The assessment of proliferating cell nuclear antigen immunostaining in myelodysplastic syndromes and its prognostic significance

Several prognostic factors for patients with myelodysplastic syndromes (MDS) have been identified in previous years. In order to determine prognostic factors characterizing haematopoietic cell kinetics, bone marrow proliferative activity and serum TNF-a levels were measured in 51 cases of MDS. Cell proliferation was evaluated by employing a monoclonal antibody directed against the proliferating cell nuclear antigen (PCNA). The PCNA proliferating index (PCNA PI) and serum TNF-a levels showed significant differences between patients with MDS and normal controls (p<0.0001). PCNA PI and serum TNF-a were significantly higher in the high risk for leukemic transformation FAB subgroups (RAEB, RAEB-t and CMML) in comparison to the low risk group (RA and RARS) (p<0.001). PCNA PI and TNF-a also increased with increasing IPSS score (p<0.05). A positive correlation was noted between TNF-a concentrations and PCNA PI (r:0.36, p<0.008). Univariate analysis using the log-rank test showed that a higher PCNA PI was associated with a significantly shorter survival (p<0.001). We conclude that elevated PCNA PI and TNF-a serum levels are increased in high risk myelodysplastic disease and that a high PCNA PI is predictive of a shorter survival in this group of patients.     

Biological clock mutants and parameter changes in mathematical models

A number of recent experiments have revealed the existence of mutants with different free run periods in their circadian rhythms. Parameter variations in mathematical models can be used to simulate such changes. In addition, phase response curves (PRC) are derived and the effect of parameter variation in their shape is studied. It is shown that changes in global parameters can also distort their shape. Therefore one cannot conclude that genetic experiments provide evidence in favor of “chronon” models since “kinetic” models can also simulate their outcome.     

A model for circadian clocks

An extension of an earlier model simulating the effects of light on the drosophila eclosion rhythm is presented. The effects of variable light intensity are described. This allows not only the simulation of certain experiments not covered by the earlier model, but also it permits an extension of the model to other organisms. By changing only its sensitivity to light the model simulates the phase response curves of certain mammals as well as Aschoff’srule.     

A mathematical model for the light affected system in the drosophila eclosion rhythm

This paper describes some analytical models for the system which regulates the daily eclosion rhythm of the drosophila. A general topological model is described which can simulate practically all the known experimental results about the behavior of the system under various light stimuli. From that a more specific model is proposed which can shortly be described as follows: The system contains a basic oscillator whose output is a substances. This is produced in the presence of an enzymer. During part of the cycler is deactivated ands dissipates until it reaches a lower level whenr is reactivated again. Light has the effect of deactivatingr immediately. The substances causes the production of a second substanceq which triggers a series of reactions leading to eclosion when it exceeds a threshold. The main oscillator (s—r) is temperature-compensated, but the production ofq is accelerated in the presence of light or higher temperature.