Studies of Iodoalbumin Metabolism. I. A Mathematical Approach to the Kinetics*

Abstract

During the clinical study and treatment of a group of patients with thyroid carcinoma, we have studied the effects of thyroid hormone on several metabolic systems under conditions in which the thyroid status of the patients could be controlled at will. Early in the tracer studies of iodoalbumin metabolism in these patients it was apparent that it was necessary to employ a mathematical approach somewhat different from published methods of compartment analysis. Accordingly a suitable mathematical approach was developed by one of the present authors (1). In this report, the practical difficulties encountered in application of the approach to experimental data and the theoretical implications of the approach are discussed.The kinetic analysis of the data of a single tracer study comprises the body of the report. Additional data from other tracer studies are included only insofar as they contribute to the development of the model chosen for analysis. METHODSGeneral. The methods of dialysis of the commercial 1131 labeled human serum albumin employed and details of the injection procedure, collection of blood and urine samples, quantitation of radioactivity in urine and plasma, determination of serum albumin and quantitation of total radioactivity removed in blood sampling have been given elsewhere (2). Stool collections were made only in the case of M. H. in Experiment III. The individual specimens were suspended in concentrated sodium hydroxide and distilled water to known volume, allowed to digest partly, and then agitated until a uniform pipettable mixture was obtained. The counting procedure was the same as that for urine and plasma (2). None of the patients studied showed albuminuria No chemical fractionation of label was done routinely on urine or plasma samples.

Studies of Iodoalbumin Metabolism. Ii. The Effects of Thyroid Hormone*

“…Two experiments carried out on six patients comprise the basis of this report. Some aspects of these experiments have been discussed in another report (4).…”

“…In addition to the iodoalbumin studies, all patients were subjected to ancillary NaIls' tracer studies in either the euthyroid or myxedematous state, and the rate constant of renal iodide excretion, Kie, was computed by the approach described by Keating The plasma and urine data of Experiment I and that of Patients C. C. and R. B., Experiment II, Part 1, were subjected to graphic analysis as described elsewhere (4). The data of E. L., Experiment II, were not subjected to compartmental analysis because of the presence of unblocked, functioning metastases which presumably vitiated her excretion data.…”

An application of Berman's work on pool-model invariants in analyzing indistinguishable models for whole-body cholesterol metabolism

“…If P can be chosen so that PAP −1 , CP −1 , and Px(0) satisfy the e characteristic equality constraints [Equation (2)] of the second model as well as the inequality constraints that any pool model must satisfy [Equation (1)], the first model is indistinguishable from the second. If the n 2 elements of P cannot be chosen to satisfy the e equations (2) and the general pool-model conditions (1), the first model is distinguishable from the second.…”

“…But outside of research that Berman himself was involved in [2,3], it was not used very much for nearly twenty years after the publication of the original paper [4,5].…”

STUDIES OF THE VENTILATION-PERFUSION RELATIONSHIPS IN THE LUNGS OF SUBJECTS WITH CHRONIC PULMONARY EMPHYSEMA, FOLLOWING A SINGLE INTRAVENOUS INJECTION OF RADIOACTIVE KRYPTON (Kr85). I. PRESENTATION AND VALIDATION OF A THEORETICAL MODEL *

“…As the slug of dissolved Kr85 passes through the pulmonary capillaries almost all of it diffuses into the alveolar gas spaces because of the relative insolubility of krypton (8 and the tissue space (T). Three-compartment systems, both closed (10,11) and open (12)(13)(14), have previously been described; the algebraic treatment is therefore abbreviated here. It is noteworthy that in the present model direct access is limited to one compartment (T).…”