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Biomedical subjects

J M Bell

Publications and source records attributed to J M Bell.

At least 73 records · Page 4Linked to original sources
PubMed1989

Incorporation of plasma [14C]palmitate into the hypoglossal nucleus following unilateral axotomy of the hypoglossal nerve in adult rat, with and without regeneration.

Incorporation of plasma [14C]palmitate into the hypoglossal nucleus of the rat following transection, with and without regeneration of the hypoglossal nerve, was studied using quantitative autoradiography. The left hypoglossal nerve of 3-month-old, male Fischer-344 rats was transected using either: (1) an R-operation, which allowed nerve regeneration; or (2) a D-operation, in which regeneration was prevented. One to 84 days after axotomy, [14C]palmitate was injected intravenously and its rates of incorporation into stable structures of the left and right hypoglossal nuclei were measured at 4 h after injection. Following the R-operation, incorporation into the left hypoglossal nucleus was increased during and following axonal regeneration (up to 23% compared to control side), whereas incorporation was decreased 6-7% in the absence of regeneration, using the D-operation. The time courses of incorporation in both cases corresponded to histological changes, especially cell membrane changes following axotomy and suggest that [14C]palmitate incorporation reflects regenerative and degenerative neuronal changes associated with changes in lipid synthesis.

Animals↗
PubMed1989

The utilization of nitrogen for growth in mice fed blends of purified proteins.

Reasons for differences in growth of weanling mice fed different blends of purified proteins in diets apparently adequate in indispensable amino acids were investigated. Dietary nitrogen provided at increasing levels from a mixture of casein, gelatin, and zein, or from these plus gliadin and lactalbumin resulted in similar weight gains and efficiency of feed utilization in weanling mice. These responses were always lower (P less than 0.05) than for mice fed the control diet. When diets were based on true digestible nitrogen and amino acids, weight gains and feed efficiency decreased (P less than 0.05) as the dietary nitrogen level increased. High plasma glycine concentrations and high phenylalanine to tyrosine ratios were associated with high dietary glycine levels provided by gelatin. When a mixture of constant proportions of protein sources, predominantly casein, supplied most of the dietary nitrogen, small increases in weight gains and feed efficiency were observed as the nitrogen level in the diet increased. Varying the proportions of sources, which increased the percentage of gelatin, resulted in decreased gains in response to more dietary nitrogen. Replacing the amino acids found in gelatin by crystalline L-amino acids and replacing glycine by glutamic acid improved gains and feed efficiency (P less than 0.05) compared with gelatin-containing diets. These studies demonstrated that glycine at dietary concentrations of approximately 1-2%, either from gelatin or as the free amino acid, inhibited growth and feed utilization of growing mice.

Amino Acids↗
PubMed1988

CO oxidoreductase from Streptomyces strain G26 is a molybdenum hydroxylase.

CO oxidoreductase was purified to 95% homogeneity from crude mycelial extracts of Streptomyces G26. The purified preparation has a specific activity of 25.7 units/mg, a 13-fold improvement on crude soluble mycelial extracts. The native enzyme (Mr 282,000) is composed of non-identical subunits of Mr 110,000 and 33,000. It is a molybdenum hydroxylase containing 1.6 mol of FAD, 7.3 mol of Fe, 8.3 mol of acid-labile sulphide and 1.3 mol of Mo per mol of enzyme. Purified CO oxidoreductase catalyses the reduction of benzyl viologen, confirming the previously reported ability of this enzyme to interact with low-potential acceptors. Cytochrome c reduction cannot be accounted for entirely by non-enzymic reduction by superoxide radicals. NAD+ and NADP+ are not reduced, nor is clostridial ferredoxin.

Aldehyde Oxidoreductases↗
PubMed1988

Regional cerebral palmitate incorporation after unilateral auditory deprivation in immature and adult Fischer-344 rats.

