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Biomedical subjects

A A Spector

Publications and source records attributed to A A Spector.

At least 199 records · Page 11Linked to original sources
PubMed1976

Modification of the Ehrlich ascites tumor cell nuclear lipids.

The fatty acid composition of Ehrilich ascites tumor cell nuclei was differend when the tumor-bearing mice were fed diets rich in either coconut or sunflower oil. When coconut oil was fed, the monoenoic fatty acid content of many of the nuclear lipids was increased and their polyenoic fatty acid content was reduced as compared with the sunflower oil diet. By contrast, only small changes were produced in the saturated fatty acid contents of the nuclear lipids. The nuclear membrane choline phospholipid, ethanolamine phospholipid and combined serine phospholipid plus inositol phospholipid fractions exhibited statistically significant changes in fatty acid composition, but the sphingomyelins were not altered appreciably by dietary lipid modification. The fatty acid composition of the small quantity of phospholipids associated with the chromatin was much more resistant to diet-induced mosification. Except for sphingomyelin, the fatty acid composition of the chromatin phospholipids was different from that of the corresponding nuclear membrane phospholipids, containing much larger amounts of fatty acids having less than 16 carbon atoms. The fatty acid compositons of the nuclear triaclglycerols and cholesterol esters, which were associated almost entirely with the chromatin, were modified by the dietary lipid modifications. There were no changes in the DNA, RNA or lipid content of these nuclei. Therefore, this experimental system can be used to prepare mamalian nuclei that differ appreciably only in their fatty acyl composition.

Animals↗
PubMed1976

Modification of the fatty acid composition of Ehrlich ascites tumor cell plasma membranes.

The fatty acyl group composition of Ehrlich ascites tumor cell plasma membranes was modified by feeding the tumor-bearing mice diets rich in either coconut or sunflower oil. When coconut oil was fed, the oleate content of the membrane phospholipids was elevated and the linoleate content reduced. The opposite occurred when sunflower oil was fed. Qualitatively similar changes were observed in the plasma membrane phosphatidylethanolamine, phosphatidylcholine and mixed phosphatidylserine plus phosphatidylinositol fractions. These diets also produced differences in the sphingomyelin fraction, particularly in the palmitic and nervonic acid contents. Unexpectedly, the saturated fatty acid content of the plasma membrane phospholipids was somewhat greater when the highly polyunsaturated sunflower oil was fed. The small quantities of neutral lipids contained in the plasma membrane exhibited changes in acyl group composition similar to those observed in the phospholipids. These fatty acyl group changes were not accompanied by any alteration in the cholesterol or phospholipid contents of the plasma membranes. Therefore, the lipid alterations produced in this experimental model system are confined to the membrane acyl groups.

Animals↗
PubMed1976

Changes in (Na+ + K+)-ATPase activity of Ehrlich ascites tumor cells produced by alteration of membrane fatty acid composition.

The fatty acid composition of plasma membrane derived from Ehrlich ascites tumor cells was altered in vivo by changing the dietary lipid of the tumor-bearing mice. The activity of (sodium + potassium)-adenosinetriphosphatase ((Na+ + K+ATPase), in partially purified plasma membranes, was measured ass a function of temperature. Arrhenius plots of the data were biphasic. Striking differences, dependent on the membrane fatty acid composition, were observed in the transition temperature and in the energies of activation below the transition temperature. The transition temperatures for the (Na+ + K+)-ATPase of plasma membrane derived from tumor cells grown in mice fed a regular chow diet containing a mixture of fatty acids (PMC), a 16% sunflower oil diet (PMSU), or a 4% tristearin diet (PMTS) were 20, 21, and 13.5 degrees C, respectively...

Adenosine Triphosphatases↗
PubMed1976

Characterization of the Ehrlich ascites tumor plasma lipoproteins.

