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Biomedical subjects

G Hollander

Publications and source records attributed to G Hollander.

At least 37 records · Page 2Linked to original sources
PubMed1993

Coronary atherectomy versus angioplasty: the CAVA Study.

Directional coronary atherectomy was developed with the hope that it would lower the risk of acute closure and restenosis by leaving a larger smoother lumen and fewer dissections than angioplasty. To evaluate this hypothesis, we compared the clinical and angiographic results of directional coronary atherectomy with those of percutaneous transluminal coronary angioplasty in well-matched groups. We studied 126 consecutive atherectomies and 127 angioplasties performed on similar lesions. Procedural results were evaluated with regard to dissections, complications, acute closure, and residual stenosis. Each patient's clinical course was followed, and each patient was contacted at 6 months for evaluation of recurrent angina, need for repeat catheterization, and angiographic rate of restenosis. Baseline clinical and angiographic characteristics of the two groups were well matched and met the criteria established as being appropriate for atherectomy. The angiographic success rate was 98% after angioplasty and 99% after atherectomy. There were fewer dissections after atherectomy (13%) compared with the number after angioplasty (22%; p = 0.03). Residual stenosis was 8.3 +/- 9% after atherectomy compared with 15 +/- 12% after angioplasty (p = 0.0001). However, there were more complications after atherectomy (p = 0.03). There was no significant difference between the two groups in the recurrence rate of angina or in the angiographic restenosis rate at 6 months. It was concluded that when lesion characteristics and vessel size are appropriate for atherectomy, the procedural success rate of either atherectomy or angioplasty is extremely high. Although atherectomy leads to a larger residual lumen and fewer dissections, the complication rate after atherectomy is higher than that after angioplasty. There is a trend toward more occlusions after atherectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Macrophage-conditioned medium and beta-VLDLs enhance cholesterol esterification in SMCs and HSFs by LDL receptor-mediated and other pathways.

Thioglycolate-elicited mouse peritoneal macrophages were incubated for 24 hours in serum-free Dulbecco-Vogt medium containing 0.5% fatty acid-poor bovine serum albumin. This conditioned medium, designated MP medium, was used for experiments with bovine aortic smooth muscle cells (SMCs) or human skin fibroblasts (HSFs). Dulbecco-Vogt medium of the same albumin content but without macrophages served as a control medium. In SMCs labeled from plating the [3H]cholesterol and incubated with hypercholesterolemic rabbit beta-very-low-density lipoprotein (beta-VLDL) in Dulbecco-Vogt medium for 24 hours, there was an increase in cellular [3H]cholesteryl ester (CE) content compared with cells incubated without lipoprotein. When MP medium was used for the incubation of SMCs with beta-VLDL, cellular [3H]cholesteryl ester content increased threefold compared with cells incubated with Dulbecco-Vogt medium. A smaller increase in cholesterol esterification in the presence of MP medium was also encountered with low-density lipoprotein (LDL). The MP medium-induced increase in [3H]cholesterol esterification was not evident up to 6 hours of incubation. Similar results were also obtained with HSFs. The increase in [3H]cholesterol esterification with MP medium in the presence of beta-VLDL was also elicited in cells obtained from LDL receptor-negative donors with familial hypercholesterolemia (FH-HSF), even though in these cells significantly less [3H]cholesteryl ester was formed in the presence of beta-VLDL. MP medium contains numerous agents that could be responsible for the increase in cellular [3H]cholesteryl ester induced by lipoproteins. The first considered was lipoprotein lipase, but lack of inhibition of the MP medium effect by antiserum to lipoprotein lipase did not support this possibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Persistence of increased cholesteryl ester in human skin fibroblasts is caused by residual exogenous sphingomyelinase and is reversed by phospholipid liposomes.

