Biomedical subjects

Koji Ohta

Publications and source records attributed to Koji Ohta.

At least 19 recordsLinked to original sources

PubMed2006

Two-photon absorption in two-dimensional conjugated quadrupolar chromophores.

We present ultrafast z-scan measurements of the two-photon absorption (TPA) spectra of a pair of two-dimensionally conjugated quadrupolar donor/acceptor (D/A) chromophores. The all-donor substituted species displays a peak TPA cross section [sigma(2)=520+/-30 GM] that is more than twice that of the D-A species [sigma(2)=240+/-20 GM]. Unlike previous structure-property studies that have evaluated TPA behavior for D/A molecules through the comparison of dipolar and quadrupolar compounds, both molecules investigated herein are quadrupolar, ultimately providing a more consistent evaluation of the effects of donor and/or acceptor substitution on the TPA of conjugated chromophores.

Journal Article↗

PubMed2006

Origin of the enhancement of the second hyperpolarizability of singlet diradical systems with intermediate diradical character.

The origin of the diradical character dependence of the second hyperpolarizability (gamma) of neutral singlet diradical systems is clarified based on the perturbation formula of gamma using the simplest diradical molecular model with different diradical characters, i.e., H2 under bond dissociation. The enhancement of gamma in the intermediate diradical character region turns out to originate from the increasing magnitude of the transition moment between the first and second excited states and the decrease of that between the ground and first excited states, respectively, with the increase in diradical character. This feature confirms that open-shell singlet conjugated molecules with intermediate diradical characters constitute a new class of third-order nonlinear optical systems, whose gamma values can be controlled by the diradical character in addition to the conjugation length.

Journal Article↗

PubMed2006

Second hyperpolarizabilities (gamma) of bisimidazole and bistriazole benzenes: diradical character, charged state, and spin state dependences.

The second hyperpolarizabilities of bisimidazole- and bistriazole-benzene compounds have been calculated at different levels of approximation to unravel the effects of diradical character as well as of charge and spin multiplicity. The largest second hyperpolarizabilities are associated with intermediate diradical character, provided positive charging does not compensate for this effect. For the neutral diradical bisimidazole compound, the singlet diradical species possesses a second hyperpolarizability two to three times larger than the corresponding triplet, demonstrating the possibility of spin state control of the third-order NLO responses for diradical species.

Benzene Derivatives↗

PubMed2006

Theoretical investigation of two-photon absorption allowed excited states in symmetrically substituted diacetylenes by ab initio molecular-orbital method.

Symmetrically substituted diacetylene compounds, which shows large two-photon absorption (TPA) cross sections, have been theoretically investigated by the ab initio molecular-orbital method employing several theoretical models including the configuration interaction with single excitation (CIS), random phase approximation (RPA), and time-dependent density-functional theory (TDDFT) methods. The calculated excited energies are overestimated by CIS or RPA, whereas underestimated by TDDFT with the B3LYP parametrization for both one-photon absorption (OPA) and TPA allowed states. The lowest OPA state is well described by the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) transition. On the other hand, lower TPA allowed states can be represented as the superposition of the HOMO-LUMO+1 and HOMO-1-LUMO transitions, giving rise to two TPA allowed states. The absorption intensity for the lower TPA state of the diacetylenes molecules is discussed in terms of the alternancy symmetry and its breaking. The symmetry property is differently manifested for neutral and dicationic diacetylenes. Introduction of charges breaks the alternancy symmetry, which gives rise to an increase in the TPA cross sections at the lower frequency. The upper TPA state is calculated to show huge TPA cross sections, which reproduces the enhancement of the TPA cross section experimentally observed for one of the diacetylenes at the higher-frequency region. The enhancement is discussed employing an index defined as the ratio of the transition polarizability and its static limit, which represents the degree of influence of one-photon resonance on the TPA intensity. The huge TPA cross sections are found to be due to a near-resonance effect. The present theoretical calculation approves the previously proposed assumption based on the four-state (dual three-state) model, which consists of the ground, one OPA allowed, and two TPA allowed states.

