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Biomedical subjects

B F Johnson

Publications and source records attributed to B F Johnson.

At least 127 records · Page 7Linked to original sources

The nature of the beta-adrenoreceptor controlling plasma renin activity in man.

1. Seven healthy sodium-replete male volunteer subjects remained supine during and for at least 1 h before the study. Heart rate and blood pressure were recorded continuously, and peripheral venous blood samples were taken every 15 min for determinations of plasma renin activity. 2. All subjects were studied twice: after 3 days of oral practolol (100 mg, three times daily) and after a similar period on placebo. Each study consisted of an intravenous infusion of isoprenaline in graded doses (0-20 microng/min in the placebo phase; 0-16 microng/min in the practolol phase), followed after rest for 2 h by an intravenous infusion of salbutamol (0-20 microng/min after placebo; 0-80 microng/min after practolol). 3. Both salbutamol and isoprenaline produced dose-related increases in systolic blood pressure, heart rate and plasma renin activity and decreases in diastolic pressure. 4. The increases in heart rate and plasma renin activity induced by either agonist were competitively blocked by practolol, as was the fall in diastolic blood pressure induced by isoprenaline; the salbutamol-induced fall of diastolic blood pressure was unaffected by practolol. 5. Comparison of dose ratio--1 estimates confirmed that practolol selectively blocked increases in heart rate and plasma renin activity due to salbutamol; no selective blockade against isoprenaline-induced changes was shown. 6. Selective blockade of salbutamol-induced changes indicate that a beta1-adrenoreceptor mediates changes in plasma renin activity.

Albuterol↗

The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs.

1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg digoxin were used in a randomized sequence allowing at least ten days between each dose. 3 Digoxin reduced the amount of acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin. 5 These results suggest that there is little or no increased risk of cardiotoxicity during periods of transient increase in plasma levels of digoxin.

Animals↗

Comparative anti-hypertensive effects of labetalol and the combination of oxprenolol and phentolamine.

1 The interaction of phentolamine with the beta-adrenoreceptor-blocking drug, oxprenolol, was studied in a controlled trial. 2 The combination was generally well tolerated. 3 Oxprenolol alone produced modest but significant reductions in supine, standing and post-exercise blood pressures. Small reductions were observed only with sustained phentolamine administration. 4 The combined effect of the two drugs seemed to be addictive only at the lower level of oxyprenolol dosage. 5 Labetalol produced significantly greater reductions in supine and standing blood pressure than combined oxprenolol-phentolamine. At a daily dose of 400 mg, postural hypotension was not observed, although transient symptoms were frequent.

Adult↗

The anti-hypertensive efficacy of combined alpha- and beta-adrenoreceptor blockade with phentolamine-oxprenolol or with labetalol (AH 5158).

1. The interaction of phentolamine with the beta-receptor blocker oxprenolol was studied in a controlled trial. 2. The combination was generally well tolerated. 3. Oxprenolol alone produced modest but significant reductions in supine, standing and post-exercise blood pressures. Small reductions were seen only with sustained phentolamine administration. 4. The combined effect of the two drugs appeared to be additive only at the lower doses of oxprenolol. 5. Labetalol produced significantly greater reductions in supine and standing blood pressure than combined oxprenolol-phentolamine. At a daily dose of 400 mg, postural hypotension was not seen, though transient symptoms were frequent.

Adult↗

Mapping of sul, the suppressor of lon in Escherichia coli.

The suppressor sul, which is allele specific for the ultraviolet sensitivity gene lon, has been mapped by conjugation and transductional crosses in Escherichia coli K-12 and B/r. Previously, sul was reported to lie in the azi region of the Escherichia coli chromosome. Evidence is presented which positions sul close to and clockwise of fabA on the Escherichia coli map. Cotransductional frequencies of 31.3% were obtained between sul and pyrD, and frequencies of 82% were obtained between sul and fabA. Also, the mucoid phenotype of K-12 lon strains grown on minimal glucose agar plates at 37 C was not significantly effected in sul derivatives. No differences between the sul of Escherichia coli B/r and that of K-12 derivatives with regard to map location or effect on mucoid production were observed.

