
Occupational and environmental toxicology of mercury and its compounds. Author(s): Satoh H. Source: Ind Health. 2000 April; 38(2): 153-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10812838
•
Occupational exposure to airborne mercury during gold mining operations near El Callao, Venezuela. Author(s): Drake PL, Rojas M, Reh CM, Mueller CA, Jenkins FM. Source: International Archives of Occupational and Environmental Health. 2001 April; 74(3): 206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11355295
•
Occupational exposure to inorganic mercury vapour and reproductive outcomes. Author(s): Sheikh K. Source: Occupational Medicine (Oxford, England). 1998 April; 48(3): 207-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9659733
•
Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson's disease. Author(s): Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ. Source: Neurotoxicology. 1999 April-June; 20(2-3): 239-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385887
•
Oral bacteria resistant to mercury and to antibiotics are present in children with no previous exposure to amalgam restorative materials. Author(s): Ready D, Qureshi F, Bedi R, Mullany P, Wilson M. Source: Fems Microbiology Letters. 2003 June 6; 223(1): 107-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799008
•
Oral lichenoid lesions (OLL) and mercury in amalgam fillings. Author(s): Wong L, Freeman S. Source: Contact Dermatitis. 2003 February; 48(2): 74-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694209
106
Mercury
•
Oral lichenoid lesions caused by allergy to mercury in amalgam fillings. Author(s): Kalimo K. Source: Contact Dermatitis. 1996 July; 35(1): 69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8896978
•
Organic mercury compounds: human exposure and its relevance to public health. Author(s): Risher JF, Murray HE, Prince GR. Source: Toxicology and Industrial Health. 2002 April; 18(3): 109-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974562
•
Organic mercury levels among the Yanomama of the Brazilian Amazon Basin. Author(s): Sing KA, Hryhorczuk D, Saffirio G, Sinks T, Paschal DC, Sorensen J, Chen EH. Source: Ambio. 2003 November; 32(7): 434-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703900
•
Organochlorines, lead, and mercury in Akwesasne Mohawk youth. Author(s): Schell LM, Hubicki LA, DeCaprio AP, Gallo MV, Ravenscroft J, Tarbell A, Jacobs A, David D, Worswick P; Akwesasne Task Force on the Environment. Source: Environmental Health Perspectives. 2003 June; 111(7): 954-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782498
•
PCBs, mercury, and organochlorine concentrations in lake trout, walleye, and whitefish from selected tribal fisheries in the Upper Great Lakes region. Author(s): Gerstenberger SL, Dellinger JA. Source: Environmental Toxicology. 2002 December; 17(6): 513-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12448018
•
Percutaneous penetration of inorganic mercury from soil: an in vitro study. Author(s): Sartorelli P, Montomoli L, Sisinni AG, Barabesi L, Bussani R, Cherubini Di Simplicio F. Source: Bulletin of Environmental Contamination and Toxicology. 2003 December; 71(6): 1091-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756275
•
Photodegradation of 17alpha-ethynylestradiol in aqueous solution exposed to a highpressure mercury lamp (250 W). Author(s): Liu XL, Wu F, Deng NS. Source: Environmental Pollution (Barking, Essex : 1987). 2003; 126(3): 393-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963302
Studies
107
•
Pink ladies: mercury poisoning in twin girls. Author(s): Weinstein M, Bernstein S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 January 21; 168(2): 201. Erratum In: Cmaj. 2003 February 18; 168(4): 400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538551
•
Placental to fetal transfer of mercury and fetotoxicity. Author(s): Yoshida M. Source: The Tohoku Journal of Experimental Medicine. 2002 February; 196(2): 79-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498319
•
Predominant anthropogenic sources and rates of atmospheric mercury accumulation in southern Ontario recorded by peat cores from three bogs: comparison with natural “background” values (past 8000 years). Author(s): Givelet N, Roos-Barraclough F, Shotyk W. Source: Journal of Environmental Monitoring : Jem. 2003 December; 5(6): 935-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710936
•
Preliminary study on total mercury in the common prepared subsistence foods of a rural Alaskan village. Author(s): Rothschild RF, Duffy LK. Source: Alaska Med. 2002 October-December; 44(4): 89-93, 103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650086
•
Prevalence and antibiotic resistance profile of mercury-resistant oral bacteria from children with and without mercury amalgam fillings. Author(s): Pike R, Lucas V, Stapleton P, Gilthorpe MS, Roberts G, Rowbury R, Richards H, Mullany P, Wilson M. Source: The Journal of Antimicrobial Chemotherapy. 2002 May; 49(5): 777-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003971
•
Protecting the public from mercury exposure: success through microexchange events. Author(s): Shoemaker PA, Ghaemghami J. Source: American Journal of Public Health. 2003 December; 93(12): 1997-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652320
•
