Search PubMed⌕ Search

Biomedical subjects

C Haurie

Publications and source records attributed to C Haurie.

6 recordsLinked to original sources
PubMed2000

Modeling complex neutrophil dynamics in the grey collie.

We have developed a mathematical model for the peripheral regulation of neutrophil production mediated by granulocyte colony-stimulating factor. We have used that model to show that the pattern of neutrophil oscillations in nine grey collies is consistent with the hypothesis that cyclical neutropenia is due to an oscillatory stem cell input to the neutrophil regulatory system, and not due to autonomous oscillations in the peripheral neutrophil regulatory system. In the process of interfacing our model with the laboratory data, we have estimated parameters for the peripheral neutrophil control system consistent with higher than normal apoptotic cell loss within the recognizable neutrophil precursors. This is in agreement with other experimental data. Our estimated model parameters also predict that the peripheral neutrophil production system is globally stable in the grey collies we studied. This further supports our hypothesis that the origin of the oscillatory behavior in cyclical neutropenia is in the stem cell population, consistent with other clinical and experimental evidence.

Animals↗
PubMed1999

Occurrence of periodic oscillations in the differential blood counts of congenital, idiopathic, and cyclical neutropenic patients before and during treatment with G-CSF.

Using techniques developed in astrophysics to deal with unequally sampled data sets, we have analyzed serial differential cell counts from 45 congenital, idiopathic, and cyclic neutropenic patients before and during treatment with recombinant human G-CSF (rhG-CSF). Our results show that the occurrence of significant cycling in the absolute neutrophil count (ANC) of neutropenics not classified as cyclical is much more prevalent than had been previously thought, and that not all the patients classified as cyclic show significant ANC periodicity. In these patients, cycling in more than one cell line may be involved. The range of periods encountered in these patients is much broader (between 11 and 52 days) than is usually associated with classical cyclical neutropenia, and there is no obvious connection between the range of periods and the patient's diagnostic category. Administration of rhG-CSF is able to induce significant cycling in neutropenic patients that were not cycling prior to treatment. In patients who had significant cycling before treatment, rhG-CSF may either decrease the period to between 11 and 14 days, or may obliterate any statistical evidence of cycling.

Adult↗
PubMed1999

Hematopoietic dynamics in grey collies.

Using Lomb periodogram analysis we have quantified variations in the peripheral neutrophil and platelet counts of the cyclical neutropenia animal model-the grey collie. We found that the amplitudes of the oscillations in these two cell lineages vary concomitantly. Further, the power spectrum and the shape of the oscillations in the absolute neutrophil counts vary together with the amplitude of the oscillations. As the amplitude of the oscillations increases, the height of the second subharmonic increases, giving rise to a distorted oscillation with two peaks per cycle. The particular dynamics of the absolute neutrophil counts can be reproduced by a combination of a delayed peripheral feedback, representing the peripheral control of granulopoiesis through granulocyte colony stimulating factor, together with a sinusoidal input representing an oscillatory input from the pluripotential stem cells to the granulocytic lineage. The same pluripotential stem cell input is probably responsible for the sinusoidal oscillations observed in the other cell lineages.

Animals↗
PubMed1998

Cyclical neutropenia and other periodic hematological disorders: a review of mechanisms and mathematical models.

Although all blood cells are derived from hematopoietic stem cells, the regulation of this production system is only partially understood. Negative feedback control mediated by erythropoietin and thrombopoietin regulates erythrocyte and platelet production, respectively, but the regulation of leukocyte levels is less well understood. The local regulatory mechanisms within the hematopoietic stem cells are also not well characterized at this point. Because of their dynamic character, cyclical neutropenia and other periodic hematological disorders offer a rare opportunity to more fully understand the nature of these regulatory processes. We review the salient clinical and laboratory features of cyclical neutropenia (and the less common disorders periodic chronic myelogenous leukemia, periodic auto-immune hemolytic anemia, polycythemia vera, aplastic anemia, and cyclical thrombocytopenia) and the insight into these diseases afforded by mathematical modeling. We argue that the available evidence indicates that the locus of the defect in most of these dynamic diseases is at the stem cell level (auto-immune hemolytic anemia and cyclical thrombocytopenia seem to be the exceptions). Abnormal responses to growth factors or accelerated cell loss through apoptosis may play an important role in the genesis of these disorders.

Anemia, Aplastic↗
PubMed1998

Cyclical neutropenia and the peripheral control of white blood cell production.

Cyclical neutropenia (CN) is an interesting dynamic hematological disease in which the neutrophils spontaneously oscillate from approximately normal levels to near zero with a period between 19 and 21 days. In the only known animal model for this disorder, the grey collie, the disease's single apparent difference from human CN is the smaller period of 11-15 days. CN can be treated using the cytokine G-CSF which decreases the period (to about 14 days in humans), increases the mean value, and elevates the amplitude of the oscillations. After reviewing the clinical and laboratory data on this disease, we examine the proposition that CN is due to a loss of stability in the peripheral negative feedback control of neutrophil production. This is accomplished by the development of a physiologically realist mathematical model for the system. We conclude that there is no consistent way in which such a destabilization can give rise to either the clinical or laboratory characteristics of CN. Rather it seems more likely that the oscillations of CN are generated within the pluripotential stem cell population.

Feedback↗