Search PubMed⌕ Search

Biomedical subjects

D J Rowlands

Publications and source records attributed to D J Rowlands.

At least 109 records · Page 6Linked to original sources

Biochemical mapping of the foot-and-mouth disease virus genome.

Four primary cleavage products, mol. wt. 10(3) X 100, 88, 56 and 52 (P100, P85, P56 and P52 respectively) are present in BHK 2I cells infected with foot-and-mouth disease virus (FMDV). However, no precursor polyprotein equal to the sum of their mol. wt. was detected, even when amino acid analogues and proteolytic enzyme inhibitors were used. Three of the primary products were shown to cleave to smaller polypeptides, including the capsid polypeptides of the virus. Polypeptide P88, which was shown to be the precursor of the capsid polypeptides, is translated from the gene located at the 5'-end of the genome. The order of the structural polypeptides, determined by the use of emetine, is VP4, VP2, VP3, VP1. The order of the remaining primary cleavage products is P52, P56 and P100. P56 is a stable product, identical with the virus infection associated (VIA) antigen found in virus harvests. The function of the other two products P52 and P100 is not known. EMDV thus differs from other picornaviruses in that there is an extra primary cleavage product, apparently resulting from translation of more of the virus genome.

Aphthovirus↗

Physicochemical characterization of two serologically unrelated equine rhinoviruses.

The physicochemical properties of two serologically distinct equine rhinoviruses have been examined. Each virus sedimented at approximately 160S but co-centrifugation of the two viruses in a sucrose gradient revealed a small difference in their sedimentation coefficients. The two viruses also have different buoyant densities in cesium chloride. The equine rhinovirus type 1 equilibrated as a sharp peak at 1.45 g/ml whereas the type 2 virus equilibrated as a heterogeneous band with a peak at 1.44 g/ml but ranging in density from 1.41 to 1.45 g/ml. The relative sedimentation coefficients of the two virus RNAs were 35S for rhinovirus 1 and 37S for rhinovirus 2. A limited number of base composition analyses also showed differences between the two virus RNAs. The polypeptide profile of each serotype in polyacrylamide gels was generally similar to those of other picornaviruses but the two serotypes could be distinguished readily from each other.

Antigens, Viral↗

Characterization of the minor polypeptides in the foot-and-mouth disease particle.

In addition to the four major polypeptides VP1 and VP4, foot-and-mouth disease virus particles contain two minor polypeptides, mol. wt. 40 X 10(3) (P40) and 52 X 10(3) (P52). Extensive purification procedures failed to remove these minor polypeptides from the virus particles. Polypeptide P40 co-electrophoresed in SDS-polyacrylamide gels with VP0, the probable precursor of VP2 and VP4 and was inaccessible to iodination in situ. The second minor polypeptide, P52, co-electrophoresed with the virus infection associated (VIA) antigen found in large amounts in harvests of the virus grown in BHK 21 cells. Polypeptide P52 was shown to be located near the surface of the virus particle by iodination experiments and by its removal on incubating the particles with trypsin or chymotrypsin. Pactamycin mapping showed that this polypeptide was not a precursor of the structural polypeptides. About one copy of P52 and 4 copies of P40 were found in the virus particles sedimenting at 146S. However a larger number of copies was found in those virus particles sedimenting faster than the 146S peak.

Animals↗

Human pharmacokinetic and pharmacodynamic studies on the atenolo (ICI 66,082), a new cardioselective beta-adrenoceptor blocking drug.

The beta-adrenoceptor blocking effects of orally administered atenolol on tachycardia induced by intravenous isoprenaline or by exercise have been studied in normal volunteers, and compared with the effects of similar doses of propranolol. The blood levels of atenolol at various times after oral administration were determined by g.l.c. and correlated with the degree of inhibition of tachycardia. Atenolol was shown to be a beta-adrenoceptor blocker in man, as in animals, in that it antagonized the chronotropic effects of isoprenaline and of exercise. The inhibitory effect of atenolol on exercise-induced tachycardia was evident at a concentration in blood of 0.2 mug/ml and virtually complete at 0.5 mug/ml. Higher concentrations than this did not produce significantly greater blockade. The effects of atenolol on exercise-induced tachycardia were similar to those of propranolol but it was less effective in blocking the rise in heart rate and fall in diastolic blood-pressure induced by intravenous infusion of isoprenaline. This separation of effects is considered characteristic of drugs causing preferential blockade of cardiac beta-adrenoreceptors. The half-life of atenolol in blood was calculated to ablut 9 hours.

Adult↗

Test of reliability of echocardiographic estimation of left ventricular dimensions and volumes.

