PubMed Health⌕ Search

Biomedical subjects

E K Silbergeld

Publications and source records attributed to E K Silbergeld.

At least 19 recordsLinked to original sources
PubMed1992

Lead inhibits secretion of osteonectin/SPARC without significantly altering collagen or Hsp47 production in osteoblast-like ROS 17/2.8 cells.

In an effort to better understand the consequences of lead (Pb2+) on skeletal growth, the effects of Pb2+ were investigated using ROS 17/2.8 bone-like cells in vitro. These studies revealed that Pb2+ (4.5 x 10(-6) M -4.5 x 10(-7) M) has little or no effect on cell shape except when added immediately following seeding of the cells. However, proliferation of ROS cells was inhibited, in the absence of serum, at concentrations of 4.5 x 10(-6) M Pb2+. Protein production was generally increased, however, the major structural protein of bone, type I collagen, production was only slightly altered. Following treatment of ROS cells with Pb2+, intracellular levels of the calcium-binding protein osteonectin/SPARC were increased. Osteonectin/SPARC secretion into the media was delayed or inhibited. Coincident with retention of osteonectin/SPARC there was a decrease in the levels of osteonectin/SPARC mRNA as determined by Northern analysis. These studies suggest that processes associated with osteonectin/SPARC translation and secretion are sensitive to Pb2+.

Animals↗
PubMed1992

Mechanisms of lead neurotoxicity, or looking beyond the lamppost.

Despite several decades of research on the neurotoxicology of lead and its continued prominence as a major environmental and occupational health hazard, the mechanisms of its toxic action in the nervous system are still unknown. The differential effects of lead exposure in young children and adults, as well as inconsistencies between in vivo and in vitro studies, suggest that lead toxicity may have multiple mechanisms in the central nervous system (CNS). Two are: neurodevelopmental toxicity, possibly involving interference with cell adhesion molecules, resulting in miswiring of the CNS during early development and possibly permanent dysfunction; and neuropharmacological toxicity, which might involve interactions between lead and calcium and lead and zinc, resulting in interference with neurotransmission at the synapse. This may be reversible.

Central Nervous System↗
PubMed1991

Alterations in protein synthesis in rat liver cells by in vitro and in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Alterations in protein synthesis in rat liver cells were examined following in vitro and in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Primary cultured rat liver parenchymal cells were exposed to 1 nM TCDD for 23 and 47 hr. Synthesis of two proteins with molecular weights (Mr) of 26,000 and 39,000 (designated 26k-P and 39k-P, respectively), other than cytochrome P450, was increased markedly in the cells. These proteins did not have the same antigens as cytochromes P450IA1 and P450IA2. Synthesis of three proteins with Mrs of 24,000, 25,000 and 29,000, respectively, was decreased by TCDD. TCDD was administered to rats at a dose of 100 micrograms/kg body weight. The amount of five proteins (two proteins with Mr of 26,000, one of 36,000 and two of 39,000) was increased in TCDD-treated rat liver. However, the proteins increased in vivo by TCDD were distinguishable from 26k-P and 39k-P by two dimensional gel electrophoresis.

Animals↗
PubMed1991

Lead in bone: implications for toxicology during pregnancy and lactation.

Advances in understanding the distribution and retention of lead in mineralized tissues are important for two reasons: first, bone lead may be a more accurate dosimeter of integrated absorption associated with chronic exposures, and second, bone lead may be a source of internal exposure to the host organism. Little attention has been paid to this second aspect, the remobilization of lead from bone. Mobilization of lead from bone is likely to occur during periods of altered mineral metabolism; since calciotropic factors determine the uptake and storage of lead in this compartment, changes in calcium-related regulatory factors are likely to affect lead compartmentation. Calcium metabolism changes drastically in humans during pregnancy and lactation; although relatively little is known of lead kinetics during these critical periods, it is likely that bone lead is mobilized and transferred to the more bioavailable compartment of the maternal circulation, with potential toxic effects on the fetus and the mother.

Bone and Bones↗
PubMed1990

Toward the twenty-first century: lessons from lead and lessons yet to learn.

A consideration of recent research on lead is instructive for developing research strategies in environmental toxicology. Lead research has demonstrated fruitful interactions between clinical and basic science. Thus, while epidemiological studies have suggested that central nervous system (CNS) effects in children are observed at the lowest increments of lead exposure, basic research has elucidated some of the molecular events that underly this lack of threshold at the neuronal level. Similarly, clinical studies indicate that early exposure to lead produces functionally irreversible damage to the CNS; experimental research demonstrates that this irreversibility may involve failure to remove lead from brain, permanent effects on synaptogenesis; and chelant-induced redistribution of lead from the periphery to the CNS. Lead toxicokinetics demand reevaluation. New data on release of bone stores of lead during physiological conditions of demineralization indicate that mobilization of bone lead adds to in utero exposure of the fetus. Furthermore, postmenopausal demineralization of bone can increase blood lead levels in women by 25%; this raises concern about the potential effects of lead in an aging population and the difficulties in comprehensive exposure assessment.

Animals↗
PubMed1990

Implications of new data on lead toxicity for managing and preventing exposure.

Recent advances in research on low-level lead poisoning point to the need to increase efforts to prevent exposure. Current biomedical consensus accepts that blood lead levels as low as 5 to 15 mcg/dL are risky to fetuses, young children, and adults. Lead at low dose is associated with increased blood pressure in adults, and chronic exposure has been associated in cohort studies with kidney disease and cancer. Data on lead toxicokinetics also points to the hazards of low-level, chronic exposure, since the lead that is accumulated over time in bone can be released at a relatively rapid rate during pregnancy and menopause. Sources that contribute to current lead exposure of the general population include unabated lead-based paint and contaminated soils, as well as lower level but pervasive sources in drinking water, food, and consumer products.