Public health consequences of mercury spills: Hazardous Substances Emergency Events Surveillance system, 1993-1998. Author(s): Zeitz P, Orr MF, Kaye WE. Source: Environmental Health Perspectives. 2002 February; 110(2): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836139
108
Mercury
•
Quantitative analysis of rapid pointing movements in Cree subjects exposed to mercury and in subjects with neurological deficits. Author(s): Beuter A, de Geoffroy A, Edwards R. Source: Environmental Research. 1999 January; 80(1): 50-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9931227
•
Rapid communication: acute exposure to mercury from dental amalgam does not affect the levels of C-reactive protein or interleukin-6 in peripheral blood. Author(s): Sandborgh-Englund G, af Geijersstam E, Loftenius A. Source: Journal of Toxicology and Environmental Health. Part A. 2003 March 28; 66(6): 495-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12712592
•
Reference intervals of cadmium, lead, and mercury in blood, urine, hair, and nails among residents in Mansoura city, Nile delta, Egypt. Author(s): Mortada WI, Sobh MA, el-Defrawy MM, Farahat SE. Source: Environmental Research. 2002 October; 90(2): 104-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483800
•
Relationship between mercury concentration in blood, cognitive performance, and blood pressure, in an elderly urban population. Author(s): Johansson N, Basun H, Winblad B, Nordberg M. Source: Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine. 2002 June; 15(2): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046928
•
Relationship between semen parameters and mercury concentrations in blood and in seminal fluid from subfertile males in Hong Kong. Author(s): Choy CM, Yeung QS, Briton-Jones CM, Cheung CK, Lam CW, Haines CJ. Source: Fertility and Sterility. 2002 August; 78(2): 426-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137888
•
Release of mercury from dental amalgam and its influence on salivary antioxidant activity. Author(s): Pizzichini M, Fonzi M, Sugherini L, Fonzi L, Gasparoni A, Comporti M, Pompella A. Source: The Science of the Total Environment. 2002 February 4; 284(1-3): 19-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846163
Studies
109
•
Release of mercury from dental amalgam and its influence on salivary antioxidant activity. Author(s): Pizzichini M, Fonzi M, Sugherini L, Fonzi L, Comporti M, Gasparoni A, Pompella A. Source: Bull Group Int Rech Sci Stomatol Odontol. 2000 May-December; 42(2-3): 94-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799733
•
Report on the levels of cadmium, lead, and mercury in imported rice grain samples. Author(s): Al-Saleh I, Shinwari N. Source: Biological Trace Element Research. 2001 October; 83(1): 91-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11694006
•
Results of multiyear international interlaboratory comparison program for mercury in human hair. Author(s): Gill US, Schwartz HM, Bigras L. Source: Archives of Environmental Contamination and Toxicology. 2002 November; 43(4): 466-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399918
•
Review: mercury in waste incineration. Author(s): van Veizen D, Langenkamp H, Herb G. Source: Waste Management & Research : the Journal of the International Solid Wastes and Public Cleansing Association, Iswa. 2002 December; 20(6): 556-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549668
•
Role of reactive oxygen species and glutathione in inorganic mercury-induced injury in human glioma cells. Author(s): Lee YW, Ha MS, Kim YK. Source: Neurochemical Research. 2001 November; 26(11): 1187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874199
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Scientific comment on the German human biological monitoring values (HBM values) for mercury. Author(s): Drasch G, Bose-O'Reilly S, Maydl S, Roider G. Source: International Journal of Hygiene and Environmental Health. 2002 October; 205(6): 509-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455274
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Selenium protection against mercury-induced apoptosis and growth inhibition in cultured K-562 cells. Author(s): Frisk P, Wester K, Yaqob A, Lindh U. Source: Biological Trace Element Research. 2003 May; 92(2): 105-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746570
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Selenoprotein P in subjects exposed to mercury and other stress situations such as physical load or metal chelation treatment. Author(s): Falnoga I, Kobal AB, Stibilj V, Horvat M. Source: Biological Trace Element Research. 2002 October; 89(1): 25-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413048
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Sources and variations of mercury in tuna. Author(s): Kraepiel AM, Keller K, Chin HB, Malcolm EG, Morel FM. Source: Environmental Science & Technology. 2003 December 15; 37(24): 5551-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717163
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Square-wave adsorptive cathodic stripping voltammetric determination of antiinflammatory indomethacin drug in tablets and human serum at a mercury electrode. Author(s): El-Hefnawy GB, El-Hallag IS, Ghoneim EM, Ghoneim MM. Source: Analytical and Bioanalytical Chemistry. 2003 May; 376(2): 220-5. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682707
