Hiram E. Hart

Scintillation Proximity Assay (SPA)—A new method of immunoassay: Direct and inhibition mode detection with human albumin and rabbit antihuman albumin

Abstract Scintillation Proximity Assay (SPA) was used to measure concentrations of human albumin (HA) and rabbit anti-human albumin (RAHA). In one form of this assay, dilute aqueous suspensions of tritiated latex particles (LH) and scintillant latex particles (L∗) covalently coated with antigen are counted in a standard liquid scintillation counter energy gated for tritium. The count rate reflects the extent of(LH)-(L*) dimer formation and is therefore a very sensitive measure of the concentration of antibody present. Concentrations of less than 2.5 ng/ml of RAHA and, in the inhibition mode, less than 1 ng/ml of HA were easily and reproducibly detected.

Determination of equilibrium constants and maximum binding capacities in complexIn vitro systems: I. The mammillary system

It is shown that in a system containingn types of mutually noninteracting binding sites, the association constants are then roots of annth order polynomial while the maximum binding capacities can be evaluated by solving a set ofn simultaneous linear equations. Thenth order polynomial and the system ofn linear equations are defined in terms of 2n intermediate coefficients, the coefficients being themselves evaluated by substituting 2n sets of appropriate experimental data into an auxiliary system of 2n linear equations. The existence and uniqueness of the solutions are established.

Bayesian image processing of data from constrained source distributions—II. Valued, uncorrelated and correlated constraints

Bayesian image processing formalisms which incorporatea priori information about valued-uncorrelated and valued-correlated (patterned) source distributions are introduced and the corresponding iterative algorithms are derived using the EM technique. Striking improvement in image processing is demonstrated when applying these algorithms to Poisson and Gaussian randomized data in one-dimensional cases.

Strontium85 metabolism in man and effect of calcium on strontium excretion.

Summary Within 4 days after whole body x-irradiation (650 r), globule leucocytes were reduced to 1-2% of their normal number in the intestine of the rat. Reestablishment of normal numbers of cells began toward end of the first week after irradiation and was completed by the 5th week. The effect of irradiation on globule leucocytes was chiefly a local one, being prevented by shielding the intestine with lead during irradiation. Only with the LDioo 30 days dosage (800 r) was there a significant reduction in number of globule leucocytes in lead-shielded intestinal segments. This appeared to be the indirect result of stress induced by irradiation, since the effect was prevented by hypophysectomy. Hypophysectomy alone reduced markedly the number of intestinal globule leucocytes.

Rate of initial entry of Ca47 and Sr85 from the intestine into the vascular space.

Summary The rate of initial entry of both radioactive calcium and strontium from the gastrointestinal tract into the vascular system has been determined in man by adapting an integral equation approach for use with a digital computer. A single tracer dose of Ca47 and of Sr85 was given both by the oral and intravenous route in separate studies and serial samples of plasma were obtained for radioassay. The maximal rate of initial entry of Ca47 per 15-minute interval ranged from 2.2% to 3.8% of the dose and was reached within 1 1/2 hours. This rate was sustained for about one hour and decreased thereafter with time. The rate of initial entry for Sr85 was less than that for Ca47, not exceeding 1.5% of the dose in any 15-minute interval, but was relatively more sustained from the first to the fourth hour After the fourth hour, the rates of initial entry of Sr85 and Ca47 were almost proportional.

Interaction of yttrium compounds with serum and serum constituents in vitro

Abstract A simple method for determining the relative metal-binding strength of chelating agents in physiological media has been proposed and the nature of yttrium chelate interaction with serum has been studied. Filterability of yttrium from serum and serum filtrate was found to be related to the stability (log K 1 ) of the yttrium chelate. The pressure filtration data correspond also with animal and human excretion data obtained in our laboratory. The experiments with serum filtrate show that the diffusible serum components play a role in these yttrium interactions. The yttrium interaction with an isolated serum protein, albumin, was studied by the method of equilibrium dialysis. The moles of yttrium bound per mole of albumin increased as the metal-ion concentration was increased and the binding was found to be reversible, indicating that this is a multiple equilibrium reaction. The yttrium-albumin binding was affected by changes in pH and temperature.

