Pub Date : 1900-01-01DOI: 10.1080/10273660500264684
S. Lubkin, S. Funk, E. Sage
A wide variety of measures is currently in use in the morphometry of vascular systems. We introduce two additional classes of measures based on erosions and dilations of the image. Each measure has a clear biological interpretation in terms of the measured structures and their function. The measures are illustrated on images of the arterial tree of the quail chorioallantoic membrane (CAM). The new measures are correlated with widely-used measures, such as fractal dimension, but allow a clearer biological interpretation. To distinguish one CAM arterial tree from another, we propose reporting just three independent, uncorrelated numbers: (i) the fraction of tissue which is vascular (VF0, a pure ratio), (ii) a measure of the typical distance of the vascularized tissue to its vessels (CL, a length), and (iii) the flow capacity of the tissue (P, an area). An unusually large CL would indicate the presence of large avascular areas, a characteristic feature of tumor tissue. CL is inversely highly correlated with fractal dimension of the skeletonized image, but has a more direct biological interpretation.
{"title":"Quantifying vasculature: new measures applied to arterial trees in the quail chorioallantoic membrane","authors":"S. Lubkin, S. Funk, E. Sage","doi":"10.1080/10273660500264684","DOIUrl":"https://doi.org/10.1080/10273660500264684","url":null,"abstract":"A wide variety of measures is currently in use in the morphometry of vascular systems. We introduce two additional classes of measures based on erosions and dilations of the image. Each measure has a clear biological interpretation in terms of the measured structures and their function. The measures are illustrated on images of the arterial tree of the quail chorioallantoic membrane (CAM). The new measures are correlated with widely-used measures, such as fractal dimension, but allow a clearer biological interpretation. To distinguish one CAM arterial tree from another, we propose reporting just three independent, uncorrelated numbers: (i) the fraction of tissue which is vascular (VF0, a pure ratio), (ii) a measure of the typical distance of the vascularized tissue to its vessels (CL, a length), and (iii) the flow capacity of the tissue (P, an area). An unusually large CL would indicate the presence of large avascular areas, a characteristic feature of tumor tissue. CL is inversely highly correlated with fractal dimension of the skeletonized image, but has a more direct biological interpretation.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121210596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273660290015170
L. Arlotti, A. Gamba, M. Lachowicz
In this paper, a model of cellular tumor dynamics in competition with the immune system is proposed. The characteristic scale of the phenomenon is the cellular one and the model is developed with probabilistic methods analogous to those of the kinetic theory. The interacting individuals are the cells of the populations involved in the competition between the tumor and the immune system. Interactions can change the activation state of the tumor and cause tumor proliferation or destruction. The model is expressed in terms of a bi-linear system of integro-differential equations. Some preliminary mathematical analysis of the model as well as computational simulations are presented.
{"title":"A Kinetic Model of Tumor/Immune System Cellular Interactions","authors":"L. Arlotti, A. Gamba, M. Lachowicz","doi":"10.1080/10273660290015170","DOIUrl":"https://doi.org/10.1080/10273660290015170","url":null,"abstract":"In this paper, a model of cellular tumor dynamics in competition with the immune system is proposed. The characteristic scale of the phenomenon is the cellular one and the model is developed with probabilistic methods analogous to those of the kinetic theory. The interacting individuals are the cells of the populations involved in the competition between the tumor and the immune system. Interactions can change the activation state of the tumor and cause tumor proliferation or destruction. The model is expressed in terms of a bi-linear system of integro-differential equations. Some preliminary mathematical analysis of the model as well as computational simulations are presented.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116918562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273660008833054
G. Solyanik, A. Serikov
The problern of regulation of the proliferation-differentiation processes is analysed in the framework of the model of unipotential cell clone dynamics, assuming two alternative ways (scenarios) of an every new-born cell development, which in the long run define correspondingly the proliferating or differentiated cell status. The scenario choice is then supposed to be a random event influenced by both the inherent mitotic activity of the cell and the differentiation factors — special messengers synthesized by the differentiated cells. Differentiation factors being accepted by every-new born cell can change the way of cell development. Taking into account the clonal heterogeneity it was shown that such mechanism of the regulation of proliferation-differentiation processes can result in the selection of actively proliferating and insensitive with respect to differentiation factors action cells (that is to say, the cells with cancer phenotype). In the framework of investigation the cells with cancer phenotype (which is heritable within the variability of mother-daughter correlations)appears through the series of the permanent nonmutational changes in the proliferating cells by autoselection mechanism retaining for the division and generation of the progeny only that actively proliferating cells which are less sensitive with respect to the action of the differentiation factors. The progression of normal cell clone towards the appearance and increase of the number of the cells with cancer phenotype can be considered as a possible mechanism of carcinogenesis which is alternative to the clonal selection theory of cancer origin.