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Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption. Author(s): Carta P, Flore C, Alinovi R, Ibba A, Tocco MG, Aru G, Carta R, Girei E, Mutti A, Lucchini R, Randaccio FS. Source: Neurotoxicology. 2003 August; 24(4-5): 617-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900074
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Subcutaneous injection of metallic mercury. Author(s): Soo YO, Wong CH, Griffith JF, Chan TY. Source: Human & Experimental Toxicology. 2003 June; 22(6): 345-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856958
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Subcutaneous metallic mercury injection of the hand. Author(s): Ellabban MG, Ali R, Hart NB. Source: British Journal of Plastic Surgery. 2003 January; 56(1): 47-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706151
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Survey of total mercury and methylmercury levels in edible fish from the Adriatic Sea. Author(s): Storelli MM, Giacominelli-Stuffler R, Storelli A, D'Addabbo R, Palermo C, Marcotrigiano GO. Source: Food Additives and Contaminants. 2003 December; 20(12): 1114-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726274
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Survey of total mercury in total diet food composites and an estimation of the dietary intake of mercury by adults and children from two Canadian cities, 1998-2000. Author(s): Dabeka RW, McKenzie AD, Bradley P. Source: Food Additives and Contaminants. 2003 July; 20(7): 629-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888388
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Th2-type immunopathological manifestations induced by mercury chloride or gold salts in the rat: signal transduction pathways, cellular mechanisms and genetic control. Author(s): Fournie GJ, Saoudi A, Druet P, Pelletier L. Source: Autoimmunity Reviews. 2002 August; 1(4): 205-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848997
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The chemical form of mercury in fish. Author(s): Harris HH, Pickering IJ, George GN. Source: Science. 2003 August 29; 301(5637): 1203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947190
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The inhibition of mercury absorption by dietary ethanol in humans: cross-sectional and case-control studies. Author(s): Martin MD, Naleway C. Source: Occupational and Environmental Medicine. 2004 February; 61(2): E8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739392
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The role of mercury in pustulosis palmaris et plantaris. Author(s): Dantzig P. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003 May; 45(5): 468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12762071
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The toxicology of mercury. Author(s): Wendroff AP. Source: The New England Journal of Medicine. 2004 February 26; 350(9): 945-7; Author Reply 945-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988939
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The toxicology of mercury. Author(s): Ross DA. Source: The New England Journal of Medicine. 2004 February 26; 350(9): 945-7; Author Reply 945-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988938
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The toxicology of mercury. Author(s): Koral SM. Source: The New England Journal of Medicine. 2004 February 26; 350(9): 945-7; Author Reply 945-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988937
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The toxicology of mercury. Author(s): Block LS. Source: The New England Journal of Medicine. 2004 February 26; 350(9): 945-7; Author Reply 945-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985496
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The toxicology of mercury. Author(s): Patterson B, Ryan J, Dickey JH. Source: The New England Journal of Medicine. 2004 February 26; 350(9): 945-7; Author Reply 945-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988940
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The toxicology of mercury--current exposures and clinical manifestations. Author(s): Clarkson TW, Magos L, Myers GJ. Source: The New England Journal of Medicine. 2003 October 30; 349(18): 1731-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585942
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Uncertainty analysis methods for comparing predictive models and biomarkers: A case study of dietary methyl mercury exposure. Author(s): Ponce RA, Bartell SM, Kavanagh TJ, Woods JS, Griffith WC, Lee RC, Takaro TK, Faustman EM. Source: Regulatory Toxicology and Pharmacology : Rtp. 1998 October; 28(2): 96-105. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9927559
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UNEP takes first steps to control worldwide mercury releases. United Nations Environmental Programme. Author(s): Burke M. Source: Environmental Science & Technology. 2002 December 1; 36(23): 441A-442A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12523393
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Untreated abandoned mercury mining works in a scenic area of Asturias (Spain). Author(s): Loredo J, Pereira A, Ordonez A. Source: Environment International. 2003 July; 29(4): 481-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705946
