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Biomedical subjects

T Thompson

Publications and source records attributed to T Thompson.

At least 19 recordsLinked to original sources
PubMed1992

Effects of methadone on free feeding in satiated rats.

A variety of opioids and opiates are known to increase short-term food intake. In the present study, we evaluated the effects of methadone on free feeding in satiated rats. We assessed the effect of methadone (0, 1.5, 3.0, 5.0, and 10.0 mg/kg) on food intake 1, 2, 4, and 6 h after injection for 3 consecutive days. Two hours after methadone administration, food intake was inversely related to dose, but after 6 h a direct relationship between dose and feeding was obtained. Food intake increased with repeated methadone administration. In Experiment 2, methadone (5.0 mg/kg) was injected and food was made available 0, 1, 2, or 3 h later. Maximal food intake occurred in the third and fourth hours following methadone administration. As in Experiment 1, food intake increased with repeated methadone administration. Increases in food intake following repeated methadone administration may have been due to the development of tolerance to effects of methadone that may interfere with feeding, such as sedation. In Experiment 3, methadone was administered daily or every fifth day, assuming that spacing injections would retard tolerance development. Repeated daily methadone administration was associated with increased food intake earlier in the session, whereas increases in food intake following spaced methadone administration occurred later in the session. These data indicate that methadone increases short-term feeding in satiated rats. This is in contrast to the reported decrease in food-reinforced behavior noted in operant studies. This contrast may be due to sedating or other disabling effects of methadone.

Animals↗
PubMed1992

Effects of neuropeptide Y on food-reinforced behavior in satiated rats.

The effect of NPY on behavior and food intake of food-satiated rats was examined under three different food availability conditions. Food was available during times when rats normally do not eat under either a fixed-ratio or fixed-interval reinforcement schedule, or it was freely available in the bottom of the cage (FF). Forty responses were required for each 45-mg food pellet under the ratio schedule (FR 40) and for the first response to occur 15 s after the previous reinforcement under the interval schedule (FI 15"). NPY (5 micrograms) significantly increased food intake under all conditions and increased food-reinforced responses under the FR and FI schedules. NPY's effect on food intake was greatest when food was freely available and least for rats working under the schedule requiring the most effort (FR 40). Food intake peaked after 3 days under repeated daily administration of NPY. Under free food access and under the fixed-interval schedule, eating and/or responding occurred almost immediately following the onset of the initial 4-h session under NPY. However, during the first session following NPY administration under the FR, rats emitted few responses during the first 2 h of the session. The onset of robust responding under the FR schedule began earlier with each successive daily administration of NPY. These data show NPY substantially increases food-maintained behavior and is a potent inducer of food intake even under conditions where considerable effort is required to obtain food. Further, the conditions under which food is made available can dramatically alter NPY's effect on the temporal pattern of food-maintained responding, feeding, and latency to eat.

Animals↗
PubMed1992

Measurement variability in duplex scan assessment of carotid atherosclerosis.

BACKGROUND AND PURPOSE: The reproducibility of duplex scan measures of carotid atherosclerosis was evaluated as part of a study assessing the prevalence of carotid disease in elderly adults. METHODS: Doppler measures of blood flow velocity were used to evaluate disease severity, and extent of carotid plaque was scored from the B-mode image. A reader assigned a grade from 0 to 3 to each of seven segments in the carotid system, based on the number and size of lesions present. Reproducibility data were obtained from 30 study participants who underwent a repeat scan by a second sonographer. Each scan was then scored by two readers. RESULTS: Doppler measures of blood flow velocity were found to be highly reproducible, with intraclass correlation coefficients of 0.81 for the common carotid artery, 0.84 for the internal carotid artery, and 0.77 for the internal carotid artery velocity to common carotid artery velocity ratio. Reproducibility of plaque grade was evaluated using segment as the unit of analysis, and both sonographer and reader variation were analyzed. When readers differed perfect agreement was achieved in 84% of the segments (K = 0.67), and when sonographers differed perfect agreement was obtained in 78% of the segments (K = 0.56). When both sonographer and reader differed, perfect agreement was obtained in 77% of the segments (K = 0.53). The plaque index, created by summing plaque grades from selected segments, was highly reproducible, with an intraclass correlation coefficient of 0.86. CONCLUSIONS: The duplex scan protocol described here provides reliable measures of both extent and severity of carotid disease that are appropriate for use in cross-sectional studies.

Aged↗
PubMed1992

Forearm P-31 nuclear magnetic resonance spectroscopy studies in oculopharyngeal muscular dystrophy.

