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Biomedical subjects

E L Bennett

Publications and source records attributed to E L Bennett.

At least 73 records · Page 4Linked to original sources
PubMed1978

Inhibition of adenocarcinoma TA3 ascites tumor growth by rifamycin derivatives.

A growth inhibitory effect on adenocarcinoma TA3 ascites tumors in LAF1/J mice resulted from the repeated IP administration of subtoxic doses of 3 rifamycin derivatives: rifampicin (Rif)1, dimethylbenzyldesmethylrifampicin (DMB), and rifazone-82 (R-82). A high-viscosity methylcellulose vehicle was found to be essential for obtaining a uniform drug suspension and a significant antitumor effect by the least water soluble derivatives, DMB and R-82. The more hydrophilic derivative, Rif, was found to have a comparable growth inhibitory effect on TA3 cells when prepared in 0.9% NaCl solution with or without added methylcellulose. Oral or SC drug injections did not have an antitumor effect. The results of this study point to the importance of vehicle and route of administration in chemotherapy trials with these compounds.

Adenocarcinoma↗
PubMed1977

Neurotoxins of Bungarus multicinctus vernom. Purification and partial characterization.

The purification to homogeneity of nine neurotoxic components of the venom of Bungarus multicinctus is described. The purified components include alpha-bungarotoxin and two other alpha-type synaptic toxins and beta-bungarotoxin and five other beta-type synaptic toxins. The purified toxins have been characterized by electrophoresis, isoelectric focusing, amino acid analysis, and N-terminal amino acid determination. The alpha-type synaptic neurotoxins constitute a discrete class with molecular weights of 7000-8500, isoelectric points (pI) of 9.0-9.2, and N-terminal isoleucine or methionine. The beta-type synaptic neurotoxins constitute a second group with molecular weights of 20 000-22 000 and pI = 8.8-9.7. Fractions 10 through 13 exhibit a chain structure consisting of a 6000-7000 light chain and a 11 000-15 000 heavy chain apparently covalently stabilized by interchain disulfides. Fractions 9A and 14 were single chains of 11 000-14 000 which resemble the sequenced beta-type synaptic neurotoxin notexin (Halpert, J., and Eaker, D. (1975), J. Biol. Chem. 250, 6990). All of the beta-type synaptic toxins have a single tryptophan and N-terminal aspartic acid or asparagine.

Acetylcholinesterase↗
PubMed1977

Protein synthesis inhibition and memory for pole jump active avoidance and extinction.

This study utilizes a pole jump active avoidance task to investigate the effects of protein synthesis on memory formation. An extinction training procedure for this task is also described. Amnesia for extinction is produced by inhibition of protein synthesis and is also demonstrated by active responding, so it is clear that there is no general impairment sufficient to disrupt motor skill, motivation, or retrieval of stored memories. It was found that while inhibition of protein synthesis in brain for 2 hr did not produce amnesia, inhibition for 6 to 8 hr did. These results demonstrate that for both shock-motivated learning and non-shock motivated extinction learning, the duration of inhibition of protein synthesis is important in determining whether amnesia occurs. We conclude that inhibition of cerebral protein synthesis can best account for amnesia induced by anisomycin, cycloheximide, and acetoxycycloheximide.

Animals↗
PubMed1977

Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats.

Enriched postlesion experience aided in overcoming effects of simultaneous bilateral cerebral lesions made at 30 days of age in one experiment with inbred Fischer rats and in a second experiment with the Berkeley S1 strain. The lesions were directed to the occipital cortex, but in most cases there was also some impairment of the hippocampus. For 60 days after operations, half of the rats lived in small individual cages and half lived in groups in large enriched-environment cages. They were then pretrained and tested on the standard 12 Hebb-Williams problems. Daily injections of methamphetamine (vs. saline) during the period of differential experience in the first experiment produced no effect on the behavioral scores. The second experiment included groups that received only 2 hr/day of enriched experience, and they benefited as much as groups that remained in the enriched environment 24 hr/day. The results of both experiments demonstrated significant beneficial effects of environment when bilateral lesions were made at a later age and when the periods of enriched experience were shorter than had previously been tested. Two additional experiments revealed significant effects of both lesions and environment on weight and RNA/DNA of brain regions.

Age Factors↗
PubMed1976

Poly rC-oligo dG specific template activity of mouse viral DNA polymerase detected by isoelectric focusing.

An acid fraction from polyacrylamide gel isoelectric focusing contained only DNA polymerase template activity for (rC)n-(dG)12-18 with little or no activity with (rA)n-(dT)12-18. A factor which stimulated (rC)n-(dG) 12-18 activity was also detected in low molecular weight fractions from G-100 Sephadex chromatography of the purified enzyme. Since (rC)n-(dG)12-18 acitivty is thought to be descriptive of viral DNA polymerase, this stimulation is proposed to be significant for the regulation and specificity of viral DNA synthesis.

Animals↗
PubMed1976

Effects of environment on morphology of rat cerebral cortex and hippocampus.

