Kinetics of pharmacologic response II: Equation for turnover time of goldfish as a function of concentration of ethanol and a theoretical derivation based on a combination of occupation and rate receptor theories

1969 ◽  
Vol 58 (9) ◽  
pp. 1077-1085 ◽  
Author(s):  
Anthony R. Disanto ◽  
John G. Wagner
1971 ◽  
Vol 125 (2) ◽  
pp. 425-432 ◽  
Author(s):  
M. D. Hatch

1. Leaves were exposed to 14CO2 under steady-state conditions for photosynthesis. The kinetics of entry or loss of label in pools of CO2 and other compounds was examined during the period of the pulse and a ‘chase’ with 12CO2. 2. With maize the kinetics of labelling of the major CO2 pool and of depletion of label during a ‘chase’ was consistent with this pool being derived from the C-4 of malate and being the precursor of the C-1 of 3-phosphoglycerate. 3. Similar results were obtained for Amaranthus leaves except that the C-4 of aspartate rather than malate was apparently the primary source of CO2. 4. The size and turnover time of the CO2 and C4 acid pools was calculated. These results provided the basis for estimating the concentration of CO2 in the bundle-sheath cells or chloroplasts assuming the pool was largely restricted to one or other of these compartments. 5. These findings are considered in relation to current schemes for the C4-pathway and the operation of a CO2 concentrating mechanism to serve ribulose diphosphate carboxylase.


1972 ◽  
Vol 126 (4) ◽  
pp. 869-876 ◽  
Author(s):  
J. E. A. McIntosh ◽  
C. Lutwak-Mann

1. To investigate the influence of hormonal conditions upon the kinetics of zinc transport, specific radioactivity of 65Zn was determined in certain tissues and fluids from unmated or pregnant rabbits during the first half of gestation. 2. Compartmental analysis was used to find the simplest mathematical model that simulated satisfactorily tracer behaviour. Models were fitted to experimental results by a numerical procedure using a computer. 3. The kinetics of zinc exchange in most tissues investigated could adequately be described by a three-compartment model, in which total tissue zinc content was divided into a rapidly exchanging pool, with a turnover time of about 1h, and a slowly exchanging pool, the turnover time of which was in liver 15h, in peak-stage corpus luteum 8h, and in the other tissues 30–70h. 4. In rabbit endometrium zinc transport varied with hormonal conditions, the turnover rate being higher in non-pregnant than pregnant endometrium. 5. Uptake of 65Zn by uterine fluid was slow, and in the free-lying embryos (blastocysts) slower still, in keeping with uterine fluid acting as carrier of zinc into the unimplanted embryos. 6. In placental tissue zinc transport varied with gestational stage. Foetal placenta exchanged zinc with blood plasma four times faster than maternal placenta. In foetuses zinc turnover time and flux equalled that of the slow zinc compartment in foetal placenta. 7. Corpus luteum on days 5–6 of gestation showed peak specific radioactivity and zinc flux values, which exceeded those of all other tissues. 8. In liver the slow zinc compartment had a higher rate of turnover than corresponding compartments in tissues other than peak-stage corpus luteum, but no hormone-dependent changes were observed. 9. Zinc uptake by erythrocytes was the slowest of all examined.


1981 ◽  
Vol 50 (2) ◽  
pp. 383-391 ◽  
Author(s):  
J. A. Estep ◽  
J. P. Zorn ◽  
M. G. Marin

Previous studies on mucous glycoprotein secretion in respiratory epithelium most often provided qualitative, rather than quantitative, data. This study describes a new technique to measure the secretion rate, pool size, and turnover time of the pool of sulfated mucous glycoproteins of dog tracheal epithelium. The technique involved interposing dissected tracheal epithelium between the halves of an Ussing-type chamber, incubating the submucosal side of the tissue with 35SO4, and measuring the rate of appearance of nondialyzable 35SO4 on the luminal side of the chamber of both during the labeling and "washout" of the mucous pool. By analyzing the pattern of elimination, we showed that 1) a steady secretion rate of labeled mucous glycoprotein occurs within 3-4 h when free 35 SO4 is present on te submucosal side of the tissue, 2) secretion is consistent with first-order kinetics from a single pool, 3) puromycin decreases the rate of secretion of labeled mucous glycoprotein, 4) secretion rate is greater in medium 199 than in modified Krebs-Henseleit solution, and 5) 1.2 mM SO4 supports maximal baseline secretion. In six tracheas, bathed in Krebs-Henseleit solution, the secretion rate was (mean +/- SE) 467 +/- 74 pmol SO4 x cm-2 x h-1, pool size, 964 +/- 144 pmol SO4/cm2, and turnover time, 2.12 +/- 0.16 h. This technique provides a quantitative method to characterize kinetics of sulfated mucous glycoprotein secretion.


Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 780-803 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
J. W. ATHENS ◽  
M. M. WINTROBE

Abstract Present knowledge concerning the kinetics of granulopoiesis has been reviewed and quantitative data concerning granulokinetics in normal human subjects are presented. A. When granulocytes are labeled in vitro and returned to the circulation of the donor, the distribution of the cells in the circulation and the rate of disappearance of the cells from the circulation can be measured. 1. The total blood granulocyte pool (TBGP) consists of two compartments which are in equilibrium with each other. These pools have been designated the circulating granulocyte pool (CGP) and the marginal granulocyte pool (MGP). The size of the pools has been measured in 109 normal male subjects. The mean values, expressed as numbers of cells x 107 per Kg. of body weight were as follows: TBGP, 70; CGP, 31; and MGP, 39. The mean ratio of the CGP to the TBGP was 0.44. 2. The labeled granulocytes leave the TBGP in an exponential fashion with a mean half-time disappearance (T½) of 6.7 hours as determined in 56 normal male subjects. No evidence has been obtained for a return of granulocytes to the blood. 3. The mean value for the granulocyte turnover rate (GTR) in 56 normal male subjects was 163 x 107 granulocytes per Kg. of body weight per day. Thus, the TBGP turns over 2.3 times per day and the turnover time for the TBGP is 10.4 hours. B. When granulocytes are labeled in vivo by the intravenous administration of DFP32, the rate of disappearance of granulocytes from the circulation and the time required for myelocytes to divide, mature and appear in the blood can be measured. In addition, the generation time of myelocytes can be approximated. From the time parameters and the GTR, the bone marrow pool sizes and turnover times can be calculated. These determinations and calculations have been made for a group of 21 normal male subjects. 1. The mean half-time disappearance (T½) of in vivo labeled granulocytes from the circulation was 7.2 hours. This value agrees well with the value of 6.7 hours obtained after the in vitro labeling of granulocytes. 2. The mean time required for myelocytes to divide, mature and appear in the blood was 11.4 days. 3. The mean generation time of myelocytes was estimated to be not more than 2.9 days. 4. The total granulocyte pool in the bone marrow (neutrophilic myelocytes, neutrophilic metamyelocytes and PMN neutrophils) was calculated to be 186 x 108 cells per Kg. of body weight with a mean turnover time of 11.4 days. The myelocyte pool was estimated to be 41 x 108 cells per Kg. with a turnover time of 2.5 days; the metamyelocyte pool consisted of about 76 x 108 cells per Kg. with a turnover time of 4.7 days; the average size of the mature marrow PMN neutrophil pool was 69 x 108 cells per Kg. of body weight with a turnover time of 4.2 days. C. A kinetic model for granulopoiesis, based on the studies with the DFP32 label, is presented. In this model, myelocytes are depicted as approaching a self-perpetuating population of cells. Some cells enter this population from populations which are less mature but this latter source of cells is small under conditions of normal steady state kinetics. One of the daughter cells of a myelocyte division remains in the myelocyte population to divide again. The other daughter cell enters the metamyelocyte population. The metamyelocyte and PMN neutrophil population is incapable of division and cells move through this population in sequential fashion in the process of maturation. The cells then enter the blood where they equilibrate rapidly between the two blood compartments. The cells are removed from the total granulocyte pool in a random fashion. There is no appreciable pool of granulocytes in the extramedullary tissues of normal subjects and granulocytes do not return from the tissues to the blood. The entire movement of granulocytes from marrow to tissues is uni-directional.


