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Biomedical subjects

T A Cooper

Publications and source records attributed to T A Cooper.

43 records · Page 3Linked to original sources
PubMed1984

Differences in hypothalamo-pituitary-adrenocortical activity in the rat after acute and prolonged treatment with morphine.

The influence of opioid substances on the secretion in vivo and in vitro of corticosterone, corticotrophin (ACTH) and corticotrophin releasing factor (CRF) in the rat was studied. Rats given a single injection of morphine exhibited a marked hypersecretion of ACTH and an exaggeration of the hypothalamo-pituitary-adrenocortical (HPA) response to stress. In contrast, animals rendered tolerant to morphine failed to release ACTH or corticosterone in response either to a subsequent injection of the opiate or to stress. The development of the inhibitory effect paralleled the development of tolerance to the analgesic actions of the drug. The production of ACTH by pituitary segments removed from control animals was not affected by the addition of opioid substances to the incubation medium. However, morphine, met-enkephalin and leu-enkephalin stimulated the secretion of CRF by hypothalami and their effects were competitively antagonized by naloxone. The secretory activity of hypothalami removed from rats treated acutely with morphine was enhanced. In contrast hypothalami from morphine-tolerant rats failed to secrete CRF in response to morphine, met-enkephalin, acetylcholine or 5-hydroxytryptamine. Neither the density nor the affinity of 3H-naloxone binding sites in the hypothalamus was influenced by the morphine treatment. The results suggest the opioid peptides and their receptors play a major role in the regulation of HPA function.

Adrenal Cortex↗
PubMed1983

Strong homology in promoter and 3'-untranslated regions of chick and rat alpha-actin genes.

We report here a comparison of the nucleotide sequences of the chick and rat skeletal muscle alpha-actin genes which reveals strongly conserved blocks of sequence in the putative transcriptional promoter and 3'-untranslated regions. This is the first instance of strong sequence conservation in untranslated gene regions between birds and mammals, other than the CAAT and ATA promoter homologies and the putative poly(A) addition signal, AATAAA. The strong conservation of these sequences suggests that they may have a role in the tissue-specific expression of the skeletal muscle alpha-actin gene.

Actins↗
PubMed1978

Clozapine plasma levels and convulsions.

Two patients receiving clozapine developed grand mal seizures. The plasma levels in one of the patients at the time of the seizure were approximately 100% higher than on 12 previous occasions. This finding led to the conclusion and the patient's admission that she had taken an overdose. Plasma levels in the other patient exceeded the range the authors had noted in previous studies. The authors emphasize the usefulness of plasma level monitoring in relation to safety, drug defaulting, and side effects.

Adult↗
PubMedDate not supplied

Progression of chronic renal disease in the dog.

Progressive loss of nephron function may be caused by persistence of factors that initiated renal disease. However, newer studies suggest that nephron damage is self-perpetuating once renal mass is reduced to some critical level. Original theories on mechanisms of self-perpetuated nephron injury focused on intraglomerular hypertension and glomerular hypertrophy, but several other factors have now been incriminated, including tubulointerstitial responses, proteinuria, and oxidative stress. Studies of dogs with surgically reduced renal mass (remnant kidney model of chronic renal disease) have allowed investigation of the self-progression theory in this species. Use of this model eliminates pre-existing renal disease as a confounding factor. Data from these studies indicate that self-perpetuated renal injury is initiated when mild azotemia is induced (plasma creatinine concentration = 2 to 4 mg/dL). Thus, with naturally occurring renal disease(s), it is likely that self-perpetuated nephron damage is occurring before or at the time when most cases of chronic renal disease are diagnosed. In dogs with remnant kidneys, loss of renal function often occurs at a linear rate over time, but non-linear patterns are common as well. The reciprocal of plasma creatinine concentration, which has been used to monitor rate of progression, is only a fair marker of renal function when compared to GFR. Thus, clinical results from creatinine measurements on cases of naturally occurring disease should not be interpreted too stringently. In remnant kidney dogs, the magnitude of proteinuria (UPC ratio) was not predictive of the rate in decline of GFR, casting doubt on importance of proteinuria in causing progression of renal disease. However, progressive increases in UPC may be a marker of an accelerated rate of renal injury. Self-perpetuation of renal injury in dogs could be the sole mechanism by which naturally occurring renal diseases progress. When more information is available on the rate of progression of naturally occurring diseases, it may become apparent whether factors initially inciting renal damage have an additive effect on rate of progression.

Animals↗
PubMedDate not supplied

Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs.

The objective of this study was to determine if plasma iohexol clearance, computed by a 1-compartment model defined by 3 plasma samples. was an accurate measure of glomerular filtration rate (GFR) in dogs. Twenty-two adult Beagle dogs of both genders were studied. Ten dogs had intact kidneys, and 12 dogs had surgically reduced renal mass. A bolus injection of iohexol was made, and blood was obtained for plasma iohexol assay after 120, 180, and 240 minutes. Plasma was analyzed for iohexol concentration by means of 3 assay methods: chemical, high-performance liquid chromatography (HPLC), and inductively coupled plasma emission spectroscopy (ICP). Urinary clearance of exogenous creatinine was used to measure GFR for three 30-minute periods occurring between 150 and 240 minutes after iohexol injection. Plasma clearance of iohexol and renal clearance of creatinine were compared by linear regression analysis and by limits of agreement techniques. Plasma iohexol clearance and urinary exogenous creatinine clearance were significantly correlated (chemical R2 = .90; HPLC R2 = .96; and ICP R2 = .96). The 1-compartment iohexol clearance:exogenous creatinine clearance ratios were 1.04 +/- 0.17, 1.05 +/- 0.14, and 1.10 +/- 0.15 for the chemical, HPLC, and ICP methods of assay, respectively, indicating that plasma iohexol clearance slightly overestimated GFR. Assuming a +/- 2 standard deviation interval for error, corrected plasma iohexol clearance measured GFR with +/-34% accuracy for the chemical, +/-26% accuracy for the HPLC, and +/-27% accuracy for the ICP method. These results indicate that plasma iohexol clearance should have utility for detection of renal dysfunction earlier in the course of progressive renal disease than is possible with measurement of plasma creatinine or urea concentrations.

Animals↗
PubMedDate not supplied

Automating the measurement of locomotor activity.

General locomotor activity is assessed in many ways ranging from observer ratings to sophisticated computer-assisted electronic monitoring with the aim of determining the unconditioned and conditioned effects of various pharmacological compounds. A system was constructed utilizing 6 independent test chambers each equipped with 14 infrared emitters and detectors arranged in two tiers and controlled by a microcomputer. The effects of the stimulant, d-amphetamine and its antagonism by the tranquilizer, pimozide, on unconditioned and conditioned activity as assessed using this system were found to be almost identical to results obtained using observer rating techniques. Other data showed that activity assessed by the system was subject to habituation and that this learning interacted with the effects of some drugs. Activity as measured by the system showed dose and time effects of various stimulants assessed over a 6 hr test period. Finally, the breakdown of activity into counts on the upper and lower tier of beams resulted in the finding that these two components of behavior were differentially affected by stimulants. These results demonstrate the validity and reliability of automated systems for assessing locomotor activity and show their promise for gaining further insight into the elements of behavior that are affected by various drugs.

Animals↗