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Biomedical subjects

T Cooper

Publications and source records attributed to T Cooper.

At least 109 records · Page 6Linked to original sources

Cyclic AMP, the hyperresponsiveness factor from hog kidney.

The isolation and identification of a material present in the plasma of hypertensive dogs and hypertensive human patients has been under study since 1972. The earliest experiments in relation to this work, noted that plasma from hypertensive dogs cause a hyperresponse to norepinephrine when both were administered by way of the vein. Employing a rat assay system that consisted of an anesthetized rat with polyethylene catheters in the vein for giving norepinephrine and the test fractions and a catheter in the artery for blood pressure monitoring, fractions from hog kidney were tested for hyperresponsiveness activity. The active material is very comparable to cyclic AMP in molecular weight, ultraviolet spectrum, paper chromatography, Enzyme hydrolysis and activity in the anesthetized rat system. This evidence indicates that the hyperresponsiveness factor of renal origin is cyclic AMP.

Angiotensin II↗

The effect of imipramine treatment on brain serotonin receptors and beta-adrenoceptors and on pineal beta-adrenergic function in adult and aged rats.

The effect of age and of imipramine treatment on cortical serotonin and beta-adrenergic binding sites and on pineal N-acetylserotonin and melatonin were examined in Fischer-344 rats. Cortical serotonin-1 and -2 receptor binding was reduced by 15 and 22.5% respectively, in 24 vs. 6 months old animals. Ten single daily imipramine (10 mg/kg) injections in the aged animals resulted in reductions in both types of serotonin sites, while in adult animals significant binding reduction occurred only at the 5HT2 site. Cortical beta-adrenoceptor binding was also diminished in the aged rats. Imipramine treatment elicited a significantly greater decrease in these adrenergic sites in the aged (39.2%) than in the adult (27.6%) animals. In the pineal gland, N-acetylserotonin and melatonin content were reduced by age; imipramine treatment induced decreases in both indoles in the adult animals and a reduction in N-acetylserotonin in the aged animals. These age-related effects of imipramine on cortical serotonin receptor and beta-adrenoceptor binding and on pineal indoles may be a consequence of the higher drug and metabolite (desmethylimipramine) blood and tissue concentrations which were found in the aged animals.

Aging↗

Imipramine in adolescent major depression: plasma level and clinical response.

Thirty-four adolescents with mean age 14.25 years who met RDC criteria for major depressive disorder as assessed with the K-SADS, were treated for 6 weeks on a fixed schedule of imipramine hydrochloride titrated to a dosage of 5.0 mg/kg/day except as limited by side effects. Mean dose was 246 mg/day (4.5 mg/kg/day). In spite of good indications of compliance with treatment only 44% of the adolescents improved to the level of no or only slight depressed mood or anhedonia, though most had less depressive symptomatology at the end of treatment. There was neither a linear nor curvilinear relationship between total plasma level of IMI plus DMI and clinical response, despite a wide range of both plasma level (77 ng/ml to 986 ng/ml) and outcome. Adolescents with associated separation anxiety had significantly poorer response to treatment of their depressive disorder than those with major depression alone. Poor response was also weakly associated with being female, having endogenous subtype of depression, and having higher plasma IMI (but not DMI) level. In the context of similar studies of IMI on depression in other age groups, it is hypothesized that high levels of sex hormones during adolescence and young adulthood may interfere with IMI's antidepressant effects. It is concluded that other types of antidepressants should be tested in adolescents with major depression.

Adolescent↗

Different pattern of association of beta-endorphin and cortisol responses to dextroamphetamine in postmenopausal women and young men.

A negative correlation between plasma beta-endorphin and cortisol responses to 0.15 mg/kg dextroamphetamine i.v. was found in a group of seven normal postmenopausal women, while the responses of the two hormones were positively correlated in nine normal young men. These results suggest that even though the adrenocorticotropic hormone (ACTH)-cortisol and beta-endorphin are usually regulated by the same mechanism (both ACTH and beta-endorphin are derived from proopiocortin), there are situations in which these systems can be associated in a different pattern. The elucidation of these situations may contribute to the understanding of regulatory mechanisms of the two systems.

Adult↗

Regional differences in the effect of pargyline on dopamine concentrations in the rat hypophysis.