Five siblings with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) underwent P-31 Nuclear Magnetic Resonance Spectroscopy studies of forearm flexor muscles. Mean values of PCr/(PCr+Pi) in the patients were reduced (p = 0.01) and pH elevated (p = 0.02) in resting muscle when compared to controls. During exercise PCr/PCr+Pi) fell quickly to values less than controls (p less than 0.0001) despite submaximal exercise output and developed exercise-induced acidosis which exceeded that of controls (p = 0.05). Acidosis recovered slowly despite relatively normal recovery of PCr/(PCr+Pi) following exercise. Within the patient group, however, one member had normal resting, exercise and recovery values. The studies suggest that OPMD is a more widespread disorder of striated muscle than clinically appreciated. The pattern of findings observed in OPMD differs from those identified in denervation, disuse and mitochondrial myopathy.

Acidosis, Lactic↗
PubMed1991

The discriminative stimulus effects of neuropeptide Y.

Neuropeptide Y (NPY), an endogenous peptide which strongly induces food intake, is demonstrated to have discriminative stimulus properties when administered intracerebroventricularly. Rats rapidly learned to press the appropriate lever during training. NPY discrimination was dose-dependent. NPY's discriminative stimulus properties were compared to those of two doses of Peptide YY (PYY) and 24 and 48 h of food deprivation, conditions which also increase feeding. Both doses of PYY generalized to NPY, supporting previous findings that PYY has effects similar to NPY. Although food deprivation increases feeding in a manner similar to NPY, food deprivation did not result in NPY-appropriate responding.

Animals↗
PubMed1991

Effects of two rescue doses of a synthetic surfactant on mortality rate and survival without bronchopulmonary dysplasia in 700- to 1350-gram infants with respiratory distress syndrome. The American Exosurf Neonatal Study Group I.

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 21 American hospitals, two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air were administered to 419 infants weighing 700 to 1350 gm who had respiratory distress syndrome and an arterial/alveolar oxygen pressure ratio less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to those infants remaining on ventilatory support. Infants were stratified at entry by birth weight and gender. Among infants receiving synthetic surfactant, improvements in alveolar-arterial oxygen pressure gradient, arterial/alveolar oxygen pressure ratio, and oxygen and ventilator needs through 7 days of age were apparent. Death from respiratory distress syndrome was reduced by two thirds (21 vs 7; p = 0.007), and the overall neonatal mortality rate was reduced by half (50 vs 23; p = 0.001). Although there was no significant reduction in the incidence of bronchopulmonary dysplasia (39 vs 31; p = 0.107), the hypothesis that survival through 28 days without bronchopulmonary dysplasia would be enhanced by two rescue doses of synthetic surfactant was proved true (21% improvement, from 132 to 156 patients; p = 0.001). In addition, the incidence of pneumothorax was reduced by one third (62 vs 40; p = 0.022), and the incidence of pulmonary interstitial emphysema was reduced by half (102 vs 51; p = 0.001). The only side effect identified was an increase in the incidence of apnea (102 vs 134; p = 0.001). These findings indicate that rescue use of a synthetic surfactant can improve the morbidity and mortality rates for premature infants with respiratory distress syndrome.

Bronchopulmonary Dysplasia↗
PubMed1990

Construction of a human chromosome 3 specific NotI linking library using a novel cloning procedure.

Two new diphasmid vectors (lambda SK17 and SK22) and a novel procedure to construct linking libraries are described. A partial filling-in reaction provides counter-selection against false linking clones in the library, and obviates the need for supF selection. The diphasmid vectors, in combination with the novel selection procedure, have been used to construct a chromosome 3 specific NotI linking library from a human chromosome 3/mouse microcell hybrid cell line. The application of the new vectors and the strong biochemical and biological selections resulted in a library of 60,000 NotI linking clones. As practically all of them are real NotI linking clones (no false recombinants) the library represents approximately 3,000 human recombinants (equal to 10-15 genomic equivalents of chromosome 3). Previously published methods for construction of linking libraries are compared with the procedure described in the present paper. The advantages of the new vectors and the novel protocol are discussed.

Animals↗
PubMed1990

A new quantitative nitroblue tetrazolium reduction assay based on kinetic colorimetry.

