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Biomedical subjects

R L Hamilton

Publications and source records attributed to R L Hamilton.

At least 127 records · Page 7Linked to original sources
PubMed1983

Lecithin:cholesterol acyltransferase-mediated modification of discoidal peripheral lymph high density lipoproteins: possible mechanism of formation of cholesterol-induced high density lipoproteins (HDLc) in cholesterol-fed dogs.

Peripheral lymph high density lipoproteins (HDL) of the cholesterol-fed dog differ in a number of characteristics from plasma HDL of the same animal. Their high content of free cholesterol, phospholipid, apoprotein E, and apoprotein A-IV, their greater heterogeneity in size, and the presence of many discoidal particles suggest that a portion of lymph HDL is assembled within the interstitial fluid. The present experiments demonstrate that the endogenous lecithin:cholesterol acyltransferase (LCAT) activity of whole peripheral lymph of the cholesterol-fed dog is far less (less than 1%) than that found in the plasma of the same animal (0.3 nmol/hr per ml versus 40.6 nmol/hr per ml). Addition of partially purified LCAT to whole lymph induced many changes in the chemical composition of peripheral lymph lipoproteins. After incubation with LCAT, the free cholesterol and phospholipid contents of lymph HDL decreased, from 17% to 12% and from 46% to 33%, respectively, whereas cholesteryl ester content increased from 7% to 13%. These changes were accompanied by a mass transfer of apoprotein E and cholesterol to the p less than 1.05 g/ml fraction, the complete disappearance of the discoidal particles, and a decrease in size heterogeneity of lymph HDL. These results suggest that, in the cholesterol-fed dog, cholesterol efflux into the interstitial spaces may occur in the absence of significant LCAT activity. Furthermore, our studies suggest that the subsequent reaction between lymph HDL and LCAT within the vascular compartment leads to the generation of apoprotein E and cholesteryl ester-rich cholesterol-induced HDL.

Animals↗
PubMed1983

Secretion of lipoproteins from the liver of normal and Watanabe heritable hyperlipidemic rabbits.

We compared the rate of accumulation of lipoproteins in perfusates of isolated livers from normal New Zealand White rabbits and Watanabe heritable hyperlipidemic (WHHL) rabbits, in which a gene mutation has produced a virtually complete deficiency of low density lipoprotein (LDL) receptors. The rate of accumulation of apolipoprotein B-100 did not differ in perfusates of livers from normal and mutant animals and little or no apolipoprotein B-48 was detected. In both groups, virtually all apolipoprotein B accumulated in very low density lipoprotein (VLDL). Experiments in which [3H]lysine was added to the perfusates showed that the apolipoprotein B that accumulated in VLDL was newly synthesized by the liver whereas the small amount of apolipoprotein B found in lipoproteins of higher density appeared to be washed out of extravascular spaces during perfusion. Perfusate VLDL from both groups contained more triglycerides and less cholesteryl esters than their counterparts from blood plasma. As compared with perfusate VLDL from normal livers, those from livers of WHHL rabbits were enriched in cholesteryl esters. Experiments in which Triton WR-1339 was injected into the blood of intact rabbits confirmed the observations with perfused livers. Previous studies have shown that the extent to which VLDL is converted to LDL is increased several-fold in WHHL rabbits. Taken together with our present results, which fail to provide evidence for increased secretion of apolipoprotein B or de novo secretion of lipoproteins other than VLDL that contain apolipoprotein B, it can be concluded that overproduction of LDL in rabbits lacking LDL receptors is solely the result of altered metabolism of VLDL.

Animals↗
PubMed1983

Lung tumor-associated antigens: thin layer immunoassay.

Six hundred eighty-four rapid, sensitive thin layer immunoassays (TLI) were performed using an adapted visualization of condensation on plastic surface (VCS) method, for testing squamous cell and adenocarcinoma monospecific (TAA) and monoclonal antibody derived lung tumor-associated antigens (TAA epitopes) against small amounts of coded human test sera. The TAA epitopes selected for VCS-TLI were more specific, but both forms of TAA gave positive tests in 94% of lung cancer test sera of the appropriate histological types. The four antigens (adeno TAA and TAA epitope, squamous TAA and TAA epitope) did not react in VCS-TLI with coded sera from preselected normal individuals with known medical histories. With both TAA epitopes, 5% of non-lung cancer test sera were positive. There were indications that such tests may be useful in aiding pathological evaluations and in detecting precancerous conditions in patients with asbestosis. Cross-reacting (with other non-lung cancers) and specific peptide sequences of TAA were indicated in the comparative tests with the corresponding TAA epitopes, suggesting the tests for probing and analyzing portions of the antigens. Of immediate use is VCS-TLI for monitoring patients on specific active TAA immunotherapy.

