Biomedical subjects

Guanyu Wang

Publications and source records attributed to Guanyu Wang.

13 recordsLinked to original sources

PubMed2007

Estimation of the proliferation and maturation functions in a physiologically structured model of thymocyte development. Function estimation in thymocyte model.

The thymus provides a stable microenvironment for post-natal thymocyte development that is finely regulated by a complicated network of cytokines, chemokines, cell-cell contacts, etc., the dysregulations of which contribute to many immunologic diseases including malignant lymphomas. A physiologically structured model in the form of first order partial differential equation (PDE) was developed to simulate the whole process. The combined effects of the thymic microenvironment were conceptualized into two (proliferation and differentiation) fields to serve as kernels of the PDE. In this paper, a novel method is developed to estimate the maturity-time structures of the two fields based solely on cell population data that are experimentally viable. Numerical examples demonstrate the effectiveness of the present method in revealing the two-dimensional (maturity and time) landscapes of the thymic microenvironment.

Algorithms↗

PubMed2006

Physical theory of the competition that allows HIV to escape from the immune system.

Competition within the immune system may degrade immune control of viral infections. We formalize the evolution that occurs in both HIV-1 and the immune system quasispecies. Inclusion of competition in the immune system leads to a novel balance between the immune response and HIV-1, in which the eventual outcome is HIV-1 escape rather than control. The analytical model reproduces the three stages of HIV-1 infection. We propose a vaccine regimen that may be able to reduce competition between T cells, potentially eliminating the third stage of HIV-1.

Biological Evolution↗

PubMed2004

Crude-oil-degrading thermophilic bacterium isolated from an oil field.

Thermophilic bacterium strain C2, which has the ability to transform crude oils, was isolated from the reservoir of the Shengli oil field in East China. The Gram-negative, rod-shaped, nonmotile cells were grown at a high temperature, up to 83 degrees C, in the neutral to alkaline pH range. Depending on the culture conditions, the organism occurred as single rods or as filamentous aggregates. Strain C2 was grown chemoorganotrophically and produced metabolites, such as volatile fatty acids, 1,2-benzenedicarboxylic acid, bis(2-ethylhexyl)ester, dibutyl phthalate, and di-n-octyl phthalate. It could metabolize different organic substrates (acetate, D-glucose, fructose, glycerol, maltose, pyruvate, starch, sucrose, xylose, hexadecane). The G+C content (68 mol%) and the 16S rRNA sequence of strain C2 indicated that the isolate belonged to the genus Thermus. The strain affected different crude oils and changed their physical and chemical properties. The biochemical interactions between crude oils and strain C2 follow distinct trends characterized by a group of chemical markers (saturates, aromatics, resins, asphaltenes). Those trends show an increase in saturates and a decrease in aromatics, resins, and asphaltenes. The bioconversion of crude oils leads to an enrichment in lighter hydrocarbons and an overall redistribution of these hydrocarbons.

Alkanes↗

PubMed2003

Mathematical model to simulate the cellular dynamics of infection with human herpesvirus-6 in EBV-negative infectious mononucleosis.

Acute infection with human herpesvirus-6 induces physiological cell proliferation in persons without major immune deficiency. It thus can serve as a parameter to validate a mathematical model designed to simulate cell proliferation under physiological and pathological conditions. Such a mathematical model is presented to simulate various cell changes of the T-cell immune system during the course of HHV-6 infection. Model development follows several steps, beginning with a basic model containing physiological T-cell pools to the introduction of infectious stimuli in the final model. A search algorithm designed to optimize the system parameters, as well as initial variables of the model, is presented. The results of simulation runs for acute HHV-6 infection of the final computational model correspond well to the data, as documented in human patients; they suggest that the computational model presented for the simulation of T-cell levels in a given viral infection may well serve as a tool for similar studies of other viral infections, including those that lead to cellular aplasia or neoplasia.

Adolescent↗

PubMed2002

[Influence of spleen on cell cycle and expression of proliferating cell nuclear antigen of the liver during diethylnitrosamine-induced rat hepatocarcinogenesis].

