scholarly journals The calculation of errors and the choice of sampling times in the determination of irreversible disposal rates in vivo by isotope experiments

1975 ◽  
Vol 152 (2) ◽  
pp. 417-420 ◽  
Author(s):  
Dennis F. Heath ◽  
Vincent J. Cunningham

In well-known methods of estimating rates of irreversible disposal (utilization) in vivo the rates are calculated from the areas to infinity under specific radioactivity–time (S–t) or quantity-of-label–time (q–t) curves obtained by measurements on samples of plasma after intravenous injection of labelled substrate. The errors in the calculated rates are mostly those of the estimates of the areas. These errors are of two kinds: random, caused by the variances of the values of S or q, and systematic, caused by differences between the curves used to interpolate between these values and the true curves. A rigorous method is given for calculating the random errors from the variances of the values of S or q, and is applied to choosing the best times to sample the plasma from small animals from which few plasma samples can be taken. A procedure for estimating systematic errors is also given. Programs in BASIC language to carry out the calculations are deposited as Supplementary Publication SUP 50058 (5 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1975) 145, 5.

1978 ◽  
Vol 48 ◽  
pp. 7-29
Author(s):  
T. E. Lutz

This review paper deals with the use of statistical methods to evaluate systematic and random errors associated with trigonometric parallaxes. First, systematic errors which arise when using trigonometric parallaxes to calibrate luminosity systems are discussed. Next, determination of the external errors of parallax measurement are reviewed. Observatory corrections are discussed. Schilt’s point, that as the causes of these systematic differences between observatories are not known the computed corrections can not be applied appropriately, is emphasized. However, modern parallax work is sufficiently accurate that it is necessary to determine observatory corrections if full use is to be made of the potential precision of the data. To this end, it is suggested that a prior experimental design is required. Past experience has shown that accidental overlap of observing programs will not suffice to determine observatory corrections which are meaningful.


1985 ◽  
Vol 248 (4) ◽  
pp. R391-R399 ◽  
Author(s):  
J. Katz

A mitochondrial model of gluconeogenesis and the tricarboxylic acid cycle, where pyruvate is metabolized via pyruvate carboxylase and pyruvate dehydrogenase, and pyruvate kinase is examined. The effect of the rate of tricarboxylic acid flux and the rates of the three reactions of pyruvate metabolism on the labeling patterns from [14C]pyruvate and [24C]acetate are analyzed. Expressions describing the specific radioactivities and 14C distribution in glucose as a function of these rates are derived. Specific radioactivities and isotopic patterns depend markedly on the ratio of the rates of pyruvate carboxylation and decarboxylation to the rate of citrate synthesis, but the effect of phosphoenolpyruvate hydrolysis is minor. The effects of these rates on 1) specific radioactivity of phosphoenolpyruvate, 2) labeling pattern in glucose, and 3) contribution of pyruvate, acetyl-coenzyme A, and CO2 to glucose carbon are illustrated. To determine the contribution of lactate or alanine to gluconeogenesis, experiments with two compounds labeled in different carbons are required. Methods in current use to correct for the dilution of 14C in gluconeogenesis from [14C]pyruvate are shown to be erroneous. The experimental design and techniques to determine gluconeogenesis from 14C-labeled precursors are presented and illustrated with numerical examples.


1985 ◽  
Vol 59 (1) ◽  
pp. 205-210 ◽  
Author(s):  
T. A. Standaert ◽  
W. A. LaFramboise ◽  
R. E. Tuck ◽  
D. E. Woodrum

This report describes the design of an apparatus and the procedures used to serially measure the total lung capacity and the functional residual capacity of small animals utilizing the N2-washout technique. The calibration data indicate that the technique is accurate to within 1 ml and has a variance of less than 5%. The in vivo lung volume measurements of rats were validated by comparing them with values obtained with a water-displacement technique; the means were within 0.3 ml. Examples of the precision and changes in lung volume of animals during studies are included to demonstrate the reliability and usefulness of the technique.


1974 ◽  
Vol 142 (1) ◽  
pp. 171-183 ◽  
Author(s):  
Joseph Katz ◽  
Arnold Dunn ◽  
Maymie Chenoweth ◽  
Sybil Golden

1. Glucose labelled with 3H in position 2 and uniformly with 14C was administered simultaneously to rabbits and rats either as a single injection or by continuous infusion. Plasma glucose specific radioactivity and the yield of 3H in the plasma water were monitored. 2. The rates of synthesis, recycling of carbon and total body mass of glucose were calculated, without assuming a multicompartmental model and without fitting data by exponential expressions. 3. The rate of synthesis of glucose in starved-overnight rabbits was 4mg/min per kg (range 3–4.5mg/min per kg) and 25–35% of the glucose carbon was recycled. The mass of total body glucose in starved rabbits was 290mg/kg (range 220–390mg/kg). About one-third of the total body glucose equilibrates nearly instantaneously with plasma glucose. 4. In rats starved overnight, glucose synthesis was about 10mg/min per kg and recycling of carbon ranged from 30–40%. Total body mass (per kg body weight) is similar to that in rabbits. 5. The activity in plasma water after injection of [2-3H]glucose was determined. The initial rate of 3H2O formation is rapid, indicating that the major site of glucose catabolism is in the rapidly mixing pool. The curve of total body glucose radioactivity was obtained from the 3H2O yield, and total mass of glucose was calculated. This agrees with that obtained from the 3H specific-radioactivity curve.