Human skin fibroblasts (HSF) were exposed to sphingomyelinase 50 or 5 mU/ml for 60 min, washed with 5 mM EDTA or 20% serum and with phosphate-buffered saline, and postincubated for 24 h in the presence of [14C]16:0 sphingomyelin (SP) liposomes. The recovery of up to 48% of label in the medium in ceramide provided evidence of persistence of sphingomyelinase activity. The rate of hydrolysis of [14C]16:0 SP remained the same irrespective of whether the liposomes were added immediately after the wash, or 3 or 6 h thereafter. In HSF labeled with [3H]cholesterol exposure to 50 mU/ml of sphingomyelinase for 60 min resulted in an increase in labeled cholesteryl ester (CE) at 6 and 24 h of postincubation. Addition of sphingomyelin liposomes reduced markedly the fraction of cellular labeled cholesteryl ester recovered after 24 h, while phosphatidylcholine liposomes were not effective. When the enzyme concentration had been reduced 5-20 fold the effect of sphingomyelin liposomes on cellular 3H-CE was evident already after 6 h of postincubation and some effect was seen also with phosphatidylcholine liposomes. Increase in the concentrations of SP liposomes to 150 micrograms/ml restored labeled cholesteryl ester to control values at 24 h. A significant reduction occurred also with 18:1 phosphatidylcholine liposomes but labeled cholesteryl ester remained 50-100% higher when compared with 18:1 or 18:2 SP. No correlation was seen between the rates of cholesteryl ester decrease and free cholesterol efflux into the medium. The inability to remove residual sphingomyelinase by regular washing procedures exaggerates and prolongs the recovery period of sphingomyelin during postincubation and delays the return of the cholesteryl ester pool to control levels. This can be counteracted by addition of phospholipid liposomes that can compete for the enzyme with the plasma membrane sphingomyelin and also substitute the hydrolyzed molecule in the plasma membrane to impede cholesterol flow to cell interior.

Cells, Cultured↗
PubMed1992

Modulation of sphingomyelinase-induced cholesterol esterification in fibroblasts, CaCo2 cells, macrophages and smooth muscle cells.

The present study has focused on three questions concerning the effect of sphingomyelinase on release of free cholesterol from the plasma membrane and its intracellular translocation: (i) Can one change the direction of the flow of cholesterol? (ii) Can one modulate the flow? (iii) May such a mechanism be relevant in atherogenesis? (i) The results obtained show that even in the presence of potent nonlipoprotein cholesterol acceptors in the medium, the intracellular flow of cholesterol is not reduced as measured by cholesterol esterification. Moreover, in sphingomyelinase-treated cells, cholesterol efflux in presence of nonlipoprotein acceptors was not enhanced even when intracellular esterification was inhibited. (ii) Modulation of the sphingomyelinase induced cholesterol flow can be obtained by 100 microM verapamil which reduces it. In human skin fibroblast, interference with the delivery of free cholesterol to its site of esterification was found in the presence of brefeldin A. (iii) Aortic smooth muscle cells in culture are sensitive to low concentrations of sphingomyelinase and the increase in esterified cholesterol is evident also after exposure to the enzyme for 24 h. The present results suggest that in the plasma membrane, free cholesterol bound to sphingomyelin may be in a compartment which renders it more available for transport to the cell interior than for efflux. In view of the sensitivity of aortic smooth muscle cells to sphingomyelinase, this mechanism for enhanced esterification of cholesterol could be relevant to the transformation of arterial smooth muscle cells into foam cells in the process of atherogenesis.

Brefeldin A↗
PubMed1992

Dissimilar effects of Brefeldin A on cholesteryl ester and triacylglycerol metabolism in CaCo2 and HepG2 cells as compared to peritoneal macrophages.

The effect of Brefeldin A (BFA) on lipid metabolism was studied in two cell lines and in primary cultures of peritoneal macrophages. In both CaCo2 and HepG2 cells, which are models for human liver and intestine, addition of BFA resulted in a 2-10-fold increase in recovery of labeled cholesteryl ester when the cells had been prelabeled with free cholesterol or with [3H]oleic acid. This effect was linear for up to 6 h and could be elicited with doses of BFA as low as 0.03 micrograms/ml. The increase in cholesteryl ester induced by BFA was completely abolished by the ACAT inhibitor (Sandoz 58-035) and partly by forskolin. Intracellular hydrolysis of labeled cholesteryl ester was studied in the presence of the ACAT inhibitor and while in the controls 30-40% was hydrolyzed in 6 h, the values were 7-16% in the BFA treated cells. The slower rate of hydrolysis in the BFA treated cells could not account for the entire increase of cholesteryl ester and there was also no decrease in cholesteryl ester secretion. Even though activation of acyl-CoA:cholesterol acyltransferase by BFA was not demonstrated in cell homogenates, we hypothesize that in the intact cell the BFA induced increase in cholesteryl ester might have been related to the pronounced increase in modified endoplasmic reticulum which results from the dispersion of the Golgi apparatus. In the macrophages, BFA at doses of 0.25-1 micrograms/ml resulted in a 90% reduction in the incorporation of [3H]oleic acid into triacyglycerol. Incorporation of [3H]oleic acid into triacyglycerol in CaCo2 cells was not affected by BFA. In view of the ever-increasing use of BFA in cell biology, it seems important to emphasize that BFA may affect different pathways of lipid metabolism in various cells.

