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Biomedical subjects

S Abraham

Publications and source records attributed to S Abraham.

At least 253 records · Page 14Linked to original sources

Effect of maternal diet on fetal hepatic lipogenesis.

The effects of: a, maternal diet; b, cyclic-3',5'-adenosinemonophosphate (cyclic AMP) and c, clofibrate on hepatic lipogenesis in fetal rats were studied. The experimental diets contained 22% protein, 40--50% carbohydrate, adequate vitamins, and minerals. In addition, the fat-containing diets were supplemented with either 15% corn oil, 25% corn oil, or 5% cholesterol + 10% oleic acid. In the clofibrate feeding studies, 0.3% (w/v) of the ethyl ester was added to a stock ration or to fat-free diet. Lipogenesis was measured in liver slices incubated with [2-14C]pyruvate, [1-14C]acetate, or 3H2O. In addition, activities of lipogenic enzymes were measured in cytosol fractions from liver homogenates. The effec-s of the experimental diets on liver composition were also examined. Lipogenic activity was higher in fetal than in maternal liver. When 15% corn oil was added to the maternal diet, fatty acid synthesis in fetal liver did not decrease as it did in maternal liver. Maternal fasting decreased fetal fatty acid synthesys by 50% when measured with 14C and less than 10% when measured with 3H2O. Although the addition of cholesterol to the maternal diet decreased cholesterol synthesis in maternal liver, no such decrease was observed in fetal liver. Changes in enzyme activities paralleled alterations in lipogenesis in maternal but not in fetal liver. Corn oil feeding or fasting increased the rate of transfer of linoleate from the dam to the fetus. However, accumulation of linoleate in fetal liver did not correlate with a decreased rate of fatty acid synthesis as it did in maternal liver. Maternal hepatic glycogen stores were depleted by fasting, but glycogen levels in fetal liver remained high under these conditions.

Acetates↗

Enhanced growth rate of transplanted mammary adenocarcinoma induced in C3H mice by dietary linoleate.

Three-month-old C3H female mice were given injections of 5-mg pieces of mammary adenocarcinoma and were then fed diets that either were fat free or contained saturated fat (15% hydrogenated cottonseed oil) or linoleate (1-15% corn oil). After 6 weeks, the tumors in mice fed the linoleate diet weighed 3-4 times more than those in mice fed the fat-free or saturated-fat diets. Despite a linoleate-free diet, tumors contained appreciable amounts of linoleate and arachidonate (approximately 2 and 9% of the total fatty acids, respectively). When the level of dietary corn oil was increased from 1 to 15%, the linoleate content of the tumors increased from 4 to 18% of the total fatty acids. However, in these instances, the tumor arachidonate levels increased to maximum values even when the 1% corn oil diet was used. These observations showed that mammary tumor growth was depressed by a fat-free or saturated-fat diet and enhanced by dietary linoleate. Furthermore, they suggested that the growth rate was related to the arachidonate content rather than the linoleate content of the tumors.

Animals↗

Immunologic methods for the identification of cell types. I. Specific antibodies that distinguish between mammary gland epithelial cells and fibroblasts.

Antibodies were produced against intact mouse mammary epithelial cells and cleared fat pad fibroblasts; after appropriate absorption, two specific antibody preparations were obtained. The antimammary epithelial cell preparation did not appear to be strain- or species-specific. The antimammary fibroblast preparation recognized both mammary and fetal fibroblasts. These findings suggested that each cell type possessed distinct immunogenic components. These components were characteristic of each cell type and could be used to identify the respective cells by an immunofluorescence technique. Characterization of the antigenic component of mouse mammary epithelial cells demonstrated that this antigen was released during enzymatic cell dissociation and was regenerated underin vitro culture.

Animals↗

The stimulation of cardiac prostaglandin production by blood plasma and its relationship to the regulation of coronary flow in isolated isovolumic rabbit hearts.

