Kenichi Sakamoto

Fluvastatin Prevents Vascular Hyperplasia by Inhibiting Phenotype Modulation and Proliferation Through Extracellular Signal-Regulated Kinase 1 and 2 and p38 Mitogen-Activated Protein Kinase Inactivation in Organ-Cultured Artery

Objective— We examined the inhibitory mechanisms of fluvastatin on FBS-induced vascular hypertrophy assessed by organ-cultured rat tail artery. Methods and Results— After 5 days of culture with 10% FBS, hyperplastic morphological changes in the media layer were induced. Treatment with 1 &mgr;mol/L fluvastatin significantly inhibited these changes. In the FBS-cultured arteries, the protein expression ratio of α-actin/β-actin was significantly decreased, indicating the change to synthetic phenotype. Fluvastatin restored the decreased expression ratio, and the addition of mevalonate (100 &mgr;mol/L) suppressed this recovery. In accordance with the synthetic morphological changes, the absolute force of contractions induced by stimuli was decreased. Fluvastatin treatment also restored the decreased contractility, and the addition of mevalonate suppressed this recovery. In the arteries cultured with FBS, extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation were significantly increased. Fluvastatin inhibited these phosphorylations, and mevalonate prevented the action of fluvastatin. Conclusion— These results suggest that fluvastatin inhibits vascular smooth muscle phenotype modulation to synthetic phenotype and proliferation by inhibiting the local metabolic pathway of cholesterol in smooth muscle cells, which inhibits hyperplastic changes in the vascular wall. The antihyperplastic actions by statins may be induced by inhibiting the ERK1/2 and p38MAPK activities, possibly through inhibition of prenylated Ras.

TOBACCO BY-2 CELLS: THE PRESENT AND BEYOND

SummaryAmong the established plant cell lines, tobacco BY-2 cell line is unique, as it can be highly synchronized by established procedures. Because of this reason, the cell line has become invaluable for various studies, particularly on cell cycle issues. The importance of several characteristics of the cell line, some of which have not been handled thus far, is described in this article. We also include some preliminary characterization of an auxin-autotrophic cell line 2B-13 derived from the BY-2 cell line. Thus, the repertoire using the BY-2 cell line in plant sciences is expanding. The importance of this cell line could increase further as the expressed sequence tag (EST) database of the cell line became publicly available recently. The scientific achievements on this cell line that have been accumulated in recent years are being compiled and will be published as the 53rd volume in the monograph series of Biotechnology in Agriculture and Forestry (Nagata et al., 2004); readers are referred to this source.

Inverse heat source problem from time distributing overdetermination

For parabolic equations parametrized by a diffusion coefficient, we consider an inverse problem of finding a source function from a time distributing overdetermining data. We prove that the inverse problem is well-posed in the sense of Hadamard except for a finite set of diffusion parameters. The proof is based on the real analyticity on the parameter and the analytic Fredholm alternative theorem.

Parameter identification in non-isothermal nucleation and growth processes

We study non-isothermal nucleation and growth phase transformations, which are described by a generalized Avrami model for the phase transition coupled with an energy balance to account for recalescence effects. The main novelty of our work is the identification of temperature dependent nucleation rates. We prove that such rates can be uniquely identified from measurements in a subdomain and apply an optimal control approach to develop a numerical strategy for its computation.

A revisited Johnson-Mehl-Avrami-Kolmogorov model and the evolution of grain-size distributions in steel

The classical Johnson-Mehl-Avrami-Kolmogorov approach for nucleation and growth models of diffusive phase transitions is revisited and applied to model the growth of ferrite in multiphase steels. For the prediction of mechanical properties of such steels, a deeper knowledge of the grain structure is essential. To this end, a Fokker-Planck evolution law for the volume distribution of ferrite grains is developed and shown to exhibit a log-normally distributed solution. Numerical parameter studies are given and confirm expected properties qualitatively. As a preparation for future work on parameter identification, a strategy is presented for the comparison of volume distributions with area distributions experimentally gained from polished micrograph sections.

Nucleation Rate Identification in Binary Phase Transition

In this chapter, we study a PDE-ODE system arising from binary phase transition coupled with an energy balance to account for recalescence effects. The phase transition is described by classic arguments on nucleation and growth process. The main novelty of our work is the identification of temperature dependent nucleation rates from measurements in a subdomain. We prove the uniqueness of the parameter identification problem and numerical results support the theoretical results.

Block Points in the Cell Cycle Progression of Plant Cells: Deduced Lessons from Tobacco BY-2 Cells

The proliferation of cells is an essential framework for plant growth and development, as cells supplied by cell division constitute plant body; however, a lot of issues on this subject remain to be clarified. Although there are common features in the proliferation of eukaryotic cells, there are several unique characteristics that are inherent in plant cells. For instance, the septum formation at the completion of cytokinesis results in the alignment of daughter cells side by side which constitute plant bodies with a sessile nature. Although a cytological description of plant cell division has been done with a few cells in tissues such as root tips, comprehensive views particularly on molecular terms cannot be demonstrated with such microscope methods and can be done only with the use of highly synchronized cell populations. As noted by Nagata in the first chapter of this volume, this high synchrony was attained in 1982, some 20 years ago, when the cell cycle arrest at G1/S phase by aphidicolin, an inhibitor of DNA polymerase a, and the release of this drug allowed a synchronized cell population starting from S phase to be obtained (Nagata et al. 1982). In addition, a combination of aphidicolin treatment and subsequent propyzamide treatment, a microtubule destabilizing drug, brought us an even more highly synchronized system starting from M phase (Kakimoto and Shibaoka 1988, Nagata et al. 1992). Since then, the high cell synchrony methods using tobacco BY-2 cells are the only available ones for higher plants and even today, no alternative systems in higher plant cell lines have been reported. For this reason, this system is considered to be the inevitable one for studies of various aspects of plant cells and many other issues (Nagata et al. 1992), major themes of which are handled in other chapters of this volume.