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K K Carroll

Publications and source records attributed to K K Carroll.

At least 73 records · Page 4Linked to original sources
PubMed1987

A comparative study of serum lipoproteins in rabbits fed a natural ingredient diet or low-fat, cholesterol-free, semipurified diets containing casein or isolated soy protein.

In rabbits fed a cholesterol-free, semipurified diet containing isolated soy protein, the average total serum cholesterol level was similar to that of rabbits fed a natural ingredient (chow) diet. However, the cholesterol and protein levels in very low density (VLDL) and low density lipoproteins (LDL) tended to increase, while the levels in high density lipoproteins (HDL) were reduced to about half of those on the chow diet, with little change in the cholesterol to protein ratio. Substitution of casein for soy protein in the semipurified diet caused a four- to five-fold increase in total serum cholesterol and a doubling of lipoprotein protein, with an increase of 1.4- to 3.0-fold in the cholesterol to protein ratio of the different lipoprotein fractions. Analysis of the apoproteins (apo) of the plasma lipoproteins indicated that apo B, E, and C all tended to increase in the VLDL and LDL of rabbits fed the soy protein diet compared with those fed chow diet. The levels of each of the apoproteins were increased further by substituting casein for soy protein in the semipurified diet. In this case, apo E showed the greatest relative increase (2.7-fold) in VLDL, while apo B and E were increased to a similar extent (about 4-fold) in LDL. Apo C was approximately doubled in each of these fractions. The apo A content in HDL of rabbits fed the semipurified diets was about half that of rabbits fed chow diet. No marked changes were noted in the apo E or C content of HDL. Separation of isoforms of the soluble apoproteins showed variations between individual animals, but these variations seemed largely unrelated to diet. The results of these studies indicate that semipurified diets produce changes in the serum lipoprotein patterns of rabbits that are only partly due to the protein component of these diets.

Animals↗
PubMed1986

Fat and cancer.

Experimental studies and epidemiologic data both indicate that high-fat diets increase the risk of cancer at sites such as breast, colon, and pancreas. Dietary polyunsaturated vegetable oils promote tumorigenesis in animals whereas saturated fats and polyunsaturated fish oils either have little effect or are inhibitory. A blend of fats typical of the American diet enhanced mammary tumorigenesis effectively when fed as 40% of calories. After 9 to 10 weeks on this diet, reducing the fat to 10% of calories inhibited subsequent tumor development. Although dietary fat appears to act as a promoter, the exact mechanisms are still unknown. Cancer mortality in humans correlates better with total dietary fat than with degree of unsaturation, perhaps because most diets contain more than the amount of polyunsaturated fatty acids required for maximum effect on tumorigenesis in animals. A reduction in total dietary fat is recommended to reduce the current high cancer mortality.

Animals↗
PubMed1986

Diet and carcinogenesis: historical perspectives.

Some 40-50 years ago, experiments with animals began to provide conclusive evidence that diet can significantly influence carcinogenesis. Underfeeding or severe restriction of caloric intake to between one-half and two-thirds of normal had a general inhibitory effect on development of tumors of various types. On the other hand, high fat diets were found to enhance tumor yields relative to low fat diets. The effect of dietary fat was shown to be independent of caloric intake and was more selective for certain types of tumors. Both dietary fat and caloric restriction appear to exert their effects mainly at the promotional stage of carcinogenesis, although the exact mechanisms are not known. Interest in the role of diet in carcinogenesis has been revived in recent years by epidemiologic data that show correlations between certain dietary constituents, such as dietary fat, and cancer incidence at particular sites in the body and mortality. These epidemiologic observations have, in turn, led to an increase in research on effects of diet on carcinogenesis in animal models.

Animals↗
PubMed1986

Biological effects of fish oils in relation to chronic diseases.

The low incidence of cardiovascular disease in Greenland Eskimos appears to be due to their high intake of seal, whale and fish. The lipids of these marine animals lower serum triglyceride and cholesterol levels and help to prevent blood clotting. The latter effect has been related to a change in the balance of prostacyclin and thromboxane as a result of replacing n-6 polyunsaturated fatty acids in the body by n-3 polyunsaturated fatty acids present in marine lipids. Dietary fish oils have also been shown to inhibit development of mammary, pancreatic, intestinal and prostatic tumors in experimental animals. This effect may likewise be due to changes in the production of prostaglandins or related compounds. The involvement of prostaglandins and leukotrienes in immune responses has led to studies on the effects of fish oil on various chronic diseases associated with abnormalities of the immune system. Some of these diseases, such as multiple sclerosis and psoriasis, are also relatively uncommon in Eskimos. Preliminary results of these studies are encouraging, but more work is required to assess the usefulness of dietary fish oils in treatment of these diseases. In addition to their apparent therapeutic value, n-3 fatty acids are considered essential dietary components since they cannot be synthesized in the body and appear necessary for normal vision and probably other body functions.

