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Biomedical subjects

S Abraham

Publications and source records attributed to S Abraham.

At least 181 records · Page 10Linked to original sources

Evidence for an increased risk for hypertension with centrally located body fat and the effect of race and sex on this risk.

Data from the First Health and Nutrition Examination Survey (HANES), 1971-1974, were used to examine the relationship between blood pressure and the distribution of subcutaneous body fat in 5506 survey participants, ages 30-59. Triceps and subscapular skinfolds were used as approximations of peripheral and centrally located body fat. The effects of race, sex and age on the obesity-blood pressure relationship were analyzed. Subscapular skinfold was the better predictor of both systolic and diastolic blood pressure in each race-sex group, sharing all of the association of triceps with blood pressure and having significant predictive power unshared by triceps. The slopes of regression of subscapular skinfolds with systolic blood pressure for each race-sex group were not significantly different. A 1 mm increase in skinfold thickness increased the predicted mean systolic blood pressure by 0.63 +/- 0.03 mmHg (F = 519). Mean diastolic blood pressure rose 0.43 +/- 0.02 mmHg per unit increase of skinfold in whites (F = 549), and 0.14 +/- 0.04 mmHg less in blacks (F = 13), indicating a significant racial difference. Age and subscapular skinfold contributed independently to the variability in blood pressure in each race-sex group. These results demonstrate that the blood pressure of middle-aged Americans is more directly associated with centrally deposited body fat. This finding is true across race and sex groups, and is independent of age.

Adult↗

Effect of dietary fat on tumorigenesis in the mouse mammary gland.

The effects of dietary polyunsaturated fat in BALB/c mice were determined for several stages of mammary tumorigenesis: a) growth of intact and transplanted normal mammary tissue, b) growth of hyperplastic alveolar nodule (HAN) lines D1/ UCD and Z5C1 , c) incidence of tumors occurring in D1/ UCD , and d) growth rate of the tumors. Growth of transplanted normal mammary epithelium as well as intact glands was faster in mice fed a 10% corn oil (CO) diet, which contains linoleate, than in those fed 10% hydrogenated cottonseed oil ( HCTO ), a diet free of the polyunsaturated fatty acid. We concluded that transplantation itself does not alter the response of mammary tissue to dietary fat. The growth of both HAN lines was unchanged by the presence of CO in the diet. For ascertainment as to whether the difference in response was specific to the tissue, ducts and HAN line D1/ UCD were transplanted into left and right gland-free fat pads of the same mice. The duct tissue grew faster when the hosts were fed the 10% CO diet than in the hosts fed the 10% HCTO diet; however, no effect of dietary fat was noted with the HAN. Although indomethacin retarded the growth of normal tissue in the mice fed CO diet, this prostaglandin inhibitor had no effect on the growth of the HAN transplants. Both incidence and growth rate of tumors arising from transplants of HAN line D1/ UCD were greater in mice fed diets containing either 0.3, 1, or 10% CO than in those fed 10% HCTO . The smaller number of tumors arising in mice fed with 10% HCTO diet may be the result of the slower growth rate of the neoplasms in mice fed diets devoid of linoleate.

Animals↗

Structure-activity requirements for hypotension and alpha-adrenergic receptor blockade by analogues of atropine.

The hypotensive action of various antimuscarinic compounds structurally related to atropine was studied in conscious, unanesthetized rats. The alpha-adrenolytic activity of these agents was assessed both in vivo (blockade of norepinephrine-induced pressor response) and in vitro (displacement of [3H]WB-4101 binding). Benztropine, homatropine and hyoscyamine caused hypotension and produced alpha-adrenergic receptor blockade similar to atropine. Other analogues were either inactive (atroscine, scopolamine, tropic acid and tropine) or evoked nonspecific changes in blood pressure and lacked alpha-adrenolytic activity (benactyzine, eucatropine, methylatropine, methylhomatropine and methylscopolamine). Based on these data, we propose the following structure-activity relationship for hypotension and alpha-adrenolytic activity: (a) the tropine moiety is inactive unless it is attached to another group by an ester linkage, (b) chemical modification of the tropine moiety, including quaternization, decreases potency, (c) the d-stereoisomer appears to be more potent than the corresponding 1-form.