Acetylation↗
PubMed1992

Giant T-wave inversion in patients with acute coronary insufficiency.

We have observed an electrocardiographic (ECG) pattern of deep T-wave or "giant T wave" inversion in patients with acute coronary insufficiency. We reviewed the ECGs of 936 patients admitted to our coronary care unit during a one-year period. We found the pattern of giant T-wave inversion was present in nine patients (1 percent). We examined the echocardiograms of all of these patients and we analyzed the coronary angiograms on the seven patients in whom it was performed. We found that giant T-wave inversion was usually found in patients with stenosis in the left coronary system. In addition, the majority of these patients also had echocardiographic evidence of left ventricular hypertrophy. We conclude that the high frequency of a partially patent vessel in the left coronary system suggests that this ECG pattern may be useful in identifying patients who might benefit from coronary revascularization.

Acute Disease↗
PubMed1991

Metabolism of 3-[3H]sphingosine sphingomyelin labeled with [14C]palmitic or [14C]linoleic acid by Hep G2 cells and rat liver in vivo.

The metabolism of sphingomyelin labeled with 3-[3H]sphingosine and [14C]16:0 or [14C]18:2 fatty acid was studied in cultured Hep G2 cells or macrophages and after injection into rats. In pulse-chase experiments, the loss of 3H and 14C-label was more rapid when the cells had been pulsed with 18:2 than with 16:0 sphingomyelin. At the end of 24 h chase, the labeled ceramide contained more [14C]18:2 fatty acid than [14C]16:0. In addition, the 3H-label derived from 3-[3H]sphingomyelin was recovered also as free sphingosine. After injection in vivo, more [3H]sphingosine-labeled sphingomyelin was present in the liver 3 and 24 h after injection of 16:0 than after injection of 18:2 sphingomyelin. The ratio of [3H]ceramide derived from 16:0 sphingomyelin to that derived from 18:2 sphingomyelin as percent of injected dose was 1.84 3 h after injection and 1.31 after 24 h. The ratio of 3H/14C in liver ceramide was 6.4 3 h after injection of 18:2 sphingomyelin and 3.4 after 16:0 sphingomyelin. The present results show that 3-[3H]sphingomyelin is metabolized quite extensively and that the fate of the sphingosine moiety is related to the type of fatty acid present in the phospholipid. These findings indicate that there is little or no reutilization of 18:2 ceramide for sphingomyelin formation and suggest that sphingosine derived from 18:2 sphingomyelin is channeled primarily for catabolism.

Animals↗
PubMed1991

Removal of cholesteryl ester from hepatic reticuloendothelial cells in vivo is not enhanced by plasma cholesteryl ester transfer protein.

The putative role of cholesteryl ester transfer protein (CETP) in the removal of cholesteryl ester from hepatic reticuloendothelial cells in vivo was studied in hamsters. The parameter tested was retention of [3H]cholesteryl linoleyl ether ([3H]CLE), a nonhydrolysable analog of cholesteryl ester, in the liver after injection of [3H]CLE labeled acetylated LDL, which is targetted to nonparenchymatous littoral cells. In hamsters fed laboratory chow, plasma cholesteryl ester transfer activity (CETA) was 10.6 +/- 0.9 units and the retention of [3H]CLE in the liver 28 days after injection was 86% of the 4 h value. It was about 55% in rats fed the same diet, in which CETA was not detectable. When the diet was supplemented with 2% cholesterol and 15% margarine, CETA activity in hamsters increased 2-fold, yet no change in retention of [3H]CLE in liver was seen after 28 days. In rats, the retention of [3H]CLE in the liver was also not changed by the dietary fat supplementation. These results do not support the role of CETP in vivo in removal of cholesteryl ester from intact reticuloendothelial cells.

Acetylation↗
PubMed1991

Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins.