Infusion of small amounts of blood plasma into isolated, isovolumic rabbit hearts perfused with Tyrode's solution resulted in coronary vasoconstriction followed by a decrease in left ventricular developed pressure and dP/dt. Maximal effects were obtained with a perfusate plasma concentration of 1%. Increasing the plasma concentration beyond 1% did not appreciably increase the coronary vasoconstriction. During perfusion with 2% plasma, the coronary flow-oxygen uptake ratio was unchanged over a range of perfusion pressures (40-100 mm Hg) and vascular resistance increased with pressure. In the absence of plasma, the coronary flow-oxygen uptake ratio increased with pressure and vascular resistance decreased. Thus, cardiac regulation of coronary flow in response to changes in perfusion pressure occurred in the presence of plasma but not in its absence. The effects of plasma were reduced with two different inhibitors of prostaglandin synthesis (5,9,11,14-eicosatetraynoic acid and indomethacin). At a perfusate concentration of 50 mug/ml, indomethacin abolished the effects of 2% plasma. Rat stomach strip bioassay for prostaglandin activity indicated that the vasoconstrictor effect of plasma was accompanied by a 4-fold increase in the release of prostaglandin activity by the isolated hearts. The vasoconstrictor effect of plasma also was accompanied by an increase in the conversion of 3H-arachidonate to radiolabeled prostaglandins E2 and F2alpha. These results indicate that a relationship exists between a coronary vasoconstrictor in plasma, cardiac prostaglandin synthesis, and the regulation of coronary flow in response to changes in perfusion pressure in isolated rabbit hearts.

5,8,11,14-Eicosatetraynoic Acid↗

Acyl specificity in triglyceride synthesis by lactating rat mammary gland.

We have studied the specificity of the acyl-CoA:diglyceride acyltransferase reaction in lactating rat mammary gland to provide a rational explanation at the enzyme level for the nonrandom distribution of fatty acids in milk fat triglycerides. Acyl-CoA:diglyceride acyltransferase activity was measured using various diglyceride and radioactive acyl-CoA substrates; products were identified as triglycerides by thin-layer and gas-liquid chromatography. Most of the enzymatic activity was located in the microsomal fraction and showed a broad specificity for the acyl donors tested C10, C12, C14, C16, C18, and C18:1 CoA esters). The acyltransferase activity was highly specific for sn-1,2-diglyceride enantiomers; rac-1,3- and sn-2,3-diglycerides were relatively inactive. The acyl-CoA specificity was not affected by the type of 1,2-diglyceride acceptor offered, although dilaurin was the best acceptor and sn-1,2-dilaurin greater than sn-1,2-dimyristin greater than sn-1,2-dipalmitin greater than sn-1,2-distearin. We have previously shown that in the microsomal fraction from lactating rat mammary gland, the acyltransferase activities concerned with the conversion of sn-glycero-3-phosphate to diacylglycerophosphate show a very marked specificity for long chain acyl-CoA's. Therefore, we conclude that the predominant localization of long chain fatty acids in the 1 and 2 positions, and of shorter chain fatty acids in the 3 position of the glycerol backbone, results at least in part from the specificities of the mammary gland acyltransferases.

Acyltransferases↗

The absolute rate of fatty acid synthesis by mammary gland slices from lactating rats.

Mammary gland utilizes a combination of substrates in vivo. To determine if and how the substrates presented to the gland alter milk fat synthesis, slices of mammary gland of lactating rats were incubated with combinations of glucose, L-lactate, and pyruvate. Uptakes and conversions of uniformly and specifically labeled substrates to CO2 and fatty acid were measured. The absolute rate of fatty acid synthesis was measured by incoporation of tritium from tritiated water into fatty acid. The extent, but not the type, of fatty acids synthesized was affected by the substrates utilized. Glucose stimulated uptake and conversion to fatty acid of l-lactate and, to a smaller extent, of pyruvate. Analysis of CO2 and fatty acid yields revealed that (a) the major stimulatory effect of glucose was on the conversion of acetyl coenyzme A from other substrates to fatty acid; (b) the rate of fatty acid synthesis paralleled the activity of the hexose monophosphate pathway up to a point. A likely source of the NADPH required beyond this point is provided by oxidation of malate to pyruvate. Reduction of NADH of oxaloacetate, produced during citrate cleavage, would yield malate. Hence, maximal synthesis would require production of NADPH and NADH, a condition met when glucose and L-lactate were substrates. Decreased fatty acids synthesis in pyruvate's presence supports this suggested requirement for cytosolic NADH in rat mammary gland.

Animals↗

Stearoyl-CoA desaturase activity in mammary adenocarcinomas carried by C3H mice.

