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Biomedical subjects

R L Taylor

Publications and source records attributed to R L Taylor.

At least 127 records · Page 7Linked to original sources

Properties of [3H](3-Me-His2)TRH binding to apparent TRH receptors in the sheep central nervous system.

[3H](3-methyl-His2)thyrotropin releasing hormone ([3H]MeTRH) binds to sites in the sheep central nervous system (CNS) whose properties closely resemble both those of CNS binding sites for [3H]TRH and those of pituitary binding sites for [3H]MeTRH. Detailed studies for binding of [3H]MeTRH in the sheep nucleus accumbens and retina have yielded equilibrium dissociation constants of about 4 nM and densities of binding sites of about 3 and 2 pmol/g wet weight, respectively. The binding affinity of [3H]MeTRH was 8- to 10-fold higher than that of [3H]TRH, resulting in much lower non-specific binding with the new ligand. The association reaction had a rate constant of about 2-3 x 10(7) M-1 min-1, while the biphasic dissociation reaction had rate constants of 8-9 x 10(-2) min-1 for the fast phase and 1-2 x 10(-2) min-1 for the slow phase. The regional distribution of binding in the sheep CNS was similar to that observed previously with [3H]TRH. Highest binding outside the pituitary was in the nucleus accumbens area and retina, with another peak in the amygdala-temporal cortex area. Binding was widely distributed, so that no CNS region appeared totally devoid of binding. Nineteen TRH analogs, ranging in potency over 6 orders of magnitude, showed nearly identical abilities to complete for binding of [3H]MeTRH in the CNS areas and in the sheep anterior pituitary gland in side-by-side experiments. These findings argue strongly for identification of [3H]MeTRH binding sites in the CNS as TRH receptors.

Animals↗

Guanine nucleotides modulate TRH-receptor binding in sheep anterior pituitary.

Binding of thyrotropin-releasing hormone (TRH, thyroliberin) to receptors in chilled membrane resuspensions from sheep anterior pituitary glands is reduced in affinity almost 2-fold by micromolar concentrations of guanosine 5'-triphosphate (GTP) and the hydrolysis-resistant analog guanyl-5'-yl imidodiphosphate (GppNHp) added to tissue during a 10-min preincubation at 37 degree C. Guanosine 5'-diphosphate (GDP) produced a similar effect at 1 mM, while GMP, ATP, ADP and AMP appeared relatively inactive. The number of TRH-binding sites was not affected by the nucleotide treatments. These results are consistent with reports of guanine nucleotide effects on other receptor types and with evidence suggesting an adenylate cyclase mechanism for some of TRH's effects in the anterior pituitary.

Adenine Nucleotides↗

Physical fitness and intraocular pressure.

The ability of moderate to intense aerobic exercise to reduce intraocular pressure (IOP) has been reported. Previous studies have focused on a single postexercise recovery period not considering the long-term effect of improved physical fitness on IOP. A total of 32 adult subjects, all having IOP's of greater than 18 mmm Hg in each eye as determined by an American Optical Corporation Non-Contact Tonometer, were selected for the study. After a complete medical and visual evaluation, participants were randomly assigned to either an intervention group (N = 18) receiving a 6-month supervised exercise program to improve physical fitness or into a control group (N = 14). After 6 months, each group was reevaluated to observe changes in physical fitness and IOP. Pre- and poststudy measurements of maximum oxygen uptake (ml/kg/min) made with a Beckman O2 analyzer showed significant improvement in physical fitness in the intervention group (p less than 0.05). There was a significant decrease (p less than 0.05) in IOP, 2.0 mmm Hg in the right eye and 1.3 mm Hg in the left eye, in the intervention group; however, decreases in IOP were comparable and significant (p less than 0.05) in the control group. Results from multiple regression analysis for each individual group and for combined groups indicated that changes in IOP were not dependent upon changes in physical fitness.

Adult↗

Muscarinic receptors in the posterior pituitary gland.

