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Biomedical subjects

D M Thompson

Publications and source records attributed to D M Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Epidermal growth factor stimulates phosphatidylinositol turnover in human foreskin fibroblasts without activation of protein kinase C.

Epidermal growth factor stimulates phosphatidylinositol turnover in human foreskin fibroblasts. This is a primary cell culture with normal numbers of epidermal growth factor receptors that is stimulated to divide by epidermal growth factor. Increases are seen in the inositol phospholipids and inositol phosphates. Despite this activation of phosphatidylinositol turnover, there is no detectable activation of protein kinase C.

Cell Division↗
PubMed1988

Epidermal growth factor stimulates phosphatidylinositol turnover for ten hours in A431 cells without activation of protein kinase C.

Epidermal Growth Factor stimulated phosphatidylinositol turnover in A431 cells for up to ten hours. There was an increase in phosphatidylinositol, phosphatidylinositol-4-phosphate, phosphatidylinositol-4,5-bisphosphate and phosphatidic acid at all time points. The effects on the inositol phosphates were variable. Despite the activation of the phosphatidylinositol cycle, we were unable to demonstrate activation of protein kinase C.

Animals↗
PubMed1988

Partial purification and characterization of phosphatidylinositol kinase from bovine brain.

Purification of Phosphatidylinositol (PI) kinase was attempted from bovine brain. A seven step purification protocol increased the specific activity 100 x but attempts at further purification were unsuccessful. Labeling of the partially purified PI kinase with the ATP analog fluorosulfonylbenzoyl adenosine reproducibly identified three bands on polyacrylamide gel electrophoresis of 76 K, 45 K, and 29 K, one of which likely represents PI kinase. Kinetic studies showed a Km of 17 microM for ATP, 0.02 mg/ml for PI and a Vm of 1830 pmol/min/mg protein for ATP and 820 pmol/min/mg protein for PI.

1-Phosphatidylinositol 4-Kinase↗
PubMed1987

Effects of phencyclidine, ketamine and MDMA on complex operant behavior in monkeys.

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three levers in the presence of four numerals (acquisition). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. After IM administration, phencyclidine, ketamine, and MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") each produced dose-related decreases in overall response rate in both schedule components, though ketamine and MDMA were less potent (on a mg/kg basis) than phencyclidine. At high doses of each drug, the marked decrease in overall response rate was due primarily to a long initial pause. Ketamine was similar to phencyclidine in producing dose-related increases in percent errors in both schedule components, but the maximal error-increasing effect was considerably smaller with ketamine. This quantitative difference appeared to be related to the shorter duration of ketamine's effects on accuracy. Unlike phencyclidine and ketamine, MDMA had no effect on accuracy in either acquisition or performance. The results indicate that MDMA disrupts complex operant behavior to a lesser extent than phencyclidine-type drugs.

3,4-Methylenedioxyamphetamine↗
PubMed1986

Nicotine can attenuate the disruptive effects of phencyclidine on repeated acquisition in monkeys.

Patas monkeys acquired a different four-response chain each session by responding sequentially on three levers in the presence of four discriminative stimuli (numerals). The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-min sessions, with a 10-min intersession interval. Cumulative dose-effect curves for phencyclidine were obtained by giving an IM injection before each of the four sessions; successive injections increased the cumulative dose by 1/4 log-unit steps. When phencyclidine was administered alone, overall response rate decreased and percent errors increased with increasing doses. When nicotine was administered alone (IM) before the first session, the higher doses initially produced large decreases in overall response rate. Unlike phencyclidine, nicotine alone generally had no effect on percent errors. When intermediate or high doses of phencyclidine were administered after pretreatment with certain doses of nicotine, both the rate-decreasing and error-increasing effects were smaller than those produced by phencyclidine alone. This attenuation of the disruptive effects of phencyclidine on acquisition occurred at a time when nicotine alone had little or no behavioral effect.

Animals↗
PubMed1986

Repeated acquisition and delayed performance as a baseline to assess drug effects on retention in monkeys.

