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Biomedical subjects

D M Thompson

Publications and source records attributed to D M Thompson.

At least 19 recordsLinked to original sources
PubMed1992

C-ets-1 protooncogene expression alters the growth properties of immortalized rat fibroblasts.

Ets family genes have been cloned and characterized from a variety of species ranging from human to Drosophila. The ets proteins encode transcription factors that activate transcription via specific binding to GGAA core sequence present in various promoter/enhancers. To investigate the role of ets protooncogene expression on the growth properties of rat embryo fibroblasts (REF), we constructed and introduced ets expression vectors into primary, as well as immortalized REF cells. The transfected cells contained multiple copies of the vector DNA, and the Northern blot analysis demonstrated overexpression of the c-ets-1-specific mRNA. Although the expression of the ets genes was unable to immortalize primary rat embryo fibroblasts, the expression of ets-1 in REF-1 cells enabled their growth in serum-free medium and effected tumorigenic activity in nude mice.

Animals↗
PubMed1992

Differential interaction of cholecystokinin with morphine and phencyclidine: effects on operant behavior in pigeons.

To extend previous operant research in rats with morphine and cholecystokinin (CCK), these two substances were given alone and in combination to pigeons. In one component of a multiple schedule, responding of pigeons (key pecking) was reinforced under a fixed-ratio (FR 50) schedule of food presentation. In the other component, responding had no programmed consequence (timeout). Each session consisted of four 10-min timeout components alternating with four 5-min FR components. In Experiment 1, cumulative dose-effect curves for morphine were obtained by giving an IM injection before each of four FR components; successive injections increased the cumulative dose by 1/4 log-unit steps. In general, as the cumulative dose of morphine increased, the overall response rate in each FR component decreased. Dose-dependent decreases in response rate also occurred when single noncumulative doses of CCK were administered alone 20 min prior to the start of the session. This effect of CCK alone diminished as the session progressed. When CCK was given as a pretreatment before cumulative doses of morphine, the morphine dose-effect curve for response rate shifted to the left. At intermediate doses of CCK, the "potentiation" was so complete that two of three subjects failed to respond during any of the four FR components (i.e., the dose-effect curve for morphine had shifted approximately 1 log-unit to the left). In order to evaluate the pharmacological specificity of this effect, cumulative doses of phencyclidine were administered in combination with CCK (Experiment 2). Unlike the interaction between morphine and CCK, the interaction between phencyclidine and CCK was reciprocal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Association between rDNA alleles and quantitative traits in doubled haploid populations of barley.

Doubled haploids (DH) were generated from reciprocal F1 hybrids which were heterozygous for alleles at the Nor-H3 locus on chromosome 5H of barley. The r-DNA alleles did not deviate significantly from the expected 1:1 ratio and the DH progenies were classified into two groups based on the allelic constitution of the Nor-H3 locus. The DHs were grown in a randomized, replicated field experiment and a range of agronomic and quality traits were recorded. The Nor-H3 locus was associated with a significant portion of the genetic variation for: yield, thousand corn weight, water sensitivity and milling energy requirement of the grain. However, the magnitude of the differences between groups was dependent on the direction of the cross. The milling energy requirement of the grain was consistently associated with alleles at the Nor-H3 locus. These results are presented in relation to the dynamics of rDNA evolution and variability. The potential of molecular markers in conjunction with doubled haploids to map quantitative traits in barley is also discussed.

Alleles↗
PubMed1992

Degradation products of the mRNA encoding the small subunit of ribulose-1,5-bisphosphate carboxylase in soybean and transgenic petunia.

The degradation of a soybean ribulose-1,5-bisphosphate carboxylase small subunit RNA, SRS4, was investigated in soybean seedlings and in petunia plants transformed with an SRS4 gene construct. Polyacrylamide RNA gel blot, primer extension, and S1 nuclease analyses were used to identify and map fragments of the SRS4 mRNA generated in vivo. We showed that SRS4 mRNA is degraded to a characteristic set of fragments in soybean and transgenic petunia and that degradation is not dependent on position of insertion of the gene construct within the genome, on the expression level of the SRS4 mRNA, or on the rbcS promoter. Degradation products lacked poly(A) tails and fractionated with poly(A)-depleted RNA on oligo(dT)-sepharose columns. These products pelleted with polysomes and were released from polysomes prepared with EDTA. Sequences at the 5' end of the SRS4 mRNA were more stable than those at the 3' end of the mRNA. Three models for SRS4 mRNA degradation involving endonucleolytic and exonucleolytic degradation were presented to explain the origin of the 5' proximal fragments.