Journal Article↗

PubMed2006

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.

Adult↗

PubMed2005

Two-photon absorption properties of self-assemblies of butadiyne-linked bis(imidazolylporphyrin).

Supramolecular porphyrin self-assemblies have been prepared from butadiyne-linked bis(imidazolylporphyrin) by complementary coordination of imidazole to zinc, and their two-photon absorption (2PA) and higher-order nonlinear absorption properties were investigated over femtosecond time scales using an open-aperture Z-scan method. The self-assembled porphyrin dimer of the conjugated monozinc bisporphyrin 7D was shown to have a large 2PA cross section (7.6 x 10(3) GM, where 1 GM = 10(-50) cm(4) s molecule(-1) photon(-1)) at 887 nm. By comparison of this result with that for a meso-meso-linked porphyrin array without the butadiyne connection (3.7 x 10(2) GM at 964 nm), it was demonstrated that the predominant factor in this significant enhancement of the cross section was the expansion of porphyrin-porphyrin pi-conjugation. Self-coordination and monozinc metalation were also found to be contributing factors. Furthermore, a novel self-assembled porphyrin polymer 8P consisting of a biszinc complex with a mean molecular weight of M(n) = 1.5 x 10(5) Da was shown to exhibit an extraordinarily large two-photon absorption cross section (4.4 x 10(5) GM at 873 nm). Nanosecond Z-scan experiments for 7D and 8P were also undertaken and resulted in the measurement of large effective 2PA cross sections, including the excited-state absorption (2.1 x 10(5) GM for 7D and 2.2 x 10(7) GM for 8P, respectively). Finally, three-photon absorption was observed by femtosecond Z-scan experiments at 1188 nm (7.1 x 10(-89) m(6) s(2)) and 1282 nm (1.8 x 10(-89) m(6) s(2)), an observation which is the first of its kind in porphyrin chemistry.

Alkynes↗

PubMed2005

Generation of antigen-presenting cells using cultured dendritic cells and amplified autologous tumor mRNA.

Novel antigen-presenting cells (APCs) were generated using cultured dendritic cells (DCs) and amplified tumor mRNA, and the potential of tumor antigen-reactive T cell induction by the tumor RNA-introduced DCs (DC/tumor RNA) was analyzed in a patient with melanoma antigen-encoding gene (MAGE3)-positive malignant melanoma of the esophagus. DCs were generated from an adherent fraction of peripheral blood mononuclear cells in the presence of granulocyte macrophage colony-stimulating factor and interleukin-4. Tumor mRNA was purified from tumor tissue, amplified in vitro using a T7 RNA polymerase system, and then introduced into DCs by electroporation (150 V/150 microF or 100 V/200 microF). The gene introduction efficiency was 44-55% as measured by enhanced green fluorescent protein reporter gene expression, and the viability of RNA-introduced DCs was approximately 80%. DC/tumor RNA could induce tumor antigen-reactive cytotoxic T lymphocytes (CTLs) in an mRNA-specific manner, but had no effect on the self-antigen-reactive T cells. DC/tumor RNA could induce the polyspecific antigen-reactive CTL responses mediated by both human leukocyte antigen class I and class II molecules, whereas MAGE3 peptide-pulsed DCs induced only the monospecific MAGE3-reactive CTL responses mediated by human leukocyte antigen class I molecules, showing the superiority of the DC/tumor RNA over the DC/peptide. It is suggested that the use of DC/tumor RNA as antigen-presenting cells may be more effective, convenient and practical for the DC-based anti-cancer immunotherapy.

Antigen-Presenting Cells↗

PubMed2005

Thickness measurements on transparent substrates based on reflection ellipsometry. I. Optical effects of high-refractive-index additional layers.