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Updated toxicological profile for mercury. Author(s): Risher JF, De Rosa CT, Jones DE, Murray HE. Source: Toxicology and Industrial Health. 1999 August; 15(5): 480-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487359
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Urinary markers of workers chronically exposed to mercury vapor. Author(s): Abdennour C, Khelili K, Boulakoud MS, Nezzal A, Boubsil S, Slimani S. Source: Environmental Research. 2002 July; 89(3): 245-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176008
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Urinary mercury excretion following amalgam filling in children. Author(s): Khordi-Mood M, Sarraf-Shirazi AR, Balali-Mood M. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(7): 701-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11778667
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Urinary mercury levels in patients with autoantibodies to U3-RNP (fibrillarin). Author(s): Arnett FC, Fritzler MJ, Ahn C, Holian A. Source: The Journal of Rheumatology. 2000 February; 27(2): 405-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10685806
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Urine mercury in micromercurialism: bimodal distribution and diagnostic implications. Author(s): Ely JT, Fudenberg HH, Muirhead RJ, LaMarche MG, Krone CA, Buscher D, Stern EA. Source: Bulletin of Environmental Contamination and Toxicology. 1999 November; 63(5): 553-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541672
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Use of inductively coupled plasma-emission spectroscopy and mercury vapor analyses to evaluate elemental release from a high-copper dental amalgam: a pilot study. Author(s): Cohen BI, Penugonda B. Source: The Journal of Prosthetic Dentistry. 2001 April; 85(4): 409-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11319540
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Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Author(s): Roels HA, Hoet P, Lison D. Source: Renal Failure. 1999 May-July; 21(3-4): 251-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416202
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Vacuuming a mercury-contaminated dental office may be hazardous to your health. Author(s): Votaw AL, Zey J. Source: Dental Assistant (Chicago, Ill. : 1994). 1991 January-February; 60(1): 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1860523
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Validation and calibration of mercury intake through self-referred fish consumption in riverine populations in Pantanal Mato-grossense, Brazil. Author(s): Yokoo EM, Valente JG, Sichieri R, Silva EC. Source: Environmental Research. 2001 May; 86(1): 88-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386746
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Validity of spot urine samples as a surrogate measure of 24-hour porphyrin excretion rates. Evaluation of diurnal variations in porphyrin, mercury, and creatinine concentrations among subjects with very low occupational mercury exposure. Author(s): Woods JS, Martin MD, Leroux BG. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 1998 December; 40(12): 1090-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9871886
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Variability in airborne and biological measures of exposure to mercury in the chloralkali industry: implications for epidemiologic studies. Author(s): Symanski E, Sallsten G, Barregard L. Source: Environmental Health Perspectives. 2000 June; 108(6): 569-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856033
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Varying mercury exposure with varying food source in a James Bay Cree community. Author(s): Girard M, Noel F, Dumont C. Source: Arctic Med Res. 1996 April; 55(2): 69-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8754601
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Visual functions in 6-year-old children in relation to lead and mercury levels. Author(s): Altmann L, Sveinsson K, Kramer U, Weishoff-Houben M, Turfeld M, Winneke G, Wiegand H. Source: Neurotoxicology and Teratology. 1998 January-February; 20(1): 9-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9511165
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Voltammetric behaviour of immunoglobulin G at stationary mercury electrodes. Author(s): Emons H, Werner G, Heineman WR. Source: The Analyst. 1990 April; 115(4): 405-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2363518
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What every nurse should know about mercury. Author(s): Tillman K. Source: Home Healthcare Nurse. 2002 May; 20(5): 319-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12045699
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What will replace the mercury sphygmomanometer? Author(s): Pickering TG. Source: Blood Pressure Monitoring. 2003 February; 8(1): 23-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604932
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When the mercury soars. Author(s): Elliott F. Source: Occup Health Saf. 2001 July; 70(7): 94-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484563
