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R B Dell

Publications and source records attributed to R B Dell.

At least 37 records · Page 2Linked to original sources
PubMed1986

Assessment of cortical and trabecular bone distribution in the beagle skeleton by neutron activation analysis.

The distribution of bone calcium between morphologically identifiable cortical and trabecular bone obtained by dissection and quantitated by neutron activation analysis (NAA) is described. The skeleton of a female beagle dog was dissected into approximately 400 pieces and assayed for 49Ca produced in the University of California, Irvine TRIGA reactor. For each of the skeletal sections, we give the initial weight of the alcohol-fixed tissue, which includes cortical bone, trabecular bone, marrow, and cartilage, and a final tissue weight after the marrow and trabecular bone have been dissected away; total section and cortical section calcium weights are reported. The level of detail is represented, for example, by the vertebrae, which were divided into three parts (body, spine, and transverse processes) and by the long bones, which were divided into 10-12 parts such that characterization of the epiphysis, metaphysis, and diaphysis was accomplished. The median percentage cortical calcium values for cervical, thoracic, and lumbar vertebrae were 82%, 56%, and 66%, respectively; however, variation within these groups and among individual vertebral sections was about a factor of 2. For long bones, the median percentage cortical calcium varied from 90-100% in the midshaft to below 50% in the proximal and distal sections. The final calculated cortical tissue-to-calcium mass ratio (TCR) varied from about 4.5 for midshafts of the long bones to about 9 for thoracic vertebral bodies and indicated that the mineral fraction of cortical bone is not constant throughout the skeleton. The ratio of cortical to trabecular calcium in the skeleton was 79.6:20.4.

Activation Analysis↗
PubMed1986

Effects of varying protein and energy intakes on growth and metabolic response in low birth weight infants.

Growth (weight, length, head circumference, and skinfold thickness), retention of major nutrients (nitrogen, sodium, potassium, chloride, calcium, and phosphorus), and chemical indices of protein adequacy (plasma albumin and transthyretin concentrations) and excess (blood urea nitrogen concentration and acid-base status; plasma amino acid concentrations) were determined serially from the time desired intake was tolerated until discharge weight (2200 gm) was reached in low birth weight infants (birth weight 900 to 1750 gm) fed one of three formulas, which provided protein and energy intakes, respectively, of 2.24 gm/kg/day and 115 kcal/kg/day (group 1), 3.6 gm/kg/day and 115 kcal/kg/day (group 2), and 3.5 gm/kg/day and 149 kcal/kg/day (group 3). Weight gain and rate of increase in length and head circumference were less in group 1 than in groups 2 and 3. Retention of most major nutrients also was less in group 1, as was blood urea nitrogen concentration, plasma albumin and transthyretin concentrations, and plasma concentrations of several amino acids. The rate of weight gain was not significantly greater in group 3 than in group 2, but the rate of increase in skinfold thickness was greater in this group. Neither nutrient retention nor metabolic indices differed between groups 2 and 3. These results suggest that a protein intake of 2.24 gm/kg/day is inadequate for the type of LBW infants studied, that the higher protein intakes are well tolerated, and that an energy intake of 149 vs 115 kcal/kg/day does not enhance utilization of the higher protein intakes studied.

Acid-Base Equilibrium↗
PubMed1986

Lack of relationship in humans of the parameters of body cholesterol metabolism with plasma levels of subfractions of HDL or LDL, or with apoE isoform phenotype.