Transplantable mammary adenocarcinomas and livers of C3H mice fed a stock diet or a linoleate rich diet (15% corn oil) contain similar amounts of oleate (ca 3 mg/gm tissue). On feeding either a high carbohydrate, fat free or a high carbohydrate, saturated fat-containing (15% hydrogenated coconut or cottonseed oil) diet for 6 weeks, oleate levels increased 2-fold in tumor and 5-fold in liver. The specific activity of stearoyl-CoA desaturase in liver microsomes was similar to that in the corresponding fractions of mammary glands of lactating mice. In liver, this activity was enhanced 2- to 3-fold by feeding a high carbohydrate, fat free or a high carbohydrate, saturated fat diet. The desaturase activity in mammary tumor microsomes, while only 10% of that in hepatic microsomes, remained unaltered regardless of the type of diet fed. These observations suggest that (a) a major portion of the oleate in the mammary tumor is not produced within the tissue, (b) dietary adaptation is not a general characteristic of stearoyl-CoA desaturase in neoplastic tissues, and (c) enhanced desaturase activity in liver is directly related to the absence of linoleate or oleate, or to a large decrease in oleate in the diet.

Adenocarcinoma↗

Stimulatory effect of glucose upon triglyceride synthesis from acetate, decanoate, and palmitate by mammary gland slices from lactating mice.

Slices prepared from the mammary glands of lactating mice incorporate only small amounts of (1--14C) acetate, (1--14C) decanoate, or (1--14C) palmitate into lipids. However, when glucose is added to the incubation medium, fatty acid incorporation is stimulated-13-fold from acetate, 17-fold from decanoate, and 2-fold from palmitate. Over 90% of the -14C activity in the lipid fraction is in triglycerides. Analysis of fatty acids in the triglycerides showed that almost all of the decanoate and the palmate were incorporated as intact molecules, while acetate yielded acids of varying chain lengths. The glucose stimulation of triglyceride synthesis is not solely due to its effect upon chain elongation but also could involve glyceride-glycerol availability, as well as other unknown factors. However, from measurements of the amounts of glycerol 3-phosphate in the tissue incubated in the presence of palmitate, it would appear that glyceride-glycerol availability is not rate limiting in triglyceride synthesis.

Acetates↗

Dietary alteration of fatty acid composition of lipid classes in mouse mammary adenocarcinoma.

The composition of total fatty acids in serially transplanted mammary adenocarcinomas of C3H mice which were fed a fat free diet or a stock diet containing 4% fat for 8 weeks were significantly different, although fatty acid amounts were similar. The difference in composition was manifested in the triglyceride, phosphatidyl choline, and phosphatidyl enthanolamine fractions. Tumors of mice fed fat free diet has appreciable amounts of eicosatrienoic acid, whereas neoplasms of stock diet fed animals had none. In addition, higher levels of oleic acid and lower contents of linoleic acid were found in tumors from mice fed fat free diet than in those from mice fed the stock diet. Thus, mechanisms which maintained the triglyceride fatty acid composition in some tumors, such as 7288CTC hepatoma, were not observed in mouse mammary adenocarcinomas, and, therefore, were not a general phenomena associated with carcinogenesis.

Adenocarcinoma↗

Lipogenesis by intact hepatocytes from normal and diabetic rats.

Intact hepatocytes isolated from livers of diabetic rats demonstrate the characteristic decreased lipogenic capacities as compared to normal. Administration of insulin to diabetic rats restores these capacities to near normal levels. The results emphasize the potential that the hepatocyte system has for the study of hormonal regulation of lipogenesis.

Acetates↗

A study of the immunological status of patients with dermatophytoses.

22 patients with Trichophyton rubrum infection were studied for some of their immunological parameters. The trichophytin skin test performed with commercially available Dermatophytin (Hollister-Stier) gave immediate positive reaction in 3 patients. All the other patients gave negative delayed and retarded reactions. In vitro response to PHA of the peripheral lymphocytes was significantly depressed in patients compared to the controls. No relationship could, however, be established between the severity, duration or extent of the disease and the depression of the lymphocyte response. IgG and IfA were found to be within normal limits. IgM levels were significantly depressed which was probably artefactual in nature.

Humans↗

Nonequilibration of acetyl units from fatty acids and glucose in mammary glands of lactating mice.

Lipid synthesis by lactating mouse mammary gland slices from [1-carbon14] propionate, [1-carbon14] valerate, and [1-carbon-14] heptanoate, in the presence of glucose and from [uniformly labeled carbon-14] glucose in the presence of propionate, valerate, and heptanoate was studied. Regardless of the labeled substrate, almost all of the radioactivity incorporated into the total lipid fraction was in triglycerides. In experiments with labeled glucose and either the propionic. the valeric, or the heptylic acid, the carbon-14 fatty acids in triglycerides were almost exclusively composed of even-chain fatty acids. When the substrate was either [1-carbon-14] propionate, [1-carbon-14] valerate, or [1-carbon-14] heptanoate, in the presence of glucose, the pattern changed to one in which a larger proportion of the radioactivity was in the odd-chain fatty acids. These findings suggest that in mouse mammary gland, acetyl units produced via beta-oxidation of fatty acids may not equilibrate with those formed from oxidation of pyruvate which is derived from glucose.