Acetylcholine↗

Acyl specificity in triacylglycerol synthesis by mammary adenocarcinoma R3230AC in Fischer rats.

Activities and acyl specificities of both sn-glycero-3-phosphate and diacylglycerol acyltransferases in microsomal fractions isolated from homogenates of the mammary adenocarcinoma R3230AC carried by Fischer rats were compared to those from normal mammary glands of lactating Fischer rats. Although the neoplasm exhibited lower activities for these two enzyme reactions, the specificities for acyl-CoAs as donors were quite similar to those found in the normal tissue counterpart. Long-chain acyl-CoAs were preferred substrates for the sn-glycero-3-phosphate acyltransferase reaction while acyltransferase with diacylglycerol as acceptor showed much less preference. With both normal and neoplastic tissues, the products of each reaction were the same, i.e., phosphatides with sn-glycero-3-phosphate and triacylglycerol with diacylglycerol as acyl acceptors, respectively. All results support the concept of a non-random distribution of fatty acids in the triacylglycerol of this mammary adenocarcinoma in virgin rats which is the same as that from the normal tissue in lactating animals.

Acyltransferases↗

Effect of specific dietary fatty acids on lipogenesis in the livers and mammary glands of lactating mice.

The effects of linoleic, linolenic and columbinic acids fed as 4% of a high carbohydrate (50% glucose) diet on the activities and the amounts of several enzymes associated with fatty acid synthesis in livers and mammary glands of lactating mice were compared with those for stearic and oleic acids. Fatty acid synthesis, measured in vivo, was significantly lower in livers of mice ingesting all 3 polyunsaturated fatty acids (PUFA), whereas in mammary glands synthesis was lower only in mice receiving columbinic acid. The activities of fatty acid synthetase (FAS) and acetyl CoA carboxylase were significantly reduced in liver by all 3 PUFA, as wee activities of glucose-6-phosphate dehydrogenase, malic enzyme (ME) and citrate cleavage enzyme (CCE), also associated with lipogenesis. In mammary gland, on the other hand, the activities of these enzymes were unaffected by dietary PUFA. The tissue contents of FAS, ME and CCE, measured by rocket immunoelectrophoresis, were found to be significantly reduced in liver by linoleate, linolenate and columbinate but were not significantly altered in mammary gland. The decrease in hepatic lipogenesis observed was principally due to a decrease in the amounts of these enzymes induced by the dietary PUFA but the inhibition in mammary gland caused by columbinate could not be accounted for by a reduction in enzyme contents and therefore may be due to allosteric effects which occur when fatty acid synthesis is measured with 3H2O. The fatty acid composition in liver and mammary gland of dams and in liver and kidney of pups completely reflected dietary fatty acids. Columbinate made up ca. 20% of the total fatty acids in both tissues of the columbinic acid-fed mice and ca. 15% in the pup tissues. This suggests that columbinate is incorporated into milk lipids of dams and is easily absorbed by pups. The elevated ratios of 16/16:1 and 18/18:1 in liver and mammary gland of dams and liver and kidney of the pups from dams fed linoleate, linolenate and columbinate suggest that each of these polyunsaturated fatty acids in the diet can inhibit the activity of delta 9 desaturase.

Animals↗

Asymmetric distribution of decanoate in triacylglycerol synthesized in vitro by mammary glands of lactating mice.

Slices, prepared from the mammary glands of lactating mice, were incubated with either [1-14C]acetate, [U-14C]glucose, or [1-14C]decanoate. From all 3 substrates, radioactivity in the synthesized lipids was found mainly in triacylglycerols (TG). When acetate or glucose served as substrate, decanoate (C10) accounted for 24% of the fatty acids in TG. Hydrolysis of the TG by pancreatic lipase yielded [14C] fatty acids which had relatively more C10 (38%) than did either of the other hydrolysis products mono- or diacylglycerol (14-17%). However, when TG produced by slices from C10 were hydrolyzed, the acid was found to be esterified equally at the C-1, C-2 and C-3 of glycerol. Thus, when fatty acids are synthesized de novo and are converted to TG by gland slices, C10 is predominantly located in the C-3 position, a finding in accord with the situation in milk TG, although such preferential incorporation does not occur when the free acid is presented to the tissue slices.