{"title":"Autoselection Phenomenon in the Normal Cell Clone Undergoing Differentiation: From Cell Population Heterogeneity to Cancer Phenotype via Nonmutational Changes","authors":"G. Solyanik, A. Serikov","doi":"10.1080/10273660008833054","DOIUrl":"https://doi.org/10.1080/10273660008833054","url":null,"abstract":"The problern of regulation of the proliferation-differentiation processes is analysed in the framework of the model of unipotential cell clone dynamics, assuming two alternative ways (scenarios) of an every new-born cell development, which in the long run define correspondingly the proliferating or differentiated cell status. The scenario choice is then supposed to be a random event influenced by both the inherent mitotic activity of the cell and the differentiation factors — special messengers synthesized by the differentiated cells. Differentiation factors being accepted by every-new born cell can change the way of cell development. Taking into account the clonal heterogeneity it was shown that such mechanism of the regulation of proliferation-differentiation processes can result in the selection of actively proliferating and insensitive with respect to differentiation factors action cells (that is to say, the cells with cancer phenotype). In the framework of investigation the cells with cancer phenotype (which is heritable within the variability of mother-daughter correlations)appears through the series of the permanent nonmutational changes in the proliferating cells by autoselection mechanism retaining for the division and generation of the progeny only that actively proliferating cells which are less sensitive with respect to the action of the differentiation factors. The progression of normal cell clone towards the appearance and increase of the number of the cells with cancer phenotype can be considered as a possible mechanism of carcinogenesis which is alternative to the clonal selection theory of cancer origin.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132473786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273660290015224
W. Schubert
Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T-cell invasion in situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T-cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T-cells. This indicates, that the T-cell invasion is enciphered combinatorially in the T-cells' adhesive cell surface proteome fraction. Given 217 possible combinations, the T-cell appears to have at its disposal a highly non-random restricted repertoire to specify migratory pathways at the cell surface. These higher-level order functions in the cellular proteome cannot be detected by large-scale protein profiling techniques from tissue homogenates. High-throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.
{"title":"Polymyositis, Topological Proteomics Technology and Paradigm for Cell Invasion Dynamics","authors":"W. Schubert","doi":"10.1080/10273660290015224","DOIUrl":"https://doi.org/10.1080/10273660290015224","url":null,"abstract":"Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T-cell invasion in situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T-cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T-cells. This indicates, that the T-cell invasion is enciphered combinatorially in the T-cells' adhesive cell surface proteome fraction. Given 217 possible combinations, the T-cell appears to have at its disposal a highly non-random restricted repertoire to specify migratory pathways at the cell surface. These higher-level order functions in the cellular proteome cannot be detected by large-scale protein profiling techniques from tissue homogenates. High-throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133403004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273669908833028
B. Kovatchev, L. Farhy, D. Cox, M. Straume, V. Yankov, L. Gonder-Frederick, W. Clarke
A dynamical network model of insulin-glucose interactions in subjects with Type I Diabetes was developed and applied to data sets for 40 subjects. Each data set contained the amount of dextrose + insulin infused and blood glucose (BG) determinations, sampled every 5 minutes during a one-hour standardized euglycemic hyperinsulinemic clamp and a subsequent one-hour BG reduction to moderate hypoglycemic levels. The model approximated the temporal pattern of BG and on that basis predicted the counterregulatory response of each subject. The nonlinear fits explained more than 95% of the variance of subjects' BG fluctuations, with a median coefficient of determination 97.7%. For all subjects the model-predicted counterregulatory responses correlated with measured plasma epinephrine concentrations. The observed nadirs of BG during the tests correlated negatively with the model-predicted insulin utilization coefficient (r = -0.51, p < 0.001) and counterregulation rates (r = -0.63, p < 0.001). Subjects with a history of multiple severe hypoglycemic episodes demonstrated slower onset of counterregulation compared to subjects with no such history (p < 0.03).
