t'hese theories have been litt'le used for biological systems. Sheppard and Householder (1951) and Hart (1955) deal with a closed mammillary syst'em and derive equations which require measurements in all compartment's for their solut'ion. Berman and Schoenfeld (1956) work out a method of treating more complex systems when the compartment' model is not known. In t'his paper a method will be given of applying t'he theory of Rescigno (1956) t o experiment's in which the label is injected into t'he central compartment of an open mammillary system. Measurement's are made, at suitable time intervals, of activity in the central compartment and of activity leaving the syst'em. From these curves the compart'ment, sizes and rate constants can be obtained in cert'ain cases. 9 2. THEORY The central compartment' (compartment' l ) represents int'ravascular protein and the outer compart'ments (3, 4 . . . . n ) , connected reversibly

No abstract

The experiments described here have been carried out over a period of two years and the author is greatly indebted to numerous colleagues who have helped at different times. In particular, thanks are due to G.

The normal regulation of intravascular plasma protein mass has not been fully investigated. It has long been known that plasma proteins rapidly return to normal concentrations after plasmapheresis, but the means by which this takes place has not been clearly demonstrated. In pathological states, such as nephrosis and hypercatabolic hypoproteinemia, where there may be a steady loss of plasma protein, some compensatory mechanism (see next paragraph) must be involved in cases in which the intravascular plasma proteins are in a steady state. Frequently the protein concentration alone is determined, so that it is not known whether changes are due to variations in plasma volume or in total intravascular protein mass. A steady state can only be said to exist when the plasma protein synthesized is equal to that catabolized, so that the total mass of protein, but not necessarily the concentration, is constant.Disturbances of intravascular protein mass could be compensated for by a) change in synthesis rate, b) change in catabolic rate, c) net transfer of protein between extravascular and intravascular protein pools or d) a combination of several of these. There is also the possibility that the proportion of the different protein fractions is altered and that loss of one fraction is replaced by an increase of another fraction.The purpose of this investigation was to obtain further evidence on this problem by removing protein by plasmapheresis and observing the effect on the catabolic rate, intravascular pool mass, concentration and volume, and on the sum of synthesis rate plus net transfer rate from extravascular to intravascular pool. Rabbits on a normal diet were used, and a single protein fraction, albumin, was considered.I131-rabbit albumin was injected intravenously into rabbits, and plasma albumin specific activity (microcuries per gram), total body radioactivity * Present address: Radiotherapeutic Research Unit, Hammersmith Hospital, London, England. and urinary radioactivity were measured. It is assumed throughout that I131-albumin behaves as normal rabbit albumin (1, 2), that after catabolism the I131 is rapidly excreted, and that there is rapid mixing in each separate protein pool so that within any one pool the specific activity is uniform.A control period of ten days from the injection was allowed before starting plasmapheresis. The normal catabolic rate and pool masses were thus determined for each animal. Daily determinations of intravascular protein mass, concentration and volume were also made throughout each experiment in a control animal not subject to plasmapheresis.Intravascular protein mass and plasma volume were determined by isotope dilution. Since the proportion of albumin to total plasma protein was found to be constant throughout the experiment, albumin masses could be calculated from total protein masses. METHODS TheoreticalExtravascular pool. During the control period, the extravascular protein mass was determined by the equilibrium time method (3-5). In this method the ratio of extravascular t...

During 1957-1962 the routes and rates of B,, excretion were studied by faecal and whole-body counter techniques, and long-term studies of plasma clearance performed. In the present analyais, the equations of the experimental curves were obtained with an analogue computer, and the simplest compatible model selected. The equations were solved mathematically for a particular model and hence, using Berman and Schoenfeld's method, all other possible models were calculated. Finally, the time curves for radioactivities in experimentally inaccessible pools were generated with the computer. Three pools were required, one apparently intracellular (containing over 99% of the body-B,,), one extracellular B,,, and the third unidentified. In this model, therefore, B,, is assumed to have n t least an approximately uniform turnover rate in most of the intracellular pool. The present method can be used to measure total body content of B,,, which was found t o be 3.03 mg in the subjects studied. The physiological loss of B,, was calculated to be 1.2 pg/day, and the relations of this figure to B,, requirements in man were discussed. Preliminary results in pernicious anaemia indicate a decreased cellular uptake of Bls.