Exchange of various phospholipids and of cholesterol between liposomes in the presence of highly purified phospholipid exchange protein.
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Biomedical subjects
Publications and source records attributed to D B Zilversmit.
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Ponies fasted for up to 8 days showed, both by agarose electrophoresis and preparative ultracentrifugation, the appearance of a pre-beta-migrating, very low density lipoprotein fraction in plasma. This lipoprotein differs from the very low density lipoprotein found in humans and rats in that it contains a relatively smaller amount of total cholesterol, 85% of which is present in the unesterified form. By the 8th day of fasting, plasma triglyceride concentrations had increased from a prefasting level of 20 mg/dl to as high as 1000 mg/dl. The increase in plasma lipid concentrations as a result of fasting was highly variable. Accumulation of plasma cholesterol and triglyceride after injection of Triton WR 1339 was not related to the degree of fasting hyperlipidemia. This suggests that the hyperlipoproteinemia of fasting may result from an impaired utilization of very low density lipoproteins.
New Zealand white rabbits showed large decreases in plasma cholesterol and phospholipid concentrations during the second half of pregnancy. All lipoproteins (very low density, low density, and high density) participated in the decrease. Very large decreases in plasma cholesterol concentrations were observed even when the animals were maintained on high cholesterol diets. Increases in plasma cholesterol concentrations, after the intravenous administration of Triton WR 1339, were at least as great in pregnant as in nonpregnant animals. It is concluded that the decrease in plasma cholesterol concentrations is not the result of impaired plasma lipoprotein production.
Unesterified radioactive cholesterol, both bound to serum lipoproteins and dispersed in ethanol-saline, was injected into bile fistula and intact rats. Due to phagocytosis, mainly by the liver macrophages, intravenously injected cholesterol in ethanol-saline disappears from the bloodstream significantly faster than lipoprotein-bound cholesterol. Soon after the initial phagocytosis, the particulate isotopic cholesterol started to reappear in blood, reaching a maximal radioactivity in blood 10-24 hr after injection. Although the radioactive cholesterol reappears in serum in both esterified and unesterified form, it is likely that cholesterol is released from the phagocytic cells as unesterified cholesterol which is then esterified intravascularly or at other sites. In the bile fistula rats, somewhat more of the lipoprotein cholesterol than of the particulate cholesterol appeared in bile early after injection. However, cholesterol turnover calculated from a twopool model was the same for rats injected with lipoproteinbound or particulate cholesterol.
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Rat and guinea pig liver microsomes labeled with phospholipid (32)P were incubated with rat, guinea pig, and rabbit plasma in a KCl-Tris-EDTA buffer. A net transfer of microsomal phophatidylcholine and phosphatidylethanolamine to plasma was observed. In addition, an exchange of phospholipids between microsomes and plasma took place. During 20-min incubations at 37 degrees C, the exchange of phosphatidylcholine was the most extensive. Microsomal sphingomyelin exchanged with plasma sphingomyelin only very slowly. A soluble protein factor in liver, which had previously been observed to stimulate the exchange of liver mitochondrial and microsomal phospholipids, also increased the exchange of phosphatidylcholine between liver microsomes and plasma. The pronounced differences in the relative percentages of phosphatidylethanolamine of guinea pig, rabbit, and rat plasmas did not appear to be related to differences in the relative exchange of this phospholipid compared to that of other phospholipids in these plasmas.
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The daily administration of labeled cholesterol to humans or animals leads to an isotopic steady state. The specific activity of plasma cholesterol in the isotopic steady state gives information about the fraction of plasma cholesterol derived from endogenous and exogenous sources. A method, based on a two-pool model, is presented which allows the estimation of an optimal priming dose of labeled cholesterol whereby the time to reach the isotopic steady state is reduced to a minimum. A graphic procedure is presented which allows the estimation of an optimal priming dose for two-compartment systems with widely differing characteristics.
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