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Biomedical subjects

R S Lees

Publications and source records attributed to R S Lees.

At least 109 records · Page 6Linked to original sources
PubMed1975

Effects of intravenous hyperalimentation of plasma-lipoproteins in severe familial hypercholesterolaemia.

The plasma-lipoprotein response to intravenous hyperalimentation was studied in three patients with severe familial hypercholesterolaemia. Hyperalimentation substantially lowered plasma concentrations of cholesterol, low-density lipoproteins (L.D.L.P.), and high-density lipoproteins. The chemical composition of L.D.L.P. did not change. Triglyceride levels increased slightly in two patients and decreased in the third. Turnover of radiolabelled L.D.L.P. was disturbed as L.D.L.P. concentration fell but then returned to normal. The mechanism by which intravenous hyperalimentation rapidly lowers plasma-cholesterol in severe hypercholesterolaemia is unknown.

Adolescent↗
PubMed1975

Apoprotein stability and lipid-protein interactions in human plasma high density lipoproteins.

Temperature-dependent conformational changes of the principal apoprotein of human plasma high density lipoprotein (HDL), apoA-I, have been studied in the isolated apoprotein, in complexes of apoprotein with phospholipid, and in intact HDL. Differential scanning calorimetry shows that in solution apoA-I undergoes a reversible, two-state thermal denaturation (midpoint temperature 54 degrees). The enthalpy (2.4 cal/g)(10.0 J/g) and specific heat change (0.08 cal/degrees C per g)(0.33 J/degrees C per g) associated with the denaturation were used to calculate the free energy difference (deltaG) between native and unfolded apoA-I at 37 degrees. DeltaG (2.4 kcal/mol)(10.0 kJ/mol) is less than that of other globular proteins (typically 8-14 kcal/mol)(33-59 kJ/mol), indicating that at 37 degrees native apoA-I has a loosely folded conformation. Turbidity studies show that apoA-I is able to solubilize phospholipid in its native but not in its denatured form. Mixtures of apo-HDL (the total apoprotein of HDL) or apoA-I with dimyristoyl lecithin show a thermal transition at about 85 degrees not present in the lecithin or the apoprotein alone, which indicates that the native conformation of the apoprotein is stabilized by phospholipid. Scanning calorimetry of intact HDL shows a high-temperature endotherm associated with disruption of the HDL particle, suggesting that in HDL the conformation of apoA-I is also stabilized by interaction with lipid. The loosely folded conformation of native, uncomplexed apoA-I may be especially adapted to the binding of lipid, since this process may involve both hydrophobic sites on the surface of the protein and concealed apolar amino acid residues that are exposed by a cooperative, low energy unfolding process.

Apoproteins↗
PubMed1974

Assay of total plasma apolipoprotein B concentration in human subjects.

We have developed a double antibody radioimmunoassay (RIA) for human apolipoprotein B (ApoB). The assay measures not only the ApoB content of beta-lipoproteins (low density lipoproteins [LDL]) but also that contained in the other lipoproteins in plasma. Purified lymph and plasma chylomicrons and plasma very low density lipoproteins (VLDL) produced displacement curves in the assay system which paralleled those produced by pure LDL. Thus, the ApoB found in chylomicrons, VLDL, and LDL were immunologically identical. ApoB accounted for about 25 and 35%, respectively, of the total protein of chylomicrons and VLDL by RIA. VLDL and LDL preparations from normal and hyperlipoproteinemic subjects also produced parallel displacement curves, suggesting that the ApoB of normal and hyperlipoproteinemic subjects were immunologically identical. High density lipoproteins and abetalipoproteinemic plasma displaced no counts, nor did the sera of several animal species produce any useful displacement curves in this system. The fasting total plasma ApoB concentration of normal subjects was 83+/-16 mg/dl (mean+/-SD). ApoB levels were high in Type II (162+/-16), and less so in Type IV (112+/-24) and Type V (105+/-17).When plasma ApoB concentration in Type IV patients was graphed against plasma glycerides, two subpopulations, which may represent different genetic or biochemical subgroups, were apparent.ApoB concentration in individuals on constant diet and drug regimen was stable over weeks to months. Greater than 90% of ApoB of normal and Type II subjects was in the d > 1.006 plasma fraction. By contrast, only 50-80% of ApoB was in the d > 1.006 fraction in Types IV and V. Thus, hypertriglyceridemia was associated primarily with a redistribution of ApoB to the lighter density fractions; by contrast, in hypercholesterolemia absolute ApoB concentration was markedly increased.