Base Sequence↗
PubMed1992

The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors.

All cellular ets proteins contain a region of high amino acid identity to those found in the last two exons of the ets-1 gene (C domain). We have identified and characterized a new member of the human ETS gene family, ERGB. The ERGB gene shows extensive amino acid identity to the human ERG and the mouse Fli-1 genes. The ERGB gene is found to be transcriptionally active in a variety of human cell lines and tissues, in contrast to the more restrictive expression pattern of the ERG gene. The ERGB gene encodes for a 3.2-kilobase mRNA containing an open reading frame of 451 amino acids. The ERGB gene, like human ETS1, is located on chromosome 11 and is transposed to chromosome 4 as a result of the translocation t(4;11) associated with leukemia. Pulse-field gel analysis suggests that ETS1 and ERGB are more than 200 kilobases apart. Similar to the other members of the ets family (ets 1, ets 2), this new member is also able to trans-activate transcription of a reporter gene linked to the ETS-binding sequences derived from either the GATA-1 promoter or an optimal Ets-binding site.

Amino Acid Sequence↗
PubMed1991

Cocaine self-administration in pigeons.

Pigeons with chronic indwelling intravenous catheters responded under a multiple schedule of food and cocaine presentation. In one component, responding was maintained by food presentation under a fixed-ratio (FR 50) schedule, whereas in the other component, responding was maintained under the same schedule by IV infusions of cocaine (0.03 or 0.1 mg/kg/injection). A 30-s timeout followed each cocaine infusion. Components alternated after 3 presentations of either food or cocaine, and each session was terminated after 18 cocaine infusions or 2 h, whichever occurred first. In general, under baseline conditions, the response rate was higher in the food component than in the drug component. Under control conditions where saline was substituted for cocaine, the response rate gradually decreased across sessions, while food-maintained responding was generally unaffected. Substituting doses lower or higher than the training dose decreased the rate of cocaine-maintained responding. Food-maintained responding only decreased at higher doses of cocaine. When blackout periods were substituted for the food component (Experiment 2), the response rate in the cocaine component decreased and then stabilized at levels well above zero. Saline substitution on this baseline produced a further decrease in the rate of FR responding. In Experiment 3, the effects of pretreatment with haloperidol (0.056 or 0.1 mg/kg) on both food- and cocaine-maintained responding were examined using a multiple schedule similar to that used in Experiment 1. Each dose was given for a period of 7-10 days. In general, haloperidol dose-dependently decreased both the overall rate of cocaine-maintained responding and the percent of available reinforcers obtained, while having little or no effect on food-maintained responding. This research indicates that cocaine can serve as a reinforcing stimulus for maintaining self-administration behavior in pigeons, and that this behavior is sensitive to antagonism by haloperidol.

Animals↗
PubMed1990

Transcriptional and post-transcriptional processes regulate expression of RNA encoding the small subunit of ribulose-1,5-biphosphate carboxylase differently in petunia and in soybean.

The effects of white light, far-red light and darkness on the in vitro transcription and RNA levels of the small subunit of ribulose-1,5-bisphosphate carboxylase (rbcS) were investigated in petunia and in soybean. In petunia plants treated with 48 hours of darkness the in vitro transcription rate of two of the rbcS subfamilies of petunia, rbcS A and rbcS C, declined 32- and 8-fold respectively, whereas treatment of dark-adapted plants with light caused the in vitro transcription rate of these subfamilies to return to their light-grown levels. Relative RNA levels of rbcS A and rbcS C declined in parallel with in vitro transcription rate changes upon treatment of petunia plants with darkness. However, while relative RNA levels of rbcS C changed in parallel with in vitro transcription rate under all conditions of far-red light and white light tested, there were differences between the changes in rbcS A in vitro transcription rate and RNA levels which were consistent with post-transcriptional regulation of rbcS A RNA. In addition we observed that nuclei isolated from the leaves of plants which were exposed to darkness for periods of 72 hours or longer were transcriptionally inactive. Similar experiments on the in vitro transcription and relative levels of the rbcS RNA in soybean seedlings have lead to the hypothesis that rbcS RNA is less stable in light than in darkness. In contrast, small decreases in rbcS in vitro transcription rate in mature soybean plants treated with darkness were accompanied by large decreases in rbcS RNA, suggesting that rbcS RNA was degraded more rapidly in darkness than in light in these plants. We have shown that differences in the modulation of rbcS RNA levels by post-transcriptional mechanisms exist between plants which belong to different orders, and between different developmental states of the same plant species.

