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Z Bajzer

Publications and source records attributed to Z Bajzer.

34 records · Page 2Linked to original sources
PubMed1990

Padé-Laplace method for the analysis of time-resolved fluorescence decay curves.

The interpretation of fluorescence intensity decay times in terms of protein structure and dynamics depends on the accuracy and sensitivity of the methods used for data analysis. The are many methods available for the analysis of fluorescence decay data, but justification for choosing any one of them is unclear. In this paper we generalize the recently proposed Padé-Laplace method to include deconvolution with respect to the instrument response function. In this form the method can be readily applied to the analysis of time-correlated single photon counting data. By extensive simulations we have shown that the Padé-Laplace method provides more accurate results than the standard least squares method with iterative reconvolution under the condition of closely spaced lifetimes. The application of the Padé-Laplace method to several experimental data sets yielded results consistent with those obtained by use of the least squares analysis.

Fluorescence↗
PubMed1990

Quantitative aspects of autocrine regulation in tumors.

Autocrine regulation is defined as a mechanism of self-control in growth and differentiation; this mode of regulation among histologically homologous cells is mediated humorally. Autocrine mechanisms involve: 1. Autonomously controlled production and secretion of autocrine mediators. 2. Distribution of autocrine mediators among cells. 3. Expression by cells of functional receptors for autocrine mediators. 4. Transduction and intracellular integration of signals mediated by autocrine mediators. 5. Growth response. 6. Maintenance of autonomous control of growth and/or differentiation state in the progeny Biochemical and biological evidence for most of these steps in various transformed cells makes it possible to analyze autocrine control as a multifaceted process. This process depends on tumor cellularity and histoarchitecture, on time and on external influences on secretion of autocrine mediators (e.g., estrogens in estrogen-dependent breast cancer). We review the quantitative aspects of experimental evidence for autocrine control in tumors and examine the phenomenological and some mechanistic concepts in creating integrative, quantitative, and experimentally verifiable mathematical models of autocrine regulation.

Breast Neoplasms↗
PubMed1990

Kinetics of receptor-mediated uptake and processing of interferon-alpha 2a and tumor necrosis factor-alpha by human tumor cells.

The kinetics of uptake and processing of recombinant human interferon-alpha 2a (IFN) and recombinant human tumor necrosis factor-alpha (TNF) were studied in human epithelial tumor cell lines differing in sensitivity to growth inhibition by IFN and TNF. Concentrations of [125I]IFN or [125I]TNF at the cell surface and internalized by confluent cell monolayers incubated at 37 degrees C were measured as a function of time. Cells incubated with [125I]IFN exhibited transient maxima of surface-associated and internalized [125I]IFN after 1-2 hr of incubation followed by a steady-state attained after approximately 6 hr of exposure to [125I]IFN. Concentration of [125I]TNF associated with the plasma membrane displayed a maximum within 20 min of incubation. Internalized radioactivity increased with time and did not achieve a steady state. We analyzed the time-dependent concentrations of membrane-associated and internalized cytokines by use of a compartmental model. This model describes changes in concentrations of free surface receptors, of ligand-receptor complex at the membrane and of internalized ligand and contains a term for receptor recycling. The rate constants for concentration changes were evaluated by fitting model functions to data. The best fits for IFN were obtained without receptor recycling. The best-fit values for the endocytotic rate constant (ke,IFN) varied among cell lines from 2.4 x 10(-4) to 7.8 x 10(-4) sec-1. To obtain fits to time-dependent concentrations of surface-associated and internalized [125I]TNF, introduction of a term for receptor recycling was required. Best-fit values for ke,TNF ranged among cell lines from 8.4 x 10(-4) to 2.5 x 10(-3) sec-1. For every cell line, the value of ke,TNF was larger than the value of ke,IFN. We tested the significance of these differences by substituting ke,IFN for ke,TNF as fixed parameters in fits to data for TNF and v.v., respectively. Under these conditions, fits were significantly worse. Our data indicate that recycling is insignificant in kinetics of Type-I IFN receptor; recycling is necessary to explain the kinetics of TNF receptor. Upon binding, TNF is taken up by cells faster than IFN and is eliminated from cells more slowly than IFN.

Biological Transport, Active↗
PubMed1989

Binding, internalization, and intracellular processing of proteins interacting with recycling receptors. A kinetic analysis.

We measured time-dependent concentration changes of human interferon-alpha 2a (IFN) and human tumor necrosis factor-alpha (TNF) bound at the plasma membrane and internalized by human lung alveolar carcinoma A549 cells in the presence of excess free ligand. Concentration changes for these two ligands were substantially different. We modified our compartmental kinetic model encompassing receptor synthesis and receptor loss (Myers, A. C., Kovach, J. S., and Vuk-Pavlović, S. (1987) J. Biol. Chem. 262, 6494-6499) to include receptor recycling. We solved analytically the equations of three variants of the model of receptor recycling. All parameters (rate constants) were identifiable when the data sets consisted of time-resolved concentrations of IFN and TNF at the cell surface and internalized by cells. By least squares fitting we derived the best fit values for the first order rate constants for internalization of the ligand-receptor complex, receptor recycling, turnover of free receptors, elimination of the ligand from cells, and the rate of insertion of free receptors into the membrane. The best fit to data for interactions of cells with IFN was obtained without inclusion of the term for recycling of receptors to the membrane. The simplest model including receptor recycling was necessary and sufficient for the fit to the respective data for TNF. These results demonstrate that the contribution of receptor recycling to the metabolism of the ligand and the receptor can be quantitated by compartmental modeling. Receptor recycling does not contribute to the kinetics of Type I IFN receptor in A549 cells. In contrast, recycling contributes significantly to endocytosis mediated by the TNF receptor.