Adult↗
PubMed1982

Characterization of unusual intermediate density lipoproteins.

We report on the physicochemical properties of unusual lipoproteins isolated from both lymph and blood of ruminating cattle. The densities of most of these particles fall within the range between 1.006 and 1.020 g/ml, although densities of 0.97-0.99 g/ml are calculated from chemical composition, assuming a liquid core. The triglycerides of these particles have a high content of saturated fatty acids. The major apoprotein has a mobility on polyacrylamide-SDS gels consistent with a molecular weight of 40,000. The negatively-stained particles appear flattened and asymmetric in electron micrographs. The particles are very large, with molecular weights in the 20 to 250 million dalton range, and they scatter light strongly. The hydrodynamic frictional ratio is about 1.4, consistent with oblate ellipsoids with axial ratios of about 8 to 1. The flat appearance, asymmetric shape, and anomalous densities of the particles would be explained if these lipoproteins consisted of a core of crystallized triglycerides encapsulated within a phospholipid monolayer. Crystallization of the saturated triglycerides could occur during routine lipoprotein isolation, in which temperatures much lower than the melting points of their core lipids are employed. when protocols are done entirely at 37 degrees C, the unusual structures are not observed in the intermediate density class. Although the saturated fats in these bovine lipoproteins are derived from ruminal fermentation, we feel that any triglyceride-rich lipoprotein highly enriched in saturated fats will behave similarly if isolation temperatures are well below the melting points of the core lipids.

Animals↗
PubMed1982

Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.

Triglyceride-rich very low density lipoproteins (VLDL) are the major lipoprotein in perfusates of normal guinea pig livers. Their component apoprotein B is mainly B-100 together with some B-95. This apoprotein is actively synthesized, as are C apoproteins and small amounts of apoprotein E. Only trace amounts of intermediate density lipoproteins (IDL, 1.015 < d < 1.05 g/ml) are found in perfusates, but appreciable amounts of low density lipoproteins (LDL, 1.05 < d < 1.10 g/ml) accumulate. These LDL are not newly synthesized, but rather appear to be gradually washed out of the liver. High density lipoproteins (HDL, 1.10 < d < 1.21 g/ml) both discoidal and spheroidal, also accumulate, which contain newly synthesized apoproteins A-I, E and C. Fatty livers of guinea pigs fed cholesterol secrete less VLDL and more IDL than normals, but the combined amount of protein is unchanged. These lipoproteins contain newly synthesized apoprotein B, are enriched in cholesteryl esters and newly synthesized apoprotein E, and have reduced electrophoretic mobilities, making them resemble remnants. Large amounts of LDL also accumulate in perfusates of livers from cholesterol-fed animals, much of which does not appear to be newly synthesized, as judged from single pass perfusions. However, the LDL fraction is complex and includes particles that contain newly synthesized apoprotein B. Thus, these livers appear to secrete a spectrum of cholesteryl ester-rich particles, containing newly synthesized apoproteins B and E that span the density range of VLDL, IDL, and LDL. Livers of cholesterol-fed guinea pigs secrete large amounts of discoidal HDL with a free cholesterol-phospholipid molar ratio of 2:1. Accumulation of protein (almost entirely newly synthesized apoprotein E) in HDL is increased 25-fold over that in perfusates from normal guinea pig livers.-Guo, L.S.S., R.L. Hamilton, R. Ostwald, and R. J. Havel. Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.

Animals↗
PubMed1982

Structural and metabolic heterogeneity of beta-very low density lipoproteins from cholesterol-fed dogs and from humans with type III hyperlipoproteinemia.