Gene Expression Regulation↗
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

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↗
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

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↗
PubMed1979

Effects of methamphetamine and scopolamine on variability of response location.

Methamphetamine and scopolamine were studied in monkeys responding under a multiple fixed-ratio fixed-interval schedule of reinforcement. A response on any one of six levers could satisfy the schedule requirements. Variability of response location was evaluated in terms of switches, where a switch was defined as a response on one lever followed by a response on a different lever. Under baseline conditions the fixed-ratio schedule generated a high rate of responding and a low level of variability, while the fixed-interval schedule generated a low rate of responding and a high level of variability. Both methamphetamine (0.1 to 0.5 mg/kg) and scopolamine (2.4 to 240 microgram/kg) decreased overall response rate and increased variability of response location in each component of the multiple schedule with increasing doses of drug. At lower doses both drugs were found to decrease rate without affecting response variability.

Animals↗
PubMed1979

An experimental analysis of the effects of d-amphetamine and cocaine on the acquisition and performance of response chains in monkeys.

In one component of a multiple schedule of food presentation, 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). Both d-amphetamine and cocaine, at the higher doses, disrupted the behavior in the learning component; the overall response rate decreased, the overall accuracy was impaired (i.e., percent errors increased), and there was less within-session error reduction. The performance component was generally less sensitive than the learning component to the disruptive effects of both drugs on rate and accuracy. After pre-feeding or during an extended session, the response rate decreased in both components, but accuracy was generally unaffected. When the four discriminative stimuli in both components were removed, the behavior was disrupted to a greater extent in the performance component. The disruptive effects of both drugs on behavior in the learning component were attenuated when the drugs were administered during the session after the response chain had been acquired. It was concluded that the greater sensitivity of the learning component to disruptive drug effects is related to the relatively weak stimulus control and/or the lower rate of reinforcement associated with that component.

Animals↗
PubMed1978

Neutropenia associated with chrysotherapy for juvenile rheumatoid arthritis.

Severe neutropenia, in the absence of generalized bone marrow depression, is a rare complication in adults receiving chrysotherapy for rheumatoid arthritis and has not been described in children. Isolated, severe neutropenia developed in five children with systemic onset JRA while they were receiving gold injections. This potentially fatal complication occurred within eight weeks of beginning therapy in four patients, and after 24 weeks of well-tolerated therapy in the fifth. Leukopenia preceded neutropenia in two children. Localized infection was successfully treated in one child; septicemia was fatal to a second child. Neutropenia resolved within eight to 14 days of its onset in the four survivors; chelation with dimercaprol in one child did not appear to alter the recovery time. It is suggested that a systemic onset of JRA in children less than 6 years of age identifies a higher risk group developing severe neutropenia during chrysotherapy. Cessation of gold therapy upon recognition of a decreasing neutrophil count may prevent or ameliorate a developing neutropenia; careful observation for, and early treatment of, infection may alter its outcome.

Agranulocytosis↗
PubMed1978

Operant methodology in the study of learning.

A series of experiments is described in which operant methodology is used to study the effects of drugs on "learning." Emphasis is placed on the technique of repeated acquisition as a behavioral baseline for studying this type of transition state. In this technique, each subject is required to learn a new discrimination each session. Multiple-schedule procedures are also described in which acquisition is compared to a "performance" task, where the discrimination is the same each session. The learning baseline is more sensitive to the disruptive effects of a variety of drugs (e.g., cocaine, d-amphetamine, haloperidol) than is the performance baseline. This general finding obtains across procedural variations and species (pigeons and monkeys). The potential usefulness of these procedures for studying both acute and chronic behavioral toxicity is discussed.

Animals↗
PubMed1978

Acute and chronic effects of cocaine on extinction-induced aggression.

Pigeons worked individually in a chamber containing a response key and a mirror. Pecking on the key was controlled by a multiple schedule in which a brief period of continuous food reinforcement alternated with a 5-minute period of extinction. Under baseline conditions, aggressive behavior (responding on the mirror) occurred at the onset of each extinction period. In Experiment I (acute drug administration), the aggressive behavior was decreased by doses of cocaine that had little or no effect on key pecking. Such food-reinforced responding was disrupted, however, by higher doses of cocaine. An attempt to mimic the disruptive drugs effects by a prefeeding manipulation was unsuccessful. In Experiment II (chronic drug administration), some tolerance developed to the disruptive effects of cocaine on the food-reinforced responding, except at the highest dose tested. There was no clear-cut indication of tolerance to the initial effect of cocaine on the aggressive behavior at any dose.

Aggression↗