The characteristics of atropine-sensitive binding of l-[3H]-quinuclidinyl benzilate ([3H]-QNB) to membrane suspensions of sheep posterior pituitary indicate that the binding sites represent muscarinic cholinergic receptors. Scatchard plots of 6 saturation experiments showed a single class of binding sites, with an equilibrium dissociation constant of 16 +/- 2 pM and a density equivalent to 1.8 +/- 0.2 pmol/g wet weight of tissue. Kinetic analysis of 2 association and 3 dissociation curves yielded mean association and dissociation rate constants of 3.9 x 10(8) M-1 min-1 and 4.3 x 10(-3) min-1, respectively. The binding had a detailed pharmacology for 12 drugs consistent with muscarinic receptor identification. In rat neurointermediate lobes, superior cervical ganglionectomy had no demonstrable effect on [3H]-QNB binding. The location(s) and functional role(s) of neurohypophyseal muscarinic receptors remain to be elucidated.

Animals↗

Preparation of 3H-[3-M3-His2]TRH as an improved ligand for TRH receptors.

[3H]-3-methyl-His2]thyrotropin releasing hormone ([3H]MeTRH) binds to sites in the sheep anterior pituitary gland which appear to be the same as those occupied by [3H]TRH and which can therefore be identified as TRH receptors. In competition experiments performed in parallel, both ligands gave the same number of binding sites, 15 pmol/g wet weight, and showed the same pharmacology for 19 TRH analogs ranging over more than 5 orders of magnitude in potency. The apparent dissociation constant of binding of [3H]MeTRH was about 3.5 nM compared to 29 nM for [3H]TRH. Kinetic experiments with [3H]MeTRH yielded a rate constant for association of 1.4 x 10(7) M-1 min-1 and rate constants for the biphasic dissociation of 5 x 10(-2) min-1 (fast phase) and 7 x 10(-3) min-1 (slow phase). Detailed methods are described for preparation of [3H]MeTRH by reduction of the dehydroproline precursor and its purification by ion exchange and antibody affinity chromatography. The major advantage of the new ligand is that its higher affinity of binding gives relatively less non-specific binding than is obtained with [3H]TRH, particularly in central nervous tissue.

Animals↗

Pituitary cell cultures contain muscarinic receptors.

The presence of muscarinic receptors in 5-day dissociated cell cultures of rat anterior pituitary glands was detected by atropine-sensitive binding of 3H-quinuclidinyl benzilate (3H-QNB). Muscarinic receptor levels in cultures were compared to levels of receptors for dopamine and thyrotropin releasing hormone.

Animals↗

Differential performance of learning disabled and non-learning disabled children on the McCarthy scales, WISC-R, and WRAT.

Individually administered the McCarthy Scales of Children's Abilities, WISC-R, and WRAT to 30 learning disabled and 30 non-learning disabled second-grade students. The McCarthy General Cognitive Index and the WISC-R Full Scale IQ scores were compared for both groups. In addition, correlations between the General Cognitive Index, WISC-R IQ, and mean WRAT achievement were reported. There was marginal support for previous studies that suggested that the McCarthy Scales are more consistent with the academic functioning of learning disable students. Implications and directions for future research were discussed.

Child↗

Depression of leucine and isoproterenol induced insulin secretions in the spontaneously diabetic New Zealand white rabbit.

Rabbits were studied from a closed colony of NZW rabbits which exhibits a 19% occurrance of spontaneous diabetes mellitus. Six overtly diabetic rabbits and eight rabbits with normal glucose disposal were tested with intravenous glucose challenge (500 mg/kg), L-leucine administration (125 mg/kg), and 30 minute infusions with isoproterenol (10 microgram/kg/min.). These agents were shown to be ineffective insulin secretogogues in the overtly diabetic group when compared to the highly significant IRI response observed in colony rabbits with normal glucose disposal. The data indicate that the defect in IRI secretion observed in the spontaneously diabetic NZW rabbits is not confined to stimulation by glucose, but represents an abnormal IRI release mechanism which appears to lack secretogogue specificity.

Animals↗

Muscarinic receptor binding in sheep anterior pituitary.