This test is based on the incompressibility of myocardium, which dictates that left ventricular wall volume remains constant throughout the cardiac cycle. The volumes occupied by the left ventricular cavity, by ventricular wall plus cavity, and hence by ventricular wall alone were estimated, both at end-systole and at end-diastole, from ecocardiographic measurements of cavity transverse dimension and wall thickness. Wall volumes were determined by assuming an ellipsoid shape (the major axis being predicted from aggression equations relating angiocardiographic and echocardiographic cavity dimensions) and also by the cube method. A discrepancy between systolic and diastolic wall volume estimates indicates either that the measurements of ventricular dimensions were unreliable or that the assumptions of ventricular geometry involved in the volume calculations were incorrect. Studies were made on 60 subjects. Using the ellipsoid formula, values for wall volume ranged from 66 to 719 ml; systolic and diastolic wall volumes correlated closely (r = 0-96, mean difference = 6-8 +/- 0-9 (SEM) %) supporting the reliability of the echocardiographic dimensions and estimates of cavity and wall volume. In the 12 patients with very large end-diastolic cavity transverse dimensions (6-5 to 8-6 cm) however, correlation was less good (r - 0-81, mean difference = 14-3 +/- 2-3 (SEM) 5). Using the cube method, which does not allow for the changing relation between minor and major cavity axes with increasing cavity size, wall volumes were greater (76 to 986 ml) but correlation was similar (r = 0-94, mean difference = 7-1 +/- 0-9 (SEM)%). Having established that it is possible to obtain close agreement between wall volumes determined at different points in the cardiac cycle, this test can be used to assess the reliability of echocardiographic left ventricular dimensions and volume estimates in individual subjects.

Adolescent↗

Evaluation of a proposed index of myocardial blood flow in dogs.

An index of myocardial blood flow developed from studies with a computer and a mechanical circulatory model has been investigated in 18 dogs. An intravenous injection of 131I is used with external scintillation detection over the left ventricle and the lung. The index is given by the ratio of the half time of the downslope of the curve recorded from the left ventricle to that of the curve recorded from the lung. This index has been compared with that suggested by Mena et al in which the left ventricular half time is compared with the half time of the brain curve. The effect on these indices and on the clearance of 133Xe of clamping the anterior descending branch of the left coronary artery has been observed. Statistically significant differences in both indices and in Xenon clearance were seen to be induced by coronary artery clamping but there was overlap between the clamped and unclamped values. The method used for coronary clamping also affected the results.

Animals↗

A computer model and a mechanical model of the circulation and their use in the evaluation of indices of myocardial blood flow.

Computer and mechanical models of the circulation have been made to study isotopic techniques of determining indices of myocardial blood flow. Parameters in the program and dimensions in the mechanical model have been scaled to represent the human circulation. Single rapid injections of 131I labelled human serum albumen were given into the venous line of the mechanical model and records obtained from collimated scintillation detectors positioned over the heart, lung and brain. Similar injections and recordings were simulated in the computer model. Two indices of myocardial flow have been studied. The first, described by Mena et al. is the ratio of the half time of the downslope of the left ventricular curve to the half time of the downslope of the brain curve. This index distinguished myocardial flows of 0,5% and 10% of total cardiac output but was also affected by changes in cerebral flow. A new index is proposed in which the half time of the left ventricular curve downslope is related to the half time of the downslope of the lung curve. This index can distinguish myocardial flows of 0,5% and 10% total flow but is not affected by changes in cerebral flow.

Blood Circulation↗

A comparative chemical and serological study of the full and empty particles of foot-and mouth disease virus.

The chemical and serological properties of the full, naturally occurring empty and artificially produced empty particles of foot-and-mouth disease virus, serotype A(subtype 10, strain 16) have been studies. The full 146S particles comprised the virus RNA, three polypeptides (VP1 to VP3) mol. wt. about 30 X 10-3, one polypeptide (VP4) mol. wt. about 13-5 X 10-3, and a small amount of a polypeptide (VPo) mol. wt. about 43 X 10-3. The naturally occurring 75S empty particles contained no RNA and much less VP1 and VP4 than were found in the fall particles. However they contained a much greater proportion of VPo than the full particles. Dialysis of purified full particles against tris-EDTA, pH 7-6, produced artificial 75S empty particles which contained only a small amount of RNA and no VP4; otherwise the polypeptide composition was similar to that of the full particles. Immunological and serological tests showed that the full particles were antigenically similar to the naturally occurring empty particles but distinct from the artificial empty particles. The latter particles, however, had serological properties similar to those of the 12S protein subunit of the virus. Both the full and naturally occurring empty particles attached efficiently to susceptible cells, whereas the artificial empty particles attached only to a limited extent. The results are related to the function of the individual polypeptides of the virus particle and compared with published work on other picornaviruses.

Animals↗

A high density component in several vertebrate enteroviruses.

In addition to the major infective component, which bands at a density of 1:34 g/ml in caesium chloride ("light component"), a component with a density of 1:44 g/ml ("heavy component") has been found in harvests of poliovirus (type I), Coxsackie B5 virus, a bovine enterovirus (VG-5-27) and swine vesicular disease virus (SVDV). With SVDV about 98% of the infectivity equilibrated at 1 . 34 g/ml but approx. 2% was present as a peak at 1 . 44 g/ml. The morphology of the two forms was similar but the heavy component had a smaller diameter (28 nm) than the light component (30 nm). No inter-conversion of the two forms was observed on re-cycling in fresh caesium chloride gradients and the two components had the same proportions of RNA and protein and the same polypeptide composition. Each component gave a similar proportion of the light and heavy forms on replication, but the light component had a specific infectivity about fourfold higher than that of the heavy component and was also much more efficient in eliciting the formation of neutralizing antibodies in guinea pigs. Although these results suggest that the two particles are alternative stable configurations of the virus, iodination failed to reveal any differences in the extent or pattern of labelling of the polypeptides in the two forms.

Capsid↗