The factors involved in regulating parameters of whole body cholesterol metabolism in humans have been explored in a series of investigations. Several physiological variables have been identified (weight, excess weight, plasma cholesterol, and age) that can predict 53-76% of the variation in production rate (PR) and in the sizes of the rapidly exchanging pool of body cholesterol (M1) and of the minimum estimates of the slowly exchanging pool of body cholesterol (M3min) and of total body cholesterol (Mtotmin). Surprisingly, measurements of the plasma levels of HDL cholesterol and of the major HDL apolipoproteins (apoA-I, A-II, and E) did not provide additional information useful in predicting parameters of whole body cholesterol metabolism. A study was therefore conducted to investigate possible relationships of the plasma levels of subfractions of lipoproteins, determined by analytic ultracentrifugation, and of apoprotein E phenotype, with the parameters of whole body cholesterol metabolism. Ultracentrifugal analysis of plasma lipoprotein subfractions was performed at the Donner Laboratory in 49 subjects; all of these subjects were currently undergoing whole body cholesterol turnover studies or had previously had such studies and were in a similar metabolic state as judged by plasma lipid and lipoprotein values. Apoprotein E phenotyping was carried out in 71 subjects. Differences in model parameters were sought among subjects with various apoprotein E phenotypes. Ultracentrifugal LDL subfractions Sof 0-2 (the region of LPa), Sof 0-7 (smaller LDL), Sof 7-12 (larger LDL), Sof 12-20 (IDL), and ultracentrifugal HDL subfractions Fo1.20 0-1.5 (smaller HDL3), Fo1.20 2-9 (larger HDL3 plus HDL2), and Fo1.20 5-9 (larger HDL2 or HDL2b) were examined for correlations with each other and with parameters of whole body cholesterol metabolism.

Adolescent↗
PubMed1985

Spatial distribution of retinol-binding protein and retinyl palmitate hydrolase activity in normal and vitamin A-deficient rat liver.

A study was conducted to explore the spatial distribution within rat liver of two proteins importantly involved in retinoid metabolism in liver, namely, retinol-binding protein (RBP) and the enzyme retinyl palmitate hydrolase (RPH). The study was conducted with both vitamin A-sufficient (control) and vitamin A-deficient rats. Livers were carefully and reproducibly dissected into 11 sections each, and RBP levels and RPH activities were measured for each section homogenate. Both RBP and RPH activity displayed highly significant spatial heterogeneity in their distributions in liver. For control rats, the mean level of RBP was 39.0 micrograms/g wet weight, with a section-to-section variation of 14.5. For deficient rats, the corresponding RBP mean and variation values were 283 and 56 micrograms/g wet weight. For RPH, the mean level was 136 pmol free fatty acids (FFA) formed/(min X mg) with a section-to-section variation of 178. Both inspection of the data and analysis of variance indicated that this significant section-to-section variation (spatial heterogeneity) did not follow a consistent anatomic pattern from rat to rat. Thus, no one specific anatomic location in the liver was consistently high or low with regard to either RBP or RPH. Since the spatial distributions of both RBP and RPH activity did not follow a consistent anatomic pattern, it is not possible to obtain an accurate measure of the total liver levels for either parameter in a homogenate made from a small section. Finally, the patterns of distribution of RBP and RPH activity observed in the liver sections from both vitamin A-sufficient and deficient rats were not significantly correlated, either directly or inversely, as determined by chi-square analysis. Thus, RBP and RPH activity levels vary independently of each other in their heterogeneous anatomic distributions in rat liver.

Animals↗
PubMed1985

A convenient six-point blood sampling schedule for determining whole body cholesterol kinetics in humans.

Parameters of total body cholesterol metabolism in humans can be determined by using a three-pool model to analyze the turnover of plasma cholesterol following the injection of radiolabeled cholesterol. In the past this required a rigorous schedule of approximately 36 blood samples over a 10-month period. We have developed a convenient sampling schedule involving only six large samples, each analyzed in sextuplicate. Such a reduction in the frequency of samples is possible only when considerable confidence in the model is available. In general, the simplified sampling strategy depends upon considerable prior experience with the model, only moderate biological error, and estimatable subject to subject variation in model parameters. Because the timing of the samples is critical and because the optimal times will differ for different subjects, the six-point strategy involves using the first three samples (drawn at days 1, 7, and 24 or, for hypercholesterolemic subjects, at days 1, 8, and 28) in conjunction with results from previous studies to set the time for the next sample; the process is reiterated for the last two points. In this study, we have compared parameter estimates obtained by the new six-point schedule with those obtained simultaneously (in the same, single turnover study) by the old 36-point schedule in the same 26 subjects. Both schedules gave comparable values. In particular, the coefficients of variation between values obtained by the two methods for each of the four parameters for which we have developed predictive equations were quite low: PR 1.5%, M1 4.1%, M3min 13%, Mtot min 4.3%. The simplified six-point schedule makes it feasible to study long-term cholesterol turnover in substantial numbers of patients.