Regional cerebral incorporation of intravenously injected [U-14C]palmitate was measured from 1 day to 13 weeks after left cochlear destruction in 11-day- and 3 month-old, awake Fischer-344 rats. In 11-day-old animals, statistically significant left-right differences in incorporation were absent 1 day after cochlear destruction and were found only in parts of the cochlear nucleus and inferior colliculus after 1 week. After 6 to 13 weeks, consistent with functional neuroanatomy of central auditory regions, incorporation was reduced by 6 to 9% in the left cochlear nucleus and left lateral superior olivary nucleus, compared with corresponding right-side regions. The right medial superior olivary nucleus, medial nucleus of the trapezoid body, lateral lemniscus nucleus, inferior colliculus, medial geniculate body, and auditory cortex had 5 to 9% less incorporation than did corresponding left-side regions. Fewer significant differences after chronic auditory deprivation occurred in 3-month-old rats than in 11-day-old rats following cochlear destruction. Reduced incorporation corresponded to reported changes in cell morphology, which also were greater in immature than mature rats following auditory deprivation. The results suggest that the palmitate method can be used to identify long-term regional changes in the turnover of brain lipids after sensory deprivation.

Animals↗
PubMed1988

Postnatal nutritional status influences development of cardiac adrenergic receptor binding sites.

Nutritional status in neonatal rats was manipulated by altering the litter size to produce overnourished (5-6 pups/litter) and undernourished animals (16-17 pups/litter) for comparison with standard nutritive status (10-11 pups/litter). Nutritionally deprived pups showed impaired body and cardiac growth and a slowing of development of cardiac membrane binding sites for alpha 1- and beta-receptor ligands. Overnourishment enhanced growth and receptor development. In all cases, restitution of receptor binding characteristics to normal occurred at the beginning of nutritional rehabilitation (i.e., at weaning), well before the return of body and organ weights. These results thus suggest that the ontogenetic pattern of receptor binding sites is dependent upon nutritional intake rather than on weight gains per se. Receptor deficits caused by neonatal malnutrition probably contribute to reduced responsiveness to adrenergic stimulation.

Adrenergic Fibers↗
PubMed1988

Digestibility of nitrogen and amino acids in selected protein sources fed to mice.

The purpose of this investigation was 1) to determine the apparent and true digestibilities in mice of nitrogen (N) and amino acids (AA) in commercially refined protein sources, and 2) to estimate metabolic fecal nitrogen (MFN) excretion. Each protein source was fed to adult female mice at 15 and 30% of a purified diet. A protein-free diet was included. Nutrient digestibility was determined by a fecal balance method with chromic oxide as a marker. Apparent digestibility of N in each protein source reflected the dietary N concentration and AA digestibility showed a similar trend. True digestibility (TD) of N was 97-98% for Animal Nutrition Research Council reference protein, casein, gelatin and gliadin, 94-96% for lactalbumin and soy protein and 81% for zein. TD of AA generally reflected TD of N. MFN excretion (g/100 g dry matter consumed) was 0.146 when the protein-free diet was fed and 0.151 by extrapolation to zero N intake. It was concluded that when commercially refined proteins are fed to mice, MFN excretion can be determined by either method, but this may not apply when the protein source contains antinutritive substances.

Amino Acids↗
PubMed1988

Neonatal nutritional deprivation or enhancement: the cardiac-sympathetic axis and its role in cardiac growth and stress responses.

To determine the mechanisms by which neuronal input influences cardiac growth during altered neonatal nutritional status, rats were reared in small, standard, or large litter sizes and the adrenergically mediated stimulation of cardiac ornithine decarboxylase was determined; ornithine decarboxylase provides a mechanistic link connecting adrenergic input to cardiac growth. Nutritionally deprived pups showed impaired development of sympathetic reflex stimulation as shown by the attenuation of the cardiac ornithine decarboxylase response to hydralazine-induced hypotension throughout the preweanling period. The subnormal reactivity to hydralazine reflected a defect in neurotransmission, as a full response was obtained with direct beta-receptor stimulation (isoproterenol). Nevertheless, cardiac hypertrophy in response to repeated isoproterenol administration was markedly suppressed in nutritionally deprived animals, suggesting that the beta-receptor/ornithine decarboxylase pathway had become uncoupled from growth. Because maturation of neural connections to peripheral tissues causes a loss of hypoxia tolerance, nutritional status also influenced the ability of neonatal rats to survive hypoxia. These data indicate that cardiac growth suppression or enhancement caused by nutritional manipulations may be mediated, in part, through alterations in the development of neuronal input to the tissue, and that similar factors influence survival during hypoxic stress.

Age Factors↗
PubMed1988

Nutritional influences on adrenal chromaffin cell development: comparison with central neurons.

