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Biomedical subjects

H N Munro

Publications and source records attributed to H N Munro.

At least 55 records · Page 3Linked to original sources
PubMed1984

Nutrition and the elderly: a general overview.

Throughout adult life, there is progressive alteration in body composition and tissue function. There is loss of lean body mass, notably by muscle, with a gain in body fat. We do not know whether nutritional factors affect these gross changes. In the case of loss of bone density (osteoporosis), however, there is evidence that the process is retarded by raising the intake of calcium and by exercise. Aging also adversely affects tissue function at the level of the whole organ and tissue as well as at the cellular and subcellular level. Animal models show similar age-related changes, and demonstrate further that alterations in nutrient intake or exercise can alter the rate of loss of tissue and cellular function. In addition to the effects of adult aging on tissue function, certain chronic diseases and disabilities are related to aging. These conditions include atherosclerosis, hypertension, coronary thrombosis, cancer, etc. Both human epidemiological studies and animal experiments on aging suggest strongly that nutrition plays a role in the onset and development of these conditions. There is a need for more accurate assessments of the nutrient needs of people over 65 years of age. A few selected nutrients are discussed. Studies of energy intake during adult life show a progressive reduction with increasing age, due mainly to reduced physical activity. Vitamin C levels in the white blood cells of elderly women can be half those of young adults; these respond to supplementary vitamin C without evidence of clinical benefit. Nitrogen balance studies suggest that the allowance of protein for older adults is not less than for young. Finally, surveys of elderly in whole populations and in selected groups show that, by the nutritional standards of young adults, there may exist a significant amount of malnutrition in people as they grow old, though we do not know whether this affects rate of loss of tissue function with age.

Aged↗
PubMed1984

Effects of intravenous glucose on whole body leucine dynamics, studied with 1-13C-leucine, in healthy young and elderly adults.

We examined whole body leucine metabolism in healthy young and elderly adults while in the postabsorptive state and during an intravenous glucose administration at two rates. Leucine flux, incorporation into whole body protein, and oxidation were estimated from a continuous intravenous infusion of L-[1-13C]leucine and determination of 13C enrichment in plasma leucine and expired air. Per unit of body weight, leucine flux and rates of incorporation into protein were similar in young and old men. Old women showed lower rates compared with young women. Rates were similar for both age groups when expressed per unit of total body water and/or of muscle protein mass. Intravenous glucose infusion (4 mg . kg-1 . min-1) reduced plasma leucine levels and flux similarly in both age groups. Thus, age-related differences in muscle mass and sensitivity of peripheral tissues to insulin-mediated glucose uptake and metabolism are not paralleled by alterations in whole body leucine kinetics in the postabsorptive state.

Adult↗
PubMed1984

Protein deficiency in pregnant rats causes decreased levels of plasma somatomedin and its carrier protein associated with reduced plasma levels of placental lactogen and hepatic lactogenic receptor number.

Rats were fed either a 20% lactalbumin (control) or a 5% lactalbumin (low protein) diet for the last 2 weeks of pregnancy. At day 20 of gestation, rat serum placental lactogen levels, measured by radioreceptor assay, were significantly decreased by the low protein diet, thus confirming our earlier findings. The number of microsomal membrane lactogenic receptors, measured on the maternal livers at the end of pregnancy, was severely reduced in the livers of the low protein group, whereas protein deficiency did not affect binding affinity. Serum concentrations of somatomedin, measured by a competitive binding assay after acid treatment of the serum to remove endogenous carrier protein, were extensively reduced in the low protein group. The amounts of the somatomedin carrier proteins in the serum were assayed by separation on Sephacryl-S300 columns into higher- and lower-molecular-weight fractions peak 2 and peak 3, respectively. For the low protein diet group, both fractions showed a reduction in binding capacity, more marked in the case of peak 2. Since placental lactogen is known to influence output of somatomedin by the liver, we hypothesize that protein deficiency during pregnancy causes a fall in serum somatomedin level by reducing secretion of placental lactogen, which regulates its production by the liver.

Animals↗
PubMed1984

Insulin-like growth factor receptors in rat placental membranes.

