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Biomedical subjects

G Lucier

Publications and source records attributed to G Lucier.

At least 19 recordsLinked to original sources
PubMed2000

Strategies for assessing the implications of malformed frogs for environmental health.

The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level. Discussions highlighted possible causes and recent findings directly related to frog deformities and provided insight into problems and strategies applicable to continuing investigation in several areas. Possible causes of the deformities were evaluated in terms of diagnostics performed on field amphibians, biologic mechanisms that can lead to the types of malformations observed, and parallel laboratory and field studies. Hydrogeochemistry must be more integrated into environmental toxicology because of the pivotal role of the aquatic environment and the importance of fates and transport relative to any potential exposure. There is no indication of whether there may be a human health factor associated with the deformities. However, the possibility that causal agents may be waterborne indicates a need to identify the relevant factors and establish the relationship between environmental and human health in terms of hazard assessment.

Animals↗
PubMed2000

Parting thoughts

It has been said that there is no stronger urge than the urge to edit someone else's writing. Upon my retirement from the National Institute of Environmental Health Sciences (NIEHS), and concurrently from my position as co-editor-in-chief of Environmental Health Perspectives, I find that perhaps the stronger urge is not to edit but rather to editorialize. Therefore, I would like to provide some parting thoughts, and with them hopefully some insights gained from my experiences, which have spanned the broad spectrum of environmental health, from basic science to public health policy to science communication. I am grateful to have had the opportunity to work on many different aspects of the environmental health continuum during my time at the NIEHS. In looking back on a career of 30 years in environmental health, including 28 years as co-editor-in-chief of this journal, I am struck by a kaleidoscope of thoughts, emotions, and nostalgia, and in juxtaposition to these remembrances, a new perspective on the future. As the field of environmental health continues to expand as both a scientific discipline and a global movement, I feel that there are some major components which it must enthusiastically encompass if the field is to continue to provide real answers to the most pressing environmental health issues of our day.

Journal Article↗
PubMed1999

Effects of intracoronary beta-radiation therapy after coronary angioplasty: an intravascular ultrasound study.

BACKGROUND: Endovascular radiation is emerging as a potential solution for the prevention and treatment of restenosis. Its effects on the morphology of unstented vessels cannot be determined by angiography and therefore require the use of intravascular ultrasound. METHODS AND RESULTS: Through a 5F noncentered catheter for delivery of a 90Sr/Y source train, 12, 14, or 16 Gy at 2 mm was delivered to native coronary arteries after successful balloon angioplasty in 30 patients. Four patients required stent deployment in the first week. Quantitative coronary angiography and IVUS were performed during the initial procedure and at 6-month follow-up. Binary angiographic restenosis was present in 3 of 30 patients, with target lesion and vessel revascularization performed in 3 and 5 patients, respectively. Angiographic late loss was -0.02+/-0.60 mm, with a -0.09+/-0.46 loss index. IVUS demonstrated no significant reduction in lumen area (from 5.69+/-1.72 mm2 after treatment to 6. 04+/-2.63 mm2 at follow-up), with no significant change in external elastic membrane area (13.71+/-4.54 to 14.22+/-4.71 mm2) over the 6-month follow-up. Wall area was 8.01+/-3.85 mm2 after radiation therapy and 8.19+/-3.44 mm2 at follow-up (P=NS). No significant differences were noted between the different dose groups. CONCLUSIONS: beta-Radiation therapy resulted in a low restenosis rate with negligible late loss by angiography. By IVUS, beta-radiation was shown to inhibit neointima formation, with no reduction of total vessel area at 6-month follow-up.

Adult↗
PubMed1999

Species, interindividual, and tissue specificity in endocrine signaling.

The activity of endocrine-active agents exhibits specificity at many levels. Differential responsiveness to these agents has been observed between different species and extends to interindividual differences within a species and between different tissues as well. In cases where they have been identified, the biologic and molecular mechanisms underlying this specificity are quite diverse. Determinants of species specificity include differences that exist in receptor binding, gene transcription, and cellular responses to endocrine-active compounds between species. Interindividual differences in responsiveness may be determined at the level of genetic polymorphisms in hormone-metabolizing enzymes, hormone receptors, and in those genes that are transactivated by these receptors, as well as during changing windows of susceptibility that occur as a function of age, such as prenatal and postmenopausal exposures. Extrinsic factors such as diet can also impact individual susceptibility to endocrine-active agents. Tissue-specific determinants of susceptibility are well documented, but little is known regarding the mechanisms underlying these different responses. Differences in the expression of accessory proteins for steroid hormone receptors and different patterns of receptor expression, estrogen receptor alpha and estrogen receptor beta; for example, may contribute to tissue specificity, as may differences in the pattern of expression of other genes such as hormone-metabolizing enzymes. The use of animal model systems and development of appropriate mathematical models has the potential to yield additional valuable information for elucidating the role of these determinants of specificity at low-dose exposures and for improved risk assessments for the adverse health effects of endocrine-active compounds.

Age Factors↗
PubMed1998

Induction of mortality and malformation in Xenopus laevis embryos by water sources associated with field frog deformities.

Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.

Animals↗
PubMed1998

The U.S. federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996.

The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and polychlorinated biphenyls are the most commonly studied chemical classes. Comparison of the inventory with the research needs should allow identification of underrepresented research areas in need of attention.