Neurotransmitter systems in the developing brain are generally protected from growth retardation associated with nutritional deprivation. To investigate if such protective mechanisms extend to similar tissues in the peripheral sympathetic system, maturation of the chromaffin cells of the adrenal medulla and development of their centrally derived splanchnic innervation were evaluated in rats whose nutritional status had been altered during the neonatal period by increasing (16-17 pups/litter) or decreasing (five to six pups/litter) the litter size from the standard (11-12 pups/litter). Ontogeny of adrenal catecholamine stores and activities of catecholamine-biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were monitored, along with activity of choline acetyltransferase, a marker enzyme for the preganglionic neurons innervating the chromaffin cells. Neonatal nutritional deprivation slowed body weight gain and retarded development of the chromaffin cells, as evidenced by subnormal catecholamine stores, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities. The effects persisted despite the complete recovery of body weights postweaning. The developmental alterations were not caused by overcrowding stress, as plasma corticosterone levels were not elevated in the large litter group. Neonatal nutritional enrichment promoted body weight gain but failed to enhance development of adrenal catecholamines; tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were elevated only in the preweaning period. In contrast to effects on the chromaffin cells, altered neonatal nutritional status had only minor, transient effects on the development of the centrally derived cholinergic innervation of the adrenal and produced only small changes (less than 10%) in brain tyrosine hydroxylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1988

Effects of various high-fat diets on myocardial contractility and morphology in rats.

The effects of various high-fat diets (20% w/w) containing commercially available fats and oils (butter, corn oil, corn oil margarine, canola oil, canola oil margarine, soybean oil, soybean oil margarine, sunflower oil, sunflower oil margarine) on myocardial contractility and morphology and on plasma lipids were investigated in male Sprague-Dawley rats fed the diets for 16 weeks. Diets containing corn oil caused significantly (P less than or equal to .05) higher plasma total cholesterol levels than diets containing butter. Significant differences were also determined in lipoprotein levels. Plasma triglyceride levels were significantly (P less than or equal to .05) higher with butter than with sunflower oil or sunflower margarine. No significant differences among the groups occurred in blood pressure, heart rate, or myocardial contractility. Histological evaluation revealed that animals fed canola oil had the highest incidence and severity of myocarditis and fibrosis and that the degree of cardiac lipidosis was not correlated to the erucic-acid content of the diet. Myocardial damage was significantly (P less than or equal to .05) negatively correlated with stearic and palmitic acids and positively correlated with oleic acid. The results indicate that diets low in saturated fats may have adverse long-term effects on the heart.

Animals↗
PubMed1987

Impaired morphological development of the dorsal cochlear nucleus in hamsters treated postnatally with alpha-difluoromethylornithine.

The dorsal cochlear nucleus is a highly organized nucleus in the auditory system in which the ramifications of depletion of specific cell types during development can be studied. Granule cells, small interneurons that are located in all layers of the DCN in the adult hamster, proliferate postnatally and are, therefore, potentially vulnerable to anti-mitotic agents that are administered after birth. The present experiments describe the effects of alpha-difluoromethylornithine, a drug that inhibits proliferation of cerebellar granule cells, on the granule cells in the dorsal cochlear nucleus. As in the cerebellum, the density of granule cells in the dorsal cochlear nucleus is reduced after alpha-difluoromethylornithine treatment. In hamsters treated with alpha-difluoromethylornithine (200 or 500 mg/kg subcutaneously (s.c.), twice daily on postnatal days 4-14), the numerical density of granule cells was reduced in the superficial dorsal cochlear nucleus at 15 days; by 40 days this effect was also apparent in the deep layer, suggesting that cells located superficially that would have migrated into the deep dorsal cochlear nucleus had either failed to develop or did not arrive at their final location. This evidence suggests that the cells normally migrate down from the superficial proliferative zone into the deeper layers. In the drug-treated animals, a layer of mixed granule cells and fusiform cells was thinner than in controls probably due to the reduction in interspersed granule cells since the number of fusiform cells was unaffected. There was also a dose-dependent effect on cell growth; fusiform cells were affected at both doses, while giant cells were only affected at the highest dose. Granule cells form a major input to the fusiform cells and their depletion may account for some of the effects on fusiform cell growth. There could also be additional direct actions of alpha-difluoromethylornithine on this population.