Cholesteryl ester-rich beta-very low density lipoproteins (beta-VLDL) are beta-migrating lipoproteins that accumulate in the d < 1.006 g/ml fraction of plasma from cholesterol-fed animals and from patients with Type III hyperlipoproteinemia. They can be separated from pre-beta-migrating very low density lipoproteins in the d 1.006 g/ml fraction by Geon-Pevikon block electrophoresis. The beta-VLDL have a general property of stimulating cholesteryl ester synthesis and accumulation in macrophages. In the present study, we demonstrated that beta-VLDL obtained from cholesterol-fed dogs fasted for 16 hr were heterogeneous and that two subpopulations of particles, referred to as Fractions I and II, could be isolated from the whole beta-VLDL fraction using gel filtration chromatography. These fractions of beta-VLDL were similar in that both were cholesteryl ester rich, had beta-electrophoretic mobility on Geon-Pevikon electrophoresis, and possessed the B and E apoproteins as major constituents. However, Fractions I and II differed in size, shape, electrophoretic mobility, chemical composition, and apoprotein B type. (Fraction I vs. Fraction II: size: 90 to 300 nm vs. 20 to 70 nm; shape: irregular with redundant surface vs. spherical; electrophoretic mobility on paper: origin vs. beta; chemical composition: rich in phospholipid and poor in protein vs. rich in protein and poor in triglycerides; apoprotein B types: equal amounts of the high and low molecular weight forms vs. predominantly the high molecular weight form.) Furthermore, Fraction I was 3- to 15-fold more active than Fraction II in stimulating cholesteryl ester formation in mouse peritoneal macrophages. The concentration of Fraction I, but not Fraction II, was diminished in plasma by prolonged fasting, and Fraction I transported more intestinal-absorbed retinol than Fraction II. In addition, the plasma clearance of Fraction I injected into cholesterol-fed dogs was distinctly different from the clearance of Fraction II, and the in vivo dieaway of Fraction I resembled that of chylomicrons and chylomicron remnants. These findings suggest that beta-VLDL in dogs are composed of cholesteryl ester-rich chylomicron remnants (Fraction I) and cholesteryl ester-rich lipoproteins, probably of liver origin (Fraction II). Finally, in studies of two patients with Type III hyperlipoproteinemia, we also identified the existence of two fractions in the beta-VLDL with characteristics similar to Fractions I and II of cholesterol-fed dogs.-Fainaru, M., R. W. Mahley, R. L. Hamilton, and T. L. Innerarity. Structural and metabolic heterogeneity of beta-very low density lipoproteins from cholesterol-fed dogs and from humans with Type III hyperlipoproteinemia.

Animals↗
PubMed1982

Characterization and quantitation of apolipoproteins A-I and E of normal and cholesterol-fed guinea pigs.

We have characterized and quantified the two major plasma apoproteins of high density lipoproteins (HDL), apolipoproteins A-I (apoA-I) and E (apoE), of guinea pigs fed standard chow (normal) or chow supplemented with 1% cholesterol (cholesterol-fed). ApoA-I isolated from plasma HDL of the normal guinea pig exists in six polymorphic forms (pI 5.75-5.40). A similar isoform pattern of this apoprotein was present in nascent HDL isolated from perfused livers of normal and cholesterol-fed animals. This apoprotein contains cysteine and isoleucine and is slightly different in overall amino acid composition from apoA-I of human and rat, but activates lecithin:cholesterol acyltransferase from human plasma with an activation curve almost identical to that obtained with human apoA-I. ApoE present in nascent VLDL and HDL from perfused liver of normal animals contains three isoforms (pI 5.42-5.34). Following cholesterol feeding, the numbers of apoE isoforms from perfused livers were increased from three to five or more by shifting the major component (pI 5.42) to more acidic isoforms (pI 5.28-5.17). This shifting was mostly reversible when apoE was treated with neuraminidase, suggesting that cholesterol feeding leads to a modification of apoE by increasing its content of sialic acid. Similar changes of apoE isoforms were also observed in plasma lipoproteins as early as 10 days after cholesterol feeding. The amino acid compositions of four apoE isoform fractions isolated from plasma HDL of cholesterol-fed guinea pigs were similar to that of parent apoE. The plasma concentrations of apoA-I and apoE, measured by electroimmunoassay, were 6.2 +/- 2.0 and 2.2 +/- 0.5 mg/dl, respectively, in guinea pigs fed standard chow. In animals that had been fed 1% cholesterol, plasma levels of apoA-I slightly increased in 1 week and showed a twofold increase in 8-10 weeks. Plasma levels of apoE, on the other hand, sharply increased by 10-fold in 1 week and up to 22-fold in 8-10 weeks on the cholesterol diet.-Guo, L. S. S., R. L. Hamilton, J. P. Kane, C. J. Fielding, and G. C. Chen. Characterization and quantitation of apolipoproteins A-I and E of normal and cholesterol-fed guinea pigs.