As an extension of previous research on repeated acquisition, a new baseline was developed to assess the effects of phencyclidine on retention in patas monkeys. Each session was divided into three phases: acquisition, delay, and performance. During acquisition, the subject acquired a four-response chain (which was different each session) by responding sequentially on three keys in the presence of four geometric forms. When the acquisition criterion (20 consecutive correct responses) was met, the keylights turned off and the delay (retention interval) began. After the delay, the keylights and a white light above the keys were turned on for 10 min (performance). The white light indicated that the response chain was the same as the chain acquired before the delay. Retention of the acquired response chain, as measured by percent "savings" in errors to criterion, decreased as the delay was increased from 5 to 180 min, and this "forgetting curve" tended to shift to the left with increasing doses of phencyclidine (administered IM 5 min before the performance phase). "Overlearning" the response chain before the 180-min delay increased retention and attenuated the disruptive effects of the lower dose of phencyclidine.

Animals↗
PubMed1985

Separation and characterization of a phosphatidylinositol kinase activity that co-purifies with the epidermal growth factor receptor.

Two retroviral protein-tyrosine kinases, v-src and v-ros, have been reported to possess phosphatidylinositol (PtdIns) kinase activity. Because the epidermal growth factor (EGF) receptor is a protein-tyrosine kinase with structural homology to p60v-src and because EGF stimulates PtdIns turnover in A431 cells, the EGF receptor has been examined for PtdIns kinase activity. Preparations of the EGF receptor, isolated from A431 cells and purified by two different methods of affinity chromatography, possessed an associated PtdIns kinase activity. This activity which co-purified with the EGF receptor represented only about 2% of the total PtdIns kinase activity of A431 membranes, and there was no correlation between the number of EGF receptors and the amount of PtdIns kinase activity in membranes from various cell types. A peptide substrate, angiotensin II, and PtdIns did not compete with each other as substrates for the protein-tyrosine and PtdIns kinase activities of the EGF receptor. When self-phosphorylated EGF receptor was fractionated by Sephacryl S-300 gel permeation chromatography, the peak of PtdIns kinase activity was separated from the comigrating peak of protein-tyrosine kinase activity and the self-phosphorylated EGF receptor. These results indicate that the protein-tyrosine kinase and PtdIns kinase activities which co-purify with the EGF receptor reside on different molecules. Angiotensin II and PtdIns did not compete as substrates for p60v-src isolated by immunoabsorption with a monoclonal antibody, suggesting that PtdIns kinase activity may also not be intrinsic to p60v-src.

1-Phosphatidylinositol 4-Kinase↗
PubMed1985

Relationship between production of epidermal growth factor receptors, gene amplification, and chromosome 7 translocation in variant A431 cells.

Synthesis of the epidermal growth factor (EGF) receptor has been analyzed in a series of variant A431 human epidermoid carcinoma cell clones reported to contain different amounts of EGF binding sites. The amount of EGF receptor protein, quantitated by immunoaffinity chromatography, and EGF receptor mRNA, quantitated by cDNA hybridization, were closely correlated to the extent of EGF receptor gene amplification. This correlation existed in variants selected for reduced EGF receptors and in revertants from those variants with increased EGF receptors. There was also a correlation between the frequency of translocation of chromosome 7, containing the EGF receptor gene, and EGF receptor protein. These results support gene amplification as the mechanism enhancing A431 cell EGF receptor protein and determining growth responses.

Carcinoma, Squamous Cell↗
PubMed1985

Cocaine potentiates the disruptive effects of phencyclidine on repeated acquisition in monkeys.

Patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-min sessions, with a 10-min intersession interval. Cumulative dose-effect curves for phencyclidine were obtained by giving an IM injection before each of the four sessions; successive injections increased the cumulative dose by 1/4 log-unit steps. When phencyclidine was administered alone, overall response rate decreased and percent errors increased with increasing doses. When cocaine was injected IM before the first session at a dose that was ineffective when given alone, the phencyclidine dose-effect curves for both rate and accuracy tended to shift to the left. After pretreatment with the lowest effective dose of cocaine, which decreased rate without affecting accuracy when given alone, the rate-decreasing and error-increasing effects of phencyclidine were generally even more pronounced in two of three subjects. The results indicate that cocaine potentiates the disruptive effects of phencyclidine on complex operant behavior in monkeys.

Animals↗
PubMed1985

Delta-9-tetrahydrocannabinol potentiates the disruptive effects of phencyclidine on repeated acquisition in monkeys.

Patas monkeys acquired a different four-response chain each session by responding sequentially on three keys or levers in the presence of four discriminative stimuli (geometric forms or numerals). The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-min sessions, with a 10-min intersession interval. Cumulative dose-effect curves for phencyclidine were obtained by giving an IM injection before each of the four sessions; successive injections increased the cumulative dose by 1/4 log-unit steps. When phencyclidine was administered alone, overall response rate decreased and percent errors increased with increasing doses. When delta-9-tetrahydrocannabinol (THC) was administered PO before the first session at a dose that was ineffective when given alone, the phencyclidine dose-effect curves for both rate and accuracy tended to shift to the left. After pretreatment with a higher dose of THC, which decreased rate in one of three subjects without affecting accuracy when given alone, the rate-decreasing and error-increasing effects of phencyclidine were generally even more pronounced. The results indicate that THC potentiates the disruptive effects of phencyclidine on complex operant behavior in monkeys.

Animals↗
PubMed1985

Effects of opioids and phencyclidine in combination with naltrexone on the acquisition and performance of response sequences in monkeys.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food under a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). Heroin, methadone, cyclazocine and phencyclidine each produced dose-related decreases in overall response rate. At high doses which produced equivalent rate-decreasing effects, cyclazocine and phencyclidine generally produced greater disruption of accuracy in the learning component than did heroin or methadone. Naltrexone 5.6 microgram/kg shifted to the right by approximately 1/2-log unit the heroin and methadone dose-effect curves, but produced little or no change in the cyclazocine dose-effect curves. At 56 micrograms/kg naltrexone completely antagonized both the rate-decreasing and error-increasing effects of heroin and methadone. The same dose of naltrexone tended to produce greater antagonism of the effects of cyclazocine on accuracy than on rate, which was shifted by only 1/4-log unit. In contrast, naltrexone failed to antagonize the effects of phencyclidine on either rate or accuracy. Thus it would appear that while cyclazocine and phencyclidine produce similar disruptions in the accuracy of a discrimination, the effects of each are differentially sensitive to antagonism by naltrexone.

Animals↗
PubMed1985

Living with an amputation: the helper.

One hundred and nine key helpers were interviewed in connection with a study of the psychosocial implications of amputation. They were found to carry formidable burdens. Social isolation was a major problem which increased over time and was associated with diminished capacity to express needs. The respondents discussed emotional problems readily. Social workers had little sustained contact with helpers: welfare agencies had intervened mainly to provide practical help. The Artificial Limb Centre did not routinely see helpers or communicate with General Practitioners. A more realistic approach to the support of those who implement community care policies is advocated, with particular reference to the need for respite care to be provided in the domestic setting. The dangers of the exploitation of women as carers are highlighted.

Adaptation, Psychological↗
PubMed1985

Comparison of drug effects on fixed-ratio performance and chain performance maintained under a second-order fixed-ratio schedule.