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Whole blood mercury concentrations in sub-fertile men in Hong Kong. Author(s): Leung TY, Choy CM, Yim SF, Lam CW, Haines CJ. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2001 February; 41(1): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11284652
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Why the concern over mercury in wastewater? Author(s): Kratzer SJ. Source: J Mich Dent Assoc. 2003 February; 85(2): 42-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640764
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Wide use of skin-lightening soap may cause mercury poisoning in Kenya. Author(s): Harada M, Nakachi S, Tasaka K, Sakashita S, Muta K, Yanagida K, Doi R, Kizaki T, Ohno H. Source: The Science of the Total Environment. 2001 March 26; 269(1-3): 183-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11305339
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Will the millimetre of mercury be replaced by the kilopascal? Author(s): Colquitt PJ. Source: Journal of Hypertension. 1999 February; 17(2): 305-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10067802
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Will the millimetre of mercury be replaced by the kilopascal? Author(s): Omvik P. Source: Journal of Hypertension. 1998 July; 16(7): 1055-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9794749
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Will the millimetre of mercury be replaced by the kilopascal? Author(s): O'Brien E. Source: Journal of Hypertension. 1998 March; 16(3): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9557917
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Wrist blood pressure-measuring devices: a comparative study of accuracy with a standard auscultatory method using a mercury manometer. Author(s): Altunkan S, Yildiz S, Azer S. Source: Blood Pressure Monitoring. 2002 October; 7(5): 281-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409888
Academic Periodicals covering Mercury Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to mercury. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 2. PATENTS ON MERCURY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.7 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “mercury” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on mercury, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Mercury By performing a patent search focusing on mercury, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
7Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on mercury: •
Calibration scheme for continuous monitoring of mercury emissions from stationary sources by plasma emission spectrometry Inventor(s): Seltzer; Michael D. (Ridgecrest, CA) Assignee(s): The United States of America AS Represented by the Secretary of the Navy (washington, Dc) Patent Number: 6,690,462 Date filed: December 5, 2001 Abstract: The disclosed invention relates to a calibration method, system and apparatus for a multimetals continuous emissions monitor system (hereinafter "multimetals CEMS"). More specifically, this invention relates to a calibration scheme for continuous monitoring of mercury emissions from stationary sources by plasma emission spectrometry. A source of mercury vapor, preferably a mercury permeation tube, entrains mercury vapor into a constant flow of carrier air. The carrier air mixes with a constant flow of diluent air in an aerosol mixer. The mixer is operably coupled to the analyzer. A gaseous mixture having a calibration mercury concentration flows from the mixer into the analyzer at a constant rate. A graph having coordinates of analyzer signal intensity and mercury concentration is used to plot the calibration scheme. A first signal intensity generated by the analyzer in response to the calibration mercury concentration is used for the first plot on the graph. A second signal intensity generated by the analyzer in response to a blank having zero mercury concentration is used as the second plot on the graph. A linear relationship between the analyzer signal intensity and the mercury concentration on the graph is established from the first plot and the second plot. The slope intercept and slope are used to create a mathematical relationship between the analyzer signal intensity and the mercury concentration. This enables the analyzer to be calibrated by inserting a known mercury concentration into the analyzer and adjusting the signal intensity to conform to the signal intensity calculated from the graph or mathematical relationship. Excerpt(s): This invention relates to a calibration scheme for a multimetals continuous emissions monitor system (hereinafter "multimetals CEMS"). More specifically, this invention relates to a calibration scheme for continuous monitoring of mercury emissions from stationary sources by plasma emission spectrometry. Almost exclusively, analyzers or continuous emission monitors for gaseous pollutants such as carbon monoxide, nitrogen oxides, hydrogen chloride, etc., are calibrated using commercially-available gas mixtures that contain precise, certified amounts of the pollutant species in question These mixtures are readily prepared by commercial vendors and then certified by suitable analytical methods. The certification is most often "traceable" to reference standards provided by the National Institutes of Standards and Technology (formerly the National Bureau of Standards). The continuous monitoring of hazardous air pollutant metals is an emerging technology that presents a number of unique technological challenges. Unlike the gaseous air pollutant described above, there are no sources for "standard" gas mixtures containing "known" amounts of metal pollutants. Metal elements exist primarily in the solid phase except at extremely high temperatures and therefore do not lend themselves to mixture and containment in the gaseous state. The one exception is mercury, which can exist as both a liquid and gas at room temperature. There have been some efforts in the commercial arena to prepare gaseous mixtures of mercury vapor (contained in cylinders) potentially useful in