Blood ◽  
1973 ◽  
Vol 42 (4) ◽  
pp. 623-636 ◽  
Author(s):  
H. Theml ◽  
F. Trepel ◽  
P. Schick ◽  
W. Kaboth ◽  
H. Begemann

Abstract Two patients with typical chronic lymphocytic leukemia received a continuous infusion of 3H-thymidine for 7 days. The production rate of lymphocytes was low in the lymph nodes, the marrow, and the blood. The fraction of newly formed lymphocytes appearing in the blood per day was only about 0.5%. The absolute production rate of blood lymphocytes however was very high, 690 cells/cu mm blood/day in one patient and 725 cells/cu mm/day in the other. The daily accumulation of newly produced lymphocytes in the circulating blood was estimated to be 3.0 x 109 cells. Most of these newly formed cells were lost from the blood lymphocyte compartment within 3 wk. They are considered to be short-lived lymphocytes with half-lives of 3-8 days. About 90% of the blood lymphocytes were long-lived with a turnover time in excess of 1 yr in the blood lymphocyte compartment. The short-lived cells were both large and small lymphocytes, the long-lived cells were almost exclusively small lymphocytes. Lymphoid cell proliferation was virtually absent in the blood, very low in the marrow, and marked in the enlarged lymph nodes. The exchange of lymphocytes seemed to be partially intact between lymph nodes and blood but more or less completely blocked between marrow and blood.


1982 ◽  
Vol 16 (2) ◽  
pp. 143-166 ◽  
Author(s):  
Nicholas H.G. Holford ◽  
Lewis B. Sheiner

Blood ◽  
1972 ◽  
Vol 39 (1) ◽  
pp. 39-56 ◽  
Author(s):  
E. O. Field ◽  
H. B. A. Sharpe ◽  
K. B. Dawson ◽  
V. Andersen ◽  
S. A. Killmann ◽  
...  

Abstract Lymphocyte kinetics have been studied in four patients treated by extracorporeal irradiation of the blood (ECIB) for immunosuppressive purposes prior to renal transplantation. The technique involves the analysis of chromosomal aberrations sustained by lymphocytes during irradiation and demonstrable in cultures stimulated with phytohaemagglutinin (PHA). Lymphocytes containing aberrations may be regarded as labeled, and this form of labeling has the advantage that it does not require the manipulation of lymphocytes outside the body. Preliminary experiments established that about half of lymphocytes irradiated with doses of 300-400 rad fail to undergo mitosis in culture and that the aberration yield per lymphocyte is the same at the end of a course of ECIB as at the beginning. Irradiated lymphocytes were found to have a mean residence time in the blood of less than 2 min, and for the first few hours of irradiation they were replaced by lymphocytes from tissue pools at a rate such that there was no appreciable fall in the peripheral count. These findings imply that a large proportion of the vascular endothelium acts as a filter for damaged lymphocytes and that initially damaged cells were replaced at the rate of one blood pool per hour; this may represent the normal turnover time of blood lymphocytes. The size of the total exchangeable lymphocyte pool was calculated by two methods depending on a series of basic assumptions concerning the kinetics of irradiated cells. According to the most likely estimate, the total pool contains some 30 times as many cells as circulate in the blood. Forty-two per cent of lymphocytes survived an irradiation dose of 300 rad, 10%-19% survived 380 rad.


1970 ◽  
Vol 46 (2) ◽  
pp. 362-369 ◽  
Author(s):  
Geert Ab ◽  
Ronald A. Malt

The labile precursors of ribosomal RNA in mouse kidney are preserved when nuclei rapidly isolated after sieving through multiple screens are swollen and cleansed in the presence of an RNase inhibitor before digestion with DNase and phenol extraction. The kinetics of nucleolar labeling analyzed on polyacrylamide gels show that 36S RNA is the major intermediate product in the catabolism of the original 45S RNA precursor to 32S RNA, from which 28S RNA is derived. Each kidney nucleus contains about 200–600 molecules of 45S RNA; the turnover time of the 45S pool is about 3 ± 2 min. Compared with HeLa cells, kidney nuclei have a different major intermediate product and a much smaller and more rapidly turning-over pool of ribosomal precursor RNA.


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