Animals↗
PubMed1986

Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats.

High fat diets promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA), and polyunsaturated fats are more effective than saturated fats. This difference is related to the linoleic acid content of polyunsaturated vegetable oils, but the amount of linoleate required for maximum tumor promotion appears to be higher than indicated by earlier experiments. Comparison of the effects of a polyunsaturated vegetable oil (corn oil) containing linoleate with a fish oil (menhaden oil) containing polyunsaturated fatty acids derived from linolenic acid showed that higher dietary levels of corn oil increased the yield of DMBA-induced mammary tumors, while corresponding levels of menhaden oil had an inhibitory effect. This is further evidence that promotion of mammary tumorigenesis by polyunsaturated vegetable oils may be mediated by prostaglandins or other biologically active eicosanoids derived from n-6 fatty acids.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Long-term distribution and metabolism of [1-14C]dolichol injected intravenously into rats.

We have previously shown that [1-14C]dolichol mixed in vitro with rat serum and injected intravenously is rapidly cleared from the circulation and appears primarily in the liver. One day after injection the liver accounted for 80% of the isotope in whole animals, whereas after 130 days it represented only 50%. During the 130 days the specific radioactivity (dpm/g liver) decreased by more than 20-fold. In contrast, the spleen retained at 130 days 85% of the radioactivity initially present and its specific radioactivity decreased by only a factor of two. At this time small amounts of isotope were also found in carcass (internal organs removed), gastrointestinal tract and contents, and lungs. Trace amounts of radioactivity were extractable from testes and kidneys, while the heart and brain were essentially free of radioactivity. At all times after injection nearly all the radioactivity present in all tissues was still associated with dolichol. Only trace amounts of [1-14C]dolichyl fatty acyl ester and no [1-14C]phosphorylated derivatives of dolichol were present in the liver and spleen removed 156 days postinjection. Fractionation of liver between 1h and 93 days after injection suggested that [1-14C]dolichol becomes associated primarily with a lysosome-enriched fraction. The accumulation of [1-14C]dolichol in this and other subcellular compartments involved both an inward and outward flow of radioactivity, suggesting that deposition of dolichol in lysosomes is not a one-way terminal process.

Animals↗
PubMed1985

Distribution, metabolism and excretion of [1-14C]dolichol injected intravenously into rats.

[1-14C]Dolichol mixed in vitro with rat serum and injected intravenously into rats was rapidly cleared from the circulation in a manner consistent with a two-compartment model. About 80% of the radioactivity recovered from animals killed after 1 day was in the liver, with smaller amounts being found in lung, carcass (internal organs removed), gastrointestinal tract and contents, and spleen. The kidneys, testes and heart contained little radioactivity, and the brain did not appear to take up any [1-14C]dolichol. The half-life for the turnover of radioactivity from [1-14C]dolichol in tissues varied considerably, being 2 days for the lung, 17 for liver and about 50 days for the carcass. After 1 day, and also after 4 and 21 days, most of the radioactivity in all tissues was as [1-14C]dolichol and as [1-14C]dolichyl fatty acyl ester, although a small amount of incorporation of [1-14C]dolichol radioactivity into phospholipids was also observed. Faeces collected over the first 4 days after injection contained 13% of the [1-14C]dolichol dose, but urine and expired air contained only small amounts of radioactivity. Radioactivity in faeces was nearly all as unchanged [1-14C]dolichol and as [1-14C]dolichyl fatty acyl ester. The [1-14C]dolichol remaining in liver after 21 days appeared to be in a pool (possibly lysosomes) where most of it was not subject to excretion.

Animals↗
PubMed1985

Distribution, metabolism and function of dolichol and polyprenols.