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applications similar to that described in the present invention disclosure. However, those devices are most directly applicable for calibrating batch-sampling mercury analyzers exclusively dedicated to the detection of mercury. Batch-sampling mercury analyzers do not continuously measure mercury in sample gas. Rather, batch-sampling mercury analyzers accumulate a mercury sample over a period of time before measuring the sample. These calibrating batch-sampling mercury analyzers use analytical methodologies that are distinctly different from those employed by the multimetals CEMS. Thus far, the developers of this product have been able to certify the contents of the gas cylinder in terms of mercury concentration, but at present, are unable to provide certification of the mercury concentration of the delivered gas stream. For the specific multimetals CEMS described above, a calibration method has been developed in which dry aerosols of known metal composition and concentration can be generated and used in lieu of unavailable gaseous calibration mixtures. This calibration method is briefly summarized here, but for a more detailed discussion please see Seltzer, M. D. and Meyer, G. A. Inductively Coupled Argon Plasma Continuous Emissions Monitor for Hazardous Air Pollutant Metals Environmental Science and Technology, Vol. 31, (1997), pp. 2665-2672, which is incorporated herein by reference. Aqueous solutions containing known amounts of dissolved metal salts, primarily metal nitrates, are delivered at a fixed rate of 1.5 mL/min into a COTS device known as an ultrasonic nebulizer. The ultrasonic nebulizer creates a fine, liquid aerosol from these solutions that is entrained by a carrier gas flow of 1.1 L/min through a desolvation system. The desolvation system consists of a heater that raises the temperature of the liquid aerosol carrier air mixture to 140.degree. C. that effectively evaporates the liquid water and produces water vapor. Following evaporation of the water from the liquid aerosol droplets, the dissolved metal salt component of each aerosol droplet coalesces into a solid metal salt particle. The metal salt particulate/water vapor/carrier air stream then passes through a thermoelectric cooler that reduces the temperature of the mixture to 4.degree. C. and effectively condenses and removes the water vapor component. Exiting the ultrasonic nebulizer device is a carrier air stream containing suspended metal salt particles. Through systematic characterization of the ultrasonic nebulizer's efficiency, the output of the nebulizer, in terms of micrograms of metal per minute, is precisely known. Therefore, the process described above is extremely useful for calibration of the multi metal CEMS. The validity of the calibration scheme has been established through rigorous performance testing in which the accuracy of the multimetals CEMS was verified in comparison to an EPA-approved test method, as described in Seltzer, M. D. Performance Testing of a Multimetals Continuous Emissions Monitor, Journal of the Air and Waste Management Association, Vol. 50 (2000), pp. 1010-1016, which is incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06690462__ •
Simulative electronic blood pressure meter Inventor(s): Hung; George (1F, No. 151, Sec. 3 Pei-Shen Rd., Shen-Keng Hsiang, Taipei County, TW) Assignee(s): None Reported Patent Number: 6,699,196 Date filed: May 31, 2001 Abstract: Simulative electronic blood pressure meter in which by means of internal program, a central processor/controller converts and outputs the sensed blood pressure
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signal to a liquid crystal display to show a column-type indication simulating the mercury column of a traditional blood pressure meter. A digital counting circuit is combined, whereby when simulating the mercury column, an auxiliary display of digital change is provided for the user to easily know the value. The central processor/controller cooperates with a sound emitting unit which synchronously emits a sound simulating the sensed pulse from the start to the end. The volume of the emitted sound is varied with the strength of the pulse. The electronic blood pressure meter is used in a state like the mercury column-type blood pressure meter for a user to more accurately and lively judge the measured value. Excerpt(s): The present invention is related to a simulative electronic blood pressure meter which displays a column-type indication on a liquid crystal display to simulate the going up and down of the mercury column of a traditional