In one component of a multiple schedule, pigeons were required to complete the same four-response chain each session by responding sequentially on three identically lighted keys in the presence of four successively presented colors (chain performance). Food presentation occurred after five completions of the chain (i.e., after 20 correct responses). Errors, such as responding on the center or right key when the left was designated correct, produced a brief timeout but did not reset the chain. In the other component, responding on a single key (lighted white) was maintained by food presentation under a fixed-ratio 20 schedule. In general, phencyclidine and d-amphetamine produced dose-dependent decreases in the overall response rates in both components. With pentobarbital, overall rate in each component generally increased at intermediate doses and decreased at higher doses. All three drugs produced dose-dependent disruptive effects on chain-performance accuracy. Phencyclidine and pentobarbital increased percent errors at doses that had little or no rate-decreasing effects, whereas d-amphetamine generally increased percent errors only at doses that substantially decreased overall rate. At high doses, all three drugs produced greater disruption of chain performance than of fixed-ratio performance, as indicated by a slower return to control responding, although the effects of d-amphetamine were less selective than those of phencyclidine or pentobarbital.

Animals↗
PubMed1985

The EGF receptor: structure, regulation and potential role in malignancy.

Retroviral onc genes are derived from cellular proto-oncogenes that may function in normal cellular growth control. The epidermal growth factor (EGF) receptor is the proto-oncogene of erbB; both possess intrinsic protein tyrosine kinase activity, a property shared by several retroviral onc genes. The EGF receptor is a transmembrane glycoprotein with an external EGF binding domain and a cytoplasmic region that is homologous with other tyrosine kinases. erbB lacks the EGF binding and carboxyl terminal regions, which are thought to be important in regulation. The EGF receptor is regulated by several mechanisms: stimulation by ligand binding and self-phosphorylation, inhibition by heterologous phosphorylation and downregulation by ligand. EGF binding stimulates several early events, including phosphatidylinositol (PI) turnover in A431 cells. A PI kinase activity copurifies with the EGF receptor and some other tyrosine kinases, but this is a contaminant as it can be separated from the EGF receptor. Although the role of proto-onc genes in human malignancy is incompletely defined, increased numbers of EGF receptors are present in several types of human tumours. Overexpression of EGF receptors, as occurs in human epidermoid carcinoma A431 cells, can augment cell growth because of increased formation of active ligand:receptor complexes. Gene amplification is the mechanism underlying overexpression of EGF receptors in A431 cells and in some glioblastoma multiforme tumours.

1-Phosphatidylinositol 4-Kinase↗
PubMed1985

Variables related to body-weight status of mentally retarded adults.

Mentally retarded male and female adult subjects displayed mean body weights in excess of their ideal weights; excessive body weight of females was also apparent in comparison to normative data for the United States. Maintenance of appropriate weight appeared to be more likely in a controlled residential setting than in the natural home environment. These sex and environmental relationships could not be explained by medication and dietary programming differences, and age, race, and level of retardation were unrelated to body weight.

Adolescent↗
PubMed1984

Phencyclidine in combination with d-amphetamine: differential effects on acquisition and performance of response chains in monkeys.

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When phencyclidine was administered alone, overall response rate decreased and percent errors increased in both components with increasing doses. d-Amphetamine alone generally decreased rate and increased errors in learning, but increased rate and had no effect on accuracy in performance. When phencyclidine was administered in combination with d-amphetamine, the phencyclidine dose-effect curves tended to shift to the left as the dose of d-amphetamine was increased. The extent to which the curves shifted, however, depended on both the schedule component and the behavioral measure. For example, with accuracy, the shift was more evident in learning than in performance. Combinations of phencyclidine with a high dose of d-amphetamine generally produced supra-additive effects: i.e., the effects on rate and accuracy were greater than expected from simple addition of the effects of each drug given alone.

Animals↗
PubMed1984

Differential effects of phencyclidine and MDA on complex operant behavior in monkeys.

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. With increasing doses of phencyclidine the overall response rate in each schedule component decreased, the percent errors in each component increased, and there was less within-session error reduction (acquisition) in the learning component. MDA (3,4-methylenedioxyamphetamine), a hallucinogen that is self-administered in nonhuman primates, was similar to phencyclidine in producing dose-related rate-decreasing effects in both schedule components. Unlike phencyclidine, however, MDA had little or no effect on accuracy in either learning or performance.

3,4-Methylenedioxyamphetamine↗