The nature and relative quantity of insulin-like growth factor (IGF) receptors in rat placental microsomal membranes was investigated by competitive binding studies and covalent cross-linking followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies revealed that 100 micrograms membrane protein specifically bound 26.5% of [125I]iodo-IGF-II, 19.6% of [125I]iodomultiplication-stimulating activity III-2 [( 125I]iodo-MSA-III-2), and 11.5% [125I]iodo-IGF-I. IGF-II was equipotent with MSA-III-2, and both were approximately twice as potent as IGF-I in competing with [125I]iodo-IGF-I for binding. In contrast, IGF-I competed for the binding of [125I]iodo-MSA and [125I]iodo-IGF-II with only 5-20% the potency of unlabeled MSA and IGF-II. Insulin competed weakly with [125I] iodo-IGF-I for binding (achieving half-maximal displacement at 20 micrograms/ml), but did not compete with [125I]iodo-MSA for binding. This evidence suggested that while IGF-I binds to both IGF-I and IGF-II receptors, the majority of IGF-I binding is due to an interaction with IGF-II receptors. Studies using [125I]iodo-IGF-I covalently cross-linked to placental membrane receptors followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed that molecular species characteristic of the subunits of IGF-I receptors are present in rat placenta. It is concluded that rat placenta, like human placenta, contains receptors for both types of IGFs. Unlike human placenta, the majority of the receptors are of the IGF-II type.

Animals↗
PubMed1983

RNA synthesis by villus and crypt cell nuclei of rat intestinal mucosa.

Rat intestinal mucosa was separated by eversion and vibration to provide a sequence of fractions from predominantly villus cells to predominantly crypt cells. The proportions of these cell types in each fraction were computed from the concentrations of alkaline phosphatase (villus cells) and thymidine kinase (crypt cells) in each population. The isolated mucosal fractions varied from about 90% villus cells to 90% crypt cells. Following injection of the rats with [3H]thymidine, the nuclei were isolated from each mucosal cell fraction and the amount of radioactivity incorporated into DNA was measured as an index of crypt cell abundance. The isolated nuclei were also incubated with ribonucleoside triphosphates and the amount of RNA synthesized was measured. Nuclei labeled with [3H]thymidine were found only in fractions rich in crypt cells, whereas capacity for RNA synthesis remained very active in mucosal fractions consisting predominantly of villus cells. It is concluded that non-dividing villus cells continue to make RNA.

Alkaline Phosphatase↗
PubMed1983

Inhibition of aminoacyl-tRNA synthetases by p-chloroamphetamine and its role in protein synthesis inhibition.

p-Chloroamphetamine inhibited to some degree all amino acid-dependent pyrophosphate-exchange activities which could be detected in a rabbit reticulocyte extract. A detailed kinetic analysis of the reaction catalyzed by reticulocyte leucyl-tRNA synthetase demonstrated that the inhibitor affected only amino acid binding. Less rigorous studies of other synthetases from both rabbit reticulocyte and Escherichia coli could be similarly interpreted, suggesting that this compound interacts in a common manner with these several enzymes. The contribution of such effects to the inhibition of protein synthesis by the drug was investigated using cell-free translation systems in which rates of amino acid incorporation were limited to varying degrees by the synthesis and availability of aminoacyl-tRNA. In a wheat germ system programmed with globin mRNA, in which levels of amino acids and aminoacyl-tRNAs were shown to limit the rate of protein synthesis, the inhibition produced by p-chloroamphetamine could be partially reversed by increasing the concentration of the limiting amino acid. In a reticulocyte lysate, in which amino acid concentrations were not limiting, inhibition failed to show an amino acid-reversible component. Thus, while the inhibition of aminoacyl-tRNA synthetases by amphetamines can be shown in some cases to play a role in the effects of these compounds on in vitro protein synthesis, other sites of interference with initiation and/or elongation reactions may predominate, depending on the construction of the system under study.

Amino Acyl-tRNA Synthetases↗
PubMed1983

Isolation of cDNA clones for the light subunit of rat liver ferritin: evidence that the light subunit is encoded by a multigene family.

