Low density lipoprotein receptor-related protein (LRP) is a recently described cell-surface protein of 4544 amino acids that contains reiterated sequences found in the 839-amino acid receptor for low density lipoprotein (LDL). In the current studies, we purified LRP from rat liver, prepared polyclonal antibodies that recognize the extracellular domain, and demonstrated an immunoreactive protein of %600 kDa in human fibroblasts. The function of this LRP was studied in mutant human fibroblasts that do not produce LDL receptors.The mutant cells were incubated with fl-migrating very low density lipoprotein (J3-VLDL) that was isolated from cholesterol-fed rabbits and artificially enriched with apoprotein (apo) E by incubation in vitro with human apo E produced in a bacterial expression system. The apo E-enriched f-VLDL, but not unincubated fl-VLDL, stimulated incorporation of [14C]-oleate into cholesteryl ["4Cioleate 20-to 40-fold in the mutant cells. This stimulation was blocked by chloroquine, suggesting that such stimulation resulted from receptor-mediated uptake and lysosomal hydrolysis of the cholesteryl esters in apo Eenriched fl-VLDL. Stimulation of cholesterol esterification was blocked by the antibody against LRP, but not by an antibody against the LDL receptor. Unlike the LDL receptor, the amount of LRP was not reduced when cells were incubated with oxygenated sterols. We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E.Lipoproteins that contain apoproteins (apo) B or E are removed from plasma by binding to high-affinity receptors on the liver and extrahepatic tissues. At least two receptors play a role (1). The low density lipoprotein (LDL) receptor binds LDL, which contains only apo B-100. It also binds apo E-containing remnants of chylomicrons and very low density lipoproteins (VLDL) that are produced by lipoprotein lipase. Approximately 70% ofLDL receptors are located in the liver, and the rest are found in adrenal gland, ovary, and other extrahepatic tissues (1).The existence of a second receptor was suggested by observations in patients with homozygous familial hypercholesterolemia (FH) and WHHL rabbits in whom LDL receptors are genetically defective (2). Although VLDL remnants and LDL accumulate in blood of affected individuals, chylomicron remnants do not (3). WHHL rabbits clear chylomicron remnants normally (4), and they also rapidly clear an appreciable fraction of large VLDL particles from blood (5). These observations suggest that the second receptor is specific for apo E-containing chylomicron remnants and large VLDL. Repeated attempts to define this receptor biochemically have been unsuccessful.A major advance has recently come from the work of Herz et al. (6), who used homology cloning to isolate a cDNA for an LDL receptor-related protein (LRP). The LRP resembles the LDL receptor in containing two types of cysteine-rich repeats, one related to complement proteins and the other related ...

The use of the automated external defibrillator aboard commercial aircraft is effective, with an excellent rate of survival to discharge from the hospital after conversion of ventricular fibrillation. There are not likely to be complications when the device is used as a monitor in the absence of ventricular fibrillation.

Performance of the Micra transcatheter pacemaker in a real-world setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%) of major complications through 30 days post implant. In particular, the rates of pericardial effusion, device dislodgement, and infection were low, reinforcing the positive results seen in the investigational study.