Amino Acids↗
PubMed1981

Normotriglyceridemic abetalipoproteinemia. absence of the B-100 apolipoprotein.

In the two genetic forms of abetalipoproteinemia described previously, recessive abetalipoproteinemia and homozygous hypobetalipoproteinemia, all lipoproteins that normally contain apolipoprotein B are absent from plasma. We describe here a new disorder in which normal low density and very low density lipoproteins are absent, but in which triglycerides are absorbed from the intestine and chylomicrons are present in plasma. The underlying molecular defect appears to be selective deletion of the hepatogenous B-100 apolipoprotein. The B-48 apolipoprotein found in chylomicrons is spared. These findings suggest that the two species of apolipoprotein B are under separate genetic control and that low density lipoproteins are not normally derived from chylomicrons.

Apolipoproteins↗
PubMed1980

Interaction of unilamellar liposomes with serum lipoproteins and apolipoproteins.

The effect of rat whole blood plasma, serum, serum lipoproteins, and apolipoproteins on the stability of unilamellar liposomes prepared with French pressure cell was evaluated by measuring the release of entrapped carboxyfluorescein and by electron microscopy. In the absence of serum components, dye escaped very slowly (hours) from egg phosphatidylcholine and phosphatidylcholine-cholesterol (43 mol % cholesterol) vesicles without apparent change in liposomal structure. This slow release was both temperature- and size-dependent. serum and some of its constituents induced a far more rapid (seconds) loss of entrapped dye from phosphatidylcholine liposomes, associated with structural changes. For equal masses of protein the order of potency of this induced activity was: free apolipoproteins (apo A-I, apo E) > isolated lipoproteins (HDL and VLDL) > whole serum or whole plasma. Substantial activity was found in three preparations of bovine serum albumin. This activity could be attributed to small and variable amounts of contaminating lipoprotein-like particles and apolipoprotein A-I. Induced release of dye from liposomes by apolipoproteins was usually associated with rapid formation of discs although other structures were sometimes formed. Purified rat apolipoproteins A-I and E appeared to interact identically with liposomes to induce dye release. This effect was progressively impaired for both apoproteins by increasing amounts of cholesterol and was completely inhibited when liposomes contained 37 mol % cholesterol.

Adult↗
PubMed1980

Unilamellar liposomes made with the French pressure cell: a simple preparative and semiquantitative technique.

A simple, rapid, and almost quantitative technique is described for the preparation of 1-40 ml of homogeneous unilamellar liposomes from dilute or concentrated aqueous suspensions of egg phosphatidylcholine. Aqueous suspensions of lipid are placed with the chamber of a French pressure cell at room temperature and rapidly extruded at 20,000 psi through the small orifice. A single pass transforms more than 70% of the extruded lipid into a homogeneous population of single-wall bilayer vesicles; more than 90% is transformed by recycling the lipid through the French pressure cell. About 95% of these liposomes range between 150-300 A in diameter (mean 200 A). The liposomes are stable for days to months when stored under nitrogen at 0.4 degrees C and can be prepared at 0 degrees, 25 degrees, or 37 degrees C. The liposomes appeared unaltered by repeated passages through the French pressure cell and no degradation of the phospholipid was detected after ten consecutive cycles at 20,000 psi in the absence of a nitrogen atmosphere. The method is especially useful for trapping small molecular weight substances because the concentration of both lipid and solute can be made quite high. Cholesterol up to 45 mole % can be incorporated into larger liposomes of egg phosphatidylcholine (mean diameter 315 A). Other phospholipids and different lipid mixtures can also be transformed into unilamellar vesicles with this method which has the advantage that additional steps of ultracentrifugation, column chromatography, dialysis, and concentrating procedures are usually unnecessary. Multilayered liposomes of small size (980 A mean diameter; > 95% between 500-1,500 A) are produced at lower pressure (3,000 psi). The latter are separated by gel permeation chromatography from a second population of homogeneous vesicles of even smaller size (580 A mean diameter; > 95% between 300-900 A) that contain two bilayer shells.

