Cardiac and metabolic activity in mild hypertensive and normotensive subjects.
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Biomedical subjects
Publications and source records attributed to D Carroll.
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The major Mn2+-activated phosphoprotein phosphatase of the human erythrocyte has been purified to homogeneity from the cell hemolysate. It is sensitive to both inhibitors 1 and 2 of rabbit skeletal muscle, preferentially dephosphorylates the beta subunit of the phosphorylase kinase, and dephosphorylates a broad range of substrates including phosphorylase a, p-nitro-phenyl phosphate, phosphocasein, the regulatory subunit of cyclic AMP-dependent protein kinase, and both spectrin (Km = 10 microM) and pyruvate kinase (Km = 18 microM) purified from the human erythrocyte. The purified enzyme is stimulated by Mn2+ and to a lesser extent by higher concentrations of Mg2+. The purification procedure was selected to avoid any change in molecular weight, hence subunit composition, between the crude and purified enzyme. Maintenance of the original structure is demonstrated by non-denaturing gel electrophoresis and gel filtration chromatography. Gel filtration of the purified holoenzyme shows a single active component with a Stokes radius of 58 A at a molecular weight position of 180,000. Sedimentation velocity in a glycerol gradient gives a value of 6.1 for S20, w. Together these data indicate a molecular weight of about 135,000. Two bands of equal intensity appear on sodium dodecyl sulfate-gel electrophoresis at molecular weights of 61,700 and 36,300, suggesting a subunit composition of two 36,000 and one 62,000 subunits. The 36-kDa catalytic subunit can be isolated by freezing and thawing the holoenzyme or by hydrophobic chromatography of the holoenzyme. The catalytic subunit shows unchanged substrate and inhibitor specificity but altered metal ion activation.
Linear molecules of pBR322 and closely related plasmid DNAs were injected into Xenopus oocyte nuclei. Such molecules were degraded unless their ends were recombined. Non-homologous ends were joined rarely, if at all, but measurable recombination was supported by homologous sequences of less than 10 base pairs (bp). The efficiency of recombination increased as the length and degree of homology improved, in the range of about 8-20 bp. The homologous sequences had to be very close to the original molecular ends (within about 20 bp); internal homologies, even when they included better matches, were never used. These observations are best accommodated by a model of recombination which envisions exonucleolytic resection to expose homologous sequences, followed by annealing of single-stranded tails, tidying up and sealing of the new joint. Some of the recombined plasmids had novel tetracycline resistance genes; their properties give some insight into the function of the tet gene product.
Extreme high and low heart rate reactors were selected on the basis of responses to two laboratory stressors; a video game, and mental arithmetic. The heart rates of the same subjects were then recorded during a public speaking competition. Heart rate reactions to this more naturalistic stressor were generally in line with the laboratory-based designations.
Heart rate was monitored while 20 young males completed MATH, a computer-operated mental arithmetic task specifically designed for use in experiments involving subjects of heterogeneous numerical ability, and a standard mental arithmetic task used in this laboratory on several occasions. Both tasks elicited sizeable increases in heart rate, and comparison of subjects' reactivity scores revealed significant inter-task consistency of reaction.
In an earlier study of blood pressure variation in middle aged parents and their young adult twin offspring, the greater blood pressure variation observed in the parent sample was accounted for in terms of an increasing influence of individual environmental experiences with increasing age and a commensurate reduction in the impact of heredity. In the present study, the sample size was enlarged to provide a more powerful test of these effects. Maximum likelihood model-fitting techniques were applied to blood pressure covariation in balanced pedigrees, consisting of 85 families (40 MZ and 45 DZ twin pairs). As before, our analysis indicated that a developmental effect was a salient factor in the older age group.
Observed increases in phenotypic variance for blood pressure during adulthood are a predictable consequence of an a priori model for developmental change and continuity previously applied to cognitive development. The implications of this model for genetic and environmental covariances depend on the mechanism which maintains developmental continuity. Using data from young adult twins and their parents, it is shown how traditionally estimated genetic and environmental parameters may be reinterpreted in the light of the developmental model. Illustrative data suggest a hypothesis that genetic effects on blood pressure are largely temporally pleiotropic, acting consistently but not cumulatively throughout adulthood, while environmental influences act haphazardly but their effects are transmitted forward with high fidelity.
Fluradoline (150 or 300 mg), a novel tricyclic with both antidepressant and analgesic properties in animals, was compared with aspirin, 650 mg, and placebo when given orally for postoperative orthopedic pain in a double-blind, single-dose, parallel-group study. Analgesic measurements were made by two trained nurse observers using standard verbal rating and visual analogue scales. Aspirin was statistically superior to placebo on all analgesic measures, demonstrating assay sensitivity. Fluradoline, 300 mg, was distinguished from placebo and fluradoline, 150 mg, but not from aspirin, 650 mg. Overall, fluradoline, 300 mg, was equivalent to aspirin, 650 mg. Fluradoline, 300 mg, produced a significant elevation in mood score. Neither aspirin, 650 mg, nor fluradoline caused untoward side effects, but fluradoline, 300 mg, increased blood pressure.
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Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing's syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing's syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland.