A new method for the quantitative assay of nitroblue tetrazolium (NBT) in which the reduction is measured by kinetic colorimetric analysis is reported. The assay is conducted along standard conditions as far as neutrophil isolation and stimulation, except that the test is performed on microtiter plates and the change of color corresponding to NBT reduction is monitored on a kinetic enzyme immunoassay (EIA) reader for 25 min at 490 nm. The results are expressed as mOD/min/in. The influence of several parameters on the results of the assay was studied, including cell concentration, the nature and concentration of the stimulus, and the freshness of the reagents. Cell concentrations of 5 x 10(6) and 1 x 10(7)/ml were found to be optimal, and IgG-coated immunobeads, at a concentration of 1 mg/ml, were found to be the ideal stimuli. NBT reduction for nine normal volunteers studied at 5 x 10(6) cells/ml ranged from 1.80 to 7.30 mOD/min (mean +/- SD = 3.66 +/- 1.69). NBT reduction values at 1 x 10(7) cells/ml in six normal individuals ranged from 2.59 to 7.41 (4.73 +/- 1.89). In contrast, NBT reduction in a child with clinical symptoms suggestive of chronic granulomatous disease was 0.31 mOD/min. This method is considerably simpler than any alternative method for the performance of quantitative NBT assays.

Colorimetry↗
PubMed1990

Effects on opioid-induced rate reductions by doxepin and bupropion.

Twelve pigeons key-pecked under a multiple variable interval 15-second, variable interval 150-second schedule of food reinforcement. Effects of two opioid drugs, buprenorphine and methadone, were determined alone and in combination with chronic daily administration of the antidepressants doxepin or bupropion. Methadone initially produced dose-dependent key-pecking rate reductions when administered acutely, prior to the session, while buprenorphine produced key-pecking rates that reached a plateau at 50-80% of baseline rate and were not reduced further by higher doses. Neither doxepin nor bupropion, given alone, had lasting effects on key-pecking rates. Chronic daily doxepin administration significantly attenuated methadone-induced response rate reductions. Bupropion reduced the effect of the highest methadone dose, but this effect was mitigated by the development of opioid tolerance. Unlike bupropion, doxepin interfered with the development of opioid tolerance. Neither antidepressant systematically altered effects of buprenorphine on key-pecking.

Animals↗
PubMed1990

Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedure.

The purpose of the present study was to examine the effects of haloperidol (0.3-10 mg/kg), molindone (0.3-5.6 mg/kg), mesoridazine (0.3-10) and thioridazine (0.3-25 mg/kg) on the behavior of pigeons exposed to a repeated acquisition procedure. At sufficiently high doses, each of these neuroleptics increased error rates (interfered with learning) and reduced rate of responding. When the drugs were compared on the basis of absolute doses administered, haloperidol disrupted behavior at doses considerably lower than the other drugs. If, however, chlorpromazine equivalent doses were examined, haloperidol was the least disruptive of the four drugs. Comparing the degree of behavioral disruption produced by the four drugs with their relative neuroreceptor affinities for dopamine D-2, cholinergic muscarinic, histamine H1, alpha-1 adrenergic and alpha-2 adrenergic receptors suggests that behavioral disruption cannot be attributed in any simple way to dopamine or acetylcholine receptor blockade. The relationship between the behavioral effects of neuroleptics and their simple neuropharmacological actions must be considered as highly tentative.

Animals↗
PubMed1990

Home-like architectural features of residential environments.

Adults who had no experience in the area of mental retardation viewed slides of residential settings, five providing housing for people with mental retardation, and rated their "home-likeness" (1 = home-like, 5 = institutional). Of 55 two-way comparisons, the mean home-likeness ratings of 48 such pairs differed significantly from one another. A .98 log-linear correlation was found between number of residents in a given facility and institutional ratings. Of 26 features of living rooms studied in detail, furniture position, lighting type, and lighting flexibility were highly correlated with home-likeness, whereas building code-specific features and seating type were minimally related to home-likeness.

Adult↗
PubMed1989

Interaction of reinforcement history with methadone on responding maintained under a fixed-interval schedule.

Twelve pigeons were initially trained under either a fixed-ratio (FR) 50 or differential-reinforcement-of-low-rate (DRL) 10-sec schedule of food presentation. After 50 sessions of exposure to the foregoing schedules all pigeons key pecked under a fixed-interval (FI) 90-sec schedule. Key-peck rates differed as a function of schedule history, with FR-history subjects responding at significantly higher rates under the FI schedule than DRL-history subjects. To better compare methadone's rate-altering effects on baseline response rates, 8 naive pigeons were trained from the outset to key peck under an FI 90-sec schedule and were subsequently divided into 2 groups based on overall response rates (groups FI-H and FI-L). After at least 40 sessions under the FI schedule methadone dose-response curves were determined at doses of 0.6, 1.2 and 2.4 mg/kg. Low and intermediate methadone doses did not effect key-peck rates by pigeons with an FR history compared to significant rate decreases by pigeons having comparable rates but without a history of responding under an FR schedule (group FI-H). No differential effects following methadone were observed in low-rate subjects (DRL history and FI-L). When methadone (9.0 and 12.0 mg/kg/day) was administered chronically, response rates of all subjects were initially suppressed, with FI control subjects showing more complete recovery of drug-free baselines than either FR- or DRL-history groups. Naloxone (1.0 mg/kg) reversed methadone's rate-decreasing effects, although these actions were significantly less in subjects with prior experience under DRL schedules. Following completion of the chronic phase, and when subjects had been drug free for at least 14 sessions, the methadone dose-response curve was redetermined. The differential effects of methadone associated with reinforcement history were no longer evident, suggesting that a drug history can interact with a schedule history. These experiments add to the growing body of evidence indicating that prior experience can influence the behavioral actions of drugs independent of control rate of responding. Moreover, the data reveal that the influence of reinforcement schedule history depends on whether drugs are administered acutely or chronically.

