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Biomedical subjects

R Ostwald

Publications and source records attributed to R Ostwald.

At least 19 recordsLinked to original sources

Depressed natural killer and lectin-induced cell-mediated cytotoxicity in cholesterol-fed guinea pigs.

Dunkin-Hartley and Hartley guinea pigs were fed a diet containing 1% cholesterol (C+) or a control diet (C-). The C+-fed guinea pigs showed a decrease in antitumor effector cell levels as measured by an in vitro 18-hour 51Cr release assay. Natural killer (NK) activity fell rapidly after initiation of cholesterol feeding, decreasing to 25.6% of control levels by 2 weeks. While the interferon inducer polyinosinic-polycytidylic acid increased NK activity as much as 3.6-fold in controls, the NK levels in C+-fed animals were not increased. NK activity was lower in both spleen and peripheral blood of C+-fed animals and against K562, MOLT-3, HL-60, and Raji target cells. Lectin-dependent cell-mediated cytotoxicity was increased in the C+-fed group over, the first 1-2 weeks on the diet, but it dropped to low levels by 6 weeks. Lipoprotein preparations from plasmas of both C+- and C--fed animals inhibited NK cell activity, but suppression was not due to lipoprotein cholesterol content. On the basis of lipoprotein protein, lipoproteins from C--fed animals were more suppressive. The results suggest that the decrease in cytotoxicity induced by dietary cholesterol is due to more than the high levels of plasma and lipoprotein cholesterol.

Animals↗

Reinfection with intestinal helminths after treatment with mebendazole and fluctuations in individual Ascaris lumbricoides infections with time.

In a group of rural school children in the highlands of Papua New Guinea with an initial prevalence of Ascaris lumbricoides 71 per cent, Trichuris trichiura 69 per cent and Necator americanus (hookworm) 95 per cent, 2 1/2 months after treatment with mebendazole the prevalence of A. lumbricoides and T. trichiura was very low, that of N. americanus was about 20 per cent and all egg counts were very low. Prevalence rates and egg counts of A. lumbricoides returned to pretreatment levels 9 months after treatment. Prevalence of T. trichiura and N. americanus, one year after treatment, was lower than before treatment and 97 per cent of egg counts were low. Two years after treatment, prevalence of all species was normal, but mean egg counts of N. americanus were about half of pretreatment levels. Thus in areas with comparable transmission rates, annual treatment with a course of anthelmintic would keep hook-worm levels low, and an additional dose at mid year would also considerably reduce ascariasis. Presence or absence of A. lumbricoides in particular subjects varied from one examination to another, and a particular child was not more likely to have the same infection status one year later, given the prevailing infection rate. 95 per cent were positive for A. lumbricoides on one or more of three examinations held at the same time of year.

Ascariasis↗

Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.

Triglyceride-rich very low density lipoproteins (VLDL) are the major lipoprotein in perfusates of normal guinea pig livers. Their component apoprotein B is mainly B-100 together with some B-95. This apoprotein is actively synthesized, as are C apoproteins and small amounts of apoprotein E. Only trace amounts of intermediate density lipoproteins (IDL, 1.015 < d < 1.05 g/ml) are found in perfusates, but appreciable amounts of low density lipoproteins (LDL, 1.05 < d < 1.10 g/ml) accumulate. These LDL are not newly synthesized, but rather appear to be gradually washed out of the liver. High density lipoproteins (HDL, 1.10 < d < 1.21 g/ml) both discoidal and spheroidal, also accumulate, which contain newly synthesized apoproteins A-I, E and C. Fatty livers of guinea pigs fed cholesterol secrete less VLDL and more IDL than normals, but the combined amount of protein is unchanged. These lipoproteins contain newly synthesized apoprotein B, are enriched in cholesteryl esters and newly synthesized apoprotein E, and have reduced electrophoretic mobilities, making them resemble remnants. Large amounts of LDL also accumulate in perfusates of livers from cholesterol-fed animals, much of which does not appear to be newly synthesized, as judged from single pass perfusions. However, the LDL fraction is complex and includes particles that contain newly synthesized apoprotein B. Thus, these livers appear to secrete a spectrum of cholesteryl ester-rich particles, containing newly synthesized apoproteins B and E that span the density range of VLDL, IDL, and LDL. Livers of cholesterol-fed guinea pigs secrete large amounts of discoidal HDL with a free cholesterol-phospholipid molar ratio of 2:1. Accumulation of protein (almost entirely newly synthesized apoprotein E) in HDL is increased 25-fold over that in perfusates from normal guinea pig livers.-Guo, L.S.S., R.L. Hamilton, R. Ostwald, and R. J. Havel. Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.

