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Biomedical subjects

A D Malcolm

Publications and source records attributed to A D Malcolm.

At least 109 records · Page 6Linked to original sources

Visual complications of mitral leaflet prolapse.

Four young women and six older men with mitral leaflet prolapse presented with visual disturbances consistent with embolism in the ophthalmic or posterior cerebral circulation. Cardiac arrhythmias were common, but these are rarely associated with focal ischaemia. The evidence that mitral leaflet prolapse caused the embolism in these patients is suggestive but not conclusive. Further studies are needed. All patients with acute cerebral or ocular ischaemia should undergo through cardiovascular assessment, which should include routine echocardiography.

Adolescent↗

A study of the quaternary structure of Escherichia coli RNA polymerase using bis(imido esters).

The quaternary structure of Escherichia coli RNA polymerase has been studied by cross-linking with a periodate-cleavable bis(imido ester), N,N'-bis(2-carboximidoethyl)tartaramide dimethyl ester dihydrochloride (CETD). The cross-linked holoenzyme gives a characteristic five-band pattern after electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. The components of each band have been unambiguously identified by (a) molecular-weight measurements, (b) comparisons of cross-linking patterns of holoenzyme and core enzyme, and (c) periodate cleavage of cross-links followed by a second dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The bands are (1) alphabeta and alphabeta', (2) sigmabeta and sigmabeta', (3) alphasigmabeta', (4) betabeta', and (5) sigmabetabeta'. Bands 2 and 4 are the most prominent at low reagent concentrations (up to 2.5 mM) but band 5 becomes the most prominent at higher concentrations. There are no bands corresponding to alphaalpha and alphasigma; a faint band has been tentatively identified as alphabetabeta'. Shorter bis(imido esters) are much less effective cross-linking reagents than CETD and they do not give rise to any other cross-linked species. On the basis of these observations, a model for the subunit arrangement of RNA polymerase is proposed.

Binding Sites↗

Digoxin kinetics during furosemide administration.

The urinary excretion of a 0.75-mg oral dose of digoxin was assessed in 8 healthy men during a control 5-day period and then, after a washout period of at least 2 wk, during a 5-day period when the subjects also took oral furosemide, 40 mg daily. Analysis of the raw data by a paired Student's test and analysis of variance of log-transformed urinary digoxin excretion data revealed no significant difference attributable to the addition of furosemide (F = 1.16; df = 1,21). The treatment by day interaction showed the slopes to be consistent between the two treatments. It seems that in the presence of normal renal function there is no need to alter loading or maintenance doses of digoxin when furosemide is also given. Analysis of variance with log transformation of data is suggested as a practical approach to handling digoxin urinary excretion results when the transformation linearizes the data through examination by the method of orthogonal polynomials.

Adult↗

Haemodynamic effects of salbutamol and nitroprusside after cardiac surgery.

The haemodynamic effects of a continuous intravenous infusion of salbutamol (15 to 30 microgram/min) and nitroprusside (50 to 100 microgram/min) were compared in 9 patients after cardiac surgical operations. The mean falls in left atrial pressure and systemic vascular resistance were similar with the two drugs but salbutamol caused a greater increase in heart rate, maximum acceleration of aortic blood flow, and maximum rate of change of left ventricular power. Because these differences would cause greater myocardial oxygen consumption with salbutamol and because the infusion of salbutamol is less easily controlled, nitroprusside is the preferred drug after cardiac operations.

Adult↗

Rifampicin binding as a probe for subunit interactions in Escherchia coli RNA polymerase.

The binding of the inhibitor rifampicin to RNA polymerase (alpha2betabeta') and its deficient subunit mixtures was investigated. The ability of beta to bind stoichiometric amounts of rifampicin was restored by formation of the alpha2beta subassembly. beta,beta' alpha, betabeta' and alpha2beta' were unable to bind rifampicin. RNA polymerase denatured with 6 M guanidine hydrochloride and dialysed against a renaturing buffer at 0degrees C ("renatured inactive enzyme") bound stoichiometric amounts of rifampicin but had lost the ability of bind dna. compared with native RNA polymerase "renatured inactive" enzyme possessed a markedly different tertiary structure as judged by limited proteolysis.