1. The lipoproteins of the Ehrlich ascites tumor plasma were separated into 3 distinct fractions, very low density, low density and high density lipoproteins by preparative ultracentrifugation combined with agarose column chromatography. 2. High density lipoproteins contained 74% of the total protein in the lipoproteins. By contrast, most of the lipids were present in the very low density lipoprotein fraction. 3. The fatty acid compositions of the cholesteryl esters were appreciably different in the very low, low and high density lipoproteins, whereas phospholipid and triacylglycerol fatty acid compositions were quite similar in the 3 lipoprotein fractions. 4. Very low and high density apoprotein electrophoretic patterns on sodium dodecyl sulfate-acrylamide gels were similar to those observed in the corresponding lipoprotein fractions obtained from other mammalian species. The low density fraction, however, contained 7 apoprotein bands, and 32% of the low density apoprotein was soluble in tetramethyl urea. 5. The average molecular weights as determined by analytical ultracentrifugation were 2-10(7) (very low density), 6-10(6) (low density) and 4.4-10(5) (high density).

Animals↗
PubMed1976

Regression of atherosclerotic stenosing lesions of the renal arteries and spontaneous cure of systemic hypertension through control of hyperlipidemia.

We describe a 49 year old woman with impressive regression of renal artery stenosing atherosclerotic lesions in response to sustained excellent control of hyperlipidemia. Initially, she had high blood pressure necessitating combined drug therapy with chlorothiazide, methyldopa and propranolol, with only moderately satisfactory control. Renal arteriography revealed a 90 per cent stenosing lesion of the right renal artery and 75 per cent narrowing of the left renal artery. Peripheral vein plasma renin was markedly increased at 32 ng/ml. With a combination of cholestyramine and clofibrate, serum lipids were maintained at normal values for several years. Increased blood pressure diminished spontaneously, and the patient has maintained normal blood pressures after discontinuation of antihypertensive therapy. Repeat renal arteriograms showed almost complete regression of the right renal artery lesion and a possible decrease in left renal artery disease. Peripheral vein plasma renin became normal at 3 ng/ml. This case illustrates that sustained control of hyperlipidemia could lead to regression of atherosclerotic nodules and impressive clinical improvement in certain patients.

Arteriosclerosis↗
PubMed1976

Differences in free fatty acid and glucose metabolism of human blood neutrophils and lymphocytes.

Comparison of isolated human neutrophils and lymphocytes in short-term tissue culture revealed marked differences in their rates of lipid biosynthesis. Ficoll-Hypaque gradients were used to separate lymphocytes and neutrophils from the blood of normal subjects. Neutrophils incorporated more palmitate into cell lipids (151.0 +/- 16.6 nmole/hr/10(8) cells) than lymphocytes (41.6 +/- 4.1). By contrast, the lymphocytes oxidized more palmitate (8.3 +/- 0.5 nmole/hr/10(8) cells) as compared to neutrophils (1.1 +/- 0.1). The greater fatty acid uptake by the neutrophils was due to a sixfold greater rate of incoporation of palmitate into their triglyceride fraction. Triglyceride synthesis by neutrophils increased as the molar ratio of free fatty acid to albumin was raised, whereas incorporation into phospholipids remained relatively constant; there was preferential labeling of neutrophil triglycerides throughout the physiologic range. Studies using linoleate and oleate gave similar results. The distribution of radioactivity into various phospholipids determined by thin-layer chromatography was similar for the two cell types. When labeled glucose was used as a substrate to measure incorporation primarily into the glycerol backbone of the cell lipids, neutrophils incorporated more radioactivity into total lipids and triglycerides than lymphocytes. These results indicate that neutrophils take up much more fatty acid than lymphocytes primarily because they synthesize much larger quantities of triglycerides, a storage form. Since cellular triglycerides may act as a source of fatty acid for lecithin synthesis during phagocytosis, the greater rate of fatty acid incorporation in the neutrophil may reflect a metabolic pattern that permits efficient phagocytosis.

Blood Glucose↗
PubMed1976

Abnormalities of cholesterol turnover in hypercholesterolemic (type II) patients.