Three-Dimensional Imaging of Multimillimeter Sized Cold Lesions by Focusing Collimator Coincidence Scanning (FCCS)

A twin-probe high-resolution focusing collimator coincidence scanning system has been developed which can tomographically image multimillimeter structures. The three-dimensional detection and imaging capabilities, the related off-focal suppression, and the sensitivity are compared with standard techniques.

DISCRETE FORMULATION AND ERROR MINIMIZATION IN APPLYING THE INTEGRO- DIFFERENTIAL EQUATION APPROACH TO MONO-COMPARTMENT DATA.

Abstract The system of equations: x(i+1)=x(i)c −BH + ∑ k=1 i=l a(i−k) x (k) e −BH 2 where H is an arbitrarily fixed time interval e −BH = x(2) x(1) and x (k)= x(k)−x(k+1) I n x(k)−I n x(k+1) is a discrete analog of the integro-differential equation for monocompartment tracer measurement which permits direct substitution of experimental data. The accuracy of numerical values calculated using statistically randomized data in the above discrete formulation is shown to depend upon the value of H chosen and the size of the initial dose. The time dependence calculation of a characteristic of the system, the cumulative external exchangeable volume, is shown to exhibit an uncertainty principle. For small values of H, statistical errors compromise results, while large time intervals introduce systematic errors.

Study and performance evaluation of statistical methods in image processing

Two statistical image processing formalisms involving the entropy concept and Bayesian analysis are studied. Iterative imaging algorithms of the formalisms are formulated by employing, for the purpose of performance evaluation and easy implementation, the steepest descent method for the solution of entropy concept and the expectation maximization technique for the solution of Bayesian analysis. Quantitative evaluation and comparison of the convergence performance of the iterative algorithms on computer generated ideal and experimental radioisotope phantom imaging noisy data are given. The study concludes that the entropy algorithm can converge relatively fast, but it is very sensitive to noise in measured data due to the ill-posed nature of inverse problems and its lack of ability to consider the statistics of data fluctuation; while the Bayesian algorithm converges monotonically even with noisy data and has the advantage of considering both the a priori source distribution information and the statistical fluctuation of measured data.

AN INTEGRAL EQUATION FORMULATION OF PERTURBATION-TRACER ANALYSIS

It was first shown by Sheppard’ and later by Sheppard and Householder’ that a steady-state general N-compartment system could be solved by means of simultaneous experimental determinations of N 1 isotopes. Subsequently it was demonstrated that a general N-compartment system could in fact be solved by measurements involving only the use of a single i~o tope .~ In these papers, a solution was defined as the determination of all the transport parameters aij and the volumes Vi . Since the aij and Vi were presumed and in fact required to be essentially constant in the above formulations, little information on the functional dependence or homeostatic regulation of the transport parameters or volumes themselves could be obtained. It was apparent that to determine such functional dependencies, it would be necessary to modify the usual tracer approach and somehow to investigate tracer response to nontracer Such investigations might involve nonsteady-state systems and consequently a method was sought whereby a,j and Vi could be determined as functions of time.4 Once a general method had been found for determining the parameter time dependencies (aij( t ) , Vi( t ) ) by tracer means, it was only necessary to correlate the time dependencies of nontracer variables with the observed behavior of the parameters.’’’ A variety of methods of correlation is discussed in the latter two papers. The important thing to note, however, is that it is only by displacing the system from homeostasis-either by a single pulse, a constant “deflecting force” or input function, or a nonconstant input function-that information on the regulatory nonlinear equations of the multi-compartment system can be obtained. This is the essence of the perturbation-tracer method. Although the differential equation representation of multi-compartment systems is probably easier to visualize, the work of Branson,’ Stephenson’ and others has served to focus attention on important advantages of the integral equation representation. It will be the purpose of this paper to show how, in certain types of systems, the integral equation approach can be employed in perturbation-tracer analysis.