Kinetics of isotope incorporation into the desoxyribonucleic acid (DNA) of tissues: Life span and generation time of cells

1958 ◽  
Vol 20 (1) ◽  
pp. 33-70 ◽  
Author(s):  
Demetrios A. Rigas
In Vitro ◽  
1981 ◽  
Vol 17 (1) ◽  
pp. 20-27 ◽  
Author(s):  
J. M. Ryan ◽  
D. G. Ostrow ◽  
Xandra O. Breakefield ◽  
Elliot S. Gershon ◽  
Leo Upchurch

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 641-649 ◽  
Author(s):  
K Miyazawa ◽  
DA Williams ◽  
A Gotoh ◽  
J Nishimaki ◽  
HE Broxmeyer ◽  
...  

Alternative splicing of exon 6 results in the production of two isoforms of Steel factor (SLF): the membrane-bound and soluble forms. To investigate differences in the kinetics of c-kit tyrosine kinase activated by these two isoforms, we used a stromal cell line (SI/SI4) established from SI/SI homozygous murine embryo fetal liver and its stable transfectants containing either hSCF248 cDNA (including exon 6; secreted form) or hSCF220 cDNA (lacking exon 6; membrane-bound form) as the source of each isoform. Interaction of factor dependent myeloid cell line MO7e with stromal cells producing either isoform resulted in activated c-kit tyrosine kinase and induction of the same series of tyrosine phosphorylated cellular proteins in MO7e cells. However, SI4- h220 (membrane-bound form) induced more persistent activation of c-kit kinase than SI4-h248 (soluble form) did. Flow cytometric analysis and pulse-chase studies using [35S]methionine showed that SI4-h248 induced rapid downmodulation of cell-surface c-kit expression and its protein degradation in MO7e cells, whereas SI4-h220 induced more prolonged life span of c-kit protein. Addition of soluble recombinant human SLF to SI4- h220 cultures enhanced reduction of cell-surface c-kit expression and its protein degradation. Because the kinetics of c-kit inactivation strikingly fits with the protein degradation rates of c-kit under the conditions described above, rapid proteolysis of c-kit protein induced by soluble SLF stimulation may function as a “turn-off switch” for activated c-kit kinase.


1962 ◽  
Vol 115 (1) ◽  
pp. 209-230 ◽  
Author(s):  
G. J. V. Nossal ◽  
O. Mäkelä

The origin and growth kinetics of plasma cells have been investigated using autoradiographic labeling techniques. Rats immunized once with Salmonella flagella were given a single pulse of H3-thymidine 4 or 40 weeks later. 2 hours after the tracer injection, they received a secondary antigenic stimulus. When animals were sacrificed immediately only certain cells from the resting primarily immunized lymph nodes, notably large and medium lymphocytes, were labeled. Subsequent to secondary stimulation, animals were killed at intervals; nearly all the plasma cells formed within the next 5 to 6 days were labeled. They must thus have been the progeny of cells already capable of synthesizing DNA in resting nodes, most probably of large lymphocytes. Plasmacytopoiesis began with little or no lag following secondary immunization, and the number of labeled plasma cells rose exponentially between the 2nd and 4th day, with a doubling time of about 12 hours. Studies of mean grain counts of primitive cells also suggested that the generation time of plasmablasts was 12 hours or less. The hypothesis was proposed that immunological memory depended on the persistence, following primary stimulation, of a continuously dividing stem line of primitive lymphocytes, reactive at all times to further antigenic stimulation.


PEDIATRICS ◽  
1985 ◽  
Vol 76 (6) ◽  
pp. 965-969
Author(s):  
Hiroshi Yoshioka ◽  
Masahiro Mino ◽  
Yuji Morikawa ◽  
Yasuo Kasubuchi ◽  
Tomoichi Kusunoki

This study was undertaken to investigate the effects of neonatal asphyxia on brain development, with special reference to the kinetics of neuronal proliferation by using autoradiography. For 30 minutes, two-day-old suckling mice, Jcl:ICR strain, were put into a chamber which was constantly flushed with 100% CO2 gas. After the exposure to asphyxia, 29% of the mice survived. Cell cycle studies were carried out at two days and at seven days on the external matrix cells, the precursor of the granule cells, at the external granular layer of the cerebellum from CO2-exposed and control mice by 3H-thymidine autoradiography. At two days the generation time of the control mice was about 15 hours, whereas that of the asphyxiated mice was about 17 hours. The prolongation of the generation time in the asphyxiated mice was caused mainly by a delay in the G2 phase. This prolongation was apparent for about five days and there-after growth caught up. These results suggest that neonatal asphyxia has an adverse effect on cerebellar neuronal proliferation that may revert to normal spontaneously in older animals.


2003 ◽  
Vol 77 (8) ◽  
pp. 5037-5038 ◽  
Author(s):  
Martin Markowitz ◽  
Michael Louie ◽  
Arlene Hurley ◽  
Eugene Sun ◽  
Michele Di Mascio ◽  
...  

ABSTRACT Mathematical models provide an understanding of in vivo replication kinetics of human immunodeficiency virus type 1 (HIV-1). With a novel intervention designed for increased potency, we have more accurately deduced the half-lives of virus-producing CD4+ T cells, 0.7 day, and the generation time of HIV-1 in vivo, approximately 2 days, confirming the dynamic nature of HIV-1 replication.


1985 ◽  
Vol 53 (03) ◽  
pp. 404-407 ◽  
Author(s):  
H F Kotzé ◽  
M G Lötter ◽  
P N Badenhorst ◽  
A du P Heyns

SummaryA fully representative and viable platelet population was isolated from the blood of 15 baboons by a multiwash procedure, and labelled with In-lll-oxine. The recovery of the total platelet population in the circulation was 85% ± 9. Mean platelet life span was 146 hr ± 13. Correcting for plasma radioactivity (always less than 3.5%) did not significantly affect the estimate of platelet life span (145 hr ± 16) or recovery (85% ± 12). Platelet survival estimates, repeated at different times, were reproducible. In 5 baboons, platelets were also harvested by a single step differential centrifugation. The mean life span of a representative platelet population was significantly longer than that of platelets harvested by a single step. Recovery values of the representative and non-representative population were similar. We conclude that it may be important to harvest and label a fully representative platelet population for kinetic studies. The proposed method is simple and reproducible, and may be applied in studies in humans.


Blood ◽  
1971 ◽  
Vol 38 (3) ◽  
pp. 372-377 ◽  
Author(s):  
CORNELIUS ROSSE

Abstract Guinea pigs were given 14 daily injections of 3H-thymidine to label a proportion of cells with a slow rate of turnover in addition to rapidly proliferating cells. In the bone marrow the only unlabeled cells were some reticular, endothelial, and plasma cells, damaged cells, and 14.1% of small lymphocytes. Six weeks after discontinuation of 3H-thymidine 7% of the marrow lymphocytes remained labeled. In guinea pigs injected every 4 hr with 3H-thymidine for 4 days to label all cells entering DNA synthesis, 14.4% of small lymphocytes remained unlabeled along with some reticular, endothelial, phagocytic, monocytoid, damaged, and plasma cells. The pattern of appearance of labeled lymphocytes was consistent with the kinetics of transitional cells that function as their precursors. Thus, in the bone marrow of the guinea pig the majority of lymphocytes have a short lifespan and a rapid turnover, whereas about 14% turn over more slowly and 7% have a life-span exceeding 4 wk. In this respect the kinetics of marrow lymphocyte production differs from that of the rat.


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.


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