Polyisoprenoid alcohols consisting of 9 or more isoprene units are present in all living cells. They can be fully unsaturated (polyprenols) or alpha-saturated (dolichol). Dolichol forms may have additional saturation at or near the omega-end. Some species contain ony dolichol or only polyprenols while others have nearly equal amounts of both types. Some polyisoprenoid alcohols consist entirely of trans isoprene units but most, including dolichol, contain both trans and cis units. Considerable advances in lipid methodology have occurred since the first review of polyisoprenoid alcohols by Hemming in 1974. For example, direct analysis of both dolichol and Dol-P by HPLC has replaced earlier methods which were often both insensitive and inaccurate. The availability of radiolabeled dolichol and polyprenols has facilitated studies concerning the metabolism and distribution of these compounds. Those studies suggest that only a small portion of the dolichol present in cells is likely to be involved in glycosylation. Polyisoprenoid alcohols are usually present at a family of homologues where each differs in size by one isoprene unit. Little or no size related specificity has been observed for any reaction involving dolichol or polyisoprenol intermediates. The overall length of polyisoprenoid alcohols may, however, affect the manner in which these compounds influence the physical and biochemical properties of membranes. Studies on the biosynthetic pathway leading from cis, trans Pol-PP by phosphatase action. The formation of the dolichol backbone from a polyprenol requires the action of an additional enzyme, an alpha-saturase. This enzyme does not always act at the level of a single common substrate, since Pol-PP, Pol-P, and polyprenol all appear to be utilized as substrates. The major product of the de novo pathway differs among different species. Dol-P would appear to be the most energy efficient end-product since it can participate directly in glycoprotein formation. Most often, however, Dol-P is not the major product of metabolic labeling experiments. In some cases, dolichol is formed so that rephosphorylation is required to provide Dol-P for participation in glycoprotein formation. The kinase responsible for this phosphorylation appears to bypass the considerable stores of dolichol present in tissues (i.e. sea urchin eggs) in favor of dolichol derived directly from de novo synthesis. Although HMGR is a major regulatory component of the pathway leading to polyisoprenoid alcohols and cholesterol, control is most often not co-ordinated.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcohols↗
PubMed1985

Digestibilities of casein and soya-bean protein in relation to their effects on serum cholesterol in rabbits.

Diets containing isolated soya-bean protein induce lower levels of serum cholesterol in animals than diets containing casein. Experiments were conducted to investigate whether differences in digestibility of the proteins might explain this effect. At pH 8 with pancreatic enzymes or intestinal peptidase, soya-bean protein was hydrolysed in vitro much less rapidly than casein. However, with pepsin (EC 3.4.23.1) at acid pH, soya-bean protein was hydrolysed more rapidly than casein. These differences in digestibility may be due to pH-dependent changes in solubility of the proteins. Casein and soya-bean protein were most soluble at alkaline and acid pH respectively. Heat treatment of the proteins resulted in lower solubilities and digestibilities. Sonication of soya-bean protein at pH 7.8 increased solubility but only slightly raised digestibility. When fed to rabbits, enzymically hydrolysed soya-bean protein induced a 2.3-fold higher concentration of serum cholesterol than did intact soya-bean protein. The hypocholesterolaemic effect of soya-bean protein may be partly attributable to its low solubility and digestibility at alkaline pH.

Animals↗
PubMed1985

Dietary fat in relation to mammary carcinogenesis.

The first evidence that dietary fat influences mammary carcinogenesis was provided by Tannenbaum, who showed that mice fed a high-fat diet developed spontaneous tumors more readily than those fed a low-fat diet. Similar observations have been made with various other animal models. Polyunsaturated vegetable oils enhance carcinogenesis more effectively than saturated fats, because of their higher linoleate content. Diets containing high levels of polyunsaturated fish oils do not stimulate carcinogenesis, however, perhaps because their polyunsaturated fatty acids belong mainly to the linolenate family. Dietary fat acts primarily as a promoting agent, but the exact mechanism is still unclear. The requirement for linoleate and the fact that the fat effect can be blocked by prostaglandin biosynthesis inhibitors suggests that it may be mediated by biologically-active compounds derived from linoleate. Other possibilities include changes in hormonal balance, alterations in the fatty acids of membrane lipids, effects on the immune system, modulation of intercellular communications, and metabolic alterations related to differences in fat and caloric intake. Interest in the role of dietary fat in mammary carcinogenesis has been greatly stimulated by epidemiological evidence of a strong, positive correlation between breast cancer and dietary fat. In these epidemiological data, total dietary fat shows a better correlation than fat from either plant or animal sources individually, and there is no apparent correlation with the polyunsaturated fatty acid content of the diet. Further studies are needed to investigate more thoroughly this apparent difference between experimental and epidemiological data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Reversal of the promotional effect of high-fat diet on mammary tumorigenesis by subsequent lowering of dietary fat.

Female Sprague-Dawley rats were given 7,12-dimethylbenz(a)anthracene at 50 days of age to induce mammary tumors, and beginning one week later were fed a high-fat, semipurified diet containing 20% sunflowerseed oil to promote tumor development. After another 7 weeks, when one third of the rats had palpable mammary tumors, the rats were randomly assigned to five groups of 31 animals each, with the same number of tumor-bearers in each group. One group was continued on the high-fat diet, another was given a fat-free diet, and the three remaining groups were fed diets containing 10% lard, butter, or coconut oil, respectively. During the next 29 weeks, rats fed the diets containing 0% or 10% fat developed significantly fewer tumors than those continued on the 20% fat diet. The diets containing 10% fat suppressed tumorigenesis at least as effectively as the fat-free diet. Rats fed the 10% butter and 10% lard diets had growth rates comparable to those fed the 20% sunflowerseed-oil diet throughout, and evidence of essential fatty acid deficiency was seen only in rats on the fat-free diet. These results provide additional evidence that high-fat diets promote development of mammary cancer and suggest that reducing the level of dietary fat might help to prevent the development and recurrence of breast cancer in humans.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Dietary fat and mammary carcinogenesis.