Animals↗

Lipoprotein lipase in cholesterol-fed and control guinea pigs.

A study of the in vitro activity of lipoprotein lipase of guinea pigs has shown that (a) the lipolytic activity of activated post-heparin serum is depressed in hypercholesteremic guinea pigs compared to the serum of normocholesteremic guinea pigs; and (b) this depressed lipolytic activity in hypercholesteremic guinea pigs is not due to the presence of an inhibitor.

Animals↗

Effects of neonatal undernutrition and cold stress on behavior and biochemical brain parameters in rats.

This study was conducted to investigate the separate and combined effects of neonatal undernutrition (U) and cold stress (S) on the behavioral and cerebral development of postweaning rats. A severe U was imposed by feeding dams a low protein diet. Postweaning all pups were fed a control diet. S consisted of daily exposure to 5 degrees for 3 minutes from day 2 to 11. Behavioral data show that U animals, stressed (S) + nonstressed (NS), exhibited a significant deficit in reversal learning of T-maze at 21 days, an enhanced passive avoidance response, but no difference in active-avoidance at 35 days when compared to controls of the same age. S had no effect on behavior development. At death (110 days), the brains were dissected into five sections and assay for acetylcholinesterase (AChE) and cholinesterase (ChE) activities. Brain weights of U animals (NS + S) were significantly lower in all sections except dorsal cortex (DC). AChE and ChE activities were significantly higher in all sections (except DC) of U animals relative to controls. S resulted in lower cerebellar weight and ChE:AChE ratios in some sections. Our results suggest a delayed behavioral maturation in U animals and an association between early postweaning behavior and brain parameters in adult rehabilitated animals.

Acetylcholinesterase↗

Effects of dietary cholesterol on antibody-dependent phagocytosis and cell-mediated lysis in guinea pigs.

The effect of dietary cholesterol on antibody-dependent phagocytosis and cell-mediated cytotoxicity (ADCC) by peritoneal cells and on the susceptibility to lysis of erythrocytes was studied in the guinea pig. We found that peritoneal cells from cholesterol-fed animals (CHOL PEC) demonstrated a decreased ability to both phagocytose and lyse antibody-coated (Ab) guinea pig erythrocytes than did those from control guinea pigs (CONT PEC). This decrease was equal in groups fed cholesterol for 5 1/2-13 weeks, preanemic or anemic, and with normal or enlarged spleens. Dose response curves varying Ab concentration showed that CHOL PEC required higher concentrations of Ab to effect phagocytosis and lysis than did CONT PEC. Dietary cholesterol, while rapidly inducing morphological changes such as spurring in guinea pig erythrocytes, was found not to affect the susceptibility of the cells to lysis or phagocytosis in this assay system. These findings suggest that the increased incidence of infection in cholesterol-fed guinea pigs may be due to impaired phagocytic function and that the anemia observed in guinea pigs after 8-10 weeks of feeding cholesterol is not due to increased antibody-dependent removal of spurred erythrocytes by the phagocytic system.

Anemia↗

Isolation and partial characterization of a guinea pig serum apolipoprotein comigrating with apo-E on sodium dodecyl sulfate-polyacrylamide electropherograms.

Study of guinea pig plasma lipoproteins has shown that they contain a polypeptide that comigrates with the arginine-rich polypeptide (apo-E) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This comigrating polypeptide differs from apo-E in its amino acid composition, immunological cross-reactivities, electrophoretic mobility in urea polyacrylamide gel, and elution volume from Sephadex gel columns. It is present in very low density lipoproteins and low density lipoproteins from both control and cholesterol-fed guinea pigs.

Amino Acids↗

The compensatory role of food-motivation in the maze learning performance of lactationally undernourished rats.

To test the hypothesis that the motivational effects of neonatal undernutrition might conceal the detrimental effects on learning, we tested previously undernourished and normally nourished Sprague-Dawley rats on learning of a novel maze pattern under either latent learning (nonappetitive) or food-motivated conditions. Under the nonappetitive conditions, the previously undernourished rats learned significantly less than the normal controls, but when motivated for food, the undernourished rats performed as well as the controls. When learning performance measures are sensitive to motivation, differential motivation between undernourished and normal subjects must be controlled or eliminated.

