PubMed Health⌕ Search

Biomedical subjects

P C Chau

Publications and source records attributed to P C Chau.

10 recordsLinked to original sources
PubMed2005

Three-dimensional cell cycle model with distributed transcription and translation.

A computational cell cycle model that can describe three state properties, cell maturation age, specific mRNA and protein content, has been developed. Cell cycle progression is monitored by maturation age, and population heterogeneity is generated by the introduction of a probable random event embedded in the G1 phase. Specific mRNA is generated with a constant transcription rate at the single-cell level, and its turnover is governed by a first-order decay. Translation is modelled as a first-order dependence on the transcripts, and the protein product is subsequently exported. Dynamic chemostat simulations are used to demonstrate the ability of the model to track evolving parent and daughter subpopulations in maturation and cellular contents. The cell subpopulations eventually converge to an equilibrium distribution corresponding to the steady state of a chemostat, and halving of cellular content at cell division is the dominant driving force leading towards the population equilibrium state.

Animals↗
PubMed2000

Identification of the immunoreactive peptide sequence for AgSK1, an adenocarcinoma-restricted antigen.

SK1, a human immunoglobulin M (IgM) monoclonal antibody was derived from regional nodal lymphocytes of a Dukes B colon carcinoma patient. The antigen recognized by the human monoclonal antibody (HuMab) SK1, termed AgSK1, was shown to be a two-chain glycoprotein with an apparent molecular weight range of 42-46 kDa and preferentially expressed by human adenocarcinomas, particularly human gastrointestinal malignancies. To identify the gene encoding the AgSK1 antigenic epitope, a cDNA expression library constructed in lambda gt22A using mRNA from the colon carcinoma cell line HT29 was screened and one of the isolated clones encoding a 1.5-kb cDNA, which showed strong immunoreactivity with HuMab SK1, was selected for further analysis. This clone consisted of an amino terminal open reading frame of 54 amino acids and the carboxyl terminal 20 amino acids of this protein coding region contained the antigenic epitope recognized by HuMab SK1.

Adenocarcinoma↗
PubMed1998

Transition probability cell cycle model with product formation.

A cell cycle population model based on the transition probability model of Smith and Martin (1973) has been extended to include product synthesis and export. The model handles two probable mechanisms. In the direct production model, the product is the protein. In the transcription model, the product is the specific mRNA. The protein is synthesized by translation of the specific mRNA and subsequently exported. In either case, the cell density is jointly distributed in the primary product and maturity age in the cell cycle. This extended model also is capable of describing a large range of conditions, including substrate dependent batch and continuous cultures. With the use of unity maturity-velocity (but the transition rate a function of limiting substrate), the model is shown to exhibit a negative growth association between the specific productivity of monoclonal antibodies from hybridomas and the dilution rates of a chemostat. Possibilities of maturity age dependent transcription and translation are considered, and the results show that these features can amplify the specific productivity negative association with specific growth rate. While this model may provide a partial elucidation of monoclonal antibody productivity in a chemostat, the present work provides a proper framework with which probable cell cycle dependent product formation can be analyzed rigorously with a comprehensive computational model.

Animals↗
PubMed1997

Transition probability cell cycle model. Part I--Balanced growth.

A cell cycle model based on the concept of a transition probability first proposed by Smith & Martin has been implemented as a differential equation model. The probabilistic A-state is modeled as a lumped parameter while the deterministic B-phase is modeled as a distributed parameter, and analytical solutions for both the population and the fraction of labeled mitosis (FLM) curves are derived under balanced growth conditions. Contributions toward cell cycle variability by single and double random transitions are considered. A double transition model provides a more realistic description of the cell cycle time distribution. For gross cell population behavior, a single transition from the A-state to the B-phase may provide acceptable approximation. In spite of the simplification, the single transition Smith & Martin model is shown to describe the gradual asynchronization of a cell population.

Animals↗
PubMed1997

Transition probability cell cycle model. Part II--Non-balanced growth.