The existence of typical muscarinic receptors in membranes of sheep anterior pituitary was detected by binding of [3H]quinuclidinyl benzilate ([3H]QNB), a potent and specific muscarinic antagonist. [3H]QNB binding sites in anterior pituitary had an equilibrium dissociation constant of about 20-40 pM, a rate constant for association at 37 degrees C of about 2 x 10(8) M-1 min-1, a rate constant for dissociation at 37 degrees C of about 4 x 10(-3) min-1, and the expected specificities for a variety of cholinergic and other drugs. The concentration of [3H]QNB binding sites in anterior pituitary, about 4-6 pmol/g tissue, was at least twice that in posterior pituitary, but less than a quarter that in the hypothalamus. Since there is no established cholinergic or other innervation of the anterior pituitary, the presence there of typical muscarinic receptors, if we assume that they are functional, suggests that acetylcholine reaches the tissue through the hypophyseal portal circulation, and that it may thus have a role in the regulation of pituitary function.

Animals↗

Binding sites for thyrotropin-releasing hormone in sheep nucleus accumbens resemble pituitary receptors.

TRH binds to sites in the nucleus accumbens-septal area of sheep brain. These sites appear to represent receptors for at least some of its behavioral effects in other species and are very similar to sheep pituitary receptors. All measurements were performed on ice to prevent peptide degradation. High affinity [3H]TRH binding in brain regions was distinguished from interfering low affinity binding by use of [3-Me-His2]TRH, a more potent and specific analog, in blank tubes at a 1-microM concentration. The nucleus accumbens-septal area, particularly the nucleus accumbens itself, showed the highest binding of any of a variety of brain regions surveyed. Binding sites in both nucleus accumbens and anterior pituitary had an equilibrium dissociation constant of about 20-40 nM, a rate constant for association of about 1-3 x 10(6) M-1 min-1, and a rate constant for dissociation of about 0.07 min-1. Seventeen TRH analogs showed closely similar potencies in competing for binding in the two tissues. Six weak analogs appeared to be more potent in the nucleus accumbens than in the pituitary, but this was an artifact of their relatively greater potency in competing for low affinity binding sites which are absent in pituitary. The only major difference between the high affinity binding sites in the two tissues was in their concentration, which was about 2- to 3-fold higher in the pituitary.

Animals↗

Use of the AAMD classification system: a review of recent research.

The present study was designed to analyze the use of the AAMD and other classification systems in recent research. Specifically, articles from the American Journal of Mental Deficiency and Mental Retardation between the years 1973 and 1979 (N = 566) were analyzed with regard to the type of classification system used. In addition, information on subject description, tests employed, test scores reported, and correctness of the classification was obtained. A surprisingly small percentage of authors used the AAMD classification system, and a relatively large percentage of investigators misclassified their subjects when test scores were reported. Implications of the data and recommendations were discussed.

Child↗

Systemic lupus erythematosus in pregnancy.

Most literature on pregnancies in patients with systemic lupus erythematosus (SLE) is retrospective and selective. This report is a detailed, prospective analysis of 13 pregnancies in eight women with SLE. Pregnancy was best tolerated by mothers without significant nephropathy or cardiopathy who had been in clinical remission for more than three months prior to conception. Management was aided by serial evaluation of complement (C3 and C4) levels and careful supervision of immunosuppressive therapy when indicated. Although fetal status was closely monitored, premature deliveries and spontaneous abortions occurred frequently. No malformations or adverse sequelae were noted in surviving infants exposed to immunosuppressive agents during gestation.

Abortion, Induced↗

Experimental sporotrichosis in Syrian hamsters.

Syrian hamsters were infected with Sporothrix schenckii by subcutaneous footpad inoculation. Two types of infection could be uniformly induced: a self-limited, lymphatic infection resembling the classical disease in humans, and a generalized nonfatal infection. An infecting dose of approximately 5,300 yeast cells produced the localized subcutaneous-lymphatic disease which was limited to a single limb. In contrast, a 1,000-fold increase in the inoculum temporarily overwhelmed the animals' defense mechanisms, producing a systemic infection involving the liver and spleen. These models were used to demonstrate the development of increased resistance to subsequent infection following either infection or active immunization with ribosomal fractions or trypsinized cell wall antigens of S. schenckii incorporated in Freund complete adjuvant. Agglutination titers were detectable in all animals that were either infected or immunized. In one group of infected animals, the titers persisted for at least 1 year after three booster doses of Formalin-killed S. schenckii. The ability to produce an infection in hamsters which closely resembles the disease seen in humans makes the animal a good model with which to study experimental sporotrichosis.

Agglutinins↗