Publications in refereed journals
Fliedner TM, Friesecke I, Graessle DH, Weiss M: Hemopoietic cell renewal as the limiting factor in low-level radiation exposure: Diagnostic implications and therapeutic options. Mil Med. 2002 Feb;167(2 Suppl ):46-8
Fliedner TM, Graessle DH, Paulsen C, Reimers K: Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm. 2002 Aug;17(4):405-26
Feinendegen LE, Graessle DH: Energy deposition in tissue during chronic irradiation and the biological consequences. Br J Radiol. 2002, Supplement_26:6-14
Graessle DH: Mathematical modelling of the blood platelet renewal system as an approach to analysing the effects of chronic irradiation on haematopoiesis. Br J Radiol. 2002, Supplement_26:202-208
Fliedner TM, Graessle DH, Paulsen C, Reimers K, Weiss M: The hematopoietic system: determinants of response to chronic ionizing radiation exposure. Br J Radiol. 2002, Supplement_ 26:247-257
Fliedner TM, Graessle DH, Paulsen C, Reimers K: Strategy and tactics for stimulation of haemopoiesis in patients developing the acute radiation syndrome. In: Follow-up of delayed
health consequences of acute accidental radiation exposure – Lessons to be learned from their
medical management. International Atomic Energy Agency, 2002, IAEA-TECDOC-1300
PhD-Thesis, University of Ulm, 2000
Dieter Hans Graessle
Abstract / Summary
The thesis presents the development and application of biomathematical models of the megakaryocyte-platelet renewal system as a tool for the analysis of radiation effects on hematopoiesis and thrombocytopoiesis. The basic structure of the used biomathematical models follows the currently accepted biological concepts of hematopoiesis and thrombocytopoiesis in mammalians and humans. It contains compartments for pluripotent stem cells, noncommitted progenitor cells, committed progenitor cells, endoreduplicating precursor cells, megakaryocytes in different ploidy groups, average megakaryocyte volume within ploidy groups and thrombocytes. Regulation functions are included to represent the compensatory feedback mechanisms of the megakaryocyte-platelet system. The compartments, the regulator structure and the cell-kinetic parameters of the model are derived from biological experiments. Seen from the mathematical perspective, the model consists of a set of concatenated nonlinear first-order ordinary differential equations. For analyzing the effects of acute irradiation to the hematopoietic system, the basic model was extended to simulate acute irradiation effects. This model was included into an estimation method based on optimization algorithms, which is capable to calculate survival fractions of stem cells, based on thrombocyte counts after radiation exposure. To analyze chronic radiation effects to hematopoiesis, the model was extended by components describing an radiation induced excess cell loss in radiosensitive compartments. A method for the estimation of excess cell loss rates from thrombocyte counts based on the model and optimization algorithms was developed. Computational mathematical analysis with stochastic simulations of the model showed the existence of a turbulence region of the excess cell loss rate, in which the hematopoietic system is at high risk to fail.
Read the full text of the PhD-Thesis.