Acetates↗

Identity, release, and binding of mitochondrial-bound hexokinases in mammary glands and adenocarcinomas of lactating mice.

The mitochondrial-bound hexokinases (adenosine triphosphate:D-hexose 6-phosphotransferase) of mammary adenocarcinoma and of normal gland were compared in lactating C3H mice. Treatment of mitochondria isolated from both the normal and neoplastic tissue with 0.5 m NaCl or 0.1 mM glucose 0-phosphate effected the release of about 50% of the bound hexokinase. In the presence of magnesium ion, enzyme from either source attached to mitochondria from either tissue and in all combinations to the same extent. Identification of the isoenzyme complement in the mitochondrial extract by diethylaminoethylcellulose chromatography revealed only types I and II. In the tumor, the hexokinase activity in both the cytosol and the fraction solubilized from mitochondria was predominantly in the form of type I ( 60%). In contrast, the activity released from mitochondria isolated from normal gland was predominately type II, while the cytosol contained almost equivalent amounts of types I and II. While this difference does not explain differences in glucose utilization between the normal and neoplastic tissue, it may provide a means of distinguishing between the two.

Animals↗

Fatty acid synthetase from a mouse mammary adenocarcinoma.

Fatty acid synthetase was isolated from transplantable mammary adenocarcinomas carried by C3H mice. Comparison of physicochemical and immunological properties of this enzyme with those of the fatty acid synthetase isolated from normal glands of lactating C3H mice indicates that the enzymes are similar in all respects. The products of the purified fatty acid synthetase from normal and neoplastic tissues were the same, mainly long-chain fatty acids. The normal gland was found to contain 30 times more enzymes per g tissue than did the neoplasm; this may account in part for the relatively low rat of fatty acid synthetase found previously in this neoplasm.

Adenocarcinoma↗

Multiple molecular forms of glucose-6-phosphate dehydrogenase in normal, preneoplastic, and neoplastic mammary tissues of mice.

Multiple molecular forms of glucose-6-phosphate dehydrogenase (G6PD) in normal, preneoplastic, and neoplastic mammary tissues were separated by polyacrylamide gel electrophoresis and identified by specific straining for enzyme activity. Mammary tissue from lactating BALB/c mice showed considerable amounts (up to 50%) of a slower-migrating G6PD species, G6PD-III, which was essentially absent from glands of pregnant mice, preneoplastic nodules, and mammary carcinomas. All tissues possessed a faster-migrating species, G6PD-II, which accounted for up to 85% of the total G6PD in the glands of pregnant mice. A third species, G6PD-I, migrating more rapidly than G6PD-II, was found in both abnormal tissues (preneoplastic and neoplastic) and accounted for up to 35% of the total enzymatic activity. G6PD-I was present in moderate amounts (less than 15%) in glands from pregnant mice and was essentially absent from the lactating gland (approximately 5%). The addition of dithiothreitol did not alter the measurable G6PD activity but did increase the relative activity of G6PD-II or G6PD-I, as judged by the intensity of the bands on the gels. Mild oxidation (stirring overnight at 4 degrees in air) resulted in a loss of G6PD activity, but preparations had greater amounts of G6PD-III; presence of dithiothreitol during aeration partially prevented loss of G6PD activity and largely prvented the appearance of G6PD-III. Molecular-weight estimations with preparations from lactating mice yielded a value of 118,000 for G6PD-II and 260,000 for G6PD-III, suggesting a monomer and dimer, respectively. The addition of nicotinamide adenine dinucleotide phosphate stabilized G6PD activity by preventing heat inactivation at 47 degrees; nicotinamide adenine dinucleotide phosphate did not alter the pattern of species present. The data from heat inactivation studies suggest that G6PD-III (dimer) was the more stable species. The addition of nicotinamide adenine dinucleotide phosphate to samples after oxidation in the absence of dithiothreitol (about 70% loss of activity) resulted in no change in patterns and in recovery of full G6PD activity during heating at 47 degrees. A potential relationship between glutathione reductase activity and the pattern of G6PD species observed in the various tissues is noted.

Animals↗