Blood Specimen Collection↗
PubMed1985

Whole body and tissue cholesterol turnover in the baboon.

Cholesterol turnover was studied in four baboons by injecting [14C]cholesterol 186 days and [3H]cholesterol 4 days before necropsy, and fitting a two- or three-pool model to the resulting specific activity-time data. At necropsy, cholesterol mass and specific activity were determined for the total body (minus the central nervous system) and for many tissues. A pool model permits the estimation, from the plasma specific activity-time curve alone, of total body cholesterol within a limited range, depending upon the extent of side pool synthesis. The principal aim of this study was to estimate the extent of cholesterol synthesis in the side pools of the model, by computing the amount of side pool synthesis needed to equal the measured total body cholesterol. Central pool synthesis varied from 61 to 89% of the total cholesterol production rate. Thus, approximately 25% (11 to 39%) of the production rate arose from peripheral (pool 3 for the three-pool, and pool 2 for the two-pool model) cholesterol synthesis. Moreover, the finding that the measured total body cholesterol fell within the range obtained from the kinetic analysis by using reasonable assumptions (namely, that zero or that half the production rate occurred in the side pools), provides evidence for the physiological validity of the model. A second aim of this study was to explore cholesterol turnover in various tissues. A pool model predicts that rapidly turning over tissues will have higher specific activities at early times and lower specific activities at later times after injection of tracer relative to slowly turning over tissues, except where significant synthesis occurs. Tissues were ranked 1 to 17 for 3H and 17 to 1 for 14C cholesterol specific activity values. Except for the GI tract and testis, the tissues had similar ranks for both 3H and 14C, further validating model predictions. Results in all four baboons were similar. Turnover rates for the different tissues loosely fell into three groups which were turning over at fast, intermediate, and slow rates. Finally, the magnitude of variation of cholesterol specific activity was moderate for several distributed tissues (fat, muscle, arteries, and the alimentary tract), but was small for liver. Cholesterol turnover in serial biopsies of skin, muscle, and fat could, however, be fitted with a single pool to estimate tissue turnover rates.

Animals↗
PubMed1985

Relationship of the parameters of body cholesterol metabolism with plasma levels of HDL cholesterol and the major HDL apoproteins.

The inverse relationship between plasma levels of high density lipoprotein (HDL) and coronary heart disease rates has suggested that HDL might influence body stores of cholesterol. Therefore, we have investigated potential relationships between the parameters of body cholesterol metabolism and the plasma levels of HDL cholesterol and the major HDL apoproteins. The study involved 55 human subjects who underwent long-term cholesterol turnover studies, as well as plasma lipoprotein and apolipoprotein assays. In order to maximize the likelihood of detecting existing relationships, the subjects were selected to span a wide range of plasma levels of lipids, lipoproteins, and apolipoproteins. Single univariate correlation analyses suggested weak but statistically significant inverse relationships of HDL cholesterol and apoA-I levels with the following model parameters: production rate (PR), the mass of rapidly exchanging body cholesterol (M1), the minimum estimate of the mass of slowly exchanging body cholesterol (M3min), and of the mass of total exchangeable body cholesterol (Mtotmin). These correlations, however, were quantitatively quite small (/r/ = 0.28-0.42) in comparison to the strength of the univariate relationships between body weight and PR (r = 0.76), M1 (r = 0.61), M3min (r = 0.58), and Mtotmin (r = 0.78). Correlations for apoA-II and apoE levels were even smaller than those for apoA-I and HDL cholesterol. In additional analyses using multivariate approaches, HDL cholesterol, apoA-I, apoA-II, and apoE levels were all found not to be independent determinants of the parameters of body cholesterol metabolism (/partial r/ less than 0.17, P greater than 0.3 in all cases). Thus the weak univariate correlations reflect relationships of HDL cholesterol and apoA-I levels with physiological variables, such as body size, which are primarily related to the model parameters. We conclude that plasma levels of HDL cholesterol and apoproteins A-I, A-II, and E are not quantitatively important independent determinants of the mass of slowly exchanging body cholesterol or of other parameters of long-term cholesterol turnover in humans. These studies give no support to the hypothesis that the inverse relationship between HDL cholesterol levels and coronary heart disease rates is mediated via an influence of HDL on body stores of cholesterol.