Endocrine Glands↗
PubMed1998

2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident.

In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD levels in soil, and cohort including all residents was enumerated. The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population. Two decades after the accident. plasma TCDD levels were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident site (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes.

Accidents, Occupational↗
PubMed1998

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗
PubMed1998

Current approaches toward chemical mixture studies at the National Institute of Environmental Health Sciences and the U.S. National Toxicology Program.

The National Institute of Environmental Health Sciences (NIEHS) has several new initiatives involving chemical mixtures and has recognized the need to develop new experimental approaches to enhance our efforts in this area. Responding to recent increases in nominations of complex occupational exposures for toxicologic assessment by the U.S. National Toxicology Program, the NIEHS and the National Institute for Occupational Safety and Health have begun a program to characterize exposures through field studies, identify biomarkers of exposure in workers, and recreate relevant mixed exposures in a laboratory setting. A second initiative with the National Center for Environmental Health/Centers for Disease Control and Prevention will examine blood samples from the U.S. National Health and Nutrition Examination Survey population surveys for selected endocrine-disrupting agents and for common patterns of persistent xenobiotics, providing critical information for the design of animal studies to assess risks of relevant chemical mixtures to humans. New toxicology testing methods (lower cost, faster) will enhance our ability to study chemical mixtures (e.g., dioxin and dioxinlike chemicals, combination AIDS therapies). Ongoing method development efforts involve in vitro functional toxicology assays, screens for estrogenic activity, and carcinogenesis studies in transgenic mice. A major scientific initiative with mixtures involves studies of individual and mixtures of dioxin and dioxinlike chemicals to determine if toxic equivalence factors predict carcinogenic potency in traditional and transgenic bioassays. Complementing these studies is an increased emphasis on physiologically based pharmacokinetic modeling, an activity central to the proper interpretation of chemical mixture studies.

Animals↗
PubMed1997

Implementation of EPA Revised Cancer Assessment Guidelines: Incorporation of Mechanistic and Pharmacokinetic Data.

A workshop entitled "Implementation of EPA Revised Cancer Assessment Guidelines: Incorporation of Mechanistic and Pharmacokinetic Data" was held in Anaheim, California, in 1996 at the 35th Annual Meeting of the Society of Toxicology (SOT). This workshop was jointly sponsored by the Carcinogenesis, Risk Assessment, and Veterinary Specialty Sections of the SOT. The thrust of the workshop was to discuss the scientific basis for the revisions to the EPA Guidelines for cancer assessment and EPA's plans for their implementation. This is the first revision to the original EPA guidelines which have been in use by EPA since 1986. The principal revisions are intended to provide a framework for an increased ability to incorporate biological data into the risk assessment process. Two cases were presented, for chloroform and triclioroethylene, that demonstrated the use of the revised guidelines for specific cancer risk assessments. Using these new guidelines, nonlinear margin of exposure analyses were proposed for these chemicals instead of the linearized multistage model previously used by the EPA as the default method. The workshop participants generally applauded the planned revisions to the EPA guidelines. For the most part, they considered that the revised guidelines represented a positive step which should allow for and encourage the use of biological information in the conduct of cancer risk assessments. Several participants cautioned however that the major problem with cancer risk assessments would continue to be the inadequacy of available data on which to conduct more scientific risk assessments.

Animals↗
PubMed1997

The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health.

Organochlorines are a diverse group of persistent synthetic compounds, some of which are detectable in nearly everyone. Many organochlorines are endocrine disruptors or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl-dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of organochlorine residues in human tissues. We reviewed relevant human data cited in the 1991-1995 Medline database and elsewhere. High-level exposure to selected organochlorines appears to cause abnormalities of liver function, skin (chloracne), and the nervous system. Of more general interest, however, is evidence suggesting insidious effects of background exposure. Of particular concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB exposure. The epidemiologic data reviewed, considered in isolation, provide no convincing evidence that organochlorines cause a large excess number of cancers. A recent risk assessment that considered animal data, however, gives a cancer risk estimate for background exposure to dioxin and dioxin-like compounds (e.g. some PCBs) with an upper bound in the range of 10(-4) per year.

Adult↗
PubMed1996

Modeling the number and size of hepatic focal lesions following exposure to 2,3,7,8-TCDD.

Data on the size and number of placental glutathione S-transferase-positive (PGST+) foci were collected from a two-stage hepatocarcinogenesis model in female Sprague-Dawley rats. the study consisted of multiple 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed dose groups including both diethylnitrosomine (DEN)-initiated and uninitiated animals. Groups were observed after 15 or 31 weeks of TCDD exposure. The parameters in the first half of a two-stage mathematical model of carcinogenesis were estimated from these data. If the model is valid, the results suggest that TCDD stimulates the production of PGST+ foci and promotes the growth of PGST+ foci. This finding suggests a complicated mechanism for TCDD-induced production of Hepatic foci that we refer to as activation, labeling TCDD as an activator. The analysis also indicates that there is an interaction between DEN and TCDD which results in dose-related formation of initiated cells throughout the study period. Best-fitting curves (using maximum likelihood methods) for TCDD-induced activation and promotion reached saturation levels at low doses of TCDD. In summary, the model fit the data well, but leads to an interpretation of the data which either questions the validity of the model or implies that our understanding of the effects of TCDD and DEN is incomplete.

Adenosine Triphosphate↗
PubMed1996

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

Animals↗