Apoproteins↗
PubMed1972

Metabolic relationships among the plasma lipoproteins. Reciprocal changes in the concentrations of very low and low density lipoproteins in man.

The changes in other plasma lipoproteins which accompany alterations in very low density lipoproteins (VLDL) were studied in 31 normal and hyperlipidemic men and women who underwent weight reduction, carbohydrate induction, or clofibrate treatment. Plasma lipids and individual lipoprotein cholesterol concentrations were measured serially during control and treatment periods. Low density lipoprotein (LDL) protein was determined by radial immunodiffusion. Oppositely directed changes in VLDL and LDL were found with each of the three metabolic perturbations. Changes in high density lipoprotein (HDL) cholesterol generally paralleled those in LDL but were less consistent. Two patients with type III hyperlipoproteinemia failed to demonstrate reciprocal increases in LDL despite more than 40% reduction in plasma glycerides or VLDL with weight reduction or clofibrate therapy. After clofibrate therapy, LDL increased in proportion to the absolute decrease in VLDL cholesterol during treatment. LDL protein changed relatively less than did LDL cholesterol. The mechanism for the interdependency of plasma VLDL and LDL concentrations over the long term is not known and may be the result of altered rates of interconversion of these lipoproteins, or to feedback inhibition by VLDL of LDL production and release.

Adolescent↗
PubMed1972

Ultrafiltration of lipoproteins through a synthetic membrane. Implications for the filtration theory of atherogenesis.

To investigate the interaction of lipoproteins with semipermeable membranes, solutions of low density lipoproteins (LDL), very low density lipoproteins (VLDL), mixtures of the two, and diluted, normal, and hyperlipidemic serum were ultrafiltered through a synthetic membrane (500 A nominal pore diameter) using a stirred laboratory ultrafiltration cell. The pressure dependence of ultrafiltrate flux showed that a concentrated layer of lipoproteins was built up at the membrane surface (concentration polarization) and that VLDL was more subject to polarization than LDL. This phenomenon controlled the observed lipoprotein transport behavior. Whereas true membrane rejection (the fraction of the solute on the membrane surface which does not pass through the membrane) was greater than 0.95 for both LDL and VLDL, observed solute rejection varied from nearly 0 to 1.0, depending upon experimental conditions. If concentration polarization occurs in the arterial system, these results suggest that lipoprotein transport into arterial wall may be influenced not only by arterial blood pressure and the properties of the arterial wall, but also by local hemodynamic conditions and by the relative as well as absolute magnitudes of LDL and VLDL concentration.

Arteriosclerosis↗
PubMed1970

Immunoassay of plasma low-density lipoproteins.

An immunoassay was developed for determining the concentration of the protein moiety of the low-density lipoproteins of human plasma. The concentration of this protein in the plasma was variable; it was higher than normal on the average in patients with familial hyperbetalipoproteinemia (type II) and endogenous hyperlipemia (type IV) and lower than normal in patients with fat-induced (type I) and mixed (type V) hyperlipemia. Patients with endogenous hyperlipemia were separable by the immunoassay into those with normal and those with supernormal low-density lipoprotein protein concentration.

Adult↗
PubMed1970

Phonoangiography: a new noninvasive diagnostic method for studying arterial disease.

Phonoangiography, the quantitative analysis of sounds produced by blood flow, has been used to investigate local fluid motion in arteries narrowed by atherosclerosis. The sound spectra measured in vivo were found to be identical to those obtained in laboratory investigations of turbulent pipe flow. A theoretical model is proposed which: (a) quantitatively relates the in vivo and in vitro data, and (b) allows estimation of the clinically important parameters of arterial diameter, flow velocity, local turbulence intensity, and wall pressure fluctuations. The results of calculations using data from human subjects agree with known arterial diameters and blood flow velocities.

Arteriosclerosis↗