Aged↗
PubMed1984

History of parenteral nutrition in pediatrics with emphasis on amino acids.

Central venous total parenteral nutrition (TPN) has proved to be a valuable and often life-saving measure in selected newborn infants with surgically repairable, major anomalies of the gastrointestinal tract and infants with chronic intractable diarrhea. However, in infants of low--and especially very low--birth weight, the TPN regimen that was so successful in older infants was frequently associated with severe risks of hyperglycemia. An alternative approach that has proved to be the most satisfactory relies on the fact that the energy expenditure of a premature infant, nursing in a thermally neutral environment, rarely exceeds 50 kcal/kg, a level that can be safely and effectively maintained. With respect to the development of parenteral amino acid solutions, three generations of such mixtures can now be identified. The first of these was represented by the protein hydrolysates. With the advent of technology for the production of pure L-amino acids, a second generation of crystalline mixtures was developed. Evaluation of these revealed that extrapolation from data on oral nutrition was often unsatisfactory for the adequate formulation of such mixtures. The direct study of the parenterally nourished patient led to the third generation of special purpose amino acid solutions such as those targeted for patients with renal failure, liver failure, or trauma or for the promotion of anabolism. It seems likely that development of other solutions will follow the trend of relying on accurate definition of a given metabolic disorder and the perfection of a specific solution to correct it.

Amino Acids↗
PubMed1983

Cholesterol turnover and metabolism in two patients with abetalipoproteinemia.

Total body turnover of cholesterol was studied in two patients with abetalipoproteinemia, a 32-year-old man and a 31-year-old woman. The patients received [14C]cholesterol intravenously, and the resulting specific activity-time curves (for 40 and 30 weeks, respectively) were fitted with a three-pool model. Parameters were compared with those from studies of cholesterol turnover in 82 normal and hyperlipidemic subjects. A three-pool model gave the best fit for the abetalipoproteinemic patients, as well as for the 82 previously studied subjects, suggesting general applicability of this model. Cholesterol production rates in the two abetalipoproteinemic subjects (0.82 and 0.89 g/day) were close to values predicted for persons of their body weight. Thus, total body turnover rate of cholesterol was quite normal in abetalipoproteinemia, confirming previous reports. Very low values (9.2 and 8.4 g) were found for M1, the size of the rapidly exchanging compartment pool 1, in the two abetalipoproteinemic subjects. These values were well below the values predicted (from the comparison study population) for normal persons of this size with low plasma cholesterol levels. For one patient, total body exchangeable cholesterol was very low, although not significantly below the predicted values for a person of his size. In the second patient, the observed estimate for total body exchangeable cholesterol was well within the range of values predicted for persons of her size with low to extremely low cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Abetalipoproteinemia↗
PubMed1982

Excessive mineralization with growth plate closure in rats on chronic warfarin treatment.

Rats maintained for 8 months on a level of warfarin sufficient to decrease the vitamin K-dependent protein of bone (bone Gla protein) to 2% of normal have an excessive mineralization disorder characterized by complete fusion of the proximal tibial growth plate and cessation of longitudinal growth. The general features of this abnormality resemble the fetal warfarin syndrome in humans, a disorder also characterized by excessive mineralization of the growth plate. These excessive mineralization disorders may be caused by the decreased levels of bone Gla protein, a protein that potently inhibits mineralization in vitro.

Animals↗
PubMed1982

Cholesterol turnover in lipid phases of human atherosclerotic plaque.

