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Biomedical subjects

T Thompson

Publications and source records attributed to T Thompson.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Treatment of pulmonary manifestations of gastroesophageal reflux in children two years of age or less.

Apnea and worsening bronchopulmonary dysplasia as well as recurrent aspiration pneumonia have been found to be consequences of gastroesophageal reflux in infants and young children. Antireflux procedures are effective in preventing gastroesophageal reflux; however, the effect of this operation on the course of these respiratory problems in very young patients is not known. We reviewed the results in 51 patients 2 years of age or less who underwent an antireflux fundoplication for pulmonary problems attributable to severe gastroesophageal reflux unresponsive to medical treatment. Twenty-eight patients had recurrent episodes of aspiration pneumonia, 14 had nonimproving or worsening bronchopulmonary dysplasia, and 9 had unexplained apneic episodes. Seventy-three percent of these patients had coexisting congenital anomalies or acquired problems. No operative deaths and no major surgical complications occurred. There were eight late deaths occurring between 1 and 25 months postoperatively: three were due to associated congenital anomalies or acquired problems, three to sepsis, and two to sudden infant death syndrome. Of the 43 surviving children, 91 percent with preoperative recurrent aspiration pneumonia had no additional episodes after Nissen procedure. Eighty-eight percent of the infants with unexplained apneic episodes showed marked benefit and 83 percent of those with bronchopulmonary dysplasia had clinical improvement. There were no late problems attributed to the operation even when it was performed in preterm infants. Therefore, we recommend fundoplication for patients 2 years of age or less who have a persistent pulmonary problem attributed to gastroesophageal reflux that does not respond to medical therapy.

Apnea↗

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↗

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↗

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↗

Congenital adrenal hypoplasia and selective absence of pituitary luteinizing hormone: a new autosomal recessive syndrome.

Congenital hypoplasia of the adrenal glands (CHA) is a rare condition, particularly in the absence of a central nervous system (CNS) anomaly. Two major types of CHA have been described in the setting of an apparently normal CNS and pituitary: a cytomegalic type usually with X-linked recessive inheritance and a miniature adult type that, when hereditary, is an autosomal recessive trait. Glycerol kinase deficiency (GKD) is an X-linked recessive trait, and it may be associated with CHA and adrenal insufficiency, presumably because of deletion of adjacent X-linked loci. We report on three sibling infants, one male and two females, with normal CNS and lethal CHA of the miniature adult type, selective absence of pituitary LH; two of the infants also had glycerol kinase (GK) activity that was decreased but not in the GKD range. Restriction fragment length polymorphism (RFLP) analysis of X chromosome markers located at Xp21-p22 was carried out on the maternal grandfather, both parents, two of three affected infants, and a living normal brother. The results excluded the X-linked type of this disorder associated with GKD in this family. Autosomal recessive inheritance is most likely.

Adrenal Glands↗

Multimodality treatment of non-small cell lung cancer: response to cisplatin, VP-16, and 5-FU chemotherapy and to surgery and radiation therapy.

Twenty-one patients with unresectable non-small cell lung cancer (NSCLC), 11 with stage III M0, five with malignant pleural effusion, and five with a single resectable metastasis were treated with multimodality therapy. All received two to three cycles of preoperative chemotherapy with a new sequential combination of cisplatin (50 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hr X 72) and etoposide (80 mg/m2/day X 3). Thirteen of 21 (62%) had a partial response, and three (14%) had a minor response to chemotherapy. Of the 19 who underwent surgical exploration, 17 were confirmed to have NSCLC. Ten patients with NSCLC and one with choriocarcinoma were rendered disease free by resection of the primary tumor and lymph nodes. Six received intra- and/or perioperative interstitial therapy with 125I and/or 192Ir. Another patient was treated with 32P. Postoperative external radiotherapy was administered in 15 patients, and adjuvant chemotherapy was administered in ten. This multimodality therapy was well tolerated, safe, and highly effective, resulting in excellent palliation even in patients with pleural effusion and metastasis. The most promising results were in unresectable stage III M0 with a partial response rate of 82% following neoadjuvant chemotherapy and a complete response rate of 73% after surgery. In this group, median survival has not yet been reached and will exceed 12 months.

Adult↗

Chromatin structure of hormone-responsive Moloney murine leukemia virus proviruses that contain sequences from mouse mammary tumor virus.

The chromatin structure of chimeric Moloney murine leukemia viruses (M-MuLVs) containing a glucocorticoid response element (GRE) from mouse mammary tumor virus (MMTV) inserted into the long terminal repeat (LTR) was investigated. Nuclear run-on assays indicated that transcription from the chimeric proviruses was induced 2- to 4-fold by dexamethasone. The wild-type M-MuLV 5' LTR contained a DNase I hypersensitive (HS) site at the TATA sequences, as well as four sites in the enhancer region. The chimeric LTRs contained these sites, as well as three additional sites in the MMTV sequences. Two of the MMTV sites were present in the absence of hormone, while one was hormone-induced. In addition, internal MMTV sequences appeared protected from DNase I digestion in the absence of hormone, suggesting bound protein. Hormone treatment resulted in loss of the DNase I protection.

Base Sequence↗

Stereotypic behavior of mentally retarded adults adjunctive to a positive reinforcement schedule.

Stereotypic behavior is one of the more common disturbed behaviors displayed by people who are developmentally disabled. This study evaluated the indirect effects on stereotypic frequency when the value of a concurrent fixed-interval reinforcement schedule for adaptive behavior was varied. Three profoundly mentally retarded adults performed a simple adaptive task reinforced under a fixed-interval schedule. The reinforcement schedule value was varied from fixed-interval 15 to 90, and 180 seconds after schedule control under each condition was demonstrated. The dependent measure was the frequency of stereotypic behavior. Stereotypic behavior increased in direct relation to the interval length. The theoretical and practical implications of treating stereotypies as an adjunctive behavior partially controlled by the reinforcement frequency for adaptive behaviors are discussed.

Adult↗