Binding Sites↗

Structural properties of Escherichia coli RNA polymerase Subunits.

1. The surface of the RNA-polymerase-DNA complex possesses an exposed polypeptide loop. 2. Proteinases with differing specificities (trypsin, chymotrypsin, subtilisin and clostripain) preferentially cleave the exposed region. 3. The cleaved polypeptide is reassembled into RNA polymerase by renaturation from a solvent which promotes a random coil conformation. 4. Isolated beta subunit has a proteolytically resistant nucleus of approximately 70000 molecular weight. This resistant polypeptide may be generated by trypsin, chymotrypsin, subiilisin or clostripain. 5. Isolated alpha subunits are comparatively resistant to proteolysis. 6. Although of similar molecular weights beta and beta' appear to have unrelated primary sequences and markedly different conformations in free solution. 7. Digestion of the beta subunit may be blocked by formation of the alpha2beta subassembly. 8. Evidence is presented suggesting that beta' in the intact enzyme (alpha2beta beta') possesses the exposed polypeptide loop.

DNA↗

Clinical features and investigative findings in presence of mitral leaflet prolapse. Study of 85 consecutive patients.

In a 14-month period mitral leaflet prolapse was diagnosed in 85 patients by echocardiography or cineangiography. Chest pain alone was the presenting complaint in 30 patients and linked with palpitation, dyspnoea, or syncope in 9. Eleven presented with major neurological disturbances (9 had transient ischaemic attacks), 10 with palpitation, 4 with undue and persistent fatigue, 2 with dyspnoea, and 2 with dizziness. Seventeen were referred not because of symptoms but because of clicks and murmurs. Overall, chest pain affected 61 patients and unless associated with coronary artery disease was not anginal. Palpitation was admitted by 42 patients; dizziness, lightheadedness, or paraesthesiae by 15, and syncope by 12. Systolic auscultatory abnormalities were noted in 69: 25 had single clicks, 3 had multiple clicks, 19 had both click(s) and murmur, and 22 had a murmur alone. Electrocardiography revealed ST segments flat for greater than 0-10 s in 21, prolonged QTc in 18, and T wave flattening or inversion in inferior limb and lateral chest leads in 14. The exercise stress test was abnormal in 13 of 27 patients. Mitral valve echograms showed definite mitral leaflet prolapse in 61, 'possible' prolapse in 14, and were normal in 8 patients with angiographic proof of mitral leaflet prolapse. Cardiac catheterization with left ventriculography showed prolapse of posterior mitral leaflet in 36, of both leaflets in 2, and left ventricular wall motion abnormalities in 16 cases. Selective coronary arteriography in 31 cases showed major vessel narrowing of larger than or equal to 80 per cent lumen diameter in 4, all with angina. This consecutive series indicates that the physical event of mitral leaflet prolapse is more common than hitherto appreciated, is priminently associated with non-anginal chest pain, palpitation, and neurological disturbances, and in 90 per cent of cases could be shown echocardiographically.

Adolescent↗

Malfunction of tricuspid valve prosthesis shown by isotope angiocardiography.

Isotope angiocardiography established prosthetic tricuspid valve obstruction in a patient 6 years after triple valve replacement. Thrombus formation is a common complication of prosthetic cardiac valves, particularly in the tricuspid position where engagement of cage with myocardium is an additional potentially obstructive hazard. Comparison is made between the information yield of the isotope investigation and cardiac catheterization with contrast cineangiography. It is suggested that the isotope technique can noninvasively provide valuable anatomic and functional data, particularly where the right side of the heart is to be examined.

Adult↗