The turnover of free cholesterol in atheromatous plaque lipid phases was studied in a patient undergoing peripheral vascular surgery. [14C]Cholesterol was injected intravenously 139 days prior to surgery, and [3H]cholesterol was injected 12 days pre-op. The plasma cholesterol specific radioactivity decay curves were determined from the times of isotope injection until surgery. At surgery, atheroma, skin, muscle, and tendon were obtained. Lipid phases of plaque homogenate were isolated by density gradient centrifugation. The top layer of the gradient, layer 1, contained the cholesteryl ester oil droplet phase, layer 2 was enriched in phospholipid bilayer phase, layer 3 contained cholesterol monohydrate crystals and the pellet, layer 4 had more dense plaque components such as collagen and elastin. The tissue:plasma specific radioactivity ratios on days 12 and 139 respectively were muscle, 0.86, 2.47; skin, 0.74, 1.20; tendon, 0.18, 1.45; total plaque, 0.22, 1.39; plaque layer 1, 0.31, 1.50; layer 2, 0.22, 1.53; layer 3, 0.08, 0.61; and layer 4, 0.20, 0.88. Thus, plaque atheroma, which contains physically distinct forms of cholesterol, had correspondingly different rates of cholesterol turnover. Cholesterol solubilized in liquid oil droplets (layer 1) and liquid crystalline phospholipid bilayers (layer 2) had specific radioactivity values similar to those of tendon cholesterol, and represented tissue cholesterol that was undergoing slow equilibration with the plasma cholesterol pool. Pellet cholesterol (layer 4), which is probably connective tissue-associated, had lower specific radioactivity values, well below those of plasma cholesterol even after 5 months. Crystalline cholesterol (layer 3) had the lowest specific radioactivity values of all tissues and plaque fractions. Therefore, cholesterol in the crystalline state is relatively inert. Since crystalline cholesterol can account for over 40% of plaque free cholesterol, resistance to mobilization of this lipid may be an important obstacle to plaque regression.

Aged↗
PubMed1981

On determining the extent of side-pool synthesis in a three-pool model for whole body cholesterol kinetics.

Whole body cholesterol turnover is well described by a three-pool model. This model has eight unknown parameters: three masses, three synthesis rates, and two intercompartmental exchange rates. Only six parameters can be estimated by fitting the model to the plasma specific radioactivity-time curve which results from the intravenous injection of labeled cholesterol. Additional information is obtained if a precursor of cholesterol, labeled with a different isotope, is also injected. Equations are derived to enable the calculation of all eight model parameters from the two sum-of-exponentials equations that are fitted to the two tracer curves. The characteristics of a satisfactory precursor are discussed.

Animals↗
PubMed1980

Prediction of the parameters of whole body cholesterol metabolism in humans.

Total body turnover of cholesterol was studied in 54 subjects by fitting a three-pool mathematical model to plasma decay curves of 32--49 weeks duration following [14C]cholesterol injection. Fifteen subjects were normal, 10 hypercholesterolemic, 21 hypertriglyceridemic, and 8 had both hypercholesterolemia and hypertriglyceridemia; 21 had a familial form of hyperlipidemia. In every subject in this heterogeneous population, the three-pool model gave the best fit for the data. An extensive search was conducted for relationships between model parameters and physiological variables (body size, serum lipid levels, age, and sex). Both linear and nonlinear relationships, and those involving interactions between pairs of variables, were explored. Fifty different forms of the model parameters and 53 forms of the physiological variables were examined. To guard against declaring statistical significance when none was present, subjects were first randomly divided into two matched groups. In the first (hypothesis-generating) group of 36 subjects, more than 100,000 regression equations were considered for each form of the model parameters. Twenty-one highly significant equations were found that were then tested in the second group (hypothesis-testing, 18 subjects). Eighteen of the 21 equations were found to be significant; of these, 6 were selected that accounted for a large part of the observed variation in the four model parameters for which equations were found (production rate (PR), and the sizes of pool 1, pool 3, and total exchangeable body cholesterol). The major determinant of cholesterol PR was body weight alone (r = 0.80). No function of serum lipid levels significantly influenced PR. Both body weight and serum cholesterol level entered into the equations for cholesterol mass. Age influenced the size of pool 3. Serum triglyceride level only had an effect on the size of pool 1. Since these equations were generated in one group of subjects and tested in another, they can be considered a confirmed set of predictive equations.

Adult↗