Theoretical studies were conducted for thickness measurements using transparent substrates on the external and internal reflection configurations. For three-phase systems consisting of ambient, film, and substrate, the refractive index of the substrate could be optimized to obtain the high sensitivity of an ellipsometric quantity delta to the film thickness and the small susceptibility of delta to errors in the incident angle. It was shown that the combination of an ordinary glass substrate and an additional dielectric layer with an appropriate layer thickness works as a synthetic high-index single substrate (SHIS). The optical effect of the combination was approximately described by use of the effective refractive index of SHIS. A method to select the refractive index of the additional layer was also given.

Journal Article↗

PubMed2005

Second hyperpolarizability (gamma) of singlet diradical system: dependence of gamma on the diradical character.

The dependence of the second hyperpolarizability (gamma) on the diradical character (y) for singlet diradical systems is investigated using a model compound, the p-quinodimethane (PQM) molecule with different both-end carbon-carbon (C-C) bond lengths, by several ab initio molecular orbital and density functional theory methods. The diradical character based on UHF calculations indicates that at equilibrium geometry PQM is in a singlet ground state and primarily exhibits a quinoid structure, whereas the diradical character increases when increasing both-end C-C bond lengths. At the highest level of approximation, that is, using the UCCSD(T) method with the 6-31G+diffuse p (zeta = 0.0523) basis set, the longitudinal static gamma of PQM presents a maximum value for intermediate diradical character (y approximately 0.5) while the gamma values are larger for intermediate and large diradical character (y approximately 0.5-0.7) than for small diradical character (y < 0.2). This feature suggests that the gamma values of singlet diradical systems in the intermediate and somewhat strong correlation regimes are significantly enhanced as compared to those in the weak correlation regime. These results are substantiated by a complementary study of the variation in gamma upon twisted ethylene.

Journal Article↗

PubMed2005

[Three advanced gastric cancer patients successfully treated by combination therapy of docetaxel and TS-1].

We have experienced three gastric carcinoma cases successfully treated by the combination therapy of docetaxel and TS-1. Case 1: 66-year-old male with advanced gastric cancer invading the pancreas with metastasis to the liver and left neck lymph nodes. Case 2: 50-year-old female with scirrhous gastric carcinoma causing huge amount of malignant ascites. Case 3: 59-year-old male with recurrent gastric cancer of the remnant stomach presenting with obstruction and vessel involvement. Primary and metastatic diseases of these patients were remarkably improved with the combination therapy, indicating that the combination therapy of docetaxel and TS-1 can be a new therapeutic tool for advanced and recurrent gastric cancer patients.

Adenocarcinoma, Scirrhous↗

PubMed2005

[A case report of bowel obstruction due to peritonitis carcinomatosa using combined administration with CPT-11 and CDDP].

We report here a case of recurrent gastric cancer that responded to third-line chemotherapy with CPT-11 and CDDP. The patient was a 61-year-old man with recurrent gastric cancer, who had administered TS-1 for first-line chemotherapy and paclitaxel for second-line chemotherapy. After such therapy, bowel obstruction was revealed due to peritoneal dissemination. The patient underwent third-line chemotherapy with CPT-11 and CDDP after drainage of gastrointestinal juice by nasogastric tube. The treatment schedule for CPT-11 and CDDP therapy consisted of CPT-11 60 mg/m2 div at day 1, day 15 and CDDP 60 mg/m2 div at day 1. It was repeated every 4 weeks. After first administration, the bowel obstruction was improved, so the treatment was continued for 8 months on an outpatient basis. These findings imply that this treatment can be a useful second-line or third-line chemotherapy for unresectable advanced or recurrent gastric cancer.

Ambulatory Care↗

PubMed2005

[Clinical study of TS-1 for inoperative and recurrent gastric cancer and evaluation of long survival cases].

