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A M Scanu

Publications and source records attributed to A M Scanu.

247 records · Page 14Linked to original sources

Response of rhesus serum high density lipoproteins to cycles of diet-induced hypercholesterolemia.

Two male rhesus monkeys underwent cyclical feeding of a hypercholesterolemic diet (2% cholesterol, 25% coconut oil) and a low-fat Purina monkey chow diet. During the latter diet, high density lipoprotein (HDL) exhibited two components with peak densities of d = 1.081 g/ml and 1.109 g/ml named HDLL and HDLH, respectively. During the initial hypercholesterolemic stage, except for apo A-II which remained unchanged, there was a transient rise in HDL (mainly HDLL) as well as in HDL cholesterol and apo A-I, all reaching maximal values after about 2 weeks from the onset of the diet. The two HDL species changed neither in size nor density as compared to their baseline counterparts, but had a comparatively higher content in cholesteryl ester and lesser amounts of triglycerides and phospholipids as compared to the normocholesterolemic animal. With the development of overt hypercholesterolemia (plasma cholesterol levels above 400 mg/dl), both HDL particles increased in density due to the loss of surface components (phospholipids and unesterified cholesterol) and core triglycerides with only minor changes in protein and cholesteryl ester contents. At this stage, the same two animals exhibited significant changes in the size and buoyant density of LDL. When returned to a normal Purina chow diet, the animals' serum cholesterol levels declined rapidly to normal levels; normalization of the HDL distribution also occurred but at a comparatively later time (26 weeks). Our studies indicate that the two HDL subsets characteristic of the normocholesterolemic rhesus monkey undergo significant changes in buoyant density as a function of the stage of hypercholesterolemia and that changes in concentration and size mainly affect the HDLL subspecies. At levels of plasma cholesterol below 400 mg/dl, this cholesterol increment is reflected by a significant increase in the number of the HDL subspecies without the overt participation of the low density lipoprotein classes characteristic of the advanced hyperlipidemic stage. Since we previously reported that greatly increased levels of cholesteryl esters enriched low density lipoproteins, beta-VLDL (very low density lipoprotein) and pre-beta-VLDL during overt diet-induced hypercholesterolemia, it is apparent that cholesterol is distributed differently among lipoprotein particles containing either apo A-I, apo B, or apo E depending on its concentration in plasma.

Animals↗

In vitro and in vivo interactions of Triton 1339 with plasma lipoproteins of normolipidemic rhesus monkeys. Preferential effects on high density lipoproteins.

Triton WR-1339 was incubated in vitro in various proportions with plasma from normolipidemic rhesus monkeys or with ultracentrifugally purified lipoproteins, and the products were examined by isopycnic density gradient ultracentrifugation, agarose column chromatography, electrophoretic and immunochemical techniques, and electron microscopy. Some experiments used apo A-I, apo A-II, or Triton labeled with either 125I or 131I. At concentrations of less than 10 mg/ml plasma, Triton interacted preferentially with HDL, changing lipoprotein size and density; Triton was progressively incorporated into the HDL particles, displacing apo E, apo A-I, and apo A-II. At concentrations above 10 mg/ml plasma, Triton displaced all apo A-I from the particle, and much lipid was dissolved into the Triton micelles. When Triton-treated HDL particles were used as a substrate for the enzyme LCAT, enzyme activity decreased in parallel to the displacement of apo A-I. There was no displacement of apo B from LDL nor any loss of lipids; but the particles became deformed and formed rouleaux. A single intravenous dose of Triton WR-1339 administered to a normolipidemic monkey (N) and to a hypercholesterolemic monkey (H) resulted in concentration-dependent HDL changes similar to those observed in vitro. LDL was less affected by Triton, with changes occurring only at high doses. After these structural changes, intravenously injected 131I apo A-I disappeared rapidly from the circulation; 125I apo A-II disappeared less rapidly. These increased clearances were accompanied by a drop in apo A-I plasma levels and the disappearance of HDL particles from plasma. The lipoprotein and apolipoprotein patterns returned to normal 14 days after Triton. We conclude that Triton WR-1339, when exposed to rhesus plasma in vitro or in vivo, interacts preferentially with HDL in a dose-dependent manner. At low concentrations, Triton acts on surface components of the HDL particle; at higher concentrations, Triton penetrates the particle, causing structural disruption. Because of its high affinity for HDL, Triton WR-1339 is a useful reagent for study of HDL structure-function relationships.

Animals↗

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia.

The possibility that low high density lipoprotein (HDL) levels may add to the risk of occlusive atherosclerosis in familial hypercholesterolemia (FH) is supported by the frequency and severity of this finding in these patients, particularly homozygotes. To investigate this abnormality in greater detail, we measured HDL lipid and apoprotein values in nine homozygotes with FH. Compared to their unaffected relatives, they had markedly reduced HDL cholesterol and apo A-I and A-II levels. The values found in heterozygote relatives were between those of homozygotes and those of controls. Density gradient ultracentrifugation of serum or isolated HDL from homozygotes demonstrated little or no HDL2; there was also a shift of homozygotes' HDL to an above normal peak density (d = 1.15 g/ml). Heterozygotes had milder abnormalities. The reduced HDL in FH seems to be related to elevated low density lipoprotein levels although the pathophysiology is unknown. These findings add weight to the concept that HDL abnormalities contribute to the relentless course of atherosclerosis in familial hypercholesterolemia.

Adolescent↗

Comparative study of density distribution of plasma lipoproteins of normo- and hypercholesterolemic rhesus monkeys and humans.