Cholesterol turnover was measured in 5 normal subjects and 14 familial hypercholesterolemic (Type II) patients. All patients were fed eucaloric cholesterol-free or very low cholesterol formula or mixed-food diets. They were given single doses of cholesterol-1,2-3H and cholesterol-4-14C simultaneously, one isotope intravenously (IV), and the other orally. Plasma cholesterol specific radioactivity decay curves for 3H and 14C isotopes in each patient conformed to the short-term (10 to 12 weeks) kinetics of the two-pool model. In type II patients, the total mass of cholesterol in pool A was significantly larger by about 17 Gm. (by the IV method) and 27 Gm. (by the oral method) as compared with normal subjects. The increase in size of pool A in Type II patients occurred equally in plasma and tissues comprising pool A (probably liver and intestine). The rate constant for the excretion of cholesterol from pool A was significantly reduced in the Type II patients. The rate constant for the transfer of cholesterol from pool A to pool B was also reduced in the Type II patients. Furthermore, the metabolic clearance fraction was decreased by 50 per cent as compared with normal subjects. In normal subjects and in Type II patients, the size of pool A was significantly larger by about 5 Gm. and 15 Gm., respectively, by the oral method as compared with the IV method. This difference in the size of pool A probably reflects differences in isotopic equilibration with the intestinal mucosal cholesterol pool. All other parameters of cholesterol turnover by the IV method as compared with the oral method were similar. Our results suggest that the expanded rapidly exchangeable pool of cholesterol (pool A) is due to a defect in cholesterol transport and excretion in familial hypercholesterolemia (Type II). The decreased rate of removal of cholesterol from the plasma and/or catabolism in tissues could be one important cause of familial hypercholesterolemia in man.

Administration, Oral↗
PubMed1975

Fatty acid biosynthesis in Erlich cells. The mechanism of short term control by exogenous free fatty acids.

We have examined the mechanism by which extracellular free fatty acids regulate fatty acid biosynthesis in Ehrlich ascites tumor cells. De novo biosynthesis in intact cells was inhibited by stearate greater than oleate greater than palmitate greater than linoleate. The amount of citrate and long chain acyl-CoA in the cells was not changed appreciably by the addition of free fatty acids to the incubation medium, indicating than free fatty acids do not regulate fatty acid biosynthesis by changing the total intracellular content of these metabolites. By measuring the incorporation of labeled free fatty acids into acyl-CoA, however, it was determined that the fatty acid composition of the acyl-CoA poolwas changed dramatically to reflect the composition of the exogenous free fatty acids. The relative inhibitory effects of different free fatty acids appear to depend on the ability of their acyl-CoA derivatives to regulate acyl-CoA carboxylase activity. The acyl-CoA concentration needed to produce 50% inhibition of purified Ehrlich cell carboxylase was found to be 0.68 mum for stearoyl-CoA, 1.6 mum for oleoyl-CoA, 2.2 mum for palmitoyl-CoA, 23 mum for myristoyl-CoA, 30 mum for lauroyl-CoA, and 37 mum for linoleoyl-CoA. In contrast to their effects on de novo synthesis, all of the free fatty acids added except stearate stimulated chain elongation in intact cells. Microsomal chain elongation, the major system for elongation in Ehrlich cells, also was regulated by the composition of the cellular acyl-CoA pool. Lauroyl-CoA, myristoyl-CoA, and palmitoyl-CoA were good substrates for elongation by isolated microsomes; oleoyl-CoA, and linoleoyl-CoA were intermediate; and stearoyl-CoA was a very poor substrate. We conclude that free fatty acids regulate fatty acid biosynthesis by changing the composition of the cellular acyl-CoA pool. These changes control the rate of malonyl-CoA production and, because of the acyl-CoA substrate specificity of the microsomal elongation system, modulate the amount of malonyl-CoA used for chain elongation.

Acetyl Coenzyme A↗
PubMed1975

Cholesteryl ester accumulation in Ehrlich cells induced by saturated fats.

The cholesteryl ester content of Erhlich cells was increased in tumors grown in mice fed saturated fat diets (coconut oil or tristearin) as compared with polyunsaturated fat diet (sunflower oil). Cholesteryl esters containing monoenoic fatty acids were the predominant species that accumulated in the cells grown on unsaturated fat. The increase in cholesteryl esters was not accompanied by corresponding increases in the cell content of phospholipids, triacylglycerols, unesterified cholestorol or proteins. This experimental system may be useful for obtaining basic information about intracelluar cholesteryl ester accumulation, process that occurs in atherosclerosis.

Animals↗
PubMed1975

Long chain fatty acid binding to human plasma albumin.