The effect of fish oil ingestion (10 g MaxEPA/day) on the susceptibility of plasma lipoproteins to peroxidation was examined in 20 smokers (study A and B) and 22 nonsmokers (study C). The subjects were examined at the onset of each study (baseline values), divided into control and experimental groups and reexamined 4 weeks later. Smokers were examined 40 h after abstention from smoking (0 time) and 90 min after acute smoking (4-6 cigarettes). The parameters studied were TBARS, which provide an indication of peroxidative injury, and metabolism of conditioned LDL by macrophages as a biological indicator. These parameters were significantly higher (P less than 0.05-0.001) when the 90 min values of smokers were compared to time 0. After 4 weeks of fish oil ingestion, a significant rise above baseline values (33-50%) in plasma and LDL TBARS was found in smokers examined at time 0 and after acute smoking. Peroxidative modification of LDL isolated from smokers fed fish oil resulted in significantly higher TBARS (34-41%) and its metabolism by macrophages was higher (65-139%) compared to baseline values. In nonsmokers, the baseline values of the above parameters were lower than in smokers. Ingestion of fish oil resulted in a significant rise in TBARS in plasma (33%), LDL (137%), conditioned LDL (36-40%) and metabolism of conditioned LDL (70%) by macrophages. In 6 nonsmokers and 4 smokers, 400 mg of vitamin E/day were given with the fish oil. In the nonsmokers, vitamin E counteracted the effect of fish oil more effectively than in the smokers. In the light of the present results, indiscriminate recommendation of fish oil supplementation to the population at large should be cautioned.

Animals↗
PubMed1991

Exercise-induced ventricular tachycardia in association with a myocardial bridge.

Sustained ventricular tachycardia induced by exercise is uncommon. This is a report of a patient who has a positive exercise test at a high level of exercise. The electrocardiogram has classic ischemic ST depressions. Following the appearance of these ST depressions, the patient developed ventricular tachycardia at a rapid rate. Workup that included an echocardiogram and cardiac catheterization revealed myocardial bridging of the left anterior descending artery as the only structural abnormality. Electrophysiologic studies revealed the patient to have ventricular tachycardia only with isoproterenol (Isuprel) infusion.

Adult↗
PubMed1990

Cholesteryl ester transfer activity in hamster plasma: increase by fat and cholesterol rich diets.

We investigated the presence of cholesteryl ester transfer activity (CETA) in plasma of hamsters kept on various dietary regimens. In hamsters kept on a regular diet, CETA activity was about 5 units/4 mg protein of d greater than 1.21 g/ml fraction of plasma, as compared to about 35 units present in human d greater than 1.21 g/ml fraction. Addition of 15% margarine or butter alone or together with 2% cholesterol resulted in a 2-3-fold increase in plasma CETA. The increase in plasma CETA was correlated with plasma cholesterol levels (r = 0.78; P less than 0.001) and plasma triacylglycerol levels (r = 0.56, P less than 0.001). Hamsters consuming the cholesterol + butter-supplemented diets had the highest plasma CETA, cholesterol and triacylglycerol levels, while CETA in plasma of rats and mice remained nondetectable even after 4 weeks on the diet. The causal relation between hypercholesterolemia, hypertriglyceridemia and evaluation in CETA in hamsters remains to be elucidated.

Animals↗
PubMed1990

Effect of vitamin C and E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking.

The effect of acute smoking on plasma lipoproteins was studied in seventeen smokers. In study 1, 7 subjects were examined prior to and 2 weeks after supplementation with vitamin C. In study 2, the effect of acute smoking was first determined in 10 additional subjects and subsequently they were divided into 3 groups, 3 and 4 subjects were supplemented with vitamin C or E, respectively, for 4 weeks, and 3 remained untreated. Plasma and LDL TBARS were examined at time zero (i.e., 40-48 h after total abstention from smoking) and at 90 min after acute smoking (5-7 cigarettes). In all 17 subjects examined prior to vitamin supplementation, significantly higher TBARS values were found in plasma, native LDL and LDL conditioned with smooth muscle cells (SMC) when the 90 min values were compared to 0 time. The LDL isolated after 90 min and conditioned with SMC was metabolized more extensively by mouse peritoneal macrophages than its zero time counterpart. The differences between the 0 time and 90 min values were not seen after the subjects had been supplemented with vitamin C for 2 or 4 weeks or with vitamin E for 4 weeks. The present results indicate that acute smoking exerts an oxidative stress on plasma lipoproteins and that higher plasma levels of natural antioxidants, such as vitamins C and E have a protective role.

Adult↗
PubMed1989

Cholesterol removal by peritoneal lavage with phospholipid-HDL apoprotein mixtures in hypercholesterolemic hamsters.

Syrian hamsters were rendered hypercholesterolemic by supplementation of their diet with 1% cholesterol and 15% butter. The hamsters were injected intraperitoneally (i.p.) with about 20 mg of phospholipid liposomes containing trace amounts of [3H]cholesteryl linoleyl ether ([ 3H]CLE) alone or combined with 10 mg delipidated high-density lipoprotein (apoHDL). After 2 h the peritoneal cavity was washed repeatedly with up to 15 ml phosphate-buffered saline. 60%-70% of [3H]CLE were retained after i.p. injection without apoHDL, 30-50% in the presence of apoHDL. The amount of free cholesterol recovered in the peritoneal lavage was significantly higher when apoHDL was combined with 18:2 sphingomyelin or dilinoleyl phosphatidylcholine liposomes, when compared to either liposomes or apoHDL alone. It is suggested that supplementation of dialysate with HDL apolipoproteins and phospholipids in patients undergoing continuous peritoneal dialysis could be of use in a cholesterol depletion regimen.