Density gradient centrifugation was used to characterize the lipoprotein distribution of rhesus monkeys and human subjects with normal and elevated cholesterol levels. The lipoprotein profile of control monkeys differed from that of normal humans in that their density distribution as a whole was shifted to lower density. The most striking difference was that both rhesus high density lipoprotein (HDL) subspecies had densities lower than human HDL3, with one component having a lower, and the other a higher, density than human HDL2. Rhesus monkeys fed a diet supplemented with 0.5% cholesterol and 15% lard were divided into two groups. Those animals with cholesterol levels less than 435 mg/dl had a high apo A-I concentration and HDL subspecies similar to human HDL2 and HDL3, whereas those with concentrations greater than 435 mg/dl had a low apo A-I concentration and HDL species with a density either similar to, or exceeding that, of human HDL3. Low density lipoprotein (LDL) density decreased in both groups of hypercholesterolemic monkeys and was particularly pronounced in animals with cholesterol levels above 435 mg/dl. When the lipoprotein profiles of normal humans were compared with those having hypercholesterolemia, increases in the density of both HDL2 and HDL3 in hypercholesterolemic men and to a lesser extent in the density of HDL2 in women were detected. The results indicate that the overall density distribution of plasma lipoprotein is different between rhesus monkeys and humans, and may vary within each species as a function of the nutritional status. It follows that it is difficult to define lipoprotein classes of one species by using density intervals determined for another. Furthermore, these intervals can be inadequate in identifying lipoprotein classes within an individual before and after dietary manipulations.

Age Factors↗

[Unusual case of benign neoplasm of the breast mimicking a carcinoma: granular cell tumor. Case report].

Granular cell tumors are rare, usually benign neoplasms of soft tissues which most commonly occur in the tongue, skin and subcutaneous tissue. Although the histogenesis is still object of debate, recent immunohistochemical studies and ultrastructural findings support the origin of this neoplasm from the peripheral nervous tissue, most likely from Schwann's cells. Occurrence of this neoplasm in the breast, although uncommon, warrants special attention, since its clinical, mammographic and pathological appearances on frozen sections "may often closely resemble" hose of breast malignancy. The authors analyze and commenton, with special reference to clinical aspects and surgical treatment, a case of benign granular cell tumor of the breast occurring in a 42 year-old woman. The mammographic and clinical findings suggested a breast carcinoma. The correct diagnosis was established by definitive microscopic examination of the paraffin-embedded specimens and the treatment was a simple local excision of the tumour and a small rim of surrounding breast parenchyma. Although the granular cell tumor of the breast is a rare entity, surgeons and pathologists should be aware of its existence in order to avoid inappropriate radical surgery not justified by the benign behavior of the neoplasm.

Adult↗

Three cases of cardiac hydatidosis: diagnosis, surgical treatment, and complications.

Three cases of cardiac hydatid disease from among the many cases of hydatidosis (>300) in various organs observed by the authors are reported. The sites of the cysts and the complications that arose are described. The first case developed hydatid pulmonary embolism caused by rupture into the right ventricular cavity, the second suffered peripheral hydatid embolism caused by rupture into the left ventricular cavity, and the third, whose diagnosis was fortuitous, had no complications. The first patient died shortly after admission. The other two underwent radical pericystectomy and partial pericystectomy with cardiopulmonary bypass. The best result was obtained in the third case where rupture had not occurred. The second patient recovered but developed hemiparesis. The various diagnostic tools available are discussed, as well as some technical aspects of pericystectomy, which has a high mortality rate. The importance of early diagnosis and treatment of this rare localization of Echinococcus granulosus is emphasized, and echocardiography is recommended even for nonspecific cardiac symptoms in areas where the parasite is endemic.

Adult↗

[Primary aortoenteric fistula. Report of a case].

Primary aortoenteric fistulas (PAEF) are rare entities associated with a high mortality. Although several causes have been reported, their occurrence is usually due to erosion of an abdominal aortic aneurysm into the intestinal tract. The most common sites for the fistula are the third and fourth portions of duodenum. The classical triad of gastrointestinal hemorrhage, abdominal mass and abdominal or back pain, though highly suggestive for PAEF, is uncommon. The typical bleeding pattern associated with PAEF is characteristically intermittent, starting with a brief "herald bleeding" followed eventually by major gastrointestinal hemorrhage, often with fatal outcome. The pre-operative examinations are often not helpful and can lead to delayed diagnosis and surgery. In a patient with risk factors for atherosclerosis and significant upper gastrointestinal bleeding in the absence of an evident source, PAEF should be suspected. A high index of suspicion of this condition allows correct diagnosis and definitive treatment to be carried out. If PAEF is suspected and the patient is unstable the surgeon should be prepared to skip the preoperative investigations in favour of early surgical exploration. Definitive treatment includes primary duodenal repair and aortic aneurismal resection with graft "in situ" replacement. The authors present a successfully treated case and stress the importance of clinical suspicion in order to achieve correct diagnosis and treatment.

Aged↗

Plasma lipoproteins and coronary heart disease.

Both plasma low-density (LDL) and high-density lipoproteins (HDL) have been associated with the genesis of cardiovascular disease. Recent studies with cells grown in culture have suggested a regularory role of these lipoproteins in cellular cholesterol metabolism and pointed at abnormalities resulting from deviations of these regulatory processes. The precise relationship between these observations in vitro and the atherogenic process remains open to investigation.

Apolipoproteins↗