1. Lipoprotein lipase activity was measured in heart homogenates and in heparin-releasable and non-releasable fractions of isolated perfused rat hearts, after the intravenous injection of Triton WR-1339. 2. In homogenates of hearts from starved, rats, lipoprotein lipase activity was significantly inhibited (P less than 0.001) 2h after the injection of Triton. This inhibition was restricted exclusively to the heparin-releasable fraction. Maximum inhibition occurred 30 min after the injection and corresponded to about 60% of the lipoprotein lipase activity that could be released from the heart during 30 s perfusion with heparin. 3. Hearts of Triton-treated starved rats were unable to take up and utilize 14C-labelled chylomicron triacylglycerol fatty acids, even though about 40% of heparin-releasable activity remained in the hearts. 4. It is concluded that Triton selectively inhibits the functional lipoprotein lipase, i.e. the enzyme directly involved in the hydrolysis of circulating plasma triacylglycerols. 5. Lipoprotein lipase activities measured in homogenates of soleus muscle of starved rats and adipose tissue of fed rats were decreased by 25 and 39% respectively after Triton injection. It is concluded that, by analogy with the heart, these Triton-inhibitable activities correspond to the functional lipoprotein lipase.

This case confirms the importance of the FSHR in female pubertal development and reproduction, and supports a relationship between phenotype and function for FSHR mutations.

Rat lymph chylomicrons were treated with Pronase resulting in particles completely devoid of surface apoproteins. On re-incubation with serum, the Pronase-treated chylomicrons re-acquired, by transfer from other lipoproteins, all apoproteins except apoprotein B, which is water-insoluble and non-transferable. When two groups of rats were injected with [3H]cholesterol-labelled control or Pronase-treated chylomicrons, radioactivity was incorporated into the liver of both groups at similar rates. It is concluded that the remnants of the control and Pronase-treated chylomicrons formed in the vascular space were recognized and taken up by liver cells by a process that does not require apoprotein B.

Objective: To test further the hypothesis that autosomal dominant neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations in the vasopressin -neurophysin II (AVP-NPII ) gene that exert a dominant negative effect by producing a precursor that misfolds, accumulates and eventually destroys the neurosecretory neurons. Methods: Antidiuretic function, magnetic resonance imaging (MRI) of the posterior pituitary and AVP-NPII gene analysis were performed in 10 affected members of three unreported families with adFNDI. Results: As in previously studied patients, adFNDI apparently manifested after birth, was due to a partial or severe deficiency of AVP, and was associated with absence or diminution of the hyperintense MRI signal normally emitted by the posterior pituitary, and with a heterozygous mutation in the AVP-NPII gene. In family A, a transition 275G ! A, which predicts replacement of cysteine 92 by tyrosine (C92Y), was found in the index patient, but not in either parent, indicating that it arose de novo. The six affected members of family B had a transversion 160G ! C; which predicts replacement of glycine 54 by arginine (G54R). It appeared de novo in the oldest affected member, and was transmitted in a dominant manner. In family C, six of 15 living affected members were tested and all had a novel transition, 313T ! C; which predicts replacement of cysteine 105 by arginine (C105R). It, too, was transmitted in a dominant manner. As in other patients with adFNDI, the amino acids replaced by the mutations in these three families are known to be particularly important for correct and efficient folding of the precursor. Conclusions: These findings are consistent with the malfolding/toxicity hypothesis underlying the pathogenesis of adFNDI. Moreover, they illustrate the value of genetic analysis in all patients who develop idiopathic diabetes insipidus in childhood, even if no other family members are affected.

The ability of the isolated perfused rat liver to differentiate between chylomicrons and remnants with either high or low apoprotein E:C ratios was investigated. Remnants were prepared in hepatectomized rats i jected with chylomicrons double-labeled with [3H]cholesterol and "'C-labeled fatty acids. By densitometric scanning of polyacrylamide gels, the apoprotein E:C ratio of the chylomicrons was 0.8 and that of the remnants was 1.5. When livers were perfused with these lipoproteins in a recirculatory system for 4 min, uptake of remnants was about 3-fold greater than that of chylomicrons. Preparation of remnants as well as chylomicrons with a low apoprotein E:C ratio was achieved by (i) removal of all apoproteins from the surface of the lipoproteins by trypsin digestion, followed by (it) transfer of soluble apoproteins from serum lipoproteins to the apoprotein-free particles. The apoprotein E:C ratio of the reconstituted lipoproteins was decreased from 1.5 to 0.3 for remnants and from 0.8 to 0.2 for chylomicrons. In spite of these changes in apoprotein E:C ratios, the hepatic uptake of the reconstituted lipoproteins with low apoprotein E:C ratios was similar to their unmodified controls. These results indicate that the hepatic discrimination between chylomicrons and remnants is not determined by the relative amounts of apoproteins E and C on the surface of the lipoproteins.The ability of liver cells to differentiate between chylomicrons and chylomicron remnants has been well documented in studies carried out in vivo, with isolated perfused livers and isolated cells (1-9). These studies have shown that chylomicron remnants, but not intact chylomicrons, are recognized and taken up at a rapid rate by liver cells. The hepatic uptake of remnants apparently involves the binding of the particle to receptors on the liver cell surface, followed by internalization of the whole remnant by the cell (5, 6, 10). Liver cells possess receptors capable of binding apoprotein E-carrying lipoproteins, and the evidence presently available suggests that it is apoprotein E on the surface of remnants that mediates the recognition and uptake of these particles (11,12). It is noteworthy, however, that intact chylomicrons also possess apoprotein E on their surface but are not taken up by the liver. The question therefore arises as to how the liver cell receptor recognizes the apoprotein E on the remnants and not the apoprotein E on the chylomicrons. It has been documented that in the process of being degraded to remnants, chylomicrons decrease in size and lose surface phospholipids and apoproteins A-I, A-IV, and C (13,14). Since the smaller size of remnant particles apparently cannot account for their preferential hepatic uptake (6), it is reasonable to assume that one or more of the alterations that occur on the surface of chylomicrons during their degradation to remnants facilitate the recognition and binding of apoprotein E to the receptor.Two hypotheses have been proposed to explain how alterations in the chylomicron surface co...