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Biomedical subjects

D B Mitchell

Publications and source records attributed to D B Mitchell.

65 records · Page 4Linked to original sources
PubMed1985

Role of glutathione depletion in the cytotoxicity of acetaminophen in a primary culture system of rat hepatocytes.

A primary culture system of postnatal rat hepatocytes was utilized to study the cytotoxicity of acetaminophen and the toxicological significance of glutathione (GSH) depletion. The relative time of onset and magnitude of GSH depletion, lipid peroxidation and cytotoxicity were contrasted in order to gain insight into their interrelationships. Exposure of the hepatocytes to acetaminophen resulted in time- and dose-dependent depletion of cellular GSH. The acetaminophen-induced GSH depletion and ensuing lactate dehydrogenase (LDH) leakage were quite modest and delayed in onset, in contrast to that caused by iodoacetamide (IAA) and by diethylmaleate (DEM), 2 well-known depletors of GSH. There was comparable LDH leakage, irrespective of drug treatment, when GSH levels decreased to about 20% of normal. Reduction of GSH levels below the 20% threshold by IAA treatment resulted in marked LDH leakage and loss of viability. Maximal LDH leakage in response to IAA and acetaminophen preceded maximal malondialdehyde (MDA) formation, suggesting that lipid peroxidation may be a consequence of cell damage as well as GSH depletion. IAA and DEM produced a comparable, modest accumulation of MDA, yet IAA was much more cytotoxic. These findings indicate that lipid peroxidation does not play a central role in hepatocellular injury by compounds which deplete GSH, although it may contribute to degeneration of the cell. As events in the cultured postnatal hepatocytes paralleled those reported in vivo, the system can be a useful and valid model with which to study mechanisms of chemical toxicity.

Acetaminophen↗
PubMed1982

Lack of cytotoxicity of ticrynafen in primary cultures of rat liver cells.

Primary cultures of hepatocytes obtained from neonatal Sprague-Dawley rats were grown in arginine-deficient, ornithine-supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary hepatocytes was used to study the potential cytotoxicity of ticrynafen by measuring cytoplasmic enzyme leakage, cell viability,, and total protein per culture dish. Hepatic cultures were treated with the drug in concentrations ranging from 10(-3)M to 10(-6)M and for durations from 2 to 8 h. The results of the study indicate that ticrynafen was minimally toxic to the hepatocytes.

Animals↗
PubMed1981

Evaluation of the cytotoxicity of tricyclic antidepressants in primary cultures of rat hepatocytes.

Primary cultures of hepatocytes from postnatal Sprague-Dawley rats were grown in arginine-deficient, ornithine-supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary cultures of rat hepatocytes was utilized to evaluate the cytotoxicity of certain tricyclic antidepressant drugs (TCAs). The compounds tested were chosen to represent two distinct chemical classifications of TCAs: the dibenzazepine derivatives, imipramine (1) and desipramine (D), and the dibenzocycloheptadiene derivatives, amitriptyline (A) and nortriptyline (N). The study also allowed direct comparison of the parent tertiary amines, A and I, and their respective demethylated pharmacologically active metabolites, N and D. The hepatotoxicity of the compounds was determined by measuring leakage of cytoplasmic enzymes, lactate dehydrogenase (LDH) and glutamic-pyruvic transaminase (GPT), into the culture medium and by assessing cell viability by the trypan blue dye exclusion test. LDH leakage was a more sensitive index of early cellular injury in this study. The compounds demonstrated a dose- and time-dependent order of toxicity; their hepatotoxicity potency was ranked as A = N greater than D greater than I.

Alanine Transaminase↗
PubMed1981

Semantic and contextual cuing of preschool children's recall.

3 experiments were carried out to investigate cuing of young children's recall. In each experiment younger (3 years) and older (4 1/2 years) preschool children were tested on free and cued recall tasks in which the presence of semantic and contextual cues was manipulated. In the first 2 experiments there was little evidence that the children's recall was facilitated by presence of contextual cues, independent of the facilitation produced by semantic information. In the third experiment, context and target items were integrated experimentally at presentation. In this case, unrelated context cues improved recall. This finding suggests that limitations in the facilitatory effects of context cues for preschool children are related to the ways these young children initially encode target and context items. In all 3 experiments semantic cues aided both younger and older children's recall. Moreover, there was evidence of a developmental increase in the effectiveness of semantic, but not contextual, cues. This finding highlights the importance of growth of the semantic knowledge base for early memory development.

Child Development↗
PubMed1980

Confirmed reservations: mental travel.

When Kosslyn, Ball, and Reiser asked subjects to scan a memorized picture, they found a strong positive linear relationship between distance scanned and reaction time. However, more recent research has suggested that this result may be as much a function of the demand characteristics of the experiment as a reflection of any structural properties of the image. To further test this possibility with complex stimuli, college subjects were either presented with Kosslyn's pictorial stimuli or verbal descriptions of same in a "nonexperiment" and were asked to predict their scanning times. The subjects were able to produce high linear correlations between scanning distance and predicted scanning time. This result is consistent with a demand characteristics explanation of the correlation between distance and reaction time that is obtained in actual image-scanning studies.

Distance Perception↗
PubMed1979

Mental travel: some reservations.

Two experiments were conducted to assess the extent of potential experimental demand characteristics inherent in the image-scanning paradigm. The results of the first "mental travel" experiment that pitted verbal versus imagery coding showed that (a) the positive correlation between physical distance and reaction time was replicated, and (b) when given a choice, subjects' reaction times varied as a function of verbal codes rather than imagery. To isolate the effects due to demand constraints from those produced by mode dominance, a nonexperiment in which subjects received only a description of the image-scanning procedure was conducted. Results demonstrated that subjects were capable of predicting the reaction time results for both verbal and imagery codes. The presence of experimental demand in the image-scanning paradigm necessitates caution when structural interpretations of visual images are considered.

Distance Perception↗
PubMedDate not supplied

Adult age differences in long-term semantic priming.

Young and older adults were first asked to decide if a list of individually presented words were "living" (e.g., "tree") or "nonliving" (e.g., "store"). This was termed the "orienting task." Next, subjects performed a pronunciation task. Semantic priming for young and older adults was indexed by determining if semantic congruence between words in the orienting task and words in the pronunciation task improved performance on the pronunciation task relative to pronounced words from semantic categories not primed in the orienting task. The present data, from two different experiments, revealed that subjects pronounced high-dominance exemplars of the "living" words primed in the orienting task faster than words not primed in the orienting task. These data indicated that semantic priming for relatively long prime-target stimulus onset asynchronies can occur, and that such priming is at least as robust for older adults as for young adults. The results are discussed in terms of four current models of semantic priming.

Adolescent↗