blood pressure meter. A sound emitting unit is combined to synchronously emit a sound simulating the sensed pulse for a user to more accurately and lively judge the measured value. Various kinds of electronic blood pressure meters have been developed. However, the conventional mercury column-type blood pressure meters are still widely used by doctors and nurses. This is because that the data measured by the electronic blood pressure meters often have errors due to various kinds of factors. Moreover, the electronic blood pressure meters can only show the measured value at the end of the measurement and fail to lively and accurately continuously indicate the value of the measured blood pressure during the entire measurement. Therefore, a user can hardly truly judge the measured value. It is therefore a primary object of the present invention to provide a simulative electronic blood pressure meter which is able to display a column-type indication simulating the mercury column of a traditional blood pressure meter. A digital counting circuit is combined, whereby when simulating the mercury column, the digital change is also shown. The central processor/controller cooperates with a sound emitting unit which synchronously emits a sound simulating the sensed pulse. The volume of the emitted sound is varied with the strength of the pulse. The electronic blood pressure meter is used in a state like the mercury column-type blood pressure meter for a user to more accurately and lively judge the value of the blood pressure. Web site: http://www.delphion.com/details?pn=US06699196__
Patent Applications on Mercury As of December 2000, U.S. patent applications are open to public viewing.8 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to mercury: •
Pocket sphygmomanometer Inventor(s): Oh, Man S.; (Old Westbury, NY) Correspondence: Ostrolenk Faber Gerb & Soffen; 1180 Avenue OF The Americas; New York; NY; 100368403 Patent Application Number: 20040044289 Date filed: September 4, 2002
8
This has been a common practice outside the United States prior to December 2000.
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Abstract: A sphygmomanometer with an air reservoir connected above a tube for a mercury column and a selectively openable and closeable valve to the air reservoir. With the valve open, first blood pressure measurements can be made by pressure rising in the mercury reservoir. With the valve closed, the air above the mercury column resists rise in the mercury column but also permits higher pressure measurements using the same mercury column. One scale at the mercury tube measures the pressure with the valve open and another scale at the tube measures the pressure with the valve closed. The measurements with the valve closed are calibrated by appropriately altering the volume of the air reservoir depending upon altitude at barometric pressure. The sphygmomanometer can be used to perform a mercury drop test for determining the altitude at which the sphygmomanometer is located. Excerpt(s): The present invention relates to a mercury sphygmomanometer that is compact, easy to manufacture, and safe from mercury spillage. A mercury sphygmomanometer is one of several blood pressure-measuring devices currently available. Other measuring devices include aneroid pressure measuring manometers and electronic manometers. Aneroid and electronic manometers tend to be smaller in size, lighter in weight, and more compact than mercury sphygmomanometers, but their accuracy is always in doubt. For most assured accuracy the standard among different blood pressure measuring devices is the mercury sphygmomanometer. The mercury sphygmomanometer measures arterial blood pressure and indicates its measurement by the height of a mercury column. The conventional mercury sphygmomanometer uses a transparent rigid plastic or glass tube through which a mercury column rises and falls during blood pressure measurement. In a typical mercury sphygmomanometer, the mercury tube is tall enough to allow the mercury column to reach a maximum height of 300 mm. Thus, the height of the mercury tube establishes the minimum height or length of the mercury sphygmomanometer when the device is stored or carried. In order to obviate the size limitation of the conventional mercury sphygmomanometer and to allow a compact size for easy portability and storage, three approaches have been taken. One approach is to use a flexible tube for the mercury column, which could be folded during storage for compactness, e.g. as disclosed in U.S. Pat. No. 2,603,210. Another approach is to provide an articulation or a hinge located part way along the tube and to fold and unfold the mercury tube at the articulation or hinge for storage and usage of the device, e.g. as disclosed in U.S. Pat. No. 1,093,199 and U.S. Pat. No. 1,077,365. In another approach using a hinge mechanism, as described in U.S. Pat. No. 1,474,853, the mercury column used for blood pressure reading is a single tube. But this device requires a third tube to act as a mercury reservoir which is placed between a tube for the mercury column used for blood pressure readings and another tube connected to the air inflation cuff. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with mercury, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “mercury” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on mercury.