OBJECTIVE: To investigate the role of the spleen on hepatocyte proliferative activity during experimental hepatocarcinogenesis in rats. METHODS: Cell-cycle and expression of proliferating cell nuclear antigen (PCNA) of hepatocytes were studied by immunohistochemical and flow cytometric technique in two groups: splenectomy (45 rats) and sham-operation with laparotomy (45 rats). RESULTS: (1) Hepatocirrhosis was formed in group A earlier than in group B. Marked degenerative changes of the liver parachyma showing vacuolization of hepatocytes were observed in hepatic lobules. (2) The proliferative level of hepatocytes increased with the progression of hepatocarcinogenesis, and topped at the 18 th week. (3) The proliferative level of the splenectomy group was lower than that of the sham-operation group in the mid-stage of carcinogenesis (t = 4.76, P < 0.05). After stopping feeding diethylnitrosamine (DENA), however, no difference was found in the hepatocyte proliferative activity between the two groups at the 18th week. CONCLUSIONS: There is a close relationship between hepatic proliferative activity and spleen, and the spleen may play an important role in facilitating hepatic proliferation.

Animals↗

PubMedDate not supplied

Dynamics of HTLV-1 leukemogenesis: data acquisition for computer modeling.

A literature search for HTLV-1-induced adult T-cell leukemia (ATL) at the National Library of Medicine resulted in 1003 publications which were evaluated with regard to HTLV-1 virus load, apoptosis and peripheral blood leukocyte changes during the latent period and leukemia development following virus infection. The data are presented in a comparable way to previous publications of infections with HHV-6 and HIV (which target the same CD4+ cell for infection) to be used for computer validation studies. After initial infection, HTLV-1 remains clinically latent for many years at low provirus copy numbers in CD4 cells. Once immune surveillance deteriorates and viral replication progresses, provirus copy numbers increase rapidly. Unlike other virus infections, apoptotic death of virus-infected "atypical" lymphocytes decreases with increasing viral load, thus favoring continued proliferation of these cells and further virus replication at the same time. Changes in the peripheral blood are characterized by coincident rises in oligoclonal lymphocyte populations including HTLV-1-positive CD4+ T-lymphocytes and their precursors with a progressive shift to immature cells as disease progresses. The pathogenesis of HTLV-1-induced adult T-cell leukemia is an example of dysregulative leukemogenesis ideal for validation of respective computer simulation models.

Adult↗

PubMedDate not supplied

A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma.

OBJECTIVE: The objective of this study was to simulate changes in the human T cell system representing Canale-Smith syndrome using a dynamic computer model of T cell development and comparing with available human data. STUDY DESIGN: Physiological stepwise maturation and function of T lymphocytes in the computer model is altered by introducing functional disturbances following lymphotropic virus infection. In the present model, acute and chronic persistent infection with the human herpesvirus-6 (HHV-6) was simulated, and ensuing changes in T cell populations were compared with those measured in human patients. RESULTS: Using our computer model we previously found that simulated acute HHV-6 infection produced T cell computer data, which resembled an infectious mononucleosis-like disease in patients. Simulated chronic persistent infection, instead, resulted in variable cell changes comparing well to patients with chronic fatigue syndrome. In one setting, however, persistent immature lymphocytosis was observed similar to what initial has been described in this journal as Canale-Smith syndrome. CONCLUSION: Using a computer model developed by us we were able to produce simulations that resemble the immune system features of Canale-Smith syndrome. Further understanding of these simulation results may possibly guide future investigations into this disorder.

Adult↗

PubMedDate not supplied

Growth factors, cytokines, chemokines and neuropeptides in the modeling of T-cells.

The T lymphocyte lineage, from initial stem cells to peripheral mature T-cells, are members of a highly reactive cell system engaged in the control of internal homoeostasis and body intactness. It fulfills its commitments in close communication with the cellular and non-cellular microenvironment and with neuroendocrine regulatory mechanisms. Tools of such communication are various substances and compounds identified as cytokines, chemokines, hormones, growth factors and neuropeptides. Any pathogenetical model of functional aberration and disease development in the T-cell system must take into account the delicate network control exerted by the above mechanisms. In the following we describe the major players in the network regulation of T-cell development and function as a basis for a computational modeling study.

