Models for the red blood cell lifespan
Models for the red blood cell lifespan
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DOI：
10.1007/s10928-016-9470-4
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发表时间：
2016-06-01
影响因子：
2.5
通讯作者：
Chait，Yossi
中科院分区：
文献类型：
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作者：
Shrestha，Rajiv P.;Horowitz，Joseph;Chait，Yossi
红细胞的寿命在各种临床疾病的研究和解释中起着重要的作用。然而，有关细胞存活及其定量的基本术语的含义在文献中仍然存在混淆。为了解决这些问题，我们从基于任意全寿命分布的红细胞种群的分区模型开始，仔细定义红细胞种群的剩余寿命、当前年龄和过剩寿命，然后推导出这些参数的分布。对于一组来自生物素标记红细胞的剩余生存数据，我们使用非线性混合效应建模和参数自助，基于威布尔、伽马和对数正态分布拟合模型。根据估计的威布尔、伽马和对数正态参数，我们分别计算了种群的平均全寿命（95%置信区间）：115.60（109.17-121.66）、116.71（110.81-122.51）和116.79（111.23-122.75）天，以及全寿命的标准差：24.77（20.82-28.81）、24.30（20.53-28.33）和24.19（20.43-27.73）。然后，我们估计了寿命分布的第95百分位数（最长寿命的替代）：153.95(150.02-158.36),159.51（155.09-164.00）和160.40（156.00-165.58）天，平均当前年龄（或平均剩余寿命）：60.45(58.18-62.85),60.82（58.77-63.33）和57.26（54.33-60.61）天，剩余半衰期：57.97(54.96-60.90),58.36（55.45-61.26）和58.40（55.62-61.37）天，分别用于威布尔，伽马和对数正态模型。对个体受试者进行了相应的估计。这三种模型提供了同样优秀的拟合优度、可靠的估计和生理学上合理的直接解释RBC生存参数值。
The lifespan of red blood cells (RBCs) plays an important role in the study and interpretation of various clinical conditions. Yet, confusion about the meanings of fundamental terms related to cell survival and their quantification still exists in the literature. To address these issues, we started from a compartmental model of RBC populations based on an arbitraryfull lifespandistribution, carefully defined theresidual lifespan,current age, andexcess lifespanof the RBC population, and then derived the distributions of these parameters. For a set of residual survival data from biotin-labeled RBCs, we fit models based on Weibull, gamma, and lognormal distributions, using nonlinear mixed effects modeling and parametric bootstrapping. From the estimated Weibull, gamma, and lognormal parameters we computed the respective population mean full lifespans (95 % confidence interval): 115.60 (109.17–121.66), 116.71 (110.81–122.51), and 116.79 (111.23–122.75) days together with the standard deviations of the full lifespans: 24.77 (20.82–28.81), 24.30 (20.53–28.33), and 24.19 (20.43–27.73). We then estimated the 95th percentiles of the lifespan distributions (a surrogate for the maximum lifespan): 153.95 (150.02–158.36), 159.51 (155.09–164.00), and 160.40 (156.00–165.58) days, the mean current ages (or the mean residual lifespans): 60.45 (58.18–62.85), 60.82 (58.77–63.33), and 57.26 (54.33–60.61) days, and the residual half-lives: 57.97 (54.96–60.90), 58.36 (55.45–61.26), and 58.40 (55.62–61.37) days, for the Weibull, gamma, and lognormal models respectively. Corresponding estimates were obtained for the individual subjects. The three models provide equally excellent goodness-of-fit, reliable estimation, and physiologically plausible values of the directly interpretable RBC survival parameters.