Animals↗

On the receiving end--patient perception of the side-effects of cancer chemotherapy.

We conducted a survey to identify and rank side-effects perceived by 99 patients receiving cancer chemotherapy. Non-physical side-effects constituted 54% of the 15 most severe symptoms, and included the thought of coming for treatment, the length of time taken by treatment and having to have a needle. Major physical side-effects were vomiting, nausea and hair loss. Differences in ranking of severity of side-effects were evident when patient groups were divided by sex, age, marital status and domestic situation, as well as by diagnosis, treatment and response. Evaluation of patient perception of the severity of side-effects is an aid to striking the cost benefit balance when deciding whether to use cancer chemotherapy.

Adolescent↗

Influence of temperature, environmental salinity and fasting on the patterns of fatty acids synthesized by gills and liver of the european eel (Anguilla anguilla).

A rise in temperature on the average from 8 to 28 degrees C resulted in an enhanced relative incorporation of [1-14C]acetate into saturated fatty acids in liver tissue. The same effect was seen in gill tissue, but only after incubation in vitro and when the precursor was injected into the eel. When [1-14C]acetate was added to the water in the incubation tank such a "homeoviscous adaption" was not observed in gill tissue. A rise in temperature resulted in less relative incorporation of radioactivity into saturated gill fatty acids. We attribute this difference to a specific labelling of salt transport cells in the gills, due to the labelled precursor itself taking part in biological ion transport when it is added to the water. It would appear that palmitoleic acid plays a special role in the function of the salt transport cell. When [1-14C]acetate was added to the water in the incubation tank there was a significantly enhanced percentage incorporation into saturated gill fatty acids in fresh water relative to sea water. Fasting led to less relative incorporation of [1-14C]acetate into saturated liver fatty acids in vitro.

Acetates↗

Biochemical changes in rat liver after 18.5 days of spaceflight.

The effect of "weightlessness" on liver metabolism was examined using tissue from rats flown in earth orbit for 18.5 days aboard the Soviet Cosmos 936 biosatellite. Changes in the activities of certain carbohydrate and lipid enzymes were noted. Of the 28 hepatic enzyme activities assayed, two, palmitoyl-CoA desaturase and lactate dehydrogenase, increased, whereas five, glycogen phosphorylase, 6-phosphogluconate dehydrogenase, both acyltransferases which act on alpha-glycerolphosphate and diglycerides, and aconitate hydratase decreased. The remaining enzyme activities measured were unchanged. In addition, increased levels of liver glycogen and palmitoleate were noted which probably resulted from the lowered glycogen phosphorylase and increased palmitoyl-CoA desaturase activities, respectively, in those animals that experienced weightlessness. These changes caused by weightlessness were transient since all of the aforementioned alterations returned to normal values when measured in the livers of other rats which had flown in the biosatellite 25 days after recovery.

Aconitate Hydratase↗

Effect of dietary 18-carbon fatty acids on growth of transplantable mammary adenocarcinomas in mice.

The growth rates of 2 spontaneously developed mammary adenocarcinomas, one in a female C3H mouse and the other in a female BALB/c mouse, were determined after transplantation into isologous female mice fed a specific diet to which various edible fats or pure fatty acids were added. The 18-carbon fatty acids used contained one (oleate), two (linoleate), or three (linolenate and columbinate) double bonds in either the 5, 9, 12, or 15 positions. The transplanted tumors grew to a larger size in C3H mice fed the 10% corn oil diet (with approximately equal to 60% linoleate content) than in those fed the 10% hydrogenated oil diet (without linoleate). The C3H mice fed diets with 1% linoleic acid developed significantly larger tumors than did those fed 1% oleic acid, whereas those fed 1% columbinic acid did not develop significantly heavier tumors compared to 1% oleic acid-fed mice. This finding occurred despite the fact that both oleate and columbinate were taken up and were incorporated into complex lipids by the transplanted tumor and the ratio of monoenoic:dienoic:polyenoic fatty acids in the neoplasms' lipids from columbinate-fed mice was similar to that from linoleate-fed mice. Columbinate, similarly to linoleate, has both 9-cis and 12-cis double bonds, but it also possesses a trans double bond in the 5 position that apparently prevents its conversion to prostaglandins (PG). These results are entirely consistent with the view that production of PG is required for tumor enhancement by dietary polyunsaturated fat. In the experiment with BALB/c mice, tumor growth was stimulated by 1% dietary linoleic acid but not by 1% linolenic acid when compared with that observed with 1% oleic acid. Thus as a result of these new experiments, PG of series 1 or 2 are more likely to be involved in the process of tumor growth enhancement than are PG of series 3.