2020 ◽  
Vol 643 ◽  
pp. A142
Author(s):  
M. Cubas Armas ◽  
A. Asensio Ramos ◽  
H. Socas-Navarro

Aims. We report the results of a novel determination of the solar oxygen abundance using spatially resolved observations and inversions. We seek to derive the photospheric solar oxygen abundance with a method that is robust against uncertainties in the model atmosphere. Methods. We use observations with spatial resolution obtained at the Vacuum Tower Telescope to derive the oxygen abundance at 40 different spatial positions in granules and intergranular lanes. We first obtain a model for each location by inverting the Fe I lines with the NICOLE inversion code. These models are then integrated into a hierarchical Bayesian model that is used to infer the most probable value for the oxygen abundance that is compatible with all the observations. The abundance is derived from the [O I] forbidden line at 6300 Å taking into consideration all possible nuisance parameters that can affect the abundance. Results. Our results show good agreement in the inferred oxygen abundance for all the pixels analyzed, demonstrating the robustness of the analysis against possible systematic errors in the model. We find a slightly higher oxygen abundance in granules than in intergranular lanes when treated separately (log(ϵO) = 8.83 ± 0.02 vs. log(ϵO) = 8.76 ± 0.02), which is a difference of approximately 2-σ. This tension suggests that some systematic errors in the model or the radiative transfer still exist but are small. When taking all pixels together, we obtain an oxygen abundance of log(ϵO) = 8.80 ± 0.03, which is compatible with both granules and lanes within 1-σ. The spread of results is due to both systematic and random errors.


1973 ◽  
Vol 136 (3) ◽  
pp. 503-518 ◽  
Author(s):  
Dennis F. Heath ◽  
Roger N. Barton

1. The two well-known methods of estimating rates of irreversible disposal (R) of blood-borne substrates in vivo by isotope experiments involve estimating the specific radioactivity (S) of the substrate in blood either after single intravenous injection of labelled substrate or during its infusion at a constant rate. The value of R is calculated from the S–time curve, usually by assuming: (i) a metabolic steady state with respect to substrate, (ii) the passage of all substrate through the blood, and (iii) the absence of certain types of recycling via blood. 2. In a theoretical investigation we show how experiments can be performed and R calculated from analyses of blood when one or more of the above assumptions is unjustified, by using glucose, ketone bodies, plasma free fatty acids and proteins as examples. In general the methods require single injection procedures, with estimation of the total quantity of label in the substrate in blood and the substrate concentration instead of only S. Such values give estimates of R with standard errors even when only one blood specimen is taken from each of a group of animals, as is convenient when working with small animals or substrates in low concentration, and when the animals are in a non-steady state in which constant infusion procedures are invalid. 3. Similar methods give the fraction of label injected as one compound which passes through another (the isotopic yield). 4. The methods are not always applicable, and cannot be applied to plasma proteins in some pathological conditions. A questionnaire for assessing their applicability is given.


1981 ◽  
Vol 194 (2) ◽  
pp. 513-524 ◽  
Author(s):  
J Katz ◽  
F Okajima ◽  
M Chenoweth ◽  
A Dunn

L-[3-3H,U-14C]Lactate was administered to starved rats either as a bolus or by continuous infusion. Tracer administration was performed two ways: injection into the vena cava and sampling from the aorta (V-A mode), or injection into the aorta and sampling from the vena cava (A-VC mode). The specific-radioactivity curves after infusion or injection differed markedly with the two procedures. However, the specific radioactivities of 14C-labelled glucose derived from [U-14C]lactate were similar in the two modes. The apparent turnover rates of lactate calculated from the 3H specific-radioactivity curves in the V-A mode were about half those obtained from the 3H specific-radioactivity curves in the A-VC mode. The apparent contribution of lactate carbon to glucose carbon calculated from specific-radioactivity curves of the A-VC mode was greater than that obtained from the V-A mode. The apparent recycling of lactate carbon calculated from the specific radioactivities for [U-14C]- and [3-3H]-lactate was greater in the A-VC mode than the V-A mode. [U-14C] Glucose was administered in the two modes, but in contrast with lactate the specific radioactivities were only slightly different. An analysis to account for these observations is presented. It is shown that the two modes represent sampling from different pools of lactate. The significance of sites of tracer administration and sampling for the interpretation of tracer kinetics of compounds present in intracellular and extracellular spaces, and with a high turnover rate, is discussed. We propose that for such compounds, including lactate, alanine and glycerol, the widely used V-A mode leads to a marked underestimate of replacement, mass and carbon recycling, and that the A-VC mode is the preferred method for the assessment of these parameters.


1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.


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