1型糖尿病患者胰岛素-葡萄糖相互作用的动态网络模型被开发并应用于40个受试者的数据集。每个数据集包含葡萄糖+胰岛素输注量和血糖(BG)测定，在1小时标准化的正糖高胰岛素钳夹和随后的1小时BG降至中度低血糖水平期间每5分钟采样一次。该模型近似于BG的时间模式，并在此基础上预测每个受试者的反调节反应。非线性拟合解释了受试者BG波动95%以上的方差，中位决定系数为97.7%。对于所有受试者，模型预测的反调节反应与测量的血浆肾上腺素浓度相关。测试期间观察到的BG最低点与模型预测的胰岛素利用系数(r = -0.51, p < 0.001)和反调节率(r = -0.63, p < 0.001)呈负相关。有多次严重低血糖发作史的受试者比无此类病史的受试者表现出较慢的反调节起效(p < 0.03)。
{"title":"Modeling Insulin-Glucose Dynamics during Insulin Induced Hypoglycemia. Evaluation of Glucose Counterregulation","authors":"B. Kovatchev, L. Farhy, D. Cox, M. Straume, V. Yankov, L. Gonder-Frederick, W. Clarke","doi":"10.1080/10273669908833028","DOIUrl":"https://doi.org/10.1080/10273669908833028","url":null,"abstract":"A dynamical network model of insulin-glucose interactions in subjects with Type I Diabetes was developed and applied to data sets for 40 subjects. Each data set contained the amount of dextrose + insulin infused and blood glucose (BG) determinations, sampled every 5 minutes during a one-hour standardized euglycemic hyperinsulinemic clamp and a subsequent one-hour BG reduction to moderate hypoglycemic levels. The model approximated the temporal pattern of BG and on that basis predicted the counterregulatory response of each subject. The nonlinear fits explained more than 95% of the variance of subjects' BG fluctuations, with a median coefficient of determination 97.7%. For all subjects the model-predicted counterregulatory responses correlated with measured plasma epinephrine concentrations. The observed nadirs of BG during the tests correlated negatively with the model-predicted insulin utilization coefficient (r = -0.51, p < 0.001) and counterregulation rates (r = -0.63, p < 0.001). Subjects with a history of multiple severe hypoglycemic episodes demonstrated slower onset of counterregulation compared to subjects with no such history (p < 0.03).","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133980142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273660008833061
J. Panetta, M. Chaplain, D. Cameron
The two drugs, Paclitaxel and Cisplatin, have important roles in the treatment of breast and ovarian cancer, with the combination currently considered the optimum first line chemotherapy of epithelial ovarian cancer. There has been a variety of experimental and clinical studies to try to determine the most effective method to deliver these drugs. These studies consistently show that giving Paclitaxel prior to Cisplatin is the more effective regimen. However, the reasons why are not fully understood. Therefore, we have developed a mathematical model to describe and predict the effects of these two drugs. This model takes into account the cytotoxic effects of the drugs on the cell-cycle and the pharmacodynamic and pharmacokinetic effects of the drugs on each other. The model agrees with the experimental and clinical studies which show that Paclitaxel given prior to Cisplatin is the better combination and, in addition, the model also predicts more effective treatment regimens. These include conditions on the time between doses and the dosing of each of the drugs.
