Cyclical neutropenia is a disease in humans and grey collie dogs in which the circulating neutrophil numbers regularly oscillate below normal values. CN can be treated using the cytokine G-CSF which decreases the period, increases the mean value, and elevates the amplitude of the oscillations. It has been theorized that this disease is a result of a periodic output of the hematopoietic stem cells in the bone marrow or a destabilization in a peripheral feedback mechanism controlled by circulating neutrophil number. We use a simple, but physiologically realistic, mathematical model, which incorporates the distribution of maturation times of neutrophils in the bone marrow, to study the latter possibility. We find that a change in the distribution of maturation times from normal to CN is insufficient to destabilize the system, and that even after a destabilization occurs, the model results are dissimilar from the observed CN dynamics. Also, G-CSF has a destabilizing effect on the system. Thus, it seems likely that the oscillations of CN are generated within the pluripotential stem cell population.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27528 |
| Date | January 1997 |
| Creators | Hearn, Taryn. |
| Contributors | Mackey, Michael C. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Mathematics and Statistics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001618402, proquestno: MQ37127, Theses scanned by UMI/ProQuest. |
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