Biochemistry↗
PubMed1978

Secretion of lipoprotein-X by perfused livers of rats with cholestasis.

The major abnormal plasma lipoprotein of cholestasis (LP-X) was isolated from blood plasma and from perfusates of isolated livers of rats with biliary obstruction. In both cases LP-X was composed mainly of about equimolar parts of phospholipids and unesterified cholesterol; the small protein component was primarily the arginine-rich apolipoprotein. By electron microscopy, LP-X appeared as a unilamellar liposome (690 A mean diameter, range 400-1000 A) with the trilaminar staining image typical of phospholipid bilayers. Extensive block staining of cholestatic livers for 48 hr with warmed uranyl acetate (37 degrees) permitted the visualization of vesicles indistinguishable from LP-X within hepatic parenchyma. These trilaminar-staining vesicles occurred predominantly within bile canaliculi. They also were seen in nearby cytoplasmic vacuoles or invaginations between hepatocytes and in the space of Disse. Similar vesicles were not seen in the endoplasmic reticulum or Golgi cisternae. These observations raise the possibility that the vesicles are formed within bile canaliculi and are transported from the canaliculi to the space of Disse within pinocytotic vacuoles.

Animals↗
PubMed1977

Changes in the plasma lipoprotein-apoproteins of guinea pigs in response to dietary cholesterol.

The major apoproteins from four plasma lipoproteins were isolated from control and cholesterol-fed guinea pigs. Apoproteins were studied by column chromatography, polyacrylamide gel electrophoresis, and amino acid analysis. Dietary cholesterol altered the plasma apolipoproteins mainly by an enrichment in the content of arginine-rich polypeptide (ARP) in all density fractions. This protein had a similar molecular weight (34 000), electrophoretic mobility, amino acid composition, and microheterogeneity as ARP reported in other mammalian species. The estimation of plasma concentration of ARP indicates a higher correlation coefficient with plasma unesterified cholesterol (r = 0.98) compared with cholesterol esters (r = 0.62).

Amino Acids↗
PubMed1977

Evidence that a separate particle containing B-apoprotein is present in high-density lipoproteins from perfused rat liver.

High-density lipoproteins (HDL) (1.075 less than d less than 1.175) from perfusates of rat liver, unlike those of blood plasma, contain protein with the properties of B-apolipoprotein. This protein remains near the origin upon electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate, has beta electrophoretic mobility in agarose gel, is insoluble in tetramethylurea, and precipitates with antisera to the B-apoprotein isolated from low-density lipoprotein. B-apolipoprotein in HDL from perfusates binds to concanavalin-A Sepharose and can thus be separated from the characteristic HDL, the chemical and physical properties of which are otherwise preserved. These observations suggest that in addition to the discoidal lipoproteins, another particle that contains B-apoprotein exists in HDL of perfusates.

Animals↗
PubMed1977

Secretion of the arginine-rich and A-I apolipoproteins by the isolated perfused rat liver.

Rates of secretion of the arginine-rich and A-I apolipoproteins into perfusates of rat livers were measured by specific radioimmunoassays. Livers were perfused for 6 hr in a recirculating system in the presence or absence of 5,5'-dithionitrobenzoic acid, an inhibitor of lecithin-cholesterol acyltransferase. Arginine-rich apoprotein (ARP) was secreted at a constant or increasing hourly rate of about 40 micro g/g liver, whereas the rate of accumulation of apoprotein A-I decreased progressively from about 12 to less than 5 micro g/g liver. These rates were not affected by inhibition of lecithin-cholesterol acyltransferase. The distribution of these two apolipoproteins was also measured in ultracentrifugally separated lipoprotein fractions from perfusates and blood plasma. Apoprotein A-I was mainly in high density lipoproteins, with the remainder in proteins of density > 1.21 g/ml. The percent of apoprotein A-I in the latter fraction was lowest in plasma (5%); in perfusates it was greater when the enzyme inhibitor was present (33%) than in its absence (11%). By contrast much less ARP was in proteins of d > 1.21 g/ml in perfusates than in blood plasma. Discoidal high density lipoproteins, recovered from perfusates in which lecithin-cholesterol acyltransferase was inhibited, contained much more arginine-rich apoprotein than apoprotein A-I (ratio = 10:1). The ratio in spherical plasma HDL was 1:7 and that in perfusate high density lipoproteins obtained in the absence of enzyme inhibitor was intermediate (2:1). It is concluded that: 1) the arginine-rich apoprotein is a major apolipoprotein whereas apoprotein A-I is a minor apolipoprotein secreted by the perfused rat liver; 2) the properties of the high density lipoproteins produced in this system are remarkably similar to those found in humans with genetically determined deficiency of lecithin-cholesterol acyltransferase.