Animals↗

Effects of the unsaturation of dietary fat and of arachidonate supplementation on cholesterol pool expansion in the guinea pigs.

We have studied the effects of methyl arachidonate supplementation on the lipid metabolism of guinea pigs fed cholesterol. Four groups of guinea pigs were fed a purified diet containing 9.5% hydrogenated coconut oil (HCNO), a highly saturated fat with or without the addition of 1% cholesterol, for 15 weeks. One half of the animals fed the control and the cholesterol-containing diets were supplemented with 15 mg methyl arachidonate three times per week. Supplementation with methyl arachidonate did not alter the concentration of plasma total (TC) or unesterified (FC) cholesterol, erythrocyte cholesterol and plasma phospholipid or the ratio of plasma FC/TC. Accumulation of cholesterol in the major organs of the cholesterol-fed groups was also unchanged. In both control and cholesterol-fed groups, methyl arachidonate decreased the proportion of oleic (18:1) and linoleic acids (18:2) and increased arachidonic acid (20:4) content of plasma and liver phospholipid. A comparison between the results of this study and studies using cottonseed oil showed that the type of dietary fat modifies the effects of cholesterol: plasma cholesterol levels were higher and liver cholesterol storage was lower in animals fed the saturated fat than in those fed the fat rich in polyunsaturated fatty acids (PUFA). Furthermore, in spite of similar changes in erythrocyte cholesterol content and shape abnormalities, no overt hemolytic anemia was observed in the groups fed cholesterol and saturated fat, in contrast to those fed cholesterol + PUFA-containing fat. We conclude that in guinea pigs supplementary methyl arachidonate had no hypocholesterolemic effect at the levels we fed, that circulating cholesterol levels are not a measure of cholesterol accumulation by organs and that the decrease of serum cholesterol in response of PUFA is due in part to an increase of cholesterol storage in the liver.

Animals↗

Plasma cholesterol esterifying activity in guinea pigs.

Plasma cholesterol esterifying activity has been measured in guinea pigs fed either a control diet or the same diet supplemented with 1% cholesterol. The extent of esterification was found to be similar in the cholesterol-fed and control guinea pigs and somewhat lower than in rats. The initial rate of esterification was also of the same magnitude as that found in rats and humans, and unaffected by dietary cholesterol if autologous plasma was used as substrate. However, LCAT activity from cholesterol-fed guinea pigs was significantly higher than that of control plasma when acting on either control or cholesterol-fed substrate. This suggests that dietary cholesterol increases the amount (or activity) of LCAT but that the substrate is unsuitable or that a necessary cofactor is present in limiting amounts. Heat treatment of guinea pig plasma seems to alter substrate availability to varying degrees. The implications of these findings in relation to substrate specificity and cofactor requirements of guinea pig LCAT are discussed.

Animals↗

Westernization of diet and serum lipids in Ethiopians.

The dietary pattern, physical work output, and blood lipids were studied in three groups of healthy, young, urban Ethiopian men differing in the degree of "Westernization." The results showed striking increases in serum lipids that were associated with the degree of Westernization of the diet. These changes could not be accounted for by differences in other group characteristics such as age, weight, smoking, or length of residence in Addis Ababa. The effects of the level of physical work output on serum lipids were equivocal because the methods used for the assessment of energy output yielded crude approximations only.

Adult↗

Cholesterol absorption and steroid excretion in cholesterol-fed guinea pigs.

Cholesterol absorption was studied in groups of guinea pigs fed diets containing 0, 0.1%, or 1% cholesterol. A similar proportion of tracer cholesterol was absorbed regardless of the cholesterol content of the diet. Furthermore, the proportion of tracer cholesterol absorbed by individual animals did not change when the cholesterol-free diet was changed to one containing 1% cholesterol. Cholesterol absorption was also measured in hyporesponding guinea pigs. These guinea pigs had been fed 1% cholesterol-containing diets for nearly a year with minimal pathological effects. These hyporesponders had a decreased intestinal transit time, which enabled them to decrease the fractional absorption of cholesterol below the levels seen in the controls, and to absorb less cholesterol/kg body weight than the hyperresponders. Excretion of total and of neutral steroids was measured in guinea pigs fed 0 or 1% cholesterol-containing diets. The 1% cholesterol-fed guinea pigs increased the excretion of steroids 3-fold over control levels. However, they absorbed more dietary cholesterol than they excreted in any form. It seems, therefore, that a major cause of the cholesterol pool expansion in the guinea pig is its inability to limit absorption of dietary cholesterol in conjunction with its inability to sufficiently increase excretion of steroids.

