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Biomedical subjects

J A Milner

Publications and source records attributed to J A Milner.

At least 109 records · Page 6Linked to original sources
PubMed1982

The influence of excess lysine on urea cycle operation and pyrimidine biosynthesis.

Rats fed a purified L-amino acid diet with 0.72, 1.50, 2.9 or 4.3% lysine excreted 117, 124, 237 and 628 micrograms/day orotic acid, respectively. Dietary arginine supplementation prevented the orotic aciduria induced by excess dietary lysine. Increased orotic acid excretion was accompanied by a significant depression in urinary urea in rats fed a diet containing 4.3% lysine compared to those fed a diet containing 0.72% lysine. As measured by incorporation of [14C]HCO3, lysine addition to liver slices or isolated hepatocytes resulted in a progressive increase in the rate of orotic acid biosynthesis. The minimum quantity of lysine tested that significantly increased the rate of orotic acid biosynthesis was 0.5 mM or 1 mM for studies with slices and hepatocytes, respectively. Ammonia at concentrations of 0, 0.75, or 5.0 mM NH4Cl linearly increased orotate and urea synthesis. Inhibition of urea biosynthesis resulting from lysine supplementation coincided with an increase in pyrimidine biosynthesis. Addition of 1 mM arginine to the liver incubation media prevented the increased rate of orotic acid biosynthesis caused by lysine. Arginine addition may overcome an approximate 90% competitive inhibition of arginase by excess lysine.

Amino Acids↗
PubMed1982

Threonine, tryptophan and histidine requirements of immature beagle dogs.

The threonine, tryptophan and histidine requirements of growing male Beagle dogs were determined using diets containing the equivalent of 14% protein as crystalline L-amino acids. For each amino acid the requirement was taken to be the minimum dietary quantity required for optimal growth, feed efficiency and nitrogen retention. In experiment 1 the threonine requirement was found to be provided by 0.52% or more dietary threonine. In experiments 2 and 3 the minimal dietary tryptophan and histidine requirements of immature dogs were estimated as 0.17 and 0.21%, respectively. The requirements for threonine and tryptophan are similar to those for growing rats. However, the histidine requirement of Beagles appears to be lower than that of rats.

Amino Acids↗
PubMed1981

Improved method for selenium determination in biological samples by gas chromatography.

A gas chromatographic assay employing electron-capture detection for the determination of selenium in biological samples is reported. A calibration curve of 4-nitro-o-phenylene-diamine derivative of selenium as a function of peak area was linear from 5-1000 pg. The limit of detection for the electron-capture detector was approximately 0.5 pg. Recoveries of selenium added to various biological materials ranged from 95-105%. This procedure reduces the number of transfers thereby reducing errors associated with losses or contamination. One advantage of the present method is that interfering compounds occurring in previously employed chromatographic methods are eliminated. This procedure can be used for routine microanalysis of selenium. Samples containing less than 2 ng selenium in 200 microliter of biological fluid can be routinely analyzed using this method.

Animal Feed↗
PubMed1981

Alterations in liver nucleic acids and nucleotides in arginine deficient rats.

Dietary arginine deficiency is associated with retarded growth and depressed feed intake. Nucleic acid biosynthesis as indicated by the incorporation of [6-14C]-orotic acid and [32P]-orthophosphate was significantly depressed in rats fed an arginine deficient diet. The activities of the pyrimidine enzymes, aspartate transcarbamylase (ATC) and dihydroorotate dehydrogenase (DHODH) were significantly increased in rats fed an arginine deficient diet. ATC and DHODH activities in rats fed the arginine deficient diet returned to control activities after 3 wk of feeding. Orotidine 5' phosphate decarboxylase and orotate phosphoribosyl transferase activities were not affected by dietary arginine availability. In the rat fed an arginine deficient diet there was an increase in total liver pyrimidine nucleotides and a decrease in the total purine nucleotides. Significant alterations in the individual liver nucleotides were also observed. Incubation of various tissues obtained from rats fed an arginine deficient diet or a complete diet with glutamine (5mM) revealed that the liver is the major site of orotic acid synthesis. Orotic acid production in liver slices using glutamine as the nitrogen source was significantly greater in rats fed an arginine deficient diet compared to controls. The orotic aciduria occurring in rats fed an arginine deficient diet is associated with increased synthesis and decreased utilization of pyrimidines.