The clinical efficacy and safety of TS-1 therapy were studied retrospectively in patients with inoperable and recurrent gastric cancer. The subjects were 67 patients who were treated with TS-1 in our department between June 1999 and September 2004. The objective overall response rate was 41.0% (16/39; 95% confidence interval, CI, 25.3-56.7). By location, the response rate of peritoneal dissemination was high (57.1%), as were those of primary lesion (53.3%) and lymph nodes (42.9%). The prevalence of adverse reactions with a grade of 3 or 4 was 12.8%. The median survival rate (MST) was 276 days with 1-year and 2-year survival rates of 48.9% and 27.8%, respectively. This resulted in 6 long-term survival cases (over 2.5 years) after TS-1 therapy, and the longest survival time was 3y 5m after TS-1 therapy. PRs or long-term NCs after TS-1 therapy were likely to be important factors for long-term survival. In conclusion, TS-1 is safe and effective for patients with inoperable and recurrent gastric cancer, and is promising as a first-line treatment.

Adult↗

PubMed2004

Quantum effect on the internal proton transfer and structural fluctuation in the H+ 5 cluster.

The thermal equilibrium state of H+(5) is investigated by means of an ab initio path integral molecular dynamics (PIMD) method, in which degrees of freedom of both nuclei and electrons at finite temperature are quantized within the adiabatic approximation. The second-order Moller-Plesset force field has been employed for the present ab initio PIMD. At 5-200 K, H+(5) is shown to have the structure that the proton is surrounded by the two H(2) units without any exchange of an atom between the central proton and the H(2) unit. At 5 K, the quantum tunneling of the central proton occurs more easily when the distance between the two H(2) units is shortened. At the high temperature of 200 K, the central proton is more delocalized in space between the two H(2) units, with less correlation with the stretching of the distance between the two H(2) units. As for the rotation of the H(2) units around the C(2) axis of H+(5) , the dihedral angle distribution is homogeneous at all temperatures, suggesting that the two H(2) units freely rotate around the C(2) axis, while this quantum effect on the rotation of the H(2) units becomes more weakened with increasing temperature. The influence of the structural fluctuation of H+(5) on molecular orbital energies has been examined to conclude that the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap is largely reduced with the increase of temperature because of the spatial expansion of the whole cluster.

Journal Article↗

PubMed2004

Interconversion behavior of the C-H bond in the CH4+ radical cation: ab initio molecular dynamics study.

Thermal motion of CH4+ is investigated by performing an ab initio molecular dynamics method with the second-order Møller-Plesset (MP2)/6-311G** force field. In the trajectories obtained at 400 K, we have observed rapid interconversion behavior of the geometrical parameters of CH4+ with the frequency of 0.6/ps, where the C-H pair forming the small angle around 55 degrees is switched to another pair on subpicosecond time scale. The switching patterns are found to be classified into the following two types. Type 1: one C-H of the small angled C-H pair is switched to one C-H of the other C-H pair. Type 2: the small angled C-H pair is switched to the other C-H pair, which has been newly observed in the present ab initio MD calculation. The four C-H bonds of CH4+ are characterized by the long and short C-H bonds in a time region of the trajectories, and also for the time-evolution of C-H bonds such interconversion behavior is observed. The switching patterns of the geometrical parameters are compared with those in the interconversion scheme between six equivalent C2v symmetry structures of CH4+ [Paddon-Row, M. N. et al., J Am Chem Soc 1985, 107, 7696]. We have also investigated the electronic energy fluctuation due to thermal motion of CH4+. The standard deviation of total electronic energy at 400 K is evaluated to be 1.2 kcal/mol.

Journal Article↗

PubMed2004

Ab initio centroid path integral molecular dynamics: application to vibrational dynamics of diatomic molecular systems.