Chemokines↗

PubMedDate not supplied

TCM-1: a nonlinear dynamical computational model to simulate cellular changes in the T cell system; conceptional design and validation.

Based upon a previously developed theory of dysregulative lymphoma pathogenesis, a computer model is designed in order to simulate cell changes occurring in disturbances of the T cell immune system and in lymphoproliferative diseases. The model is based upon the concept that factors identified as proliferation factors, differentiation factors and inhibition factors exert a network regulation upon development and function of the T cell system, and that selective disturbances of these factors may lead to hyperplastic, aplastic or neoplastic diseases. The resulting computer model (TCM-1) was validated by comparing it with data from human diseases such as acute HHV-6 (viral) infection, chronic persistent HHV-6 infection, progressive HIV1 infection and HTLV-1 infection, and comparing the simulation results with the actual cell data in the human patients. All these infections target the same T cell population (i.e. CD4 + T helper cells), yet cause different prototypical reactions (hyperplastic, aplastic, neoplastic). The described computer model, which was successfully used to simulate changes in the benign lymphoproliferative disease, Canale-Smith syndrome, will serve as the basis model for further supplementation to accommodate identified factorial influences such as by cytokines, chemokines and others.

Adult↗

PubMedDate not supplied

A simplified and comprehensive computational model to study the behavior of T cell populations in the thymus during normal maturation and in infection with mouse moloney leukemiavirus.

Based on a previously developed theory of dysregulative lymphoma pathogenesis, an advanced mathematical model was developed for simulation of thymic T cell populations and their differentiation stages. The model subsequently was tested in comparison to thymic changes in mice with Moloneyvirus infection and leukemia development. Numerical examples are given, which suggest that the model is useful to study T cell proliferation, differentiation, and may probably also be useful to simulate T cell changes in various lymphoproliferative diseases.

Animals↗

PubMedDate not supplied

A simple model to simulate cellular changes in the T cell system following HIV-1 infection.

A new mathematical model is presented to simulate various changes of cell pools in the T cell immune system with validation procedures imitating viral infections. The present paper focuses on changes during the course of an acute progressive HIV-1 infection. Parameters are optimized by a direct search method and the stability of the model is studied. Mathematical modeling supports the hypothesis that the differentiation blockade is one major reason for the depletion of CD4 cells and the proliferation of CD38 cells in HIV-1 infection. The model appears to be a useful basis for further simulating disturbances of the T cell immune system in other viral infections as well as to elucidate the pathogenesis of various immunological diseases including the development of malignant lymphomas.

ADP-ribosyl Cyclase↗

PubMedDate not supplied

A continuous model studying T cell differentiation and lymphomagenesis and its distinction with discrete models.

The development of T-lymphocytes (T cells) constitute one of the basic and most vital processes in immunology. Conventional mathematical models, being based on the systems theory, fail to sufficiently distinguish the constituents of thymocytes and are thus of limited significance. On the basis of some well thought-out definitions and concepts, a continuous model was designed to describe T cell maturation in the thymus. A partial differential equation was first derived through the analysis of an infinitesimal element of the flow of thymocytes. A computation scheme was designed to determine the growth field in the thymus based upon available experimental data. The corresponding algorithm proved quite simple. A numerical example is given that focuses on the DN stage of the T cell development. The model opens a window for investigating the thymic microenvironment. The potential of the model in studying lymphomagenesis is discussed.

Animals↗

PubMedDate not supplied

Feed-forward and feedback mechanisms in a dynamic model of human T cell development and regulation.

We describe a computational model of human T cell regulatory dynamics. We used this model to simulate changes in T cell pool numbers and for studying feedback and feed-forward responses in and among these pools. The pools identified were the bone marrow stem cell compartment, early and late thymocyte compartments and the peripheral compartment of mature T lymphocytes. Simulated data showed variable intercompartmental strengths indicative of a range of sensitivities to feedback regulation and respective variable feed-forward responses. The results compare well to known clinical and experimental data, rendering the computational model a good basis for further research in T cell development and regulation.

Cell Division↗