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Biomedical subjects

L D Grant

Publications and source records attributed to L D Grant.

At least 19 recordsLinked to original sources
PubMed1990

Research on risk assessment and risk management: future directions.

This paper has been reviewed by the Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The U.S. EPA has increasingly relied upon quantitative health risk assessments as the basis for management decisions about public health protection. Full utilization of risk assessment in management applications, however, is limited by uncertainties in the resultant accuracy of the risk estimates. This paper will discuss a research strategy to address the uncertainties in the risk assessment process and describe parallel issues to address in the risk management area. An attendant need for effective communication of complex scientific concepts is also identified.

Dose-Response Relationship, Drug↗
PubMed1989

Prenatal and postnatal effects of low-level lead exposure: integrated summary of a report to the U.S. Congress on childhood lead poisoning.

This article provides an integrated summary of a report to Congress from the Federal government (ATSDR) on childhood lead poisoning in the United States, with particular reference to low-level lead exposure and its effects on the fetus and the preschool child. As mandated by Section 118(f)(1)(C) of the 1986 Superfund Amendments and Reauthorization Act (SARA), ATSDR has examined the full spectrum of human in utero and postnatal lead toxicity, with emphasis on low-level neurotoxicity and adverse impacts on growth indices in risk populations. Especially important has been assessment of the relative persistence of these effects in later life as discernible from a number of longitudinal studies now under way around the world. Included in the Congressional report were discussions of dose-effect and dose-response relationships using blood lead levels as the indicator of lead dose.

Child, Preschool↗
PubMed1978

Stimulus properties of thyrotropin-releasing hormone.

Male Sprague-Dawley rats were trained in a two-lever operant discrimination task using 20 mg/kg thyrotropin-releasing hormone (TRH) and saline as cues. Following completion of 40 daily training sessions, 22 of 25 subjects demonstrated a high level of discriminative responding based on the TRH and saline cues. An evaluation of the time course of TRH indicated that the stimulus properties peak between 5 and 15 min and dissipate substantially by 55--65 min. During additional testing, rats showed dose-dependent generalization between the training treatments (20 mg/kg TRH and saline) and novel doses of TRH (1, 5, 10, and 40 MG/KG). However, animals failed to show generalization between the training drug (20 mg/kg TRH) and d-amphetamine sulfate (0.8, 1.6, or 2.4 mg/kg); likewise, animals trained to discriminate d-amphetamine (0.8 or 1.6 mg/kg) from saline failed to show generalization between d-amphetamine and TRH (10, 20, OR 30 MG/KG). Microgram quanitites of TRH (2.5--25 microgram administered into either the lateral or third ventricle elicited dose-dependent generalization to the training drug (TRH 20 mg/kg, i.p.), suggesting a CNS mechanism of action for this effect of TRH.

Animals↗
PubMed1978

Effects of lead on temporally-spaced responding in rats.

The effects of lead acetate and aging on temporally-spaced responding (differential reinforcement of low rate or DRL-20 seconds) were studied. Three groups of animals were considered along with their respective controls. Neonate-treated Long-Evans rats were orally intubated with 200 mg/kg lead acetate from the third to 30th day after birth. Some of these animals were tested at 3 months (adult group) and some at 21 months (geriatric group) of age. A continuously treated group was exposed to 250 ppm lead in utero and throughout their life after birth and was treated at 8 months of age. Lead-treated animals exhibited a more variable response to d-amphetamine and a more pronounced number of IRTs in the first class interval. Aging shifted the pentobarbital dose-response curve to the left in both control and lead-treated animals and flattened interresponse time (IRT) distributions.

Aging↗
PubMed1977

3H estradiol in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence.

3H setradion-17beta was localized in nuclei of catecholamine (CA) neurons of the rat lower brain stem, i.e., midbrain, pons and medulla, by employing a combined formaldehyde-induced fluorescence (FIF)-autoradiography approach which permits the direct visualization of 3H estradiol uptake in relation to CA-neuron perikarya and terminals. In the medulla, noradrenalin (NA)-containing neurons in and adjacent to the nucleus (n.) reticularis lateralis (group A1) and in the vicinity of the n. tractus solitarii (group A2) concentrated 3H estradiol. In the pons, NA neurons dorsal to the n. olivaris superior (group A5), in the locus ceruleus (group A6) and ventral to the pedunculus cerebellaris superior (group A7) displayed 3H estradiol uptake. In the midbrain, dopamine (DA)-containing neurons in the n. cuneiformis (group A8), in the zona compacta of the substantia nigra (group A9) and adjacent to the n. interpeduncularis (group A10), were not seen to concentrate 3H estradiol. This is in contrast to DA neurons in the n. arcuatus of the hypothalamus (group A12), previously reported to concentrate 3H estradiol. In addition, certain non-CA-containing neurons with nuclear uptake of 3H estradiol were observed to be surrounded by CA terminals in such areas as substantia grisea centralis, n. tractus solitarii and n. tractus spinalis nervi trigemini. This suggests a second mode of interaction between CA neurons and estrogen target neurons. The estradiol-CA neuron relationships described may provide morphological substrates underlying functional interactions between estradiol and CA neurons in the rat brain.

Animals↗
PubMed1976

Temporal parameters of d-amphetamine as a discriminative stimulus in the rat.

Three groups of rats were trained on a two-lever operant discrimination using d-amphetamine (0.8, 1.6 or 2.4 mg/kg) and saline as cues. Reinforcement of responding on one lever was associated with the drug and reinforcement on the other lever was associated with saline. Following acquisition, behavioral control was evaluated during 10-min extinction tests at 0, 15, 30, 60, 90, 120, 180 or 240 min after injection of drug or saline. Onset of the stimulus properties of d-amphetamine occurred within 10 min and maximal effects were attained by 15-30 min post-injection. Drug effects were minimal or absent 2-4 h after administration. The time course for all doses of d-amphetamine was identical when each group was tested iwth its respective training dose. When subjects were tested with doses other than their training dose, the time course of the drug effect varied as a function of training dose, test dose and time after injection.

Animals↗
PubMed1976

Research strategies for behavioral teratology studies.

Several compelling aruguments have been advanced in support of expanding the use of "behavioral teratology" evaluations as routine components of toxicologic screening procedures. As a basis for development of effective behavioral teratology screening approaches, a conceptual framework is presented which interrelates: (1) changes in relative functional brain capacity with age, (2) possible times and durations of exposures to environmental insults, and (3) various types of toxicity testing procedures carried out at appropriate time points in relation to different exposure period. Within the context, several research strategies for behavioral teratology studies are concisely posed and evaluated. These include: (1) clinical hypothesis testing, where particular effect(s) of a given agent are evaluated based on hypotheses derived from clinical or epidemiological observations; (2) comprehensive screening approaches, where multifaceted, long-term longitudinal neurobehavioral evaluations are employed to assess whether any of a large number of possible deletarious effects are exerted by an agent and at what threshold exposure levels; (3) alternative screening heuristics, by which adequate assessments of neurobehavioral toxicity of various agents may be accomplished without completion of more exhaustive, but also more expensive and time-consuming comprehensive screening protocols.

Aging↗