The shell of the iron-storage protein ferritin consists of two types of subunit (heavy, Mr = 21,000; light, Mr = 19,000). To study the structure and expression of the ferritin subunit genes, recombinant plasmids containing ferritin cDNA have been isolated. A cDNA library was constructed in the vector pBR322 from rat liver polysomal mRNA and screened by using I125-labeled antibody to rat liver ferritin. Six positive clones were identified and were shown to contain cDNA inserts ranging in length from 800 to 950 base pairs. When these cDNA clones were used for hybrid selection of rat liver mRNA and the selected mRNAs were translated in vitro, the products from each clone migrated on denaturing gels in a position similar to that of the light subunit of ferritin. No evidence of translation of the heavy subunit was obtained, indicating that the two subunits are encoded by separate mRNAs. RNA blot analysis gave a length of 1,100 nucleotides for the light-subunit mRNA. One of the cDNA inserts was fractionated into four fragments by using the restriction enzyme Sau3A. When the fragments were hybridized with Southern blots of rat spleen DNA, each fragment yielded similar patterns of hybridization to that obtained with the intact cDNA. Therefore, all regions of the cDNA sequence contain homologous sequences to similar genomic restriction fragments. This is consistent with the existence of a family of genes that encode the light subunit of rat ferritin.

Animals↗
PubMed1983

De novo purine nucleotide synthesis in the rat small and large intestine: effect of dietary protein and purines.

This study assessed the pathway for de novo purine nucleotide synthesis in rat small intestinal and colonic mucosal cells, and determined the effects of dietary purines and protein on de novo purine nucleotide synthetic activity in the small intestine in vitro. Incubation of small intestinal mucosal scrapings with [14C]glycine failed to show an active pathway of de novo synthesis; in contrast, the colon showed incorporation of [14C]glycine into RNA. Rats fed a diet deficient in purines demonstrated increased incorporation of [14C]glycine into RNA-adrenine in small intestinal mucosal cells. Measurement of glutamine-amidophosphoribosyltransferase demonstrated that, regardless of the purine content of the diet, enzyme activity in the small intestine is significantly lower than in the colon or liver. The results indicate that, in the small intestine of the rat, there is an inactive de novo pathway of purine nucleotide biosynthesis that can be stimulated when purines are omitted from the diet.

Amidophosphoribosyltransferase↗
PubMed1982

Effect of testosterone on the rate of myofibrillar protein breakdown in castrated and adrenalectomized male rats measured by the urinary excretion of 3-methylhistidine.

Urinary output in N tau-methylhistidine (3-MeHis) was used to evaluate changes in myofibrillar protein breakdown rate in the skeletal muscles of castrated and adrenalectomized-castrated young male rats, and the response of breakdown to testosterone and corticosterone replacement. The castrated rats grew less well than intact control rats and excreted significantly less 3-MeHis. Administration of low and high doses of testosterone restored the weight of the levator ani of the castrated animals but failed to affect growth rate or 3-MeHis output. Although this might suggest that testosterone has an indirect effect on muscle turnover through changes in growth rate, this parallelism was not confirmed by studies on adrenalectomized-castrated rats. Adrenalectomy of castrated rats caused a further reduction in growth rate and in output of 3-MeHis, but administration of testosterone now reduced 3-MeHis output still further while stimulating growth. Treatment of the adrenalectomized-castrated rats with low doses of corticosterone increased growth modestly, while depressing 3-MeHis output, and again output of this metabolite was further reduced when testosterone was added to the treatment, although growth rate was unaffected. Finally, large doses of testosterone given to adrenalectomized-castrated rats receiving excessive amounts of corticosterone did not prevent the growth failure or the increased output of 3-MeHis due to the corticosteroid, though it appeared to reduce the magnitude of the response to corticosterone alone. It is concluded that the effects of testosterone on growth and on 3-MeHis output are not necessarily associated and that the functional status of the adrenal cortex modifies the response of myofibrillar breakdown rate to testosterone treatment.

Adrenalectomy↗
PubMed1982

Adaptation of body protein metabolism in adult and aging man.

