Clinical and metabolic effects and wound healing metabolism in controlled total parenteral nutrition with high vs. low nitrogen content for seven days after abdominoperineal rectum resection for carcinoma.

The clinical, metabolic and anthropometric effects and wound healing metabolism of two regimens of total parenteral nutrition with different amount of nitrogen low, 0.1 g, and high, 0.3 g/body weight kg/day were examined in this prospective double-blind study in two groups of ten patients subjected to abdominoperineal rectum resection for carcinoma for seven postoperative days.

Colocalization of 15-lipoxygenase mRNA and protein with epitopes of oxidized low density lipoprotein in macrophage-rich areas of atherosclerotic lesions.

Oxidation of low density lipoprotein (LDL) enhances its atherogenicity, and inhibition of such oxidation decreases the rate of progression of atherosclerotic lesions. The mechanism of LDL oxidation in vivo remains uncertain, but in vitro studies have suggested that cellular lipoxygenases may play a role by initiating lipid peroxidation in LDL. In situ hybridization studies using a 15-lipoxygenase riboprobe and immunostaining using antibodies against 15-lipoxygenase showed strongly positive reactivity largely confined to macrophage-rich areas of atherosclerotic lesions.

Lipoproteins in normal and atherosclerotic aorta.

Each method used for the extraction and isolation of intimal lipoproteins has advantages and disadvantages. Gentle extraction methods are needed to characterize subtle modifications in the structure and biologic properties of the lipoproteins, whereas more aggressive methods are needed if the goal is to maximize the yield of lipoproteins from atherosclerotic arteries. The present paper evaluates different methods used for the isolation of intimal lipoproteins.

Distribution of oxidation specific lipid-protein adducts and apolipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits.

Antisera and monoclonal antibodies generated against autologous malondialdehyde-conjugated low density lipoprotein (MDA-LDL), 4-hydroxynonenal conjugated LDL (4-HNE-LDL), and the protein fragments of apoprotein B resulting from the copper oxidation of LDL, as well as antibodies against apoprotein B, were used to immunostain atherosclerotic lesions of varying severity from Watanabe heritable hyperlipemic rabbits. In macrophage-rich fatty streaks and transitional lesions, all of the antibodies recognizing oxidation specific epitopes exhibited predominantly cell-associated staining in particulate and annular patterns. This is in contrast to the limited, extracellular, diffuse staining obtained with the antibodies recognizing apoprotein B.

Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein.

Increasing evidence indicates that low density lipoprotein (LDL) has to be modified to induce foam cell formation. One such modification, oxidation of LDL, generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoprotein B. By immunizing animals with homologous malondialdehyde-modified LDL (MDA-LDL), 4-hydroxynonenal-LDL (4-HNE-LDL), and Cu+(+)-oxidized LDL, we developed polyvalent and monoclonal antibodies against three epitopes found in oxidatively modified LDL.

Biochemical composition of human internal mammary artery and saphenous vein.

The long-term patency of the internal mammary artery graft is better than that of the saphenous vein graft in coronary bypass surgery because of a low incidence of atherosclerosis in the internal mammary artery. In search of a possible biochemical explanation of the low degree of atherosclerosis in the internal mammary artery we compared the chemical compositions of human internal mammary artery and saphenous vein obtained from 37 patients undergoing coronary bypass surgery. The levels of esterified cholesterol and free cholesterol were higher in the internal mammary artery than in the saphenous vein (p less than 0.

Macrophages, endothelial cells, and lipoprotein oxidation in the pathogenesis of atherosclerosis.

One of the earliest phenomena in the atherogenic process in cholesterol-fed rabbits appears to be the trapping of low density lipoproteins (LDL) at lesion-prone sites in the aorta. The resulting increase in residence time may facilitate oxidation of the lipoproteins, which, in turn, may be a chemotactic signal for monocytes to enter the intima. Oxidized lipoproteins may also be the major source of the cholesterol that the cells accumulate during their transformation into macrophage-derived foam cells (MFC).

Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.

Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL.

Macrophage foam cells from human aortic fatty streaks take up beta-VLDL and acetylated LDL in primary culture.

Intimal cells from human aortic fatty streak lesions were isolated with collagenase-elastase digestion and the cellular uptake of lipoproteins fluorescently labeled with 3,3'-dioctadecylindocarbocyanine (DiI) was studied in primary culture. The majority of the cells in primary culture contained lipid droplets and the foam cells consisted of both macrophages and smooth muscle cells (SMC), identified with electron microscopy and the macrophages also using the monoclonal anti-Leu-M3 antibody. The lipid inclusions contained cholesteryl ester, as visualized with filipin staining.

Receptor-mediated binding and degradation of subfractions of human plasma low-density lipoprotein by cultured fibroblasts.

The receptor-mediated metabolism of human plasma low-density lipoprotein (LDL) subfractions was studied. LDL was isolated from healthy donors and further fractionated by density gradient ultracentrifugation into three subfractions: (I) d = 1.031-1.

Down's syndrome and atherosclerosis.

Necropsy findings in patients with Down's syndrome have suggested an absence of atherosclerosis throughout the cardiovascular system, but there are also contradictory results. We compared the left coronary arteries of 15 institutionalised Down's syndrome patients (5 males, 10 females, mean age 51 years) with those of 6 other institutionalised mentally retarded patients (4 males, 2 females, mean age 49) and 20 normal, free-living subjects (10 males, 10 females, mean age 48) by macroscopic inspection of the opened coronary arteries and by biochemical analysis of their intima-media. The arteries of Down patients contained a lower percentage of raised lesions and less calcium than the arteries of the control groups.

Low density lipoprotein undergoes oxidative modification in vivo.