Cortical depth differences were found between male rats exposed to enriched or impoverished environmental conditions for successively shorter times, i.e., for 15 days (from 25 to 40 days of age), for seven days (25 to 32 days of age), and for four days (26 to 30 or 60 to 64 days of age). If the experiments began at weaning (at 25 days of age), the cortical depth changes were caused primarily by impoverishment. If the animals were young adults (60 days of age), upon entering their respective conditions, the cortical changes were induced by enrichment. No cortical depth differences were found between enriched and impoverished rats after one day of differential experience, from 60 to 61 days of age. In every age group and for every duration, except for the one day group, the dorsal-medial segment of the occipital cortex responded to the environmental conditions. No significant hippocampal depth differences were noted between enriched and impoverished animals.

Age Factors↗
PubMed1976

Effects of ACTH peptide fragments on memory formation.

The effects of peptides derived from ACTH on the formation of long-term memory have been investigated in male mice. Post-training administration of ACTH 4-10-L-Phe-7 (ACTH-L) improved retention for both passive and active avoidance tasks. Administration of ACTH 4-10-D-Phe-7 (ACTH-D) impaired retention for both tasks. The optimum dose for ACTH-L was about 0.3 mg/kg; the optimum dose for ACTH-D was in the range of 1.0-3.0 mg/kg. Using the passive avoidance task, it was shown that either drug had to be administered within 60 min of training to be highly effective. Amnesia produced by anisomycin (Ani), an inhibitor of protein synthesis, was lessened by ACTH-L and increased by ACTH-D, ACTH-D opposed the memory facilitating effects of ACTH-L. Using intact mice, ACTH-L or ACTH-D did not significantly change the incorporation of valine into protein, nor did these peptides influence the inhibition of protein synthesis caused by anisomycin. The results show that ACTH may play a major role in memory processing, perhaps by facilitating essential protein synthesis at sites specific for the memory being established.

Adrenocorticotropic Hormone↗
PubMed1975

Differences in occipital cortical synapses from environmentally enriched, impoverished, and standard colony rats.

Initial and replication experiments were studied with littermate, S1, male rats 25-55 days of age placed in enriched (EC), standard colony (SC), and impoverished (IC) environments. Measurements of the length of postsynaptic thickenings were taken from asymmetrical axodendritic synapses in layer IV of the dorsal medial occipital cortex. This experiment differed from others of this nature, for animals from both experimental conditions were compared with the standard colony animals. The 8% (p less than 0.01) difference in postsynaptic thickening length between 675 synapses from EC and 680 synapses from IC was primarily due to the IC, as can be seen by comparing both with the SC. The number of synapses per unit area of neuropil was 15% (p less than 0.01) more in the IC than in the EC and this difference was primarily due to impoverishment. Both the original and the replication experiment verified this direction of change. Thus, environmental experience does significantly affect synaptic length and number, although the large magnitude previously reported by Mphillgaard et al. (1971) was not confirmed in the present experiments. The 7% cortical depth difference between the enriched and impoverished animals was seen to be attributed to both conditions when each was compared with the standard colony rats. The plasticity of synaptic dimensions is discussed in relation to our previous work and to work of others.

Animals↗
PubMed1975

Effects of protein synthesis inhibition on memory for active avoidance training.

Inhibition of brain protein synthesis by anisomycin and acetoxycycloheximide was studied in mice for its biochemical and behavioral effects. By employing both drugs in low doses in a series of injections, we were able to maintain inhibition of protein synthesis of 80% or greater for up to 14 hr without causing detectable permanent physiological impairment. The drugs were employed as amnestic agents in mice trained to avoid footshock in a T-maze. As the duration of inhibition increased, the percentage of mice classed as amnesic increased. This amnesia could be reduced by increasing (a) the rate of acquisition, or (b) the number of training trials. Anisomycin was shown to cause a significant degree of amnesia for the escape component as well as the avoidance component of the learning. A single injection of anisomycin given 15 min prior to training did not cause significant changes in the acquisition or retention of avoidance conditioning, when comparison was made with saline-injected controls. Only additional injections given after training to prolong inhibition caused amnesia. Thus, those injections critical in obtaining amnesia were given at a time at which interference with acquisition could not have occurred, so the results bear clearly on memory processes.

Animals↗
PubMed1975

Relation of memory formation to controlled amounts of brain protein synthesis.

Anisomycin, an inhibitor of brain protein synthesis, was used to control the time and duration of protein synthesis occurring in mice after they were trained on a one-trial passive avoidance task. It was found that if synthesis was strongly inhibited for 6 to 8 hr, a high percentage of the animals was amnesic. However, if small amounts of protein synthesis were allowed to occur by permitting intervals of partial recovery of protein synthesis during the period of inhibition, then fewer mice were amnesic. The longer the duration of this interval of controlled synthesis and the closer it occurred to training, the greater the percentage of subjects remembering the training.

Amnesia↗