A cell cycle model based on the transition probability model of Smith & Martin has been extended to non-balanced growth conditions in batch cultures. The model considers transition to a quiescent cell fraction, variable maturity-velocity, exogenous maintenance, and cell death. This extended model is capable of describing a large range of cell culture behavior which may not conform to Monod kinetics. The use of a constant quiescent transition allows the population to enter a stationary phase, but with a very large A-state to B-phase cell ratio. A substrate dependent quiescent transition helps to reduce this ratio while maintaining the general features of the population growth curves. A model with substrate dependent variable maturity-velocity qualitatively is similar to the Monod equation, while providing additional information on population distribution. The combination of quiescent transition and a substrate dependent maturity-velocity is also examined, and the resulting model is shown to capture the essence of both features.

Animals↗
PubMed1997

A transition probability cell cycle model simulation of bivariate DNA/bromodeoxyuridine distributions.

The transition probability cell cycle model is extended to describe both cell cycle variability and incorporation of bromodeoxyuridine (BrdUrd). The model can simulate BrdUrd uptake in both pulse-chase and continuous-labeling experiments. With the use of a random transition, variability due to cell cycle progression is distinguished from dispersion due to staining and machine errors in the generation of bivariate DNA/BrdUrd distributions. In a comparative test with a compartmental model developed by Yanagisawa et al. (Cytometry 6:550-562, 1985), the present model is shown to provide realistic simulations with fewer model parameters and with the ability to describe gradual asynchronization of cell cycle cohorts. With model predictions as the basis, a simulated experiment is performed to illustrate the difficulty in analyzing bivariate distributions. The simulated experiment illustrated that it is very easy to overestimate unlabeled cell fractions, and, as a result, matching the periodicity of the cell cycle cohort movements is more reliable in the estimation of model parameters.

Algorithms↗
PubMed1991

Cell cycle dependency of monoclonal antibody production in asynchronous serum-free hybridoma cultures.

The cell cycle kinetics of F3(B6) mouse hybridoma was examined by immunocytochemical staining of bromodeoxyuridine incorporated into the DNA of exponentially growing cells in three different cultures: one supplemented with 10% fetal bovine serum and two adapted to serum-free media, TABIES and BITES. The serum-free cultures, particularly the BITES, had longer cycling times and higher specific antibody production rate. Both observations were correlated to the prolongation of the G1 phase traverse time and substantiated with a starvation blocking experiment.

Animals↗
PubMed1990

Evaluation of immunocytochemical detection methods of incorporated bromodeoxyuridine in hybridomas.

Bivariate distributions obtained from nominal acid hydrolysis or thermal treatment methods used in the cell cycle analysis of incorporated bromodeoxyuridine were shown to be unacceptable with hybridomas. Four different cell treatment and staining methods were compared. These methods are acid hydrolysis, thermal denaturation, nuclei extraction with pepsin digestion, and simultaneous pepsin digestion and acid hydrolysis. The nuclei extraction method was determined to be the most appropriate for the immunocytochemical staining of incorporated bromodeoxyuridine in hybridomas. The resulting bivariate distribution provides a clear distinction between labelled and unlabelled cell fractions. The method based on nuclei extraction with pepsin digestion was optimized for a hybridoma line used in this study.

Animals↗
PubMed1986

Hybridoma growth and antibody secretion in serum-supplemented and low protein serum-free media.

Hybridoma cell growth and monoclonal antibody secretion were studied with three murine hybridomas, SS1.1, NS6.3 and 455, propagated in four low protein serum-free media and various serum-supplemented media. Cell metabolism, as indicated by cell growth and glucose uptake, and antibody production rates were measured. The analysis focused on the secretion of monoclonal antibodies as a function of the medium makeup. Although cell densities achieved were generally higher for serum-supplemented media, glucose uptake rates did not vary significantly, and antibody secretion rates measured at peak cell density were higher for serum-free media with all three hybridomas. Decreasing the serum concentration had opposite effects for the IgM and IgG secretors, NS6.3 and SS1.1; secretion rates measured at peak cell density were higher for the former and lower for the latter.

Animals↗