Chromosome Mapping↗

Maximal intestinal absorption of digoxin, and its relation to steady state plasma concentration.

In a group of 8 volunteers, peak plasma digoxin concentrations and areas under 80-hour plasma concentration curves were significantly greater after 1 mg digoxin in paediatric elixir than after 4 0,25 mg tablets. Mean cumulative urinary excretion of digoxin over 12 days was 46.4 per cent after tablets, 53.6 per cent after elixir, and 70.8 per cent after intravenous injection. Mean percentage absorption was estimated to be 63 per cent from tablets and 75 per cent from elixir, but considerable between-subject variation was noted. Individual estimates of percentage absorption were significantly correlated with plasma concentrations in the steady state. Computer programmes to relate steady state plasma concentration to oral digoxin dosage take no account of absorptive capacity, are limited to gross approximations, and cannot replace determination of plasma concentration to assess the degree of digitalization.

Adult↗

A new method of obtaining zygotes in Saccharomyces cerevisiae.

Experiments leading to a simple method of mass zygote formation in Saccharomyces cerevisiae are described. This method ordinarily requires only about 3 h of incubation, and consistently yielded 55-65% zygotes in seven different crosses among six different strains. Matings involving one strain required about 4 h of incubation but otherwise the results were comparable.

Aerobiosis↗

A kinetic analysis of spontaneous rho- mutations in yeast.

Spontaneous mutation to the petite state at the level of the individual cell was studied in a haploid strain of yeast by the technique of pedigree analysis. Results indicated that (1) the mutability of rho+ cells within a population in log phase is variable; (2) rho+ mitotic buds are, on the average, about 50% more mutable than the rho+ cells from which they arose; (3) the mutability of a rho+ cell tends to decrease as it produces consecutive buds: (4) the probability that a mother cell will become rho- at or immediately subsequent to cell division is, on the average, one third the probability that its bud will be rho-; (5) most, if not all spontaneous rho- mutant cells contain mitochondrial DNA as judged from suppressiveness measurements. The data indicate that the spontaneous production of a mutant cell is a multi-step process. Neither a replicative advantage of defective mitochondrial DNA nor the existence of a "master" mitochondrial genome provides a satisfactory explanation of the process. Either selective dispensation of defective mitochondria to the bud at cytokinesis or normal retention by the mother cell of factors influencing the amplification or rate of induction of defective mitochondrial DNA could be involved.

Extrachromosomal Inheritance↗

Computer-based hypertension clinic records: a co-operative study.

A computer-based medical record system has been developed to help with research into hypertension and the management of patients with hypertension. Standard medical records are replaced by data collection forms and case notes printed by the computer. A computer-generated document for recording information at follow-up visits contains an up-to-date summary of the important clinical features with warnings of risk factors. A blood-pressure graph and a letter for the general practitioner are produced on request. The system has been used in three clinics for two years and is being tested in general practice. Information on 900 newly-referred patients has been recorded and at present data on 30 to 40 new patients and 160 follow-up visits are added each month.

Blood Pressure↗

Biological availability of digoxin from Lanoxin produced in the United Kingdom.

Though established quality control standards were maintained, the bioavailability of digoxin from Lanoxin tablets produced in the United Kingdom fell in 1969, and was restored in 1972. After 1.5 mg doses of representative batches, tablets made between 1969 and 1972 produced mean values for area under the 50 hours plasma concentration/time curve of 36.6 ng/ml/hr and four-day urinary excretion of 340 mug, compared with respective values of 67.5 ng/ml/hr and 696 mug for recently produced tablets.After 0.5 mg doses of four recent independently produced batches of Lanoxin tablets no significant between-batch difference was found for area under the plasma concentration/time curve or cumulative urinary excretion.Absorption of digoxin from batches of Lanoxin manufactured since May 1972 is uniform and consistent. Content uniformity is an inadequate measure of tablet quality, and consistent digoxin bioavailability cannot be ensured by existing regulations.

Biopharmaceutics↗