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J M Paulus

Publications and source records attributed to J M Paulus.

At least 37 records · Page 2Linked to original sources
PubMed1982

Polyploid megakaryocytes develop randomly from a multicompartmental system of committed progenitors.

Cumulative distributions of the number of doublings undergone by mixed megakaryocytic/erythroblastic colonies and by pure megakaryocytic colonies were determined from plasma clot cultures of bone marrow (from C57BL/6 mice) supplemented with erythropoietin. Analysis of these distributions suggests that these colonies are produced by three distinct progenitors. At days 7-14, progenitors of mixed megakaryocytic/erythroblastic colonies (BFU-ME) generate tri-exponential distributions and the mean (+/- SD) fraction of this progenitor pool ceasing to proliferate per doubling (FCP) increases stepwise from 0.07 +/- 0.06 to 0.27 +/- 0.07 and 0.73 +/- 0.07. In this interval, progenitors of pure megakaryocytic colonies (CFU-M) generate bi-exponential slopes whose FCP values are compatible with the two last slopes above. Finally, CFU-M at day 3 express only the last slope. From days 5 to 9, megakaryocytes generated by BFU-ME reach lower ploidy levels than do those generated by CFU-M. It is concluded that, in the culture system used, (i) megakaryocyte progenitors that do not switch to polyploidization mature through the three consecutive compartments indicated, (ii) each progenitor population has a probability of becoming polyploid that reflects the fraction that ceases to proliferate, (iii) the exponentially distributed mitotic reserve of progenitors is determined by the combination of maturing into the next compartment and the probabilistic switch to the pathway of polyploidization, and (iv) the ploidy distribution of megakaryocytes probably depends on the progenitor from which they originate.

Acetylcholinesterase↗
PubMed1981

[Secretion of acetylcholinesterase by megakaryocytes in mice].

Acetylcholinesterase, an early and nearly specific marker of Rodent thrombocytic cells, undergoes a typical secretory cycle leading to the release of the enzyme in the demarcation system and the outer cellular space of bone marrow megakaryocytes. This secretion process suggests that megakaryocytes may adapt the amplification of their own precursors by modulating the concentration in cholinergic compounds in hematopoietic tissues.

Acetylcholinesterase↗
PubMed1981

Mouse megakaryocytes secrete acetylcholinesterase.

Acetylcholinesterase (AchE), an essentially specific and early marker of rodent thrombocytic series, in several tissues acts both as a constituent of the cellular membrane and as a secretory enzyme. This study presents the ultrastructural transport and fate of this substance in the megakaryocytes of mouse bone marrow, using Tranum-Jensen and Behnke's adaptation of the indirect thiocholine method. It is shown that megakaryoblasts and megakaryocytes undergo a typical secretory cycle consisting of (1) enzyme synthesis and segregation on the endoplasmic reticulum and nuclear envelope, (2) enzyme concentration in AchE-vesicles and AchE-granules formed from the cisternae of the Golgi apparatus, and (3) discharge in the demarcation membrane system and extracellular space. The AchE-vesicles and granules appear to be hitherto unrecognized megakaryocytic organelles as they do not resemble alpha nor the dense granules, and their mode of formation and fate differ from those of primary lysosomes and peroxidase granules. Released platelets reveal AchE activity in the open canalicular system. The data are compatible with the hypothesis that by controlling acetylcholine concentration in hematopoietic tissues, the secretion of AchE by megakaryocytes can modulate the proliferative activity of megakaryocytes progenitors.

Acetylcholinesterase↗
PubMed1980

Kinetics of platelets, megakaryocytes and their precursors: what to measure?

A sequential exploration of the kinetics of platelets, megakaryocytes, and their progenitors is devised, wherein abnormalities at one level of differentiation are the subject of further analysis at the preceding level. Platelet kinetics yield estimates of mean platelet life span, fraction of platelet mass in circulation and daily production, making it possible to recognize the disorders of hyperdestruction, hypersequestration, hypoproduction, and hyperproduction. Theoretical considerations and regression analysis of a variety of computer-simulated survival tests show that sufficient information is contained in the first four days of the disappearance curve of population labeled platelets to provide an estimate of mean life span with an error of 9%--15%. Identifying the type of destruction disorder depends on developing tests and parameters which will make it possible to integrate into a coherent model such indices as the rate of senescence, the rates of reversible and irreversible aggregation, and the rates of adhesion to and phagocytosis by the reticuloendothelial system. Foremost among the existing models is the multiple-hit theory, although its validity rests on the unproved assumption that platelets keep a permanent memory of their injuries. Identifying the type of production disorder is the purpose of megakaryocyte kinetics. The daily production of megakaryocytes could be derived from the daily platelet production and the number of platelets released per megakaryocyte; determining megakaryocyte number would also yield the mean megakaryocyte maturation time. All these parameters could be obtained by combining a simple radioiron dilution method with cytochemical identification of megakaryocytes and with advanced, automated morphometric techniques. Abnormalities of megakaryocyte number and size can be further analyzed by studying the kinetics of thrombocytic precursors in tissue culture, i.e., by recording the distribution of precursor doublings and megakaryocyte ploidy histograms. The application of these techniques to cultures of bone marrow suggest that endomitosis may be initiated by any megakaryocyte precursor and that the kinetics of this process influence the number and final ploidy level of megakaryocytes.

Blood Platelets↗
PubMed1978

Platelet formation in Mediterranean macrothrombocytosis.

Platelet size distribution and survival parameters were studied in control subjects and ten subjects presenting Mediterranean macrothrombocytosis. The comparison showed that the latter group maintains a normal platelet circulating mass (thrombocytocrit) by combining normal platelet survival, increased splenic pooling and production of a reduced number of greatly enlarged cells. In addition to offering new insight into the megakaryocytic mechanisms that determine platelet size, the study of Mediterranean macrothrombocytosis indicates that platelet size distributions and survival parameters should be integrated in order to provide a meaningful picture of human platelet kinetics.

Africa, Northern↗
PubMed1975

Platelet size in man.

The shape and parameters of platelet size distributions were studied in 50 normal persons and 97 patients in order to test the proposed thesis that platelet size heterogeneity results mainly from aging in the circulation. This thesis was contradicted (1) by size distributions of age-homogeneous, newly-born cell populations which were lognormal with increased (instead of decreased) dispersion of volumes and (2) by the macrothrombocytosis found in some populations with normal age distribution. For these reasons, thrombocytopoiesis appeared to play the major role in determining platelet size. A model was built in which the volume variation of platelet territories due to megakaryocyte growth and membrane demarcation at each step of maturation was a random proportion of the previous value of the volume. This model explains the lognormal shape of both newborn and circulating platelet size distributions. It also implies that (1) the mean and standard deviation of platelet logvolumes depend on the rates of volume change of the individual platelet territories (growth rate minus demarcation rate) as well as on megakaryocyte maturation time; (2) platelet hyperdestruction causes an increase in the mean and dispersion of the rates of territory volume change; (3) Mediterranean macrothrombocytosis and some hereditary macrothrombocytotic thrombocytopenias or dysthrombocytopoieses reflect a diminished rate of territory demarcation, and (4) platelet size heterogeneity is caused mainly by the variations in territory growth and demarcation and not by aging in the circulation.

Anemia, Aplastic↗