Animals↗
PubMed1989

The ras and myc oncogenes cooperate in tumor induction in many tissues when introduced into midgestation mouse embryos by retroviral vectors.

Midgestation embryos were infected with replication-defective retroviral vectors that either transduced the myc oncogene, the ras oncogene, or both oncogenes simultaneously. The myc virus induced tumors in diverse organs at a very low frequency and with a long latency period, while approximately 20% of the mice derived from embryos infected with the ras virus developed tumors in the skin with a latency of 4-8 weeks. In contrast, infection of embryos with the ras/myc double oncogene virus resulted in 27% of the animals developing rapidly growing and malignant tumors in a great variety of tissues after a median latency period of 2-3 weeks. All tumors were of monoclonal origin, as shown by Southern analysis using the provirus as a molecular marker. Our results are consistent with the hypothesis that the ras and myc oncogenes cooperate in transforming cells, but that additional alterations are necessary for realization of the fully malignant phenotype. Our observations also suggest that a much wider range of cell types become targets for malignant transformation when the embryos are exposed to the myc and the ras oncogenes simultaneously than when exposed to the same oncogenes separately. Infection of mouse embryos with vectors carrying different oncogenes or oncogene combinations may be an efficient and rapid method for evaluating the spectrum of cell types at risk for malignant conversion following mutation of a protooncogene to a transforming gene.

Animals↗
PubMed1989

Effects of methadone on alternative fixed-ratio fixed-interval performance: latent influences on schedule-controlled responding.

Effects of methadone on pigeons' key pecking were examined under four conditions selected to analyze the control of behavior under alternative fixed-ratio fixed-interval schedules. In Condition 1, pigeons pecked under one of three different alternative schedules (alternative fixed-ratio 50 fixed-interval 90 s, alternative fixed-ratio 75 fixed-interval 90 s and alternative fixed-ratio 200 fixed-interval 90 s) each week. In Condition 2, fixed-ratio 50 or fixed-ratio 75 schedules were in effect during baseline sessions, and alternative fixed-ratio 50 fixed-interval 90-s or alternative fixed-ratio 75 fixed-interval 90-s schedules were in effect during sessions in which methadone was administered. In Condition 3, effects of methadone on key pecking maintained under fixed-ratio 50 and fixed-ratio 75 schedules were examined, whereas in Condition 4 the effects of methadone on key pecking under a fixed-interval 90-s schedule as well as fixed-ratio 50 and fixed-ratio 75 schedules were investigated. Control by the fixed-interval contingency was assessed by computing the proportion of total session reinforcers delivered under the fixed-interval schedule. Methadone administration (0.5-4.0 mg/kg) shifted the predominant source of schedule control under the alternative schedule from the fixed-ratio schedule to the fixed-interval contingency. This shift was dependent on methadone dose and fixed-ratio size. Control by the fixed-interval contingency was greatest following extensive exposure to the interval component embedded within the alternative schedule (Condition 1), but was apparent to a lesser degree with even very limited exposure to the alternative fixed-ratio fixed-interval schedule (Condition 2). Interreinforcement intervals comparable to those under fixed-interval schedule were not observed under the fixed-ratio schedules presented alone (Condition 3). Repeated exposure to the fixed-interval contingency outside the context of the alternative fixed-ratio fixed-interval schedule did not engender performance changes under a fixed-ratio schedule which would mimic those of increased fixed-interval contingency control (Condition 4). These data suggest that drug administration can be used to unmask the influence of contingencies that are latent under baseline conditions and reveal influences of both past and present environmental variables.

Animals↗
PubMed1979

Naloxone effects on schedule-controlled behavior in morphine-pelleted rats.

The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3--4 days. Naloxone (0.25--1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7--17 days for 0.25 mg/kg naloxone, 9--22 days for 0.50 mg/kg, and 13--28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25--1.0 mg/kg) did not alter performance by placebo-pelleted rats.

Animals↗