1. 9 Studies of lymphocyte transport are reported in which the 51Cr labelling technique of Hersey (1971) was employed on 8 patients with chronic lymphocytic leukaemia (CLL) and 1 with lymphosarcoma. 2. A new approach to the analysis of the data was formulated employing the principles of impulse analysis. This allowed the quantitation of cell transport between various locations making the minimum number of assumptions. It was also possible to take account of the principal defect of this label, its tendency to elute from live cells. 3. In spite of marked lymphocytosis, numbers of cells moving between those tissues whose lymphocytes exchange relatively slowly and the bloodstream was found to be normal. The blood and lymph nodes may therefore accumulate lymphocytes in response to a transport defect which hinders the progress of these cells from one pool to another. 4. The finding that CLL lymphocytes fluxes are normal in certain locations casts doubt on the hypothesis that lymphocyte proliferation is uncontrolled in this disease. An alternative possibility is that cell proliferation is regulated so as to maintain these fluxes within the normal range.
\n \n\n \n \n1. Blood flow to the skeleton was measured by the 18F clearance method of Wooton, Reeve & Veall (1976) in 24 patients with untreated Paget's disease. In every patient but one, resting skeletal blood flow was increased. There was a significant positive correlation between skeletal blood flow and serum alkaline phosphatase and between skeletal blood flow and urinary total hydroxyproline excretion. 2. Fourteen patients were re-studied after they had received short-term (7 days or less) or long-term (7 weeks or more) calcitonin. Skeletal blood flow, alkaline phosphatase and urinary hydroxy-proline excretion fell towards normal in every case. There was some evidence from the short-term studies that calcitonin produced a more rapid fall in skeletal blood flow than in alkaline phosphatase. 3. Glomerular filtration rate appeared to increase transiently in response to calcitonin.
\n \n\n \n \n1. A whole-gut perfusion technique has been used to compare the rates of intestinal absorption of sodium and xenon. 2. The calculated transit-time spectra for sodium and xenon across the gut mucosa do not differ significantly either in mean transit time or, for the first 15 min, in shape. 3. These results support the hypothesis that the rate of transfer of sodium from the small intestinal lumen to plasma is limited by blood flow. 4. It is suggested that some features of cholera can be explained by the hypothesis.
\n \n\n \n \n1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.
\n \n\n \n \n1. Evidence has accumulated that the rate of accretion (A) of calcium to bone is the sum of two fluxes; apposition involving the laying down of new bone and augmentation which is the result of slow exchange of non-surface bone calcium with plasma calcium pools as the result of solid state diffusion. 2. A method has been devised for separating A into its two components. It requires the use of 45Ca or, for clinical studies, 85Sr as a calcium tracer. Studies which are initiated with a combined accretion rate--calcium balance study, are concluded with an estimate of the exponent of the power function which has been found to describe the whole body retention of tracer from the second month onward. 3. The impulse response function of the skeleton for the tracer is then calculated, making the assumption that in any uniform volume of bone, osteoclastic resorption is a first order process. Making in addition certain simplifying assumptions, which are shown to have a modest influence on the final results, a mean rate of bone resorption can be calculated using a development of the well known Stewart-Hamilton formula. The apposition rate is calculated as the sum of the resorption rate and the calcium balance. Augmentation and diminution, defined as equal and opposite exchange processes, are given by the difference between A and the apposition rate. 4. The results of our first thirteen studies in normal subjects and patients with metabolic bone disease are presented, together with analyses of some data from the literature. It is concluded that the development of an atraumatic method for measuring rates of bone formation and resorption in the whole body would be an important advance in the study of metabolic bone disease, and this work is presented so that critical comparisons may be initiated between this tracer method and independent histological methods for measuring these parameters.
\n \n\n \n \n1. A mathematical model has been constructed of human thyroid hormone regulation by the anterior pituitary gland, which takes account of most of the currently available experimental data. 2. Successful simulation of data on the stimulation of thyrotrophin (TSH) secretion by thyrotrophin releasing hormone (TRH) was achieved assuming that the TSH secretion rate is proportional to the logarithm of the concurrent blood TRH level. 3. Data on the regulation of triiodothyronine (T3) secretion by TSH and the inhibition of TSH secretion by thyroid hormones in contrast could not be simulated on the assumption of instantaneous proportional responses. A mixture of proportional and integral control--the latter taking account of the past history of plasma levels of the regulatory hormone--appeared to be operating at both levels. 4. The pituitary gland appears to be more sensitive to a given fractional change in TRH secretion rate than to the same fractional change in T3 plasma concentration.
\n \n\n \n \n