Animals↗
PubMed1981

Antimutagenic effect of selenium on acridine orange and 7,12-dimethylbenz[alpha]anthracene in the Ames Salmonella/microsomal system.

The antimutagenic effects of selenium as sodium selenite were investigated using the Ames Salmonella/microsome mutagenicity test. The compounds examined were acridine orange and 7,12-dimethylbenz[alpha]anthracene. Selenium (22 ppm) reduced the number of histidine revertants caused by 20 microgram acridine orange and 20 microgram 7,12-dimethylbenz[alpha]anthracene by 52 and 74%, respectively. Increasing the quantity of selenium added to the plates further suppressed the mutagenicity of the test compounds. The antimutagenic effects of selenium cannot be explained by lethality of Salmonella typhimurium.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Arginine deficiency during gestation and lactation in the rat.

The effects of dietary arginine deprivation during gestation and lactation were studied in the rat. Placental development, as indicated by the total protein and RNA content, of rats fed a diet devoid of arginine was inferior to that of pair-fed controls. Fetal cerebral protein plus body weights were reduced by maternal arginine deprivation. Urinary excretion of orotic acid and citric acid was significantly increased in arginine-deficient rats throughout the gestational period. Pups nursed by arginine-deficient dams during lactational periods had smaller body and organ weights than those nursed by pair-fed control dams regardless of their prenatal nutritional states. Nursing performance of the dam was most affected by feeding arginine-free diet throughout gestation and lactation. Consumption of an arginine-free diet by the dam during gestation resulted in lower birth weight and higher perinatal mortality of the pups nursed. Deletion of arginine from the diet after parturition significantly reduced nursing performance after 18 days of lactation. The reduction in nursing performance caused by arginine deficiency during gestation could be corrected by replenishing arginine after parturition. Mammary gland development, as indicated by nucleic acid content, was reduced by either reducing dietary arginine or food intake during lactation. All these results provided evidence that dietary arginine is required during gestation and lactation for optimal reproductive response and nursing performance in rats.

Animals↗
PubMed1981

Lysine requirements of the immature dog.

These studies examined the lysine requirement of the immature Beagle dog fed a purified L-amino acid diet. The immature female dog was found to require between 0.461 and 0.577% dietary lysine for optimum growth and nitrogen balance. Plasma and urinary urea were significantly increased in female dogs fed 0.461% or less dietary lysine. Maximum growth and nitrogen balance occurred in immature male dogs fed 0.577% or more lysine. Consumption of diets containing excess dietary lysine (1.73%) significantly reduced growth in both immature male and female dogs. Varying dietary lipid from 5 to 20% did not appear to alter the lysine requirement of the immature male dog. Increasing the nitrogen content of the diet from approximately 14% crude protein to 28% accentuated the symptoms of low lysine intakes. The lysine requirement of the immature dog appears to be lower than that reported for the growing pig or rat.

Animals↗
PubMed1981

Sulfur amino acid requirements of immature Beagle dogs.

The methionine and total sulfur amino acid requirements of growing Beagle dogs were determined using diets containing purified L-amino acids as the sole nitrogen source. In the presence of 0.60% dietary L-cystine, optimal growth, feed efficiency, and nitrogen retention were attained in dogs fed diets containing 0.20% or more L-methionine. Two additional experiments revealed that maximal growth, feed efficiency, and nitrogen retention occurred in growing dogs fed diets containing 0.20% L-methionine and supplemented with 0.15% or more L-cystine. Therefore, the total sulfur amino acid requirement was estimated to be 0.39% methionine. Cystine, on an isosulfurous basis could effectively supply up to approximately 50% of the total sulfur amino acid requirement. In crystalline amino acid diets, D-methionine, DL-methionine, N-acetyl-L-methionine and methionine hydroxy analogue were effective in replacing the L-methionine requirement of growing Beagles. N-acetyl-D-methionine, however, was not efficiently utilized as a substitute for dietary methionine.

