Yutaka Nagasawa

c-kit gene mutation at exon 17 or 13 is very rare in sporadic gastrointestinal stromal tumors.

Background and Aim:  Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the human gut. They frequently have gain‐of‐function mutations of the c‐kit gene, which encodes a receptor, tyrosine kinase. The mutations were found at exon 11 in most cases, and either at exon 9 or at exon 13 in rare cases. Recently, we found a family with multiple GIST and a gain‐of‐function mutation at exon 17. The family was the first reported GIST case with c‐kit gene mutation at exon 17 including sporadic GIST. Although we previously reported that the c‐kit gene mutation at exon 17 was not detected in 124 sporadic GIST by single‐strand conformation polymorphism (SSCP) analysis, the mutation at exon 17 observed in the familial GIST was detectable by the use of direct sequencing but not by our SSCP method. In the present study, we examined the mutations at exon 17 and exon 13 by using direct sequencing.

TEMPERATURE DEPENDENCE OF OPTICAL DEPHASING IN AN ORGANIC POLYMER GLASS (PMMA) FROM 300 K TO 30 K

The temperature dependence of the optical dephasing mechanism in an organic polymer glass, polymethylmethacrylate (PMMA), was studied from 300 K to 30 K using the dye IR144 as a probe. Transient grating and three pulse photon echo measurements were made, and the three pulse photon echo peak shift (3PEPS) was recorded as a function of temperature. The peak shift data reveal time constants of ∼6 fs and ∼60 fs, along with vibrational beats and a long-time constant value for the peak shift. The 6 fs component is attributed to intramolecular vibrations and the 60 fs component to librational degrees of freedom of the PMMA itself. This contribution appears slightly underdamped and the fitted spectral density matches well with the Raman spectrum of PMMA. The two ultrafast decays are insensitive to temperature. For temperatures above 80 K the long-time peak shift increases linearly as temperature decreases but at 80 K the shift levels off and decreases for temperatures between 80 and 30 K. Fit values for the inhom...

Three pulse stimulated photon echo experiments as a probe of polar solvation dynamics: Utility of harmonic bath models

The three pulse photon echo peak shift technique was used to study solvation dynamics in acetonitrile (297 K), methanol (297 and 323 K), and ethylene glycol (297 and 397 K) utilizing the tricarbocyanine laser dye, IR144, as a probe. The spectral density, ρ(ω), governing the solute-solvent interaction was obtained for each solvent and temperature through numerical fitting of the three pulse photon echo peak shift relaxation using finite temporal-duration optical fields. An ultrafast three pulse photon echo peak shift relaxation, ascribed to the inertial component, was nearly identical for ethylene glycol at 297 and 397 K; this indicates the spectral density is essentially temperature independent from 10 to 250 cm−1 over this temperature range. Conversely, the low-frequency spectral density (0–10 cm−1) obtained from three pulse photon echo peak shift relaxation of ethylene glycol at 297 and 397 K showed a strong temperature dependence which cannot be predicted using harmonic bath models. We calculated spect...

One-color reversible control of photochromic reactions in a diarylethene derivative: three-photon cyclization and two-photon cycloreversion by a near-infrared femtosecond laser pulse at 1.28 μm.

One-color control of colorization/decolorization reactions of diarylethene molecules was attained by using nonresonant high-order multiphoton absorption processes with a near-infrared (NIR) femtosecond laser pulse at 1.28 μm with 35 fs full width at half-maximum (fwhm). The intensity of a rather weak laser pulse (<1 nJ/pulse) can induce the simultaneous three-photon absorption leading to the colorization, while much weaker intensity induces two-photon absorption resulting in the decolorization. The spatial patterning concomitant with higher-order multiphoton absorption processes was also demonstrated.

Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cancer cells through the reduction of cyclin D1

Peroxisome proliferator-activated receptor gamma (PPARgamma) forms a heterodimeric DNA-binding complex with the retinoid X receptor (RXR) and regulates the transcription of its target genes. Activation of PPARgamma has been shown to induce G1 arrest and to inhibit cell growth of human pancreatic carcinoma cell lines. The purpose of the present study was to examine the effect of ligand activation of PPARgamma and RXR on cell growth and on the expression of G1 cyclins in a pancreatic cancer cell line PANC-1, which expresses PPARgamma at high levels. Troglitazone, a specific ligand for PPARgamma, was found to cause a reduction in the growth rate and induced G1 cell cycle arrest and this effect was additive with that of 9-cis retinoic acid (9-cis RA), a ligand for RXR. Of the G1 cyclins tested, troglitazone specifically reduced the expression of cyclin D1 mRNA and the corresponding protein and this effect was also additive with 9-cis RA. These results suggest that the activation of PPARgamma together with RXR may be useful for the suppression of pancreatic cancer cell growth through the reduction in cyclin D1 levels.