An ab initio centroid molecular dynamics (CMD) method is developed by combining the CMD method with the ab initio molecular orbital method. The ab initio CMD method is applied to vibrational dynamics of diatomic molecules, H2 and HF. For the H2 molecule, the temperature dependence of the peak frequency of the vibrational spectral density is investigated. The results are compared with those obtained by the ab initio classical molecular dynamics method and exact quantum mechanical treatment. It is shown that the vibrational frequency obtained from the ab initio CMD approaches the exact first excitation frequency as the temperature lowers. For the HF molecule, the position autocorrelation function is also analyzed in detail. The present CMD method is shown to well reproduce the exact quantum result for the information on the vibrational properties of the system.

Journal Article↗

PubMed2003

Strong two-photon absorption of self-assembled butadiyne-linked bisporphyrin.

Two-photon absorption (2PA) properties of self-assembled porphyrins were investigated. The butadiyne-linked porphyrin array exhibited a 20 times larger 2PA cross section than the meso-meso-linked self-assembled array due to the expansion of pi-conjugation. Higher-order nonlinear absorption was also observed in the former porphyrin.

Journal Article↗

PubMed2003

Adoptive immunotherapy of cancer using activated autologous lymphocytes--current status and new strategies.

After the discovery of interleukin-2 (IL-2), lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), and cytotoxic T lymphocytes (CTLs) sensitized with the mixed lymphocyte-tumor culture (MLTC) system have been conducted in adoptive immunotherapy (AIT) trials during past 15 years. Although the overall response rate of tumor shrinkage was marginal (9%), locoregional administration of TILs for malignant effusions was effective (77%) for a decrease or disappearance of the effusions even in terminally-ill patients, resulting in an improvement of QOL. Recent advances for molecular understanding of antigen presentation and recognition have promoted us to enhance the efficacy of AIT by using cultured dendritic cells (DCs) for generating antigen-specific CTLs in vitro. The peptide-pulsed DC-activated killer (PDAK) cells showed tumor recognition against antigen-expressing cells, and were efficiently propagated with the IL2 plus immobilized anti-CD3 antibody (IL-2/CD3) culture system. Clinical trials using PDAK cells against patients with lung metastases are now progressed, in which peptides suitable for generating CTLs were chosen in individual patients using the method designated as host-oriented peptide evaluation (HPOE) approach. Moreover, DCs were introduced with tumor-derived RNA, which was amplified with the T7 promoter system, and then were used for stimulating lymphocytes. The tumor RNA-introduced DC-activated killer (TRiDAK) cells showed tumor-specific interferon-gamma spots even in a patient in whom we failed to generate PDAK cells using DCs and peptides, suggesting that the clinical trial of AIT using TRiDAK cells is warranted for the treatment of patients with metastatic cancer. Thus, more understanding of antigen-presentation and -recognition mechanisms and immune regulation systems may promote clinical applications of AIT to establish a novel modality of cancer treatment.

Antigen Presentation↗

PubMed2003

[Generation of TRiDAK (tumor RNA-introduced dendritic cell-activated killer) cells].

Tumor-reactive effector lymphocytes were generated using tumor-derived amplified RNA and cultured dendritic cells (DC). Tumor RNAs were extracted from gastric cancer cell line MKN45 or cancer cells of malignant effusions, and were processed with T7 amplification. DCs were induced from an adherent cell population of peripheral blood mononuclear cells (PBMCs) with GM-CSF and IL-4. Tumor-RNA was introduced into DCs using electroporation. Effector cells were generated by stimulating a non-adherent fraction of PBMCs with tumor RNA-introduced DCs. It was observed that milligram RNA could efficiently be amplified from microgram RNA. The effector cells, designated as tumor-RNA-introduced DC-activated killer (TRiDAK) cells, showed IFN-gamma spots in a tumor-specific manner when examined using ELISPOT analysis, and demonstrated cytotoxic activities against tumor cells from which RNA was extracted. TRiDAK cells produced more tumor-specific IFN-gamma spots when stimulated repeatedly. These results suggest that TRiDAK cells are practical and may be effective lymphocytes for adoptive cancer immunotherapy.

Cell Line, Tumor↗