Evidence that dietary fat has an influence on carcinogenesis comes from both epidemiological data and experiments with animals. The experimental studies have indicated that dietary fat acts primarily as a promoter of carcinogenesis and that the effect depends on the type as well as the amount of fat in the diet. Vegetable oils containing polyunsaturated fatty acids of the linoleic acid family (n-6) have been shown to enhance mammary tumorigenesis, but a fish oil containing polyunsaturated fatty acids of the linolenic acid family (n-3) had an inhibitory effect at higher levels of intake. These and other findings suggest that the effect may be related to prostaglandins or other biologically active products of polyunsaturated fatty acids. Epidemiological data show a positive correlation between dietary fat and mortality from cancer at various sites, and this is supported by results of animal experiments in the case of colon cancer and pancreatic cancer as well as breast cancer. In the epidemiological data, cancer mortality shows strong positive correlations with total dietary fat and with animal fat, but not with fat derived from plants. Fats and oils used as spreads, cooking fats, and salad oils are the main source of fat in the American diet. Other major sources are meats and dairy products. Fat intake could probably be reduced substantially without serious deleterious effects, and this might help to decrease the risk of developing certain types of cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

The submicrosomal distribution of dolichyl phosphate and dolichyl phosphate phosphatase in rat liver.

Rat liver microsomes were isolated and fractionated into Golgi, smooth endoplasmic reticulum (SER), and rough endoplasmic reticulum (RER), and the purity of these preparations was determined. The dolichyl phosphate (Dol-P) content of whole microsomes and of each of the submicrosomal fractions was estimated using high pressure liquid chromatography. Dol-P accounts for 4 and 40% of the sum of the alcohol, the fatty acyl esters of dolichol, and monophosphate forms present in whole liver and in purified microsomes, respectively. Concentrations equal to 58, 77, and 108 ng of Dol-P/mg of protein were found in Golgi, SER, and RER, respectively. These values represent 3, 36, and 54% of the sum of the alcohol, the fatty acyl esters of dolichol, and monophosphate forms present in each of these same fractions, respectively. Increases in the Dol-P content of rat liver were observed as early as 12 h after turpentine-induced inflammation and increased 2-fold over 36 h. In this system, Dol-P accounts for no more than 50% of the sum of all phosphorylated and pyrophosphorylated dolichol intermediates present. The specific activity for dolichyl phosphate phosphatase was highest by more than a factor of 2 in Golgi membrane. Specific activities obtained for SER and RER were 42 and 11% of those present in Golgi. The major requirement for Dol-P is thought to be for the saccharide and oligosaccharide transferase reactions which are presumed to take place in RER. The discovery of significant quantities of Dol-P in Golgi and SER is consistent with a possible role of Dol-P in the transport of sugars required for glycoprotein synthesis and processing from a cytosolic to luminal orientation.

Animals↗
PubMed1983

Characterization of dolichol and dolichyl phosphate phosphatase from soya beans (Glycine max).

A series of polyprenols, ranging in length from 15 to 22 isoprene units, has been isolated from soya beans (Glycine max) and purified by high-pressure liquid chromatography. N.m.r., i.r. and mass spectra of the compounds indicated that they are alpha-saturated polyprenols of the dolichol type. The amount present in dry seeds was about 9 mg/100 g, whereas dolichyl phosphate (Dol-P) was present only in trace amounts. Dol-P phosphatase activity was detected in the microsomal fraction of 5-day-old germinating soya-bean cotyledons. The Dol-P phosphatase activity was linear with respect to time and protein concentration and exhibited a broad pH optimum (pH 7-9). Triton X-100 was necessary for significant enzyme activity. Enzyme activity was slightly enhanced by EDTA, whereas dithiothreitol was without effect. An apparent Km of 5 microM was determined for Dol-P. Bivalent metal ions were not required for enzyme activity. A number of phosphorylated compounds tested as enzyme substrates (including a number of nucleoside phosphates, glucose 6-phosphate, sodium beta-glycerophosphate and Na4P2O7) did not compete with [1-3H]Dol-P as substrate. A number of phospholipids were also tested for their ability to act as Dol-P phosphatase substrates. At 1 mM concentration, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid and lysophosphatidic acid each inhibited enzymic activity. However, at 0.1 mM concentration, phosphatidylcholine and phosphatidylethanolamine were slightly stimulatory, whereas phosphatidic acid and lysophosphatidic acid were still inhibitory. Phosphatidic acid showed competitive inhibition.

Chromatography, High Pressure Liquid↗