Solute-solvent interaction dynamics studied by photon echo spectroscopies in polymer glasses

The influence of coupling strength and temperature on the solute–solvent interaction of two chromophores in polymer glass is reported. The three-pulse photon echo peak shift method was used to study the dye IR144 in polyvinylformal (PVF) and the dye DTTCI (3,3′-diethylthiatricarbocyanine iodide) in polymethylmethacrylate (PMMA). IR144 is more strongly coupled (larger reorganization energy) to both its intramolecular modes and to the solvent than is DTTCI. Our results can be well described by the linearly coupled harmonic bath model over the range 300 to 30 K. In particular, the strikingly different temperature sensitivities of the long-time (asymptotic) peak shift are well described by the theory. Temperature-independent spectral densities and inhomogeneous widths suffice to quantitatively describe the peak shift data over this temperature range and a number of numerical predictions based on the theoretical model are experimentally confirmed. An ultrafast component corresponding to a decay of ∼100 fs time...

Three pulse echo peak shift measurements on the B820 subunit of LH1 of Rhodospirillum rubrum

Three pulse photon echo peak shift measurements 3PEPS of the detergent isolated B820 subunit of the light harvesting complex of Rhodospirillum rubrum are presented and compared with 3PEPS data for the LH1 complex of Rhodobacter sphaeroides. The comparison suggests that the 90 fs component of LH1 3PEPS is indeed the energy transfer component. The striking similarity between 3PEPS of LH1 and B820 subunit also suggests that excitation is delocalized over only a dimer unit. q 1997 Elsevier Science B.V.

Ultrafast Photodissociation Dynamics of a Hexaarylbiimidazole Derivative with Pyrenyl Groups: Dispersive Reaction from Femtosecond to 10 ns Time Regions

The photodissociation dynamics of a hexaarylbiimidazole (HABI) derivative with two pyrenyl groups was investigated by time-resolved transient absorption spectroscopy and fluorescence measurements. Transient absorption spectroscopy revealed that photodissociation took place in the wide time region of <100 fs to 10 ns. On the other hand, fluorescence time profiles showed the dynamic red shift in the time region <100 ps. The apparent dispersive photodissociation process was attributed to the increase in the interaction between the pyrenyl moiety in the excited state and the other moiety in the ground state, resulting in the gradual increase of the activation energy for the crossing between the attractive potential surface of an excited pyrenyl unit and the repulsive potential surface.

PPARγ agonists inhibit cell growth and suppress the expression of cyclin D1 and EGF‐like growth factors in ras‐transformed rat intestinal epithelial cells

Peroxisome proliferator‐activated receptor γ (PPARγ) inhibits the growth of several types of cancer cells. However, the mechanisms by which this occurs are poorly understood. The goal of the present study was to investigate the effects of PPARγ on mutated ras‐induced cell growth, activation of transcription factors and expression of genes associated with cellular transformation in rat intestinal epithelial cells. A human PPARγ cDNA was introduced to the activated H‐ras‐transfected IEC‐6 cells (IECras) and 1 clone (IECrasPR82) that stably expresses both activated ras and PPARγ was obtained. Thiazolidinedione derivatives such as troglitazone and rosiglitazone, selective ligands for PPARγ, inhibited the cellular growth of IECrasPR82 cells in a time‐dependent manner and induced G1 cell cycle arrest. Treatment with troglitazone (20 μM) decreased the expression of cyclin D1, heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and amphiregulin and suppressed the promoter activities of cyclin D1 and HB‐EGF. Furthermore, a luciferase assay and an electrophoretic mobility shift assay showed that thiazolidinedione derivatives suppressed the transcriptional activities of AP‐1 and Ets, both of which play crucial roles in the expression of cyclin D1 and HB‐EGF. These findings suggest that reduction of EGF‐like growth factors and cyclin D1 through the suppression of AP‐1 and Ets may be 1 mechanism whereby PPARγ inhibits their growth.

Coherent dynamics in ultrafast charge-transfer reaction of plastocyanin

Abstract Using a blue copper protein, plastocyanin, we have studied protein dynamics associated with optical excitation and radiationless deactivation ( τ =270 fs) of its charge-transfer state by ultrafast pump–probe spectroscopy. A coherent low frequency (33 cm −1 ) vibrational mode with its phase shifted from those of the other localized Raman modes was observed. The observed coherency of this low frequency mode appears via the excited-state deactivation, rather than arising merely from impulsive stimulated Raman. This mode most probably can be attributed to the delocalized mode including the protein skeletal motion.