Dopamine concentrations were estimated in different regions of the infundibular-pituitary system of the rat. The highest values were found in the pituitary stalk where they are comparable to the concentrations in the striatum, and higher than in the median eminence. In the anterior lobe the dopamine (DA) concentrations of the upper pole (10% of the lobe tissue) were 2-5 times higher than in the rest of the lobe. Anterior lobe DA was significantly higher in rats about 6 months old than in rats about 3 months old. After inhibition of MAO, the DA concentrations in the isolated neural lobe (NL) were more than doubled. In contrast there was no increase in the DA concentrations of the intermediate lobe, an observation which is in agreement with our previous finding that DA synthesis in the intermediate lobe after electrical stimulation of the pituitary stalk is much slower than in the neural lobe. Pargyline treatment caused an increase in the DA concentrations in the anterior lobe by about 150%. This rise (together with a DA increase in the stalk-infundibulum) may be related to the decrease in circulating prolactin which occurs in pargyline treated rats.

Aging↗

cis-Dominant mutations which dramatically enhance DUR1,2 gene expression without affecting its normal regulation.

We have isolated three cis-dominant mutations which dramatically enhance DUR1 ,2 gene expression in Saccharomyces cerevisiae. The mutant phenotype, which is expressed both in haploid and MATa/MAT alpha diploid strains, does not appear to be an alteration of the normal control system for this gene because its expression remained fully inducible and sensitive to nitrogen catabolite repression. Instead, we found much higher levels of DUR1 ,2-specific RNA under both uninduced and induced conditions, i.e., the overproduction trait was superimposed on normal regulation of the gene. The mutations seemed to affect gene expression in a unidirectional manner or to be specific for DUR1 ,2 gene expression, because other genes in proximity to the mutations were not affected. We feel that these mutations may alter the chromatin structure in the vicinity of the DUR1 ,2 upstream control sequences or, alternatively, may be Ty insertions which no longer possess the ROAM characteristics reported by others and ourselves.

Base Sequence↗

Hypothalamic-pituitary-adrenocortical function in geriatric depression: diagnostic and treatment implications.

Extensive work in the field has indicated a state-dependent hyperactivity of the hypothalamic-pituitary-adrenocortical (HYPAC) functions and unresponsiveness to dexamethasone suppression in at least 50% of patients suffering from endogenous depression. In this study, elderly outpatients, 60-85 years of age, suffering from major depressive illness according to research diagnostic criteria (RDC) were studied with the dexamethasone suppression test (DST). Careful diagnostic evaluation included RDC, the Newcastle index, and clinical interviews focusing on "endogenomorphic features." The great majority (83.3%) of patients diagnosed as endogenous depressives were nonsuppressors (abnormal DST) as compared to 16.7% nonsuppressors amongst nonendogenous patients. In addition, DST tended to normalize the clinical recovery. The research and clinical implications of our findings in this population are further discussed.

Aged↗

Nonsense suppression in Schizosaccharomyces pombe: the S. pombe Sup3-e tRNASerUGA gene is active in S. cerevisiae.

The gene encoding the efficient UGA suppressor sup3-e of Schizosaccharomyces pombe was isolated by in vivo transformation of Saccharomyces cerevisiae UGA mutants with S. pombe sup3-e DNA. DNA from a clone bank of EcoRI fragments from a S. pombe sup3-e strain in the hybrid yeast vector YRp17 was used to transform the S. cerevisiae multiple auxotroph his4-260 leu2-2 trp1-1 to prototrophy. Transformants were isolated at a low frequency; they lost the ability to grow in minimal medium after passaging in non-selective media. This suggested the presence of the suppressor gene on the non-integrative plasmid. Plasmid DNA, isolated from the transformed S. cerevisiae cells and subsequently amplified in E. coli, transformed S. cerevisiae his4-260 leu2-2 trp1-1 to prototrophy. In this way a 2.4 kb S. pombe DNA fragment carrying the sup3-e gene was isolated. Sequence analysis revealed the presence of two tRNA coding regions separated by a spacer of only seven nucleotides. The sup3-e tRNASerUGA tRNA gene is followed by a sequence coding for the initiator tRNAMet. The transformation results demonstrate that the cloned S. pombe UGA suppressor is active in S. cerevisiae UGA mutant strains.

Ascomycota↗