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You can also use this procedure to view pending patent applications concerning mercury. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 3. BOOKS ON MERCURY Overview This chapter provides bibliographic book references relating to mercury. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on mercury include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “mercury” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on mercury: •
Self - Treatment for AIDS; Oxygen Therapies, etc Contact: Aurora Books, PO Box 5852, Denver, CO, 80217. Summary: In this monograph, Persons with AIDS (PWA's), or those who are infected with Human immunodeficiency virus (HIV), are presented with the full spectrum of alternative therapies and self-care strategies for treating Acquired immunodeficiency syndrome (AIDS). The monograph is based on the premise that HIV may lead to infection if a person's immune system is weakened and unable to resist poisonous pathological microorganisms. Testimonials from PWA's, research reports, studies, and articles describe oxygen therapies, tests for Epstein-Barr virus, cytomegalovirus, herpes, food or chemical hypersensitivity, fungal hypersensitivity, immuno-nutritional profiles, safe water and nutrition strategies, chemicals, allergies, detoxification centers, colon health, parasites, acidophilus, electromagnetic health hazards and healing, silver (mercury) fillings, and stress management. Although the therapies, remedies, and treatments are deemed valid, the monograph recommends that they be incoporated
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with other avenues of healing. These include colon cleansing; bathing to release toxins; stress reduction; elimination of smoking, drinking, drug use, or poor nutrition; avoidance of low-energy people; maintenance of peace, forgiveness, positive thought, music, laughter, and joy; massage, osteopathic, acupuncture, chiropractic, and dental treatments; exercise; and avoidance of TV, computers, and other machines which emit low-level radiation. These measures may bring the body back into alignment and homeostatis. The patient is encouraged to engage a holistic-health practitioner to help raise the body's resistance level. Because oxygen starvation is the single greatest cause of disease, full oxygenation plays a critical role in the immune system. •
Dentistry, dental practice, and the community. (5th ed.) Source: Philadelphia, PA: W. B. Saunders Company. 1999. 384 pp. Contact: Available from W. B. Saunders Company, 625 Walnut Street, Suite 300, Philadelphia, PA 19106. Telephone: (215) 238-7800 or (800) 545- 2522. $39.95 plus shipping and handling. Summary: This book provides a comprehensive analysis of dentistry's social and professional role. It is divided into five sections. The first section is about dentistry and the community and includes chapters on the dental professions, the public served by dentists, professional ethics, dental public health, and the promotion of oral health. Section II is about dental practice and includes chapters on infection control and mercury safety, the structure of dental practice, financing dental care, dental personnel, dental care in Canada, and dental literature. Section III deals with methods of oral epidemiology and begins with chapter on research designs. It also includes separate chapters on measuring the following: oral disease, dental caries, periodontal diseases, dental fluorosis, and other oral conditions. Section IV covers the distribution of oral diseases and conditions with chapters about tooth loss, dental caries, periodontal diseases, dental fluorosis, and oral cancer and other oral conditions. Section V is about prevention of oral diseases in public health. It includes chapters on fluoride, fluoridation of drinking water, other uses of fluoride, fissure sealants, diet and plaque control, prevention of periodontal diseases, and tobacco and oral cancer.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: When following the link below, you may discover non-medical books that use the generic term “mercury” (or a synonym) in their titles. •
Amazon.com: http://www.amazon.com/exec/obidos/externalsearch?tag=icongroupinterna&keyword=mercury&mode=books
Chapters on Mercury In order to find chapters that specifically relate to mercury, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and mercury using the “Detailed Search” option. Go to the following hyperlink:
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http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “mercury” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on mercury: •
Neurological Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 336-373. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail:
[email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Dental staff should be able to recognize abnormalities involving the cranial nerves, especially the trigeminal, facial, glossopharyngeal, vagal and hypoglossal nerves. This chapter on neurologic disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include congenital neurological disorders, including cerebral palsy (CP), neural tube defects (spina bifida), syringomyelia, Huntington's chorea, and Friedreich's ataxia; acquired neurological disorders, including the examination and lesions of the cranial nerves, facial sensory loss (facial pain is covered in a separate chapter), facial paralysis, Bell's palsy, trigeminal motor neuropathy, abnormal facial movements (dystonias, dyskinesias, facial tics, Tourette syndrome), multiple cranial nerve palsies, blindness and visual impairment, deafness and hearing impairment, Meniere's disease, autonomic dysfunction, epilepsy, syncope (fainting), raised intracranial pressure, hypoxic encephalopathy, infections of the
