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Biomedical subjects

M J Legg

Publications and source records attributed to M J Legg.

9 recordsLinked to original sources
PubMed1992

Does vibration cause poststenotic dilatation in vivo and influence atherogenesis in cholesterol-fed rabbits?

Arterial post-stenotic dilatation (PSD) is a fusiform swelling immediately down-stream to a stenosis. It is characterized by the presence of turbulent blood flow and wall vibration which has been claimed by others to be causal by producing structural weakening. We tested the hypothesis that vibration causes PSD in vivo by attaching electromagnetic and pneumatic vibrators to the aortic wall in chronic rabbits. We also observed whether mechanical vibration of the aorta in vivo influenced the distribution of oil-red-O lesions during one percent dietary cholesterol feeding. Low mass vibration gauges were developed to measure the vibration. Electromechanical vibrators having a ceramic magnet slug within a coil supplied with 50 Hz were glued to the aorta of chronic rabbits and the vibration maintained for an average of 8 weeks. Despite greater amounts of energy imparted to the wall there was no dilatation or difference in oil-red-O staining from the controls. Five weeks vibration at 100 Hz and an amplitude equal to the normal diameter pulse also produced no dilatation. We conclude that vibration does not cause PSD in vivo and suggest that its cause is likely to involve the vascular muscle stimulated by the effect of turbulent flow on the endothelium.

Animals↗
PubMed1983

An improved microindentation technique to measure changes in properties of arterial intima during atherogenesis.

A fully automated instrument was developed that measured the amount and time-course of indentation of arterial intima by a spherical tipped probe 25 micrometers in diameter loaded routinely by forces of 10 microN. The relationship of depth of indentation to time was non-exponential but reached an apparent asymptotic value in about 6 s. Routine indentations were recorded 10 s after loading, the relationship of indentation and force being essentially linear between 0-100 microN. The instrument is an order of magnitude more sensitive than one previously described (Gow and Vaishnav, 1975, J. Appl. Physiol. 38, 344-350) and produces indentations of 1-4 micrometers in the intima of rabbit thoracic aorta with a reproducibility of 1-2%. Preliminary usage of the new microindentor has shown increases in the compliance of the thoracic aorta intima in rabbits during cholesterol feeding.

Animals↗
PubMed1980

A computerized scanner to quantify atherosclerosis.

A method is described for the quantitation of atherosclerotic lesion after excision and staining of the vessel. Essentially the device consists of a microscope with a computer-controlled stage which moves a photographic negative image over a square beam (o.1 mm sides) of light. At each translation-step of the stage a transmittance reading is taken using a photomultiplier tube for detection. The computer stores topographical values (typically around 6,000) and, by setting a threshold, can determine the fractional area of artery which is diseased.

Animals↗
PubMed1979

Staphylococcal nuclease: proposed mechanism of action based on structure of enzyme-thymidine 3',5'-bisphosphate-calcium ion complex at 1.5-A resolution.

The structure of the staphylococcal nuclease (EC 3.1.4.7)-thymidine 3',5'-bisphosphate-Ca(2+) (enzyme-inhibitor) complex has been extended to 1.5-A resolution by using much additional data and a phase refinement scheme based on an electron-density map modification procedure. By correlating this structure with the known properties of the enzyme, a mechanism of action is proposed that involves nucleophilic attack on phosphorus by a water molecule, which is bound to Glu-43, in line with the 5'-CH(2)O(H) leaving group. The carboxylate of Glu-43 promotes this attack by acting as a general base for the abstraction of a proton from the attacking water molecule. Nucleophilic attack is further facilitated by polarization of the phosphodiester by an ionic interaction between a Ca(2+) ion and a phosphate oxygen atom and by four hydrogen bonds to phosphate oxygen atoms from guanidinium ions of Arg-35 and Arg-87. These interactions may also catalyze the reaction by lowering the energy of a trigonal bipyramidal transition state. The hydrolysis of nucleic acid substrate proceeds by cleavage of the 5'-P-O bond to yield a free 5'-hydroxyl group and a terminal, 3'-phosphate monoester group. In the inhibitor complex the only general acid group found in a position to donate a proton to the leaving 5'-oxygen is the guanidinium ion of Arg-87. Alternative proton donors, presently lacking direct structural support, could be the phenolic hydroxyl group of Tyr-113 or a water molecule. The precision and rigidity of the location of the reactants at the active site and the probable dual binding and catalytic roles of the guanidinium ions of Arg-35 and Arg-87 are especially noteworthy.

Binding Sites↗
PubMed1977

The role of arginine residues at enzyme active sites. The interaction between guanidinium ions and p-nitro-phenyl phosphate and its effect on the rate of hydrolysis of the ester.

In alcoholic solutions a relatively strong complex forms among two guanidinium ions and one p-nitrophenylphosphate dianion. The effect of this complex formation on the hydrolysis of the ester is to lower the rate by a factor of 4 in solutions containing 1 M guanidine hydrochloride when compared with solutions of the same total ionic strength containing no guanidinium ion. It is therefore suggested that, for the enzymatically catalyzed hydrolysis of phosphate compounds going via the formation of a metaphosphate intermediate, the role of any arginine residues at the active site is primarily one of binding and positioning the substrate.

Arginine↗