Age Factors↗
PubMed1987

Glycogen synthase kinetics in isolated human adipocytes: an in vitro model for the effects of insulin on glycogen synthase.

Glycogen synthase which catalyzes the incorporation of uridine dipophosphate glucose into glycogen is found in muscle, liver, and fat. The activity of this enzyme is increased by insulin through a dephosphorylation mechanism. Because of the critical role of glycogen synthase in glucose storage and overall glucose metabolism, it is important to assess the status of the activity of this enzyme in normal humans as well as in individuals with pathological conditions, such as non-insulin-dependent diabetes mellitus. However, in human subjects, studies of the regulation of glycogen synthase in vivo are time consuming and tedious. The present study was, therefore, undertaken to establish whether adipocytes isolated from subcutaneous adipose tissue biopsies from normal human subjects could be used to assess the effect of insulin in vitro on glycogen synthase activity. Regulation of glycogen synthase in human adipocytes by glucose 6-phosphate and uridine disphosphate glucose was found to be somewhat different than that reported for the regulation of this enzyme in tissues from other species. The adipocyte was found to be a sensitive model for insulin activation of this enzyme. Glycogen synthase was stimulated twofold by an insulin concentration of as low as 1 ng/ml, while half-maximal activation of enzyme activity occurred at 0.4 +/- 0.1 ng insulin/ml. The present studies indicate that the isolated human subcutaneous adipocyte may serve as a useful model for in vitro investigation of the effects of insulin on glycogen synthase.

Adipose Tissue↗
PubMed1987

Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.

To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.

Glucose↗
PubMed1987

Biochemical determinants of growth sparing during neonatal nutritional deprivation or enhancement: ornithine decarboxylase, polyamines, and macromolecules in brain regions and heart.

In order to elucidate the biochemical mechanisms operating to protect the brain from growth retardation in response to nutritional deprivation, comparisons were made of markers of cellular development in brain regions (cerebellum, cerebral cortex, midbrain + brainstem) and in a tissue which is not spared (heart). Nutritional status of neonatal rats was manipulated by increasing or decreasing the litter size beginning at birth, and development of DNA, RNA, and proteins followed throughout the neonatal period. In addition, we assessed the activity and levels of ornithine decarboxylase and its metabolic products, the polyamines, which are known to coordinate macromolecule synthesis in immature tissue and to provide an early index of perturbed development. Cardiac ornithine decarboxylase and polyamines were altered within 48 h of initiating the changes in litter size, and the direction and magnitude of these biochemical effects were predictive of subsequent impairment or enhancement of organ growth and of cellular development. All three brain regions were buffered from growth alterations relative to the heart, but the cerebellum, which undergoes major phases of cell replication later than the other two regions, was somewhat less protected. The spared brain regions also showed evidence of compensatory hypertrophy in nutritional deprivation (increased protein/DNA ratio) which accounts for maintenance of growth in the presence of reduced cell numbers. Thus, brain growth sparing involves specific cellular responses which are dependent on the maturational profile of each brain region.

Animals↗
PubMed1986

Incorporation of plasma palmitate into the brain of the rat during development.

Jpalm, the rate of incorporation of plasma palmitate into brain, was determined in awake Fischer-344 rats at 15, 20, 25 and 38 days of age, by a modification of the method of Kimes et al. [14C]palmitate was injected intravenously and plasma-specific activity of unesterified palmitate was followed until the animals were killed at 4 h, when radioactivity was determined by quantitative autoradiography in 45 individual brain regions. Jpalm was calculated as the 4 h brain radioactivity divided by integrated plasma palmitate-specific activity to 4 h. Jpalm rose between 15 and 20 days of age in gray and white matter regions, then declined 4-5-fold in gray matter and 7-10-fold in white matter by 38 days and reached adult levels by 3 months. The white/gray ratio for Jpalm declined significantly between 20 and 38 days, and between 38 days and 3 months of age, consistent with a lower rate of turnover of white matter lipids in the mature brain. The results support the use of the Jpalm technique to measure brain lipid synthesis and turnover. They show that Jpalm corresponds to the time course of myelination during development of the rat brain, when there are parallel changes in the rates of palmitate incorporation into gray and white matter regions.