Adenocarcinoma↗
PubMed1989

Padé-Laplace method for analysis of fluorescence intensity decay.

This novel approach to the analysis of multiexponential functions is based on the combined use of the Laplace transform and Padé approximants (Yeramian, E., and P. Claverie. 1987. Nature (Lond.). 326:169-174). It is similar in principle to the well-known Isenberg method of moments (Isenberg, I. 1983. Biophys. J. 43:141-148) traditionally applied to the analysis of fluorescence decay. The advantage of the Padé-Laplace method lies in its ability to detect the number of components in a multiexponential function as well as their parameters. In this paper we modified the original method so that it can be applied to the analysis of multifrequency phase/modulation measurements of fluorescence decay. The method was tested first on simulated data. It afforded recovery up to four distinct lifetime components (and their fractional contributions). In the case of simulated data corresponding to continuous lifetime distributions (nonexponential decay), the results of the analysis by the Padé-Laplace method indicated the absence of discrete exponential components. The method was also applied to real phase/modulation data gathered on known fluorophores and their mixtures and on tryptophan fluorescence in phospholipase A2. The lifetime and fraction recoveries were consistent with those obtained from standard methods involving nonlinear least-square fitting.

Mathematics↗
PubMed1987

Quantitation of autocrine regulation of tumor growth: a general phenomenological model.

We present a model that considers autocrine regulation of tumor growth as a feedback control system. The model is general in that it can accommodate any growth curve which fits the data. We propose an algorithm for quantitation of the open loop gain parameter and we define the autocrine gain parameter; these parameters express the efficiency of the feedback mechanism. The model provides guidelines for design of experiments to measure the contribution of autocrine regulation to growth of biological systems, particularly tumors.

Animals↗
PubMed1987

Theoretical aspects of multiple deconvolution analysis for quantification of left to right cardiac shunts.

A new method for quantification of left to right cardiac shunts by Bourguignon et al based on multiple deconvolution analysis is critically analysed within the framework of a simple mathematical model. Underlying assumptions are explicitly stated and their validity discussed. It turns out that some reinterpretation of the method is necessary. Using the same ideas as in multiple deconvolution analysis, a new relation for the pulmonary to systemic flow ratio is proposed on a theoretical basis. This technique may be useful when diagnosing left to right cardiac shunts with radiocardiographic methods.

Coronary Circulation↗
PubMed1985

A mathematical model for the quantitative study of left to right cardiac shunt.

Non-invasive radioisotope cardiographic techniques have become a useful tool for studying the anatomy and function of the heart. The mathematical model described justifies the phenomenological analysis of pulmonary time-activity histograms and was invented for quantitative study of left to right cardiac shunt. The model also gives a theoretical insight into such an empirically proposed diagnostic method and represents an adequate framework for the understanding of other possible approaches to the problem of left to right shunt.

Blood Circulation↗
PubMed1984

Growth self-incitement in murine melanoma B16: a phenomenological model.

The growing murine melanoma B16 secretes increasing quantities of a substance or substances immunologically cross-reactive with insulin. The elevated concentrations of these substances in blood are accompanied by a decrease in blood glucose concentration and release of growth hormone, which is followed by increased tumor growth. By use of a phenomenological model based on these data, we show that B16 incites its own growth by positive feedback.

Animals↗
PubMed1980

Lung ventilation model for radioactive tracer itdal breathing.

A mathematical lung ventilation model for radioactive tracer tidal breathing is developed on the basis of the previously established simple mathematical lung model for quantitative regional ventilation measurements. In the present model, the periodicity of breathing is completely taken into account. A precise definition of the effective specific ventilation is given. This was found to be related to the ratio of tidal volume (TV) and functional residual capacity (FRC). The determination of the regional effective specific ventilation is reduced to a simple fitting to a straight line. A description is given of the method of measurement (in the framework of radioisotope dynamic studies) that makes it possible to use the mathematical model for the actual determination of lung ventilation and volume parameters. The model is experimentally verified on healthy subjects, and the value of the effective specific ventilation obtained is in agreement with comparable parameters in the literature. Furthermore, the value for TV/FRC is comparable with that determined by classical spirometrical methods.

Humans↗
PubMed1977

The use of 81mKr gas for the measurement of absolute regional lung ventilation.

In this paper a new method of using 81mKr for the measurement of specific absolute regional lung ventilation is described. Experimental data suitable for the calculation of quantitative regional ventilation are provided using an adequate respiratory system for 81mKr dosage and a scintillation gamma camera interfaced to a digital computer. A simple mathematical lung model for the inhalation of 81mKr is used to determine the specific ventilation and the parameters proportional to the ventilation for the whole lung and different lung regions in patients and in healthy subjects. The lung count rate for a given region correlated well with the ventilation of that region. Clinical examples are given and discussed.

Computers↗
PubMedDate not supplied

Gompertzian growth as a self-similar and allometric process.

The Gompertz law of growth has puzzled scientists for decades: while it successfully described growth kinetics of various biological systems (e.g., tumor growth), its foundation has remained unclear. In this paper I recognize the Gompertzian growth as founded on self-similarity, which is so abundant in natural phenomena that it justifiably represents a fundamental natural paradigm. The self-similarity leads to an allometric principle: the sizes of a given biological system at different times are related by a simple power law. The stated relation can be also viewed as basic functional growth equation with unique nonconstant solutions being the Gompertz and the exponential functions. This equation also provides the description of growth and regression dynamics in terms of a difference equation which already has found practical application in characterizing tumor growth kinetics.

Animals↗