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W Palinski

Publications and source records attributed to W Palinski.

81 records · Page 5Linked to original sources
PubMed1988

Concomitant release of sialic acids and calcium by neuraminidase from rat aorta in situ.

Male Wistar rats were heparinized and killed with pentobarbital. The upper and lower ends of the aortae were cannulated and the blood was washed out with saline until the washings contained calcium and sialic-acid-reacting material at minimal concentrations. The aortae were perfused with neuraminidase for 15 min. This caused the appearance of calcium as well as of sialic acids in the perfusate in total amounts of about 5.3 nmol and about 3.6 nmol per aorta respectively. The molar ratio of about 1.5 is sufficiently close to that determined for the association of calcium with sialic acids in vitro to suggest that their association is similar in vivo.

Animals↗
PubMed1987

Comparison of uptake and degradation of low density lipoproteins by arteries and veins of rabbits.

The uptake and degradation of low density lipoproteins were compared in arteries and veins of rabbits in vivo. Rabbits were injected with low density lipoproteins labelled singly with 125I (125I-LDL) or doubly with 131I and with [125I]tyramine cellobiose (TC-LDL) which remains trapped intracellularly. After increasing times up to 24 h the largest vessels were perfused to remove blood, fixed in situ and excised. When the uptake of 125I-LDL by arteries and veins was compared on the basis of luminal surface area, there were no significant differences up to 3.5 h. When degradation rates of double labelled LDL were compared after 24 h on the same basis, the arteries contained significantly more TC label than the veins, but when the comparison was based on dry weights there were no significant differences. These results show that veins, like arteries, take up LDL from the circulating blood; and they suggest that the preferential accumulation of LDL in arteries susceptible to atherosclerosis may be accounted for, at least in part, by more degradation of LDL in arteries than in veins.

Animals↗
PubMed1985

Unusually high concentrations of sialic acids on the surface of vascular endothelia.

Sialic acids present on luminal surfaces of vascular endothelium were determined by perfusing neuraminidase free of proteolytic activity through carotid arteries, iliac arteries and jugular veins of anaesthetized rabbits and guinea-pigs and through human umbilical veins. Total sialic acids released in I h from arteries and veins, determined fluorimetrically, were 24-51 X 10(6) molecules/micron 2 endothelial surface; this was more, by up to two orders of magnitude, than sialic acids releasable by neuraminidase from other types of cells, i.e. from 0.15 X 10(6) for human erythrocytes to 15 X 10(6) for human platelets. Sialic acids therefore provide extraordinarily high negative charge densities on vascular surfaces exposed to the flowing blood. As all circulating cells are also negatively charged, strong electrostatic repulsion must exist between them and normal vessel walls. These observations can therefore account for the general property of non-adherence of circulating cells in normal blood vessels of which the so-called 'non-thrombogenicity', meaning the non-adherence of platelets to normal vascular endothelium, is one example. It is suggested that a major biological function of these extraordinarily high negative charge concentrations is the mutual repulsion between endothelial surfaces and blood cells which promotes their unimpeded circulation.

Animals↗
PubMed1984

Pressure-induced metabolic activation of platelets demonstrated in vitro by determination of malondialdehyde formation.

Platelet rich plasma (PRP) exposed in vitro to 200 mm Hg above atmospheric pressure showed a significant increase in malondialdehyde (MDA) formation compared to PRP at atmospheric pressure. This difference is also evident when platelets are incubated with arachidonic acid. The increase of MDA demonstrates that the increased beta-thromboglobulin and platelet factor 4 in plasma and the shape changes of platelets after pressure stimulation in vitro that were described in a previous paper result from the release reaction. Pressure-induced effects in vivo are discussed.

Blood Platelets↗
PubMed1983

Influence of platelet activation of erythrocyte deformability.

Erythrocyte deformability was demonstrated to be influenced by platelet activation. Deformability of erythrocytes suspended in autologous platelet poor plasma (PPP), obtained from platelet rich plasma (PRP), was significantly reduced when PRP had previously been incubated with a platelet activating substance (arachidonic acid, adrenaline or ADP). The possibility of a direct influence of the activating substance on erythrocyte deformability was examined and malondialdehyde formation was determined as an indicator of platelet activation. Erythrocyte deformability was not impaired when endoperoxide formation in platelets was blocked by an inhibitor of cyclooxigenase (acetylsalicylic acid). Plasma viscosity was not influenced by platelet activation as demonstrated by filtration and viscosimetry. Recent studies showed that prostacyclin (PGI2) increases erythrocyte deformability (1). The antagonistic action between prostacyclin released by vessel walls and products of platelet metabolism being well known, we discuss possible mechanisms of this effect and pathophysiological relevance of our results.