{"title":"Modelling the Effects of Paclitaxel and Cisplatin on Breast and Ovarian Cancer","authors":"J. Panetta, M. Chaplain, D. Cameron","doi":"10.1080/10273660008833061","DOIUrl":"https://doi.org/10.1080/10273660008833061","url":null,"abstract":"The two drugs, Paclitaxel and Cisplatin, have important roles in the treatment of breast and ovarian cancer, with the combination currently considered the optimum first line chemotherapy of epithelial ovarian cancer. There has been a variety of experimental and clinical studies to try to determine the most effective method to deliver these drugs. These studies consistently show that giving Paclitaxel prior to Cisplatin is the more effective regimen. However, the reasons why are not fully understood. Therefore, we have developed a mathematical model to describe and predict the effects of these two drugs. This model takes into account the cytotoxic effects of the drugs on the cell-cycle and the pharmacodynamic and pharmacokinetic effects of the drugs on each other. The model agrees with the experimental and clinical studies which show that Paclitaxel given prior to Cisplatin is the better combination and, in addition, the model also predicts more effective treatment regimens. These include conditions on the time between doses and the dosing of each of the drugs.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114853148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/1027366021000003289
A. Gumel, Xue Zhang, P. Shivakumar, M. L. Garba, B. Sahai
The requirements for the eradication of HIV in infected individuals are unknown. Intermittent administration of the immune activator interleukin-2 (IL-2) in combination with highly-active antiretroviral therapy (HAART) has been suggested as an effective strategy to realize long-term control of HIV replication in vivo. However, potential latent virus reservoirs are considered to be a major impediment in achieving this goal. In this paper, a new mathematical model is designed and used to monitor the interactions between HIV, CD4a T-cells, CD8a T-cells, productively infected and latently infected CD4a T-cells, and to evaluate therapeutic strategies during the first 3 years of HIV infection. The model shows that current anti-HIV therapies, including intermittent IL-2 and HAART, are insufficient in achieving eradication of HIV. However, it suggests that the HIV eradication may indeed be theoretically feasible if such therapy is administered continuously (without interruption) under some specified conditions. These conditions may realistically be achieved using an agent (such as a putative anti-HIV vaccine) that brings about a concomitant increase in the proliferation of HIVspecific CD4a T- and CD8a T-cells and the differentiation of CD8a T-cells into anti-HIV cytotoxic T lymphocytes (CTLs).
{"title":"A New Mathematical Model for Assessing Therapeutic Strategies for HIV Infection","authors":"A. Gumel, Xue Zhang, P. Shivakumar, M. L. Garba, B. Sahai","doi":"10.1080/1027366021000003289","DOIUrl":"https://doi.org/10.1080/1027366021000003289","url":null,"abstract":"The requirements for the eradication of HIV in infected individuals are unknown. Intermittent administration of the immune activator interleukin-2 (IL-2) in combination with highly-active antiretroviral therapy (HAART) has been suggested as an effective strategy to realize long-term control of HIV replication in vivo. However, potential latent virus reservoirs are considered to be a major impediment in achieving this goal. In this paper, a new mathematical model is designed and used to monitor the interactions between HIV, CD4a T-cells, CD8a T-cells, productively infected and latently infected CD4a T-cells, and to evaluate therapeutic strategies during the first 3 years of HIV infection. The model shows that current anti-HIV therapies, including intermittent IL-2 and HAART, are insufficient in achieving eradication of HIV. However, it suggests that the HIV eradication may indeed be theoretically feasible if such therapy is administered continuously (without interruption) under some specified conditions. These conditions may realistically be achieved using an agent (such as a putative anti-HIV vaccine) that brings about a concomitant increase in the proliferation of HIVspecific CD4a T- and CD8a T-cells and the differentiation of CD8a T-cells into anti-HIV cytotoxic T lymphocytes (CTLs).","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126118720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273669908833026
H. Byrne, M. Chaplain, G. Pettet, D. McElwain
In this paper we present a simple mathematical model to describe the initial phase of placental development during which trophoblast cells invade the uterine tissue as a continuous mass of cells. The key physical variables involved in this crucial stage of mammalian development are assumed to be the invading trophoblast cells, the uterine tissue, trophoblast-derived proteases that degrade the uterine tissue, and protease inhibitors that neutralise the action of the proteases. Numerical simulations presented here are in good qualitative agreement with experimental observations and show how changes in the system parameters influence the rate and degree of trophoblast invasion. In particular we suggest that chemotactic migration is a key feature of trophoblast invasion and that the rate at which proteases are produced is crucial to the successful implantation of the embryo. For example, both insufficient and excess production of the proteases may result in premature halting of the trophoblasts. Such behaviour may represent the pathological condition of failed trophoblast implantation and subsequent spontaneous abortion.
