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Biomedical subjects

D S Fredrickson

Publications and source records attributed to D S Fredrickson.

At least 73 records · Page 4Linked to original sources
PubMed1973

Chylomicrons and the formation of foam cells in type I hyperlipoproteinemia. A morphologic study.

Light and electron microscopic study of aspirated bone marrow of a patient with type I hyperlipoproteinemia disclosed large, birefringent foam cells which develop from phagocytosis of chylomicrons by histiocytes. Chylomicrons are taken up, singly and in aggregates, by infoldings of the plasma membranes of histiocytes; these infoldings become phagocytic vacuoles within the cytoplasm. As chylomicrons are metabolized, the foam cells decrease in size, lose birefringence and develop autofluorescent, electron-dense deposits of ceroid.

Adult↗
PubMed1973

Selective measurement of two different triglyceride lipase activities in rat postheparin plasma.

Conclusive evidence has been obtained for the presence of both hepatic and extrahepatic triglyceride lipase activities (TGLA) in rat postheparin plasma, and an assay has been devised for their selective measurement. Heparin-released TGLA in plasma from the intact rat, like TGLA in postheparin hepatic perfusate, was relatively resistant to inactivation by salt and protamine. Postheparin TGLA obtained from the supradiaphragmatic portion of the rat, where any hepatic contribution was eliminated, was nearly completely inactivated by salt and protamine. Utilizing the different sensitivities to protamine inactivation of extrahepatic and hepatic TGLA, assay conditions were selected to achieve simultaneously the maximal reduction of extrahepatic TGLA with preservation of hepatic TGLA. This assay was validated using postheparin plasma from partially hepatectomized rats. The protamine-inactivated activity was independent of the amount of liver removed, whereas protamine-resistant activity was directly proportional to the amount of liver remaining. In the intact rat, liver appeared to be the major source of heparin-released TGLA measured at pH 8.6 with triolein substrate. It was further shown that both hepatic and extrahepatic lipases catalyzed hydrolysis of triglyceride-rich lipoproteins.

Animals↗
PubMed1972

Evidence for the identity of the major apoprotein in low density and very low density lipoproteins in normal subjects and patients with familial hyperlipoproteinemia.

The major apoprotein(s) from human plasma low density lipoproteins was isolated and compared with a major protein fraction (fraction I) from very low density lipoproteins (VLDL). Fraction I had been previously found to comprise approximately 40% of the total protein of VLDL. Fraction I from VLDL and apoLDL from normal subjects were indistinguishable in amino acid compositions and circular dichroic spectra. They yielded indistinguishable displacement curves of LDL-(125)I by radioimmunoassay and formed immunoprecipitin lines of complete identity. Fraction I from VLDL of normal subjects was compared with the fraction isolated from patients with familial types II, III, IV, and V hyperlipoproteinemia. There were no detectable differences between any of these fractions in amino acid compositions, circular dichroic spectra, and immunochemical properties. It was, therefore, concluded that short of peptide mapping or determination of amino acid sequence, fraction I from VLDL of each subject with familial hyperlipoproteinemia appears to be identical with fraction I and apoLDL from normal individuals.A new convenient method of preparation of soluble apoLDL, modified from a procedure previously described from this laboratory, is presented.

Amino Acid Sequence↗
PubMed1972

Enzyme deficiency in cholesteryl ester storage idisease.

Cholesteryl ester storage disease has been shown to involve severe deficiency of acid cholesteryl ester hydrolase and triglyceride lipase activity in liver, spleen, and lymph node. The cholesteryl ester hydrolase was also deficient in aorta. Tissue storage of both cholesteryl esters and triglycerides is generalized. Both the lipid and enzymatic changes are very similar to those in Wolman's disease.

Adult↗
PubMed1972

Studies on the protein defect in Tangier disease. Isolation and characterization of an abnormal high density lipoprotein.

High density lipoproteins (d 1.063-1.210 g/ml) were isolated from the plasma of normal individuals (HDL) and seven homozygous patients with Tangier disease (HDLt). In Tangier patients, the concentration of protein in the high density region (HDLt) was only 0.5-4.5% of normal. Immunochemical studies, including mixing experiments conducted in vivo and in vitro, indicated that HDLt was different from HDL. HDLt was the only high density lipoprotein detectable in the plasma of Tangier homozygotes. In heterozygotes both HDL and HDLt were present. HDLt was not detected in the plasma of over 300 normal persons and 10 patients with secondary high density lipoprotein deficiency and appeared to be a unique marker for Tangier disease.ApoHDL contained two major apoproteins designated apoLp-Gln-I and apoLp-Gln-II; together they comprised 85-90% of the total protein content. Both of the major HDL apoproteins were present in apoHDLt; but apoLp-Gln-I was disproportionately decreased with respect to apoLp-Gln-II, the ratio of their concentrations being 1: 12 in apoHDLt as compared with 3: 1 in apoHDL. Several minor apoprotein components which together comprise 5-15% of apoHDL were present in approximately normal proportions in apoHDLt. In the HDL of Tangier patients it was estimated that, compared with normal individuals, the concentration of apoLp-Gln-I was decreased about 600-fold and the concentration of apoLp-Gln-II about 17-fold. The decrease in these apoproteins was not due to preferential segregation with the lipoprotein fractions of d < 1.063 g/ml or with the plasma proteins of d > 1.21 g/ml. Tangier apoLp-Gln-I and apoLp-Gln-II appeared to be immunochemically identical with their normal counterparts, and no differences between the two sets of apoproteins were detected on polyacrylamide gel electrophoresis at pH 9.4 or 2.9. These results are most compatible with the hypothesis that the hereditary defect in Tangier disease is a mutation in an allele-regulating synthesis of apoLp-Gln-I.

Alleles↗
PubMed1972

Comparison of the triglyceride lipase of liver, adipose tissue, and postheparin plasma.

Heparin-released triglyceride lipase from three sources, adipose tissue, liver, and postheparin plasma, was compared. Heparin-released triglyceride lipase from liver differed in several major respects from that in adipose tissue. These differences included response to inhibitors and to high density lipoprotein in the incubation media. Heparin-released triglyceride lipase from liver, when compared with that from adipose tissue, was relatively inactive against lipoprotein substrates. The triglyceride lipase from postheparin plasma exhibited properties more like those of liver. These studies raise the possibility that triglyceride lipase in postheparin plasma may be heterogeneous and that levels of the enzyme in postheparin plasma may not accurately reflect the capacity for clearance of triglyceride from the plasma.

Adipose Tissue↗