Biomedical subjects

Ollivier Hyrien

Publications and source records attributed to Ollivier Hyrien.

6 recordsLinked to original sources

PubMed2006

Stochastic modeling of oligodendrocyte generation in cell culture: model validation with time-lapse data.

BACKGROUND: The purpose of this paper is two-fold. The first objective is to validate the assumptions behind a stochastic model developed earlier by these authors to describe oligodendrocyte generation in cell culture. The second is to generate time-lapse data that may help biomathematicians to build stochastic models of cell proliferation and differentiation under other experimental scenarios. RESULTS: Using time-lapse video recording it is possible to follow the individual evolutions of different cells within each clone. This experimental technique is very laborious and cannot replace model-based quantitative inference from clonal data. However, it is unrivalled in validating the structure of a stochastic model intended to describe cell proliferation and differentiation at the clonal level. In this paper, such data are reported and analyzed for oligodendrocyte precursor cells cultured in vitro. CONCLUSION: The results strongly support the validity of the most basic assumptions underpinning the previously proposed model of oligodendrocyte development in cell culture. However, there are some discrepancies; the most important is that the contribution of progenitor cell death to cell kinetics in this experimental system has been underestimated.

Algorithms↗

PubMed2005

A comprehensive stochastic model of irradiated cell populations in culture.

A comprehensive entirely mechanistic model of the kinetics of cell population in vitro exposed to continuous irradiation is formulated and analysed. The model provides a stochastic description of the processes of formation and repair of radiation-induced lesions, as well as of cell cycling, cell proliferation, and cell death. Unobservable kinetic parameters of the model are estimated from experimental data on the sizes of clones formed in synchronized cultures of S3 HeLa cells exposed to continuous irradiation by gamma-rays at various dose rates. The effects of dose rate on cell cycle duration and damage repair kinetics are studied. Continuous and acute exposures with the same total dose are compared in terms of their impact on cell survival.

Cell Cycle↗

PubMed2005

Interleukin (IL)-1A and IL-6: applications to the predictive diagnostic testing of radiation pneumonitis.

PURPOSE: To explore the application of interleukin (IL)-1alpha and IL-6 measurements in the predictive diagnostic testing for symptomatic radiation pneumonitis (RP). METHODS AND MATERIALS: In a prospective protocol investigating RP and cytokines, IL-1alpha and IL-6 values were analyzed by enzyme-linked immunosorbent assay from serial weekly blood samples of patients receiving chest radiation. We analyzed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) over selected threshold values for both cytokines in the application to diagnostic testing. RESULTS: The average coefficient of variation was 51% of the weekly mean IL-1alpha level and 39% of the weekly mean IL-6 value. Interleukin 1alpha and IL-6 became positively correlated with time. Specificity for both cytokines was better than sensitivity. IL-6 globally outperformed IL-1alpha in predicting RP, with higher PPV and NPV. CONCLUSIONS: Our data demonstrate the feasibility of applying IL-1alpha and IL-6 measurements of blood specimens to predict RP. Interleukin-6 measurements offer stronger positive predictive value than IL-1alpha. This application might be further explored in a larger sample of patients.

Adult↗

PubMed2005

Estimating the life-span of oligodendrocytes from clonal data on their development in cell culture.

This paper presents a new method to analyze clonal data on oligodendrocyte development in cell culture. The process of oligodendrocyte generation from precursor cells is modelled as a multi-type Bellman-Harris branching process as suggested in an earlier paper [K. Boucher, A. Zorin, A.Y. Yakovlev, M. Mayer-Proschel, M. Noble, An alternative stochastic model of generation of oligodendrocytes in cell culture, J. Math. Biol. 43 (2001) 22]. This model has been extended to allow for death of oligodendrocytes as well as a dissimilar distribution of the first mitotic cycle duration as compared to the subsequent cycles of precursor cells, which lengths are assumed to be independent and identically distributed random variables. Since the time-span of oligodendrocytes is not directly observable in clonal data, plausible parametric assumptions are invoked to make estimation problems tractable. In particular, the time to cell death follows a two-parameter gamma distribution, while the lapse of time between the event of cell death and the event of cell disintegration is assumed to be exponentially distributed. A simulated pseudo maximum likelihood method for estimation of model parameters has been developed using simulation-based approximations of the expected numbers and variance-covariance matrices for different types of cells. Finite sample properties of the estimation procedure are studied by computer simulations. The proposed method is illustrated with an analysis of the clonal development of O-2A progenitor cells isolated from the rat optic nerve and the corpus callosum.

Animals↗

PubMed2005

A stochastic model to analyze clonal data on multi-type cell populations.

This article presents a stochastic model designed to analyze experimental data on the development of cell clones composed of two (or more) distinct types of cells. The proposed model is an extension of the traditional multi-type Bellman-Harris branching stochastic process allowing for nonidentical time-to-transformation distributions defined for different cell types. A simulated pseudo likelihood method has been developed for the parametric statistical inference from experimental data on cell clones under the proposed model. The method uses simulation-based approximations of the means and the variance-covariance matrices of cell counts. The proposed estimator for the vector of unknown parameters is strongly consistent and asymptotically normal under mild regularity conditions, while its variance-covariance matrix is estimated by the parametric bootstrap. A Monte Carlo Wald test is proposed for the test of hypotheses. Finite sample properties of the estimator have been studied by computer simulations. The model and associated methods of parametric inference have been applied to the analysis of proliferation and differentiation of cultured O-2A progenitor cells that play a key role in the development of the central nervous system. It follows from this analysis that the time to division of the progenitor cell and the time to its differentiation (into an oligodendrocyte) are not identically distributed. This biological finding suggests that a molecular event determining the type of cell transformation is more likely to occur at the start rather than at the end of the mitotic cycle.

Biometry↗

PubMedDate not supplied

Application of pharmacokinetic/pharmacodynamic and stochastic modelling to 6-mercaptopurine micronucleus induction in mouse bone marrow erythrocytes.

This study investigates the kinetics of bone marrow micronucleated polychromatic erythrocytes and some mechanistic aspects of micronuclei induction using mathematical models. Female mice were administered a single intraperitoneal injection of the purine antagonist 6-mercaptopurine at 50 mg kg(-1). The time course evolution of the drug concentrations in the plasma and the micronucleated polychromatic erythrocyte kinetic rate in bone marrow were observed. Two mathematical models were developed for this study. The first model was built from a simultaneous pharmacokinetic/pharmacodynamic approach, but was invalidated after comparing its predictions to experimental data. The second model was a stochastic model based on some biological hypotheses involved in micronuclei induction. This model predicted a wavy kinetic rate of micronucleated polychromatic erythrocytes that was confirmed by a second data set obtained from a specifically built experimental design. The biological hypotheses were then discussed. It turned out from this work that mathematical modelling could be used as a tool to explore the cellular mechanisms of toxicity of the compound: for instance, the assumptions that 6-mercaptopurine induced micronuclei mainly in cells entering the S phase, and not only during the last cell cycle but during one of the earlier cycles preceding the extrusion of the main nucleus, were confirmed. Moreover, the use of the stochastic model would help to schedule more accurately the bone marrow or blood harvesting times in the in vivo rodent micronucleus test.

Animals↗