{"title":"A Mathematical Model of Trophoblast Invasion","authors":"H. Byrne, M. Chaplain, G. Pettet, D. McElwain","doi":"10.1080/10273669908833026","DOIUrl":"https://doi.org/10.1080/10273669908833026","url":null,"abstract":"In this paper we present a simple mathematical model to describe the initial phase of placental development during which trophoblast cells invade the uterine tissue as a continuous mass of cells. The key physical variables involved in this crucial stage of mammalian development are assumed to be the invading trophoblast cells, the uterine tissue, trophoblast-derived proteases that degrade the uterine tissue, and protease inhibitors that neutralise the action of the proteases. Numerical simulations presented here are in good qualitative agreement with experimental observations and show how changes in the system parameters influence the rate and degree of trophoblast invasion. In particular we suggest that chemotactic migration is a key feature of trophoblast invasion and that the rate at which proteases are produced is crucial to the successful implantation of the embryo. For example, both insufficient and excess production of the proteases may result in premature halting of the trophoblasts. Such behaviour may represent the pathological condition of failed trophoblast implantation and subsequent spontaneous abortion.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123634820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/1027366021000035455
A. Sonnenberg
It appears as if the failure of one organ system precipitates the subsequent failure of other organ systems. The aim of the present analysis is to model such system behavior and understand why medical complications accumulate in individual patients. The human body is first modeled as being comprised of multiple subsystems, with the health of each subsystem dependent on input regarding its own health status and that of all other subsystems. In a second step, the discrete model is generalized into a continuous model that captures system failure, as well as system repair, by a first order differential equation. Failure is approximated by a logistic decline and repair is approximated by a logistic rise in health. A small drop in health of a single subsystem spreads throughout the entire system and affects its overall health. Unless counteracted by measures of therapy or repair, any time-related loss in health of individual subsystems leads to a decline in health of the entire system. The delay in onset of therapy represents the most crucial factor to influence the overall cumulative decline in health. The model suggests that medical management needs to be expeditious to minimize the cumulative time-dependent toll of illness on the entire body.
{"title":"Why do Complications Accumulate in Individual Patients","authors":"A. Sonnenberg","doi":"10.1080/1027366021000035455","DOIUrl":"https://doi.org/10.1080/1027366021000035455","url":null,"abstract":"It appears as if the failure of one organ system precipitates the subsequent failure of other organ systems. The aim of the present analysis is to model such system behavior and understand why medical complications accumulate in individual patients. The human body is first modeled as being comprised of multiple subsystems, with the health of each subsystem dependent on input regarding its own health status and that of all other subsystems. In a second step, the discrete model is generalized into a continuous model that captures system failure, as well as system repair, by a first order differential equation. Failure is approximated by a logistic decline and repair is approximated by a logistic rise in health. A small drop in health of a single subsystem spreads throughout the entire system and affects its overall health. Unless counteracted by measures of therapy or repair, any time-related loss in health of individual subsystems leads to a decline in health of the entire system. The delay in onset of therapy represents the most crucial factor to influence the overall cumulative decline in health. The model suggests that medical management needs to be expeditious to minimize the cumulative time-dependent toll of illness on the entire body.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122151929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1080/10273660290015206
D. Ambrosi, N. Bellomo, L. Preziosi
This paper deals with the modeling of the immune response to the evolution of the progression of endothelial cells which have lost the differentiation and start their evolution towards metastatic states. The modeling is developed in the framework of the so-called kinetic cellular theory. The model is critically analyzed on the basis of analytic solutions, asymptotic behaviors and numerical simulations that illustrate the scenarios predicted by the model. Finally, possible developments and generalizations that could describe other known phenomena are pointed out.
{"title":"Modelling Tumor Progression, Heterogeneity, and Immune Competition","authors":"D. Ambrosi, N. Bellomo, L. Preziosi","doi":"10.1080/10273660290015206","DOIUrl":"https://doi.org/10.1080/10273660290015206","url":null,"abstract":"This paper deals with the modeling of the immune response to the evolution of the progression of endothelial cells which have lost the differentiation and start their evolution towards metastatic states. The modeling is developed in the framework of the so-called kinetic cellular theory. The model is critically analyzed on the basis of analytic solutions, asymptotic behaviors and numerical simulations that illustrate the scenarios predicted by the model. Finally, possible developments and generalizations that could describe other known phenomena are pointed out.","PeriodicalId":294267,"journal":{"name":"Journal of Theoretical Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131333783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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