It has been proposed that low density lipoprotein (LDL) must undergo oxidative modification before it can give rise to foam cells, the key component of the fatty streak lesion of atherosclerosis. Oxidation of LDL probably generates a broad spectrum of conjugates between fragments of oxidized fatty acids and apolipoprotein B. We now present three mutually supportive lines of evidence for oxidation of LDL in vivo: (i) Antibodies against oxidized LDL, malondialdehyde-lysine, or 4-hydroxynonenal-lysine recognize materials in the atherosclerotic lesions of LDL receptor-deficient rabbits; (ii) LDL gently extracted from lesions of these rabbits is recognized by an antiserum against malondialdehyde-conjugated LDL; (iii) autoantibodies against malondialdehyde-LDL (titers from 512 to greater than 4096) can be demonstrated in rabbit and human sera.

Stability of plasma total cholesterol, triglycerides, and apolipoproteins B and A-I during the early postmortem period.

The stability of plasma lipids and apolipoproteins during the early postmortem period was studied by taking four duplicate blood samples from eight cadavers 2, 6, 12, and 24 h after death. The bodies were kept at +4 degrees C. The plasma samples were analyzed for total cholesterol (TC), triglycerides (TG), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I).

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part II. Lipid and glycosaminoglycan analysis of intima and inner media.

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia.

Characterization of two lipoproteins containing apolipoproteins B and E from lesion-free human aortic intima.

Lesion-free areas of aortic intimas from seven men, 30 to 49 years old, were extracted with aqueous buffer within a few hours after an accidental or sudden death. Two lipoprotein fractions could be isolated by density gradient ultracentrifugation from all cases. The mean composition of fraction I (d less than 1.

Glycosaminoglycans and apolipoproteins B and A-I in human aortas. Chemical and immunological analysis of lesion-free aortas from children and adults.

To study changes in the contents of plasma lipoproteins in human arteries with age and the relationship of lipoproteins with other arterial constituents, we analyzed the contents of apolipoproteins B (apo B) and A-I (apo A-I), free and esterified cholesterol, and glycosaminoglycans (GAG) in lesion-free aortic intimas of 30 children and adults. The content of apo B increased significantly with age, whereas that of apo A-I remained relatively constant. Apo B and apo A-I had significant positive correlations with the content of chondroitin sulphates A + C (CS A + C), which comprised 35% to 47% of the aortic GAG.

Atherosclerosis and biochemical composition of coronary arteries in Finnish men. Comparison of two populations with different incidences of coronary heart disease.

Men in Eastern Finland show a substantially higher rate of coronary heart disease (CHD) than men in the Western part of the country. To study possible differences in the biochemical composition and atherosclerotic involvement of coronary arteries between these two populations, we analyzed major lipid and non-lipid components of coronary arteries from 15- to 60-year-old Finnish men after accidental death. The material consisted of 59 age-matched pairs from East and West Finland, respectively, collected at successive autopsies during 1979-1983.

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part 1. Scanning and transmission electron microscopic study.

Endothelial cell damage is considered to be the primary event in atherogenesis. In this study we compared the effects of mild hypercholesterolemia and repeated E. coli endotoxin infusions on the endothelial cells of the coronary arteries of the pig.

The effect of proteoglycans, collagen and lysyl oxidase on the metabolism of low density lipoprotein by macrophages.

To study the interactions of lipoproteins, connective tissue components and cells, mouse peritoneal macrophages were incubated in the presence of human low density lipoproteins (LDL) that had been complexed with pig aortic proteoglycans (PG) or incubated in the presence of soluble collagen and/or lysyl oxidase, which catalyses the formation of cross-linkages in collagen and elastin by oxidising epsilon-amino groups of lysine residues to aldehydes. Soluble and insoluble PG-LDL complexes increased the incorporation of [3H]oleate into cellular cholesteryl esters (CE) 1.6- and 2.

Comparison of different ways of presenting the results of biochemical analyses of human coronary arteries.

Three methods of expressing the results of biochemical analyses of normal and atherosclerotic human coronary intima-medias were compared by calculating the results per unit area of vessel surface to obtain the content, per unit weight of dry defatted tissue (d.t.) to obtain the concentration, and per unit weight of organic d.

Glycosaminoglycans in normal and atherosclerotic human coronary arteries.

Glycosaminoglycans (GAGs) were studied in normal and atherosclerotic coronary arteries of 15- to 60-year-old Finnish men who had died accidentally. The GAGs were fractionated and quantified with electrophoretic techniques. The contents of sulfated GAGs (micrograms/cm2 vessel surface area) increased continuously until 20 to 30% of the vessel surface area was covered with fibrous plaques, after which they started to decrease.

Biochemical composition of coronary arteries in Finnish children.

To study the early features of atherosclerosis, we analyzed coronary artery intima medias from 63 boys and 30 girls who were newborn to 15 years old at the time of accidental death. Fatty streaks were found in five boys and one girl and, with one exception, were not present until the second decade of life. From birth there was a continuous increase in esterified cholesterol (EC) and a two- to threefold rise in free cholesterol and phospholipid.

Effect of post-mortem time on the biochemical composition of coronary arteries.

The effects of post-mortem autolysis on the biochemical composition of coronary intima-medias were studied by keeping the coronary arteries of 25 slaughterhouse pigs at +4 degrees C for periods up to 7 days. The samples were analysed for DNA, total protein, collagen, glycosaminoglycans (GAGs), free and esterified cholesterol, triglycerides, phospholipid fractions, and fatty acid composition in various lipid classes. The content of sulphated GAGs decreased steadily, whereas that of hyaluronic acid remained unchanged.