Aging causes a selective loss in lean body mass, muscle being most extensively eroded. This presentation is an analysis of the consequences of this age-related loss for protein and amino acid metabolism. The use of stable isotopes allows us to measure the dynamics of protein metabolism in the intact human subject, while the output of 3-methylhistidine permits estimates of muscle turnover to be made which show a smaller reduction in body protein turnover per kg body weight in elderly subjects. This is due to the reduced contribution by muscle protein turnover, which decreases from 30 per cent of total body protein turnover in the young adult to 20 per cent in the elderly, and can be entirely accounted for by the reduced mass of muscle, the rate of turnover per unit muscle weight being unchanged. The consequences of the changing proportions of major tissues with age has been examined for its impact on amino acid metabolism. The interaction of various organs in order to ensure metabolism of different amino acids is described. After a meal containing abundant protein, the liver selectively degraded the excess of most essential amino acids, while allowing the three branched-chain essential amino acids to pass through, so that in consequence they account for more than 50 per cent of the amino acid outflow from the splanchnic area. During this period of absorption muscle takes up amino acids, over 70 per cent being the branched-chain amino acids where they are catabolised, the nitrogen becoming available for formation of non-essential amino acids for muscle protein synthesis. The release of large amounts of glutamine from muscle is dependent on branched-chain amino acid degradation, whereas the release of large amounts of alanine is regulated by availability of pyruvate from glucose. The study of amino acid metabolism in elderly compared with young adults and its relationship to the declining mass of muscle with age is still in its initial stages. Metabolism of glycine at different levels of protein intake fails to demonstrate any significant effects of aging on metabolism of this amino acid. On the other hand, the flux of leucine shows a significant reduction in fasting elderly female subjects. This observation should be followed up by studying leucine kinetics following a meal of meat, in order to determine whether the reduced mass of muscle in the elderly will restrict the capacity to metabolise branched-chain amino acids. It has been concluded that the extensive age-related change in muscle mass should be explored for its impact on the nutritional requirements for branched-chain amino acids, their metabolism in health and disease, and their therapeutic uses at different ages.

Journal Article↗
PubMed1982

Quantitation of muscle-specific mRNAs by using cDNA probes during chicken embryonic muscle development in ovo.

The emergence of abundant-class mRNAs specific for contractile muscle proteins and their distribution between polysomal and free mRNP fractions were studied in skeletal muscle excised from chicken embryos during the transition from myoblasts (day 9) to myotubes (day 18). Muscle-specific cDNA was selectively prepared by hybridizing cDNA to template RNA (polysomal poly(A)+ mRNA) from day-14 embryos followed by isolation of the abundant class, which represents approximately 20% of total mRNA. The specificity of the cDNA probe for this class was confirmed by the differential degree of hybridization to cytoplasmic RNA from cultured myotube and myoblast cells and by its inability to hybridize with mRNA from nonmuscle cells such as liver. Except for muscle from day-9 embryos, the concentrations of the abundant-class muscle-specific mRNAs were higher in polysomes than in free mRNP fractions. Furthermore, the levels of these mRNAs in polysomes increased 12-fold from day 9 (myoblast) to day 14 (intermediate) with a further 3.6-fold increase from day 14 to day 18 (myotube). In contrast to this 45-fold net increase in the polysomal level of these mRNAs from day 9 to day 18, the levels in the free mRNP fraction showed only a 3-fold decrease during this period. Because the amount of mRNA lost from the mRNP fraction is much less than the net increase in the polysome fraction, mRNP does not serve as a reservoir of untranslated muscle-specific mRNA for transfer to polysomes. Consequently, the emergence of muscle-specific polysomal mRNA for contractile proteins during myogenesis in ovo appears to be regulated primarily by transcriptional control.

Age Factors↗
PubMed1982

Human protein requirements: assessment of the adequacy of the current Recommended Dietary Allowance for dietary protein in elderly men and women.

A continuous 30-day metabolic N balance study was conducted in seven elderly men (75 +/- 4 yr) and eight elderly women (78 +/- 9 yr) to evaluate the current protein Recommended Dietary Allowance for older men and women. The subjects received a diet providing 0.8 g egg protein (N x 6.25) kg-1 day-1. Energy intake computed to meet needs averaged 32 and 29 kcal kg-1 day-1 for males and females, respectively. N balances, including an estimate for integumental and other miscellaneous losses, were determined for the last 5 days of three consecutive 10-day diet periods and blood biochemical measurements were made at the end of each diet period. Three of seven males and four of eight females were not in body N balance during the final 5 days of the 30-day period. These N balance data indicate that 0.8 g egg protein kg-1 day-1 is not sufficient to achieve N equilibrium in a majority of subjects older than 70 yr and confirm the results and conclusions of a previous, short-term N balance study (Uauy et al., Am J Clin Nutr 1978;31:779-85). Hence, where energy intake approximates requirement, the current Recommended Dietary Allowance is not adequate for a majority of male and female subjects age 70 yr and above.

Aged↗