Aging↗

Changes in the plasma lipoprotein-apoproteins of guinea pigs in response to dietary cholesterol.

The major apoproteins from four plasma lipoproteins were isolated from control and cholesterol-fed guinea pigs. Apoproteins were studied by column chromatography, polyacrylamide gel electrophoresis, and amino acid analysis. Dietary cholesterol altered the plasma apolipoproteins mainly by an enrichment in the content of arginine-rich polypeptide (ARP) in all density fractions. This protein had a similar molecular weight (34 000), electrophoretic mobility, amino acid composition, and microheterogeneity as ARP reported in other mammalian species. The estimation of plasma concentration of ARP indicates a higher correlation coefficient with plasma unesterified cholesterol (r = 0.98) compared with cholesterol esters (r = 0.62).

Amino Acids↗

The time course of metabolic changes induced by dietary cholesterol in guinea pigs.

The time course of the effects of dietary cholesterol on the lipid composition of liver, plasma and red cells of guinea pigs, of the pathological changes of tissues and of hematological parameters was studied. The purpose was to identify the primary injury and so to contribute to the eludication of the mechanism(s) for the development of the hemolytic anemia observed in this species after long-term cholesterol supplementation. The results showed that the initial effects observed within 1 week occur in the liver lipids and histology accompanied by changes in plasma and RBC lipids. These events were followed by further, slower increases of tissue lipids without major qualitative changes. The earliest signs of an anemia were observed between weeks 5 and 7. We conclude that the primary insult of cholesterol is liver damage leading to the production of abnormal plasma lipoproteins which in turn cause a net increase of RBC-cholesterol that is accompanied by their morphological abnormalities. The hemolytic anemia does not seem to be caused directly by either the altered composition of RBC nor their altered morphology.

Anemia, Hemolytic↗

Cholesterol turnover and tissue distribution in the guinea pig in response to dietary cholesterol.

Cholesterol turnover and tissue cholesterol distribution were studied in guinea pigs fed either a control diet or one containing 0.1% cholesterol. Dietary cholesterol caused a significant increase in the cholesterol concentration in liver, red blood cells and small intestine, but not in plasma. Most of the increase in total body cholesterol could be accounted for as an increase in liver esterified cholesterol content. Feeding the 0.1% cholesterol-containing diet did not significantly change either the absorption of an oral dose of tracer cholesterol or the endogenous cholesterol synthesis rate. Steady state cholesterol input-output rate and total traced mass of cholesterol were significantly greater, and mean transit time was significantly longer in the animals fed the cholesterol containing diet. These data suggest that the maintenance of cholesterol homeostasis in the nonhypercholesterolemic cholesterol-fed guinea pig depends on liver accumulation of esterified cholesterol as well as on increased output of cholesterol.

Animals↗

Food intake and growth of guinea pigs fed a cholesterol-containing diet.

Food intake and liveweight gain of 11 cholesterol-fed and 10 control guinea pigs were measured for 33 days to determine whether depressed growth previously observed in young guinea pigs fed cholesterol was due to decreased food intake or to reduced food utilization. The guinea pigs were fed a laboratory stock diet containing 5% cottonseed oil; 1% cholesterol was added to the diet for the experimental group. Results showed that food intake was significantly less in the cholesterol-fed group, while requirements for maintenance and for liveweight gain, as adjusted to metabolic body size (Wkg-0.75), were not significantly different. Food energy retention was estimated by comparing dry body weight and moisture, fat and protein content of two groups of four controls and four cholesterol-fed guinea pigs at the beginning and at the end of a 20-day food-intake period. Values derived for maintenance requirement in this comparative body composition study correlated well with those of the 33-day experiment. We conclude that feeding cholesterol to guinea pigs reduced food intake for unknown reasons but does not affect food utilization.

Animal Nutritional Physiological Phenomena↗