Adenocarcinoma↗

Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1.

We describe the production of the monoclonal antibody B73.1, reacting with a subset of human lymphocytes and, in about one-half of the donors, with neutrophilic polymorphonuclear leukocytes. In the peripheral blood from normal adult donors, 14.6 +/- 8.5% of the lymphocytes react with B73.1 antibody. The B73.1(+) lymphocyte subset does not bear markers of typical T or B cells and corresponds to the lymphocyte subset containing antibody-dependent killer (K) and natural killer (NK) cells. We demonstrate that: a) virtually all lymphocytes with K/NK cytotoxic activity are found in the lymphocyte subpopulation bearing the B73.1-defined antigen; b) the B73.1(+) lymphocyte subset bears the combination of antigens known to be present on K/NK cells; and c) there is a positive correlation between the level of cytotoxicity and the actual number of B73.1(+) lymphocytes in individual donors. We also report the distribution of B73.1(+) lymphocytes according to donor age and tissue types. The use of the B73.1 antibody in quantitating the actual number of K/NK cells and in performing functional studies on spontaneous cytotoxicity is discussed.

Adolescent↗

Induction of differentiation of human myeloid leukemias by phorbol diesters: phenotypic changes and mode of action.

Treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) of acute myeloblastic leukemia cells halts proliferation and induces expression of monocyte/macrophage markers. Surface characteristics of leukemic HL60 cells, as defined using a panel of monoclonal antibodies, were found to be similar to those of normal human promyelocytes. TPA treatment, however, induced a phenotype that, unlike normal monocytes, contained several myeloid-specific markers and lacked several monocyte-specific markers. TPA treatment of HL60 cells causes the rapid disappearance of the transferrin receptor from the cell surface. Because transferrin is essential for HL60 cell proliferation in culture, the disappearance of this receptor is followed by an irreversible accumulation of the cells in the G1 phase of the cell cycle. The TPA-induced arrest of cell proliferation suggests the potential of this agent in experimentally treating myeloblastic leukemias.

Animals↗

Regulation of mouse hepatic ATP-citrate lyase activity by dietary fat. Evidence for the presence of inactive enzyme.

The induction of ATP-citrate lyase activity in mouse liver dietary carbohydrate (glucose) in markedly reduced by including in the diet a source of polyunsaturated fatty acids. Within 72 h after changing from a standard mouse chow diet to a high carbohydrate diet containing 15% (W/W) of hydrogenated cottonseed oil (as a source of saturated fatty acids), the activity of mouse liver ATP-citrate lyase per milligram cytosolic protein was approx. 3-fold higher than that from mice fed a similar diet containing 15% (W/W) of corn oil. The rate of synthesis of ATP-citrate lyase relative to that for total protein and the rate of degradation of the enzyme were similar for both dietary groups. Elevated levels of enzyme activity in the hydrogenated cottonseed oil-fed livers were not accompanied by a similar increase in the amount of enzyme protein., To explain such findings, we propose that the activity of hepatic ATP-citrate lyase is regulated by dietary polyunsaturated fatty acids through a mechanism involving the conversion of a catalytically active form of the enzyme to a catalytically inactive form. A reversal of this conversion (inactive-active) is evident within 72 h of removing the mice from the corn oil diet and placing them on the hydrogenated cottonseed oil diet. Furthermore, the conversion appears to be independent of the in vivo rate of synthesis of the enzyme.

ATP Citrate (pro-S)-Lyase↗