Animals↗
PubMed1989

Effects of occlusion of the left anterior descending coronary artery during angioplasty on right-sided cardiac pressures and electrocardiographic changes.

Controversy persists regarding the presence and extent of right ventricular involvement with acute anterior injury. Also unclear are the incidence and significance of ST elevations in the right-sided leads in acute left anterior descending artery occlusion. Baseline and coronary occlusion hemodynamics and 15-lead electrocardiograms (addition of RV3 through RV5) were recorded in 42 patients during 32 left anterior descending and 13 right coronary artery angioplasties. The right coronary and left anterior descending artery angioplasties had similar baseline right and left ventricular hemodynamics, as well as identical right atrial to pulmonary wedge pressure ratios (0.51 right coronary vs 0.51 left anterior descending). Whereas the right coronary and left anterior descending occlusions produced similar elevations in right ventricular filling pressures, the left anterior descending occlusions produced greater elevations in left ventricular filling pressures. The right atrial to pulmonary wedge ratio increased with right coronary occlusions, but was unchanged with left anterior descending occlusions (0.79 right vs 0.46 left, p less than or equal to 0.0001). Presence of right-lead ST elevations in 10 left anterior descending occlusions did not con-note increased right ventricular filling pressures, but did suggest increased left ventricular ischemia and dysfunction. In conclusion, right ventricular dysfunction, as manifested by increased filling pressures, is seen with both right coronary and left anterior descending occlusions. Although it is the predominant abnormality in right coronary occlusions, in left anterior descending occlusions it is proportional to left ventricular dysfunction. ST elevations in a right lead with left anterior descending occlusions do not constitute a marker for increased right ventricular dysfunction.

Angioplasty, Balloon↗
PubMed1989

Divergent fate of unsaturated and saturated ceramides and sphingomyelins in rat liver and cells in culture.

The metabolism of sphingomyelins and ceramides with defined labeled fatty acids was compared after injection in vivo or incubation with cultured cells. The liver was the major site of uptake of sphingomyelins and ceramides with 18:2 or 16:0 fatty acids, but with both sphingolipids a higher recovery of radioactivity was found with 16:0 species. The distribution of radioactivity among liver lipids showed that 1.5 h after injection of 18:2 sphingomyelin, only 21% of the label was found as sphingomyelin, and this value was 37% in the case of 16:0 sphingomyelin. There was a very marked difference in the metabolism of 18:2 and 16:0 ceramides. After injection of 18:2 ceramide only 14% of the radioactivity was recovered as sphingomyelin, and this value was more than 50% with 16:0 ceramide. [14C]18:2 ceramide was converted also to glucoceramide and hydrolyzed more extensively than 16:0 ceramide. These observations were extended to sphingomyelins and ceramides with other fatty acids, using Hep-G2 cells in culture. Significantly more radioactivity was recovered as labeled sphingomyelin after incubation with 16:0, 18:0, 20:0 and 24:0 sphingomyelins than with 18:1 and 18:2 sphingomyelins, while more labeled phosphatidylcholine and phosphatidylethanolamine were found with the unsaturated sphingomyelins. In analogy to the findings in vivo, in the Hep-G2 cells more 16:0, 18:0 and 24:0 ceramides were converted to sphingomyelin than 18:1 or 18:2 ceramides. These differences were also seen with cultured macrophages, in which a more marked reutilization for sphingomyelin formation was found with the saturated ceramide series. The sphingomyelin liposomes were tested also for their capacity to mobilize cholesterol, and a rise in plasma unesterified cholesterol occurred after injection of 18:2 sphingomyelin. Marked enhancement of cholesterol efflux from cholesterol ester-loaded macrophages was also seen with 18:1 and 18:2, 20:0 sphingomyelin in the presence of delipidated high-density lipoprotein. The present results demonstrate that the metabolic fate of sphingolipids is related to their fatty acid composition. While ceramides with saturated fatty acids are predominantly reutilized for sphingomyelin formation, those with unsaturated fatty acids undergo probably more rapid hydrolysis with liberation of fatty acids and channeling into glycerolipids.

Animals↗