Search PubMed⌕ Search

Biomedical subjects

Tetsuji Yamaoka

Publications and source records attributed to Tetsuji Yamaoka.

25 records · Page 2Linked to original sources

Photodynamic antisense therapy: regulation of cervical carcinoma cells by psoralen-conjugated oligonucleotides.

To reinforce antisense effects, we focused on the photo-cross-linking ability of psoralen derivatives and examined the applicability of the photodynamic antisense therapy to cancer cells using psoralen-conjugated oligo(nucleosides phosphorothioate)s (Ps-S-Oligo). The regulatory effects of Ps-S-Oligos on the proliferation of cervical carcinoma were evaluated. The inhibitory effects were found to be significant (IC50=16 nM) without any drug delivery systems, and it was also found that the mechanism was associated with the p53 induced apoptosis. This result suggests that the photodynamic antisense therapy will be a promising concept for the cancer therapy.

Apoptosis↗

Effect of chemical features and stability of polyplexes on their gene transfer efficiency.

Chemically modified poly-L-lysine (PL) derivatives with two essential features, which we have recently reported on, have been used to study key factors affecting transgene expression efficiency. PL derivatives having both of N epsilon-trimethyl lysine residue and 25 mole % serine residue showed enhanced transfection efficiency. When PL was modified in either way, no marked enhancement in gene expression was observed. These PL derivatives were found to be able to deliver plasmid DNA into nucleus of the transfected cells with a similar amount. Judging from the loss of EtBr fluorescence intercalating to DNA, the condensing tendency of the DNA were greatly affected by the sequence of the polypeptides used. This loose compaction seems to enhance the transgene expression because of an easy disassembly of the formed complexes or recognition of the DNA molecules in the complexes.

Fluorescence↗

Selection of RNA-binding peptides containing Arg-rich motif.

In order to search the RNA-binding peptides, selection from randomized peptides containing Arg-rich motif was carried out using rRNA-immobilized column. As a result of the selection for 16S- and 23S-rRNA from E. coli, six peptides were identified to be the rRNA-binding peptide by MALDI-TOF MS. These peptides contained R, N, Q, or G at three randomized positions. This result indicates that amino acids with a positive residue or an amide residue might be essential for peptides to recognize the RNA.

Amino Acid Motifs↗

Mechanism for the phase transition of a genetically engineered elastin model peptide (VPGIG)40 in aqueous solution.

The concentration dependence of the pressure- and temperature-induced cloud point transition (Pc and Tc, respectively) of aqueous solutions of an elastin-like polypeptide with a repeating pentapeptide Val-Pro-Gly-Ile-Gly sequence (MGLDGSMG(VPGIG)40VPLE) was investigated by using apparent light scattering, differential scanning calorimetry, and circular dichroism methods. In addition, the effects of salts and surfactants on these properties were investigated. The Pc and Tc of the present peptide in aqueous solution were strongly concentration dependent. The calorimetric measurements showed that the enthalpy of transitions was 300-400 kJ/mol, i.e., 7-10 kJ/mol per VPGIG pentamer. The Tc of the (VPGIG)40 solution was highly affected by the addition of inert salts or SDS. The effects of salts were consistent with those observed in the lyotropic series or Hoffmeister series. The CD spectrum at low peptide concentrations indicated that the present peptide forms type II beta-turn-like structure(s) at higher temperatures, but the temperature dependence of random coil diminishment (195 nm) and beta-turn formation (210 nm) were not exactly coincident. A hypothetical mechanism of the (VPGIG)40 phase transition that could account for these observations was postulated. Observations suggest that the temperature-responsive properties of the elastin model peptides occur via a mechanism involving conformational change-association-aggregation and that the first two are strongly interactive.

Amino Acid Sequence↗

Static cardiomyoplasty with synthetic elastic net suppresses ventricular dilatation and dysfunction after myocardial infarction in the rat: an acute study.

BACKGROUND: Wrapping around the heart (static cardiomyoplasty) may help prevent a failing left ventricle (LV) from dilatation but may also interfere with diastolic relaxation, resulting in restrictive hemodynamics and diastolic heart failure. We developed a synthetic net with a dual elasticity and tested its effect early after induced myocardial infarction (MI) in the rat. METHODS: In rats undergoing occlusion of the left anterior descending artery (LAD) with and without cardiac wrapping, pressure-volume (PV) relationships were successively analyzed before, after intravenous volume load (saline 1% of body weight over 30 sec), and 10 to 40 minutes after LAD occlusion. In each situation, end-diastolic and end-systolic PV relationships were defined and LV size and function compared under standardized loading conditions. RESULTS: Ischemic increase in LV end-diastolic and end-systolic volumes was suppressed in a similar magnitude in NET with rats, resulting in preserved stroke volume and ejection fraction early after MI. While the presence of the net yielded a significant hemodynamic difference in response to acute volume load before ischemia, the difference was no longer apparent in the ischemic heart after LAD ligation. CONCLUSION: Static cardiomyoplasty using a synthetic elastic net significantly suppresses ischemic LV dilatation and dysfunction without restriction immediately after MI in the rat. The long-term result is pending. Net material and elasticity needs to be adjusted for optimal girdling effect, or greatest benefits with least functional compromise.

Animals↗