Amino Acids, Sulfur↗
PubMed1981

Arginine: an indispensable amino acid for mature dogs.

There studies examined the effect of dietary arginine deficiency in the mature dog. Deletion of arginine from the diet resulted in a slight but significant loss of body weight. Severe episodes of emesis were observed in all experiments. Muscle tremors and frothing around the mouth were also observed in the experiments where the arginine-free diet was force fed. Increasing the amount of diet force-fed to mature dogs accentuated the symptoms of emesis, muscle tremors and frothing. Elevated plasma ammonia and orotate were detected in dogs fed an arginine-deficient diet. Urinary citric and orotic acid was also increased in mature dogs fed a diet devoid of arginine. Nitrogen balance was not significantly altered by deletion of arginine from the diet. Based on the occurrence of emesis, loss of body weight and alterations in intermediary metabolism, we concluded that the mature dog does require a dietary source of arginine. Dietary inclusions of 0.28% arginine prevented the symptoms of arginine deficiency.

Animals↗
PubMed1981

Species specificity of arginine deficiency-induced hepatic steatosis.

Hepatic steatosis resulting from the consumption of an arginine-deficient diet in the rat was found to occur independent of age or size. The rate of lipid biosynthesis as indicated by in vitro incorporation of 14C-acetate was significantly increased in rats fed an arginine-deficient diet when expressed per milligram liver. Supplementation of the arginine-deficient diet with 1% ribose, 1% hypoxanthine or 0.2% adenine depressed the fatty infiltration caused by arginine deficiency. Inosine, xanthine or uracil supplementation did not significantly alter the fatty infiltration, liver orotic acid biosynthesis or urinary orotic excretion induced by the arginine deficiency. Increased orotic acid excretion was also observed in the mouse, hamster and rabbit fed a diet devoid of arginine. However, consumption of the, arginine-deficient diet for 21 days did not significantly alter the liver lipid content of mice, hamsters or rabbits. Although the fatty infiltration appears to be limited to the rat, altered liver nucleotides were observed in rats, hamsters and rabbits fed an arginine-deficient diet. Similarities of arginine deficiency and orotic acid feeding in various species are discussed.

Age Factors↗
PubMed1981

Inhibitory effects of selenium on the growth of L1210 leukemic cells.

Selenium has been shown to inhibit L1210 cells both in vitro and in vivo. The death of L1210 cells in vitro as indicated by trypan blue exclusion was dependent upon the form and concentration of selenium tested. Incubation of L1210 cells in buffer containing selenium at 1 microgram/ml for 1 hr prior to inoculation into mice significantly retarded the ability of the cells to propagate in vivo. Sodium selenite injected i.p. increased the longevity of mice inoculated with L1210 cells. Administration of 40 microgram selenium as sodium selenite daily for 7 days resulted in a 65% increase in longevity of mice inoculated with 10(5) L1210 cells. Injections of sodium selenite at doses of 40 microgram/day or less for 7 days did not significantly alter growth, liver weight, or red and white blood cell counts. The efficacy of selenium therapy was dependent upon the total number of tumor cells given in the initial inoculum. Selenium administration as sodium selenite was shown to be more effective in increasing the longevity of L1210-inoculated mice than was treatment with sodium selenate, selenocystine, or selenomethionine. Sodium selenite treatment at 20, 30, or 40 microgram/day in mice inoculated with 10(2) cells resulted in 50, 80, and 90% cures, respectively. Supplementation of the drinking water with 3 ppm selenium as sodium selenite increased the longevity of L1210-inoculated mice by approximately 30%. Combined therapy with selenium (30 microgram/day) and methotrexate resulted in a significantly longer life span of L1210-treated mice than resulted from either compound administered separately.

