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Eight plasma lipoprotein patterns currently employed in attempts to identify different forms of familial dyslipoproteinemia have been compared by two methods. The first (NIH method) is based on paper electrophoretic patterns produced by the four lipoprotein classes obtained by paper electrophoresis in albuminated buffer, coupled with the measurement of the total cholesterol of three of these lipoprotein classes and ascertainment of abnormal flotation of beta-migrating lipoproteins. The second (Donner method) is based on lipoprotein patterns obtained in the analytical ultracentrifuge, adapted for computer analysis and complemented by chemical determination of the concentration of chylomicrons (lipoproteins of S(f) degrees400). Pooled samples representing patients with five types of familial hyperlipoproteinemia and three different forms of inherited lipoprotein dificiency were separately analyzed. For six of the eight pools, both methods provided a distinctive lipoprotein pattern in terms of changes in one or more variables. For the remaining two pools, type IV hyperlipoproteinemia and the heterozygote for Tangier disease, both methods provided identical but not unique patterns. The results indicate that lipoprotein analyses obtained by either method may be used interconvertibly in further genetic and other clinical studies.

7alpha- and 7beta-hydroxycholesteryl esters, 7-ketocholesteryl esters, and 5,6alpha- and 5,6beta-epoxycholesteryl esters have been identified in tissues of patients affected by Wolman's disease. Their structural identities were determined by mass spectroscopy and nuclear magnetic resonance spectroscopy and confirmed by chemical synthesis. It is postulated that cholesteryl ester hydrolase deficiency in Wolman's disease might lead to accumulation of oxygenated steryl esters in vivo and impairment of bile acid formation.

Fasting levels of plasma cholersterol and triglyceride, lipoprotein patterns, and fasting and postintravenous glucose levels of blood glucose, serum insulin, serum growth hormone, and plasma free fatty acids in a genetic potential diabetic population were compared to those in a similar normal control population. THe potential diabetic population was further divided into groups of patients with a normal (prediabetic) or abnormal (chemical diabetic) glucose tolerance test. Although no clear-cut lipid differences were noted, certain trends appeared. More type IV hyperlipoproteinemia was seen in male prediabetic (21%) and male chemical diabetic patients (19%) than in normal male subjects (5%); in female subjects only a few type IV patterns were seen. Type II hyperlipoproteinemia was not seen in any normal subject, but was noted in nearly 9% of those with chemical diabetes. Fasting cholesterol levels correlated better with age than did fasting triglyceride levels in most of the patient groups. Fasting triglyceride levels showed a significant positive correlation with the serum insulin area of the oral glucose tolerance test in the normals wna prediabetic persons, and also showed a significant positive correlation with the blood glucose area of the prediabetic and chemical diabetic patients. It is suggested that a normal relationship between triglyceride concentration and insulin response to glucose is lost in chemical diabetes. Sex differences were also noted in the inslin response and the insulin-glucose relationships during the oral glucose tolerance test, with normal menstruation women showing a significantly lower insulin-glucose relationship than the age-related men.

Das gedankliche Fundament der biochemischen Genetik verdanken wir Sir Archibald Garrod. Im ersten Jahrzehnt unseres Jahrhunderts formulierte Garrod das Konzept von den „inborn errors of metabolism“, eine Theorie, die nicht nur das Prinzip der genetischen Steuerung des Stoffwechsels vorwegnahm, sondern ausdrucklich auch die genetisch bedingte interindividuelle Variabilitat auf der Ebene dessen, was wir heute als biochemische Merkmale bezeichnen wurden. Garrod hat auch schon das breite Spektrum von Moglichkeiten diskutiert, das sich zwischen pathogenen Enzymdefekten einerseits und biochemischen Normvarianten andererseits ausspannt. Diesen gedanklichen Rahmen sehen wir heute mit einer stetig steigenden Wissensflut angefullt, in der man sich nur noch anhand von Ordnungsprinzipien orientieren kann, die gleichwohl ihrerseits einem zeitlichen Wandel unterworfen sind. Als Ordnungsprinzipien bieten sich biochemische und genetische Zusammenhange an. Die biochemische Systematik geht vom Genprodukt mit seinem meist pleiotropen Wirkungsspektrum aus. Die genetischen Ordnungsprinzipien beziehen sich demgegenuber auf die Natur der jeweiligen genetischen Veranderungen, also auf die Art, Lokalisation und Expression der jeweiligen Mutationsereignisse.

Tangier disease (deficiency of high density plasma lipoproteins) is characterized clinically by: low levels of plasma cholesterol; enlarged, orange-yellow to yellow-gray tonsils and, frequently, peripheral neuropathy. Histologic and ultrastructural studies were made of various tissues from 5 patients with Tangier disease, and comparisons were made of these findings with those in the 12 other patients thus far known to have this disease. Deposits of cholesteryl esters were found in: reticuloendothelial cells (foam cells) in tonsils, bone marrow, skin and jejunal submucosa; Schwann cells in peripheral nerves and myenteric plexus; and in nonvascular smooth muscle cells. These deposits appeared electron lucent and intensely birefringent, varied from spherical to crystalline in shape, often were extensively confluent throughout large areas of cytoplasm, and were not limited by membranes. Certain foam cells in bone marrow also contained membrane-limited clusters of lipid particles resembling chylomicrons. The foam cells in Tangier disease differ morphologically from those in numerous lysosomal enzyme deficiency states, particularly Wolman's disease and cholesteryl ester stroage disease, and in proliferative diseases of the reticuloendothelial system in which cholesteryl esters also accumulate in abnormal histiocytes. Morphologic and biochemical data suggest several hypotheses to explain the accumulation of cholesteryl esters in tissues of patients with Tangier disease. Among these hypotheses, the most likely are considered to be the presence in plasma of abnormal lipoprotein particles that are subject to phagocytic removal by reticuloendothelial cells, and the failure of a process that normally removes locally synthesized cholesterol from cells to plasma. (Am J Pathol 78:101-158, 1975)

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.

To correlate resting levels of blood fibrinolysis with different types of hyperlipidemia, the concentrations of fibrinogen and plasminogen and the euglobulin activity (precipitated at pH 5.9 and assayed on fibrin plates prepared with bovine, plasminogen-rich fibrinogen) were determined in fasting plasma samples from a group of normal controls ( 13 subj) and from 44 patients with hyperlipoproteinemia (type I: l; type II: 12; type III: 6; type IV (untreated): 13; type IV (treated): 5; type V: 7). Group levels of fibrinogen and plasminogen were normal or near normal, with a few cases of individually low plasminogen values in some type II and type IV patients. Mean fibrinolytic activity was normal in all groups, despite abnormally wide variations within patient groups. Screening of inhibition of plasmin, urokinase, and tissue plasminogen activator (porcine) demonstrated several instances of increased inhibition of tissue plasminogen activator in the patient groups and the control group. A study of individual data failed to reveal a correlation between the data obtained and lipid levels or patterns of plasma lipoproteins, precluding any simple relationship between hyperlipoproteinemia and blood fibrinolysis. Copyright © 1974 American Physiological Society. All rights reserved.

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.