Heart rate was monitored while 22 pairs of young male monozygotic and 29 pairs of young male dizygotic twins were exposed to a video game and a mental arithmetic task. The heart rate reactions of the monozygotic twins showed much greater concordance than those of the dizygotic twins. Analysis of the data for the 102 individuals demonstrated reliable inter-task consistency of heart rate reaction. In addition, comparison of the heart rate reactions of ten pairs of monozygotic and ten pairs of dizygotic twins who had been tested more than a year earlier and their present reactivities revealed impressive temporal consistency.
Heart rate plus various metabolic and ventilatory indices were monitored while 18 young males engaged in a mental arithmetic task, structured to include 3 levels of difficulty; easy, difficult and impossible. Measurements were also taken while subjects undertook graded isotonic exercise on a bicycle ergometer; for each subject heart rate was plotted against oxygen consumption over the various exercise loads. Knowing oxygen consumption during the psychological tasks, these regression equations permitted the calculation of expected heart rates during each task condition and thus the computation of 'additional heart rate' as the difference between actual and predicted heart rate values. Additional heart rate was sensitive to variations in difficulty level; the difficult condition elicited reliably more additional heart rate than the easy and impossible conditions. Subjects' performance as well as their perceptions closely reflected the a priori classification of difficulty. Although subjects rated the easy condition as particularly unengaging, the impossible condition attracted relatively high rates of task involvement. It was argued that self-reports of this sort are probably more susceptible than cardiac activity to social demand characteristics.
A computer-operated mental arithmetic task is outlined which presents questions at a level of difficulty continuously determined by subjects' accuracy of response on the previous question. The programme incorporates 5 levels of difficulty, and all questions concern the addition or subtraction of two numbers which vary in digit-span according to the current level of difficulty. Response requirements are manual rather than verbal so that, in addition to monitoring heart rate, subjects' exhaled air may be collected throughout the task in order to determine oxygen consumption.
Although familial aggregation of blood pressure is well documented, few studies have considered the changing contribution of genetic and environmental influences during adulthood. Applying maximum likelihood model fitting to blood pressure covariation in balanced pedigrees including both parents and their young adult twin offsprings (25 MZ, 32 DZ, aged between 16 and 24 years), it is shown that the increased variation in parents is explained by such developmental changes. For DBP, an apparent reduction in heritability from 68% to 38% from young adulthood to middle age results from the increasing impact of individual environmental experience (E1), with little or no influence from shared family environmental (E2). For SBP, shared environmental effects may play a part. Given the relatively small size of the present sample, the conclusions are to be seen as tentative. An augmented family study, incorporating middle aged twins and their young adult offspring, will clarify the causation of these developmental changes.
In a double-blind, single-dose, parallel-group study, ketorolac (5, 10, or 20 mg) was compared with acetaminophen (500 or 1000 mg) when taken by mouth for postoperative orthopedic pain. Analgesic measurements were made by trained nurse observers who used standard verbal rating and visual analog scales. Acetaminophen, 1000 mg, was statistically superior to 500 mg acetaminophen, demonstrating assay sensitivity. Ketorolac, 20 mg, was distinguished from 500 mg acetaminophen, 5 mg ketorolac, and 10 mg ketorolac, but not from 1000 mg acetaminophen. The higher doses of ketorolac induced a longer lasting peak analgesic effect than did acetaminophen, but the magnitude of the peak pain relief was changed little by an increased ketorolac dose. Overall, 10 mg ketorolac appeared equivalent to 1000 mg acetaminophen. Acetaminophen, 500 mg, induced less sedation than the higher doses of ketorolac, but neither drug caused untoward side effects.
The study examined the effect of stress inoculation training on the level of self-reported stress and anxiety, overt signs of distress and the physiological impact of the stress of abseiling. Twenty volunteer subjects were randomly assigned to either a 'no training' control group or a stress inoculation training group, following which both groups of subjects had to complete a test abseil from the roof of a 21.2 m building. Prior to descent, two self-report measures were taken: an intensity score derived from the word or phrase chosen by subjects from the Perceived Stress Index to best describe their feelings and a state anxiety score from Spielberger's State Trait Anxiety Inventory. Overt distress was also evaluated by a 'blind' observer also using the Perceived Stress Index. In addition, heart rate was monitored just prior to and throughout the abseil using a telemetry system. The stress inoculation group showed significantly less self-reported anxiety and stress and less behavioural signs of distress as judged by the observer. However, there were no significant differences between the groups in terms of heart rate. In addition, while self-report and the assessment of the observer were highly inter-correlated, these measures were poorly correlated with heart rate.
The median weight-for-height of young people in Brisbane are below the 'standard' values. In most groups the weight-for-height are symmetrically distributed, suggesting that this is the range of normal variation. Only among girls aged 15-19 years was there an excess of 'obese' subjects. Almost all girls and young women say they want to lose weight, even though many are already well below the 'standard'. This trend is also present, but is less marked, among boys and young men. In these young people the desire for slenderness is causing unhappiness that seems out of proportion to the possible benefits of change. Health professionals should encourage a more balanced attitude to physiological variations in weight-for-height among young people.