Aspirin↗
PubMedDate not supplied

Radiolabeled MDA2, an oxidation-specific, monoclonal antibody, identifies native atherosclerotic lesions in vivo.

BACKGROUND: Oxidatively modified low-density lipoprotein (LDL) is present in atherosclerotic but not normal arteries and plays a crucial role in the pathogenesis and adverse consequences of atherosclerotic lesions. We previously generated a series of monoclonal antibodies (MoAb) against oxidation-specific neo-epitopes formed during the oxidative modification of LDL. MDA2, a prototype MoAb, recognizes malondialdehyde-lysine epitopes (eg, in malondi-aldehyde-modified LDL) within atherosclerotic lesions. We describe the in vivo characteristics of MDA2 and initial noninvasive imaging studies of atherosclerosis in rabbits. METHODS: To assess the in vivo specificity of MDA2 for atherosclerotic lesions, iodine 125-MDA2 was intravenously injected into 7 LDL-receptor deficient Watanabe heritable hyperlipidemic (WHHL) and 2 normal New Zealand white (NZW) rabbits, and the aortic plaque uptake was evaluated 24 hours later. 125I-Halb, an isotype-matched irrelevant MoAb that binds to human albumin, was injected into 5 WHHL and 2 NZW rabbits as a control. Aortic autoradiography was performed, and the mean uptake of MoAbs was measured as the percent injected dose per gram aortic tissue. Gamma camera imaging was then carried out in 7 WHHL rabbits and 2 NZW rabbits with 99mTc-MDA2. Imaging was carried out at 10 minutes and at 12 or 24 hours. Malondialdehyde-LDL was then injected to clear the blood pool signal, and final images were obtained 2 hours later. RESULTS: Mean uptake of 125I-MDA2 in the entire aorta was 17.4-fold higher in WHHL than in NZW aortas (P < .001), and 2.8-fold higher than 125I-Halb in WHHL aortas. 125I-MDA2 also had higher specificity for lesioned areas than 125I-Halb (plaque/normal ratio 6.3 vs 2.9, P < .001). Autoradiograph of aortas of 125I-MDA2-injected WHHL rabbits revealed uptake in lipid-stained lesions with absence of signal in adjacent normal arterial tissue. Immunostaining of WHHL lesions, which accumulated MDA2 as noted on autoradiography, revealed that uptake was highest in areas with abundant foam cells and in lipid-rich necrotic core areas. Autoradiograph of aortas from NZW rabbits injected with 125I-MDA2 did not yield any visible signal. Planar gamma camera in vivo scintigraphy revealed a visible signal in 4/7 WHHL rabbits, which was confirmed by aortic Sudan staining. CONCLUSION: Radiolabeled MDA2 shows excellent in vivo uptake and specificity for atherosclerotic lesions containing abundant oxidation-specific epitopes. The in vivo imaging studies suggest that noninvasive imaging of oxidation-rich atherosclerotic lesions with radiolabeled MDA2 may be feasible in human beings with optimization of the imaging methods.

Animals↗
PubMedDate not supplied

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. The present article characterizes an antiserum and monoclonal antibody (MAL-2 and MDA2, respectively) specific for MDA-lysine, and an antiserum and monoclonal antibody (HNE-6 and NA59, respectively) specific for 4-HNE-lysine. In addition, a monoclonal antibody (OLF4-3C10) was developed against an as yet undefined epitope generated during Cu++ oxidation of LDL. With these antibodies, we demonstrated that MDA-lysine and 4-HNE-lysine adducts develop on apo-lipoprotein B during copper-induced oxidation of LDL in vitro. The application of these antibodies for immunocytochemical demonstration of oxidized lipoproteins in atherosclerotic lesions of progressive severity is described in the companion article. These antibodies should prove useful in studying the role of oxidatively modified lipoproteins as well as other oxidatively modified proteins in atherogenesis.

Aldehydes↗
PubMedDate not supplied

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. In more advanced lesions containing areas with reduced numbers of cells, there was increased extracellular, diffuse staining with the antibodies against oxidation specific epitopes and co-localization with apoprotein B. In addition, there were annular staining patterns associated with the necrotic core and increased staining of intimal and medial smooth muscle cells. We interpret these data as suggesting that in areas of lesions rich in macrophages, LDL is oxidized and taken up by the cells. In more advanced lesions that are relatively devoid of macrophages, both native and oxidized LDL, as well as oxidation products released from dead and decaying cells, are trapped in the matrix, out of reach of those cells capable of accumulating oxidized LDL.

Animals↗