Adult↗
PubMed1989

Dioxins and the Ah receptor.

Despite continuing controversies related to public policy, information on the molecular biology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has advanced significantly over the past decade. Current understanding of the biological mechanisms of TCDD action is based upon the interactions of TCDD with a genetically expressed cytosolic macromolecule that functions as a receptor in many cells across many species. The Ah receptor recognizes TCDD and structurally similar molecules and serves as the transducing step whereby TCDD alters gene expression through the association of the TCDD:receptor complex with specific TCDD-responsive elements on the genome. Understanding these molecular events and their relevance to the organ-level manifestations of TCDD toxicity may be critical to formulating scientifically based assessments of the risk of TCDD exposure.

Dioxins↗
PubMed1989

Toxic air pollution across a state line: implications for the siting of resource recovery facilities.

Massive volumes of solid waste are produced in the United States. Options for disposal are limited. Incineration and recycling are frequently proposed solutions. However, incinerators and waste recovery facilities, such as scrap smelters, generate hazardous air pollutants and toxic ash. Their potential hazards to health have not been adequately assessed. To illustrate the policy issues surrounding waste incineration and resource recycling, we examine the case of U.S. Metals, a scrap metals recovery plant in Carteret, New Jersey. This plant emitted 20 kilograms of dioxin in its 25 years of operation. It also released 86 tons of lead annually; nearby air lead levels were repeatedly in violation of standards. Construction of a tall stack caused export of toxic emissions from the plant to Staten Island, New York; high concentrations of lead were documented in surface soil on Staten Island. Because neither the State of New Jersey nor the U.S. Environmental Protection Agency were willing to regulate emissions from the plant, New York, the downwind state, was forced to sue U.S. Metals in federal court. The suit resulted ultimately in closing the plant. The case illustrates the difficulties in regulating pollution across state lines, a difficulty compounded by the abdication of responsibility by state and federal agencies. Further, the episode appears paradigmatic of a disturbing trend by state and local governments to locate waste combustion facilities at sites which will resolve problems of solid waste by encouraging export of airborne pollutants across regulatory boundaries.

Air Pollutants↗
PubMed1988

Lead and osteoporosis: mobilization of lead from bone in postmenopausal women.

Although it has been known that humans accumulate lead in bone, mineralized tissue has been considered primarily as a sequestering compartment and not as a site of toxic action for lead. However, experimental data indicate that bone lead can be released during conditions of demineralization, such as pregnancy and lactation. We have examined lead status in women, before and after menopause, using the NHANES II dataset compiled between 1976 and 1980. In 2981 black and white women there was a highly significant increase in both whole blood and calculated plasma lead concentration after menopause. The results indicate that bone lead is not an inert storage site for absorbed lead. Moreover, lead may interact with other factors in the course of postmenopausal osteoporosis, to aggravate the course of the disease, since lead is known to inhibit activation of vitamin D, uptake of dietary calcium, and several regulatory aspects of bone cell function. The consequences of this mobilization may also be of importance in assessing the risks of maternal lead exposure to fetal and infant health.

Adult↗
PubMed1988

Threshold effect in lead-induced peripheral neuropathy.

We previously demonstrated a negative correlation between blood lead level and motor nerve conduction velocity in 202 asymptomatic 5 to 9-year-old children living near a lead smelter in Idaho. Blood lead levels ranged from 13 to 97 micrograms/dL. To determine whether a threshold exists between blood lead level and maximal motor nerve conduction velocity, we conducted three regression analyses on these data: a "hockey stick" regression, a logistic regression, and a quadratic regression. We found evidence for a threshold in all three analyses: at a blood level of 30 micrograms/dL in the "hockey stick" regression, at 20 micrograms/dL in the logistic, and at 25 to 30 micrograms/dL in the quadratic. Neither age, sex, socioeconomic status, nor duration of residence near the smelter significantly modified the relationship. These analyses confirm that asymptomatic increased lead absorption causes slowing of nerve conduction, but they also indicate that measurement of maximal motor nerve conduction velocity is an insensitive screen for low-level lead toxicity.

Child↗
PubMed1988

Risks of municipal solid waste incineration: an environmental perspective.

The central focus of the debate over incineration of municipal solid waste (MSW) has shifted from its apparent management advantages to unresolved risk issues. This shift is a result of the lack of comprehensive consideration of risks associated with incineration. We discuss the need to expand incinerator risk assessment beyond the limited view of incinerators as stationary air pollution sources to encompass the following: other products of incineration, ash in particular, and pollutants other than dioxins, metals in particular; routes of exposure in addition to direct inhalation; health effects in addition to cancer; and the cumulative nature of exposure and health effects induced by many incinerator-associated pollutants. Rational MSW management planning requires that the limitations as well as advantages of incineration be recognized. Incineration is a waste-processing--not a waste disposal--technology, and its products pose substantial management and disposal problems of their own. Consideration of the nature of these products suggests that incineration is ill-suited to manage the municipal wastestream in its entirety. In particular, incineration greatly enhances the mobility and bioavailability of toxic metals present in MSW. These factors suggest that incineration must be viewed as only one component in an integrated MSW management system. The potential for source reduction, separation, and recycling to increase the safety and efficiency of incineration should be counted among their many benefits. Risk considerations dictate that alternatives to the use of toxic metals at the production stage also be examined in designing an effective, long-term MSW management strategy.

Air Pollutants↗