Aging↗
PubMed1986

Effects of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase, on nucleic acids and proteins in developing rat brain: critical perinatal periods for regional selectivity.

Ornithine decarboxylase and its metabolic products, the polyamines, are known to coordinate macromolecule synthesis in developing neural tissues; consequently, inhibition of this enzyme by alpha-difluoromethylornithine interferes with cellular replication and differentiation. We examined the regional selectivity of the effect of alpha-difluoromethylornithine administered either postnatally (days 1-19) or during gestation (days 15-17), in order to determine whether specific phases of maturation are particularly sensitive to polyamine depletion. In the cerebellum, which undergoes major phases of replication and differentiation after birth, postnatal alpha-difluoromethylornithine administration caused a profound and progressive deficit in tissue weight gain as well as in DNA, RNA and protein content. Although regions which develop earlier (cerebral cortex, midbrain + brain stem) also showed adverse effects of postnatal alpha-difluoromethylornithine, the deficits were of much smaller magnitude and were comparable to the effect of the drug on general body growth. Despite these regional differences, inhibition of DNA synthesis ([3H]thymidine incorporation) was similar in cerebellum and in midbrain + brain stem, indicating that the direct impact of alpha-difluoromethylornithine-induced polyamine depletion is exerted in both; DNA synthesis in cerebral cortex was spared relative to the other two regions. These data suggested that the impact of alpha-difluoromethylornithine on development depends, in part, upon the relative degree of maturation of each brain region at the time of drug exposure. In confirmation of this hypothesis, prenatal alpha-difluoromethylornithine given on gestational days 15-17 resulted in loss of the specificity toward cerebellar development and enhancement of effects on cerebral cortex, the region which had displayed the least sensitivity to postnatal alpha-difluoromethylornithine.

Aging↗
PubMed1986

Critical development periods for inhibition of ornithine decarboxylase by alpha-difluoromethylornithine: effects on ontogeny of sensorimotor behavior.

The roles of ornithine decarboxylase and the polyamines in behavioral development were examined through the use of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase. alpha-Difluoromethylornithine was administered either prenatally during gestation (days 15-17) or postnatally (days 1-20) to examine critical periods of sensitivity. Prenatal alpha-difluoromethylornithine administration resulted in a deficit in early sensorimotor ontogeny: latencies in surface righting reflex (postnatal days 1-5) and negative geotaxis (postnatal days 5-8) were prolonged, and time spent pivoting (postnatal days 7, 9, and 11) was reduced. In contrast, postnatal alpha-difluoromethylornithine primarily influenced later maturing, complex integrative behaviors such as swimming and open field activity. Thus, the behavioral effects of alpha-difluoromethylornithine exposure are highly dependent upon the age at which the drug is administered, a finding in keeping with the participation of the ornithine decarboxylase/polyamine system in cell replication and differentiation during discrete periods of neural development. The behavioral consequences of ornithine decarboxylase inhibition during these critical periods are thus related primarily both to the timetable for cellular maturation in each brain region.

Animals↗
PubMed1986

Perinatal dietary supplementation with a soy lecithin preparation: effects on development of central catecholaminergic neurotransmitter systems.

Previous work has shown that exposure of developing rats to soy lecithin preparations (SLP) influences macromolecular constituents of immature brain cells and causes abnormal behavioral patterns. To determine if synaptic mechanisms are adversely affected by SLP, we examined the developmental characteristics of noradrenergic and dopaminergic pathways in discrete brain regions. Although transmitter levels were unaffected, the utilization rates of both catecholamines were profoundly disturbed in an age-dependent, regionally-selective manner. Utilization tended to be subnormal in the preweanling stage, but demonstrated a postweaning elevation in cerebellum and midbrain + brainstem. Enhanced utilization persisted in the latter region only, and cerebral cortex actually showed a lowered utilization rate in adulthood (60 days of age). Transmitter uptake capabilities were also affected by developmental exposure to SLP, as was tyrosine hydroxylase activity. The patterns of effects on these two variables indicated that the altered transmitter utilization rate probably reflected a change in impulse activity in the affected neuron populations, with promotion of activity in the midbrain + brainstem and reduced activity in the cerebral cortex. These data indicate that dietary supplementation with SLP throughout perinatal development alters synaptic characteristics in a manner consistent with disturbances in neural function.

Aging↗