The binding of six physiologically important long chain fatty acids to defatted human plasma albumin was measured at 37 degrees in a calcium-free Krebs-Ringer phosphate buffer, pH 7.4. The data were analyzed in terms of multiple stepwise equilibria. With the saturated acids, the magnitude of the equilibrium (association) constants, Ki, increased as the chain length increased: laurate smaller than myristate smaller than palmitate smaller than stearate. Oleate was bound more tightly than stearate; by contrast, linoleate was bound less tightly than stearate. The equilibrium constants, K1 through K12, ranged from 2.4 times 10-6 - 3.5 times 10-3 m-1 for laurate to 2.6 times 10-8 - 3.5 times 10-5 m-1 for oleate. Successive values of Ki decrease for each of the acids, indicating that major cooperative binding effects do not occur over the physiological range of fatty acid concentrations. In no case could the Ki be segregated into distinct classes, suggesting that any grouping of albumin binding sites is somewhat arbitrary. The results were inconclusive concerning whether premicellar association of unbound fatty acid occurs. Although corrections for premicellar association produced very little change in the Ki values for myristate, they raised the Ki for palmitate and stearate by 300 to 700 per cent. A sigmoidal relationship was obtained when the logarithm of Ki was plotted against chain length for the saturated fatty acids containing 6 to 18 carbon atoms, indicating that the binding energy is not simply a statistical process dependent only on the fatty acid chain length. This selectivity that albumin contributes to the binding process may be due to varying degrees of configurational adaptability of its binding sites as the fatty acid increases in length.

Fatty Acids↗
PubMed1975

Metabolism of glucose and fatty acid by leukocytes from patients with endogenous hypertriglyceridemia.

The metabolic abnormalities responsible for endogenous hypertriglyceridemia have not been defined. Some in vivo studies have suggested that excessive triglyceride production is the cause of this defect. In an attempt to obtain direct evidence concerning this mechanism, we have compared in vitro the metabolism of radioactive glucose and palmitate by leukocytes from patients with endogenous hypertriglyceridemia and normal subjects. Leukocytes from the patients incorporated 9.82 plus or minus 1.7 (S.E.M.) nanomoles of glucose into cellular lipid per 10-8 cells per hour. When the cell lipid extract was sugjected to mild alkaline hydrolysis, 92 per cent of the glucose radioactivity was recovered in the glycerol backbone of the lipid esters. Comparison of specific yields of CO2 from glucose labeled in the 1- or 6- position revealed that 0.53 plus or minus 0.02 per cent was metabolized via the pentose cycle. The leukocytes from hypertriglyceridemic persons incorproated 140 plus or minus 6.9 nanomoles of [1-14C]-palmitate per 10-8 cells per hour. Eighty-four per cent of the radioactivity was in triglycerides and 14 per cent in phospholipids. The major phospholipid into which palmitate was incorporated was phosphatidyl choline. The leukocytes oxidized palmitate at a rate of 2.88 plus or minus 0.23 nanomoles per 10-8 cells per hour. There were no differences in any of the above values between leukocytes from hypertriglyceridemic patients and normal subjects. Likewise, there was no correlation between the plasma triglyceride concentration and glucose or palmitate incorporation into triglycerides. To the extent that leukocytes reflect systemic metabolic processes, these data provide no support for the interpretation that the mechanism of the plasma triglyceride elevation is excessive biosynthesis.

Adult↗
PubMed1975

Fatty acid binding to plasma albumin.

A review of the available information about fatty acid binding to plasma albumin is presented. Albumin is composed of a single polypeptide chain, folded so as to form three or four spherical units. The strong fatty acid binding sites probably are located in crevices between these spherical regions. The anionic form of the fatty acid binds to albumin. Most of the binding energy comes from nonpolar interactions between the fatty acid hydrocarbon chain and uncharged amino acid side chains that line the binding sites. The binding sites are somewhat pliable, and their configuration can adapt to fit the incoming fatty acid. Stepwise association constants for binding to human albumin of fatty acids containing 6-18 carbon atoms are presented. These data indicate that each mole of fatty acid binds with a different affinity and that the association constants for multiple binding diminish sequentially, i.e., kappa 1 greater than kappa 2 greater than kappa 3 greater ... greater kappan. Because of uncertainties concerning fatty acid association in aqueous solutions, the constants for the 14-18 carbon acids probably are not definitive. In the usual physiological concentration range, free fatty acids do not displace appreciable amounts of a second organic compound from albumin. Sensitive spectrophotometric analyses revealed, however, that even small increases in free fatty acid concentration alter the molecular interaction between human albumin and another organic compound.

Anilino Naphthalenesulfonates↗