Animals↗
PubMed1976

Subcellular localization of B apoprotein of plasma lipoproteins in rat liver.

Multispecific antigen-binding fragments (Fab) from rabbit antisera against rat very low density lipoproteins (VLDL) and Fab against rat low density lipoproteins that were monospecific for the B apoprotein were conjugated to horseradish peroxidase. Conjugates were incubated with 6-mum frozen sections from fresh and perfusion-fixed livers and with tissue chopper sections (40 mum thick) from perfusion-fixed livers. In the light microscope, specific reaction product was present in all hepatocytes of experimental sections as intense brown to black spots whose locations corresponded to the distribution of the Golgi apparatus: along the bile canaliculi, near the nuclei, and between the nuclei and bile canaliculi. Perfusion fixation with formaldehyde produced satisfactory ultrastructural preservation with retention of lipoprotein antigenic determinants. In the electron microscope, patches of cisternae and ribosomes of the rough endoplasmic reticulum (ER) and particularly its smooth-surfaced ends, vesicles located between the rough ER and the Golgi apparatus, the Golgi apparatus and its secretory vesicles and VLDL particles in the space of Disse all bore reaction product. The tubules and vesicles of typical hepatocyte smooth ER did not contain reaction product, nor did the osmiophilic particles contained therin. The localization obtained in this study together with other evidence suggests a sequence for the biosynthesis of VLDL that differs in some respects from that proposed by others: (a) the triglyceride-rich particle originates in smooth ER where triglycerides are synthesized; (b) at the junction of the smooth and rough ER the particle receives apoproteins synthesized in the rough ER; (c) specialized tubules transport the particle, now a nascent lipoprotein, to the Golgi apparatus where concentration occurs in secretory vesicles; (d) secretory vesicles move to the sinusoidal surface where the particles are secreted into the space of Disse by fusion of the vesicular membrane with the plasma membrane of the hepatocyte.

Animals↗
PubMed1976

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Rat livers were perfused for 6 h without added plasma proteins using washed erythrocytes and buffer in a recirculating system. An inhibitor to the enzyme lecithin-cholesterol acyltransferase (5,5'-dithionitrobenzoic acid) was added in some experiments to prevent modification of substrate-lipids contained in secreted lipoproteins. The inhibitor did not detectably alter hepatic ultrastructure or gas exchange, but it inhibited the secreted lecithin-cholesterol acyltransferase by more than 85%. Very low density lipoproteins in perfusate were unaltered but the high density lipoproteins obtained from livers perfused with the inhibitor appeared disk-shaped in negative stain by electron microscopy with a mean edge thickness of 46 +/- 5 A and a mean diameter of 190 +/- 25 A. The high density lipoproteins were composed predominantly of polar lipids and protein with only small amounts of cholesteryl esters and triglycerides. The major apoprotein of these discoidal fractions had the same electrophoretic mobility as the arginine-rich apoprotein, whereas plasma high density lipoproteins contained mainly the A-I approtein. In all these respects the discoidal perfusate high density lipoproteins closely resemble those found in human plasma which is deficient in lecithin-cholesterol acyltransferase. Perfusate high density lipoproteins obtained in the absence of the enzyme inhibitor more closely resembled plasma high density lipoproteins in chemical composition (content of cholesteryl esters and apoproteins) and in electron microscopic appearance. Purified lecithin-cholesterol acyltransferase synthesized cholesteryl esters at a substantially faster rate from substrate lipids of perfusate high density lipoproteins than those from plasma. The discoidal high density lipoproteins were the best substrate for this reaction. Thin sections of plasma high density lipoproteins indicated a spherical particle whereas discoidal high density lipoproteins stained with the characteristic trilaminar image of membranes. These observations suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase.

Animals↗