Animals↗
PubMed1979

Orotic aciduria and increased nitrogen catabolism in rats.

In vitro incorporation of [14C] bicarbonate into orotic acid by rat liver slices was used to study the rate of orotic acid (OA) biosynthesis in the presence of physiological (0.73 mM) and saturation concentrations (5 mM) of NH4Cl. The influence of body size on OA synthesis in rats fed purified L-amino acid diets with (C) or without (-Arg) was examined. OA biosynthesis was significantly greater at both NH4Cl concentrations examined in liver slices obtained from -Arg rats for all sizes of rats. A linear decrease (r = 0.92) in OA synthesis as a function of body size was observed for rats fed either of the diets. The rate of OA biosynthesis was also found to increase linearly (r = 0.98) in livers from rats fed increasing dietary protein when determined by incubation with physiological concentrations of NH4Cl. OA biosynthesis was also found to increase with increase in length of fasting. Alteration in urinary OA and urea confirm these rates of synthesis. These results support the hypothesis that when the urea cycle is overtaxed, carbamyl phosphate (CP) synthesized intramitochondrially by CP synthetase I may be shunted into pyrimidine biosynthesis.

Aging↗
PubMed1979

Inhibitory effect of dietary arginine on growth of Ehrlich ascites tumor cells in mice.

The effect of dietary L-arginine on the growth and development of transplantable Ehrlich Ascites tumor cells was examined. Growth of tumor bearing mice was significantly inhibited by feeding a purified casein diet supplemented with 5% arginine. This diet significantly reduced the total number of free tumor cells growing in the peritoneal cavity of mice. Total free tumor cell RNA, DNA, and protein were also significantly reduced. Supplemental arginine approximately doubled the length of time for 50% death of tumor bearing mice. Arginine did not alter respiration as measured by glucose or citrate oxidation. Varying the concentration of supplemental dietary arginine revealed that 3% arginine also significantly retarded the growth of Ehrlich Ascites Tumor Cells. Tumor ornithine decarboxylase activities were significantly reduced by dietary arginine supplementation. Supplemental dietary arginine at 3 or 5% did not significantly affect the growth of non-tumor bearing mice. Dietary arginine may play a critical role in growth of normal as well as neoplastic tissue.

Animals↗
PubMed1979

Mechanism for fatty liver induction in rats fed arginine deficient diets.

Arginine deficiency is known to lead to marked alterations in pyrimidine biosynthesis and the excessive loss of urinary orotic acid. Orotic acid feeding is known to lead to hepatic steatosis. These studies show that arginine deficiency also results in a marked increase in liver lipids in the rat. The majority of the increased liver lipid can be accounted for by triglyceride accumulation. Increased liver lipid infiltration was found to be independent of the sex of the rat. Accompanying this increase was a decrease in serum triglycerides and cholesterol concentrations. Fatty infiltrations induced by arginine deficiency could be reversed by refeeding an arginine enriched diet. Adenine supplementation (0.30%) to the arginine deficient diet also completely prevented the induction of fatty livers. Adenine supplementation resulted in a dramatic increase in urinary orotic acid excretion in the arginine deficient rat. Guanine supplementation (0.5%) to an arginine deficient diet reduced but did not prevent the induction of fatty livers. The similarities of fatty livers induced by arginine deficiency and orotic acid feeding are discussed.

Adenine↗
PubMed1979

Assessment of indispensable and dispensable amino acids for the immature dog.

A completely purified L-amino acid diet was used to determine the indispensability of leucine, lysine, valine, phenylalanine and arginine in the immature dog. An additional study showed that asparagine, alanine, aspartic acid, cystine, glutamic acid, proline, tyrosine, serine and glycine can be classified as dispensable amino acids for the immature dog. Deletion of these indispensable amino acids resulted in a marked negative nitrogen balance. Increased plasma and urinary urea were also observed when a dietary indispensable amino acid imbalance occurred. Estimates are made for the dietary requirements for leucine, lysine, valine and phenylalanine in the immature dog.

Amino Acids↗