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Biomedical subjects

K Kudo

Publications and source records attributed to K Kudo.

At least 19 recordsLinked to original sources
PubMed2006

Relativistic calculation of nuclear magnetic shielding using normalized elimination of the small component.

The normalized elimination of the small component (NESC) theory, recently proposed by Filatov and Cremer, is extended to include magnetic interactions and applied to the calculation of the nuclear magnetic shielding in HX (X=F, Cl, Br, I) systems. The NESC calculations are performed at the levels of the zeroth-order regular approximation (ZORA) and the second-order regular approximation (SORA). The calculations show that the NESC-ZORA results are very close to the NESC-SORA results, except for the shielding of the I nucleus. Both the NESC-ZORA and NESC-SORA calculations yield very similar results to the previously reported values obtained using the relativistic infinite-order two-component coupled Hartree-Fock method. The difference between NESC-ZORA and NESC-SORA results is significant for the shieldings of iodine.

Journal Article↗
PubMed2006

Possible association between nonsynonymous polymorphisms of the anaplastic lymphoma kinase (ALK) gene and schizophrenia in a Japanese population.

We examined, for the first time, the possible association between schizophrenia and the anaplastic lymphoma kinase (ALK) gene which plays an important role in neurodevelopment. When two nonsynonymous polymorphisms (Arg1491Lys and Glu1529Asp) were examined, there were significant differences in genotype and allele distributions between patients and controls. Individuals homozygous for the minor allele (1491Lys-1529Asp) were more common in patients than in controls (p = 0.0064, odds ratio 2.4, 95% CI 1.3-4.6). These results suggest that genetic variations of the ALK gene might confer susceptibility to schizophrenia.

Alleles↗
PubMed2005

A phase I/II trial of irinotecan-cisplatin combined with an anti-late-diarrhoeal programme to evaluate the safety and antitumour response of this combination therapy in patients with advanced non-small-cell lung cancer.

We conducted a phase I/II study in patients with advanced non-small-cell lung cancer (NSCLC) to increase the therapeutic index of the cisplatin-irinotecan combination by institution of an anti-late-diarrhoeal program (ADP). A total of 77 chemotherapy-naive patients with advanced NSCLC were enrolled. The cisplatin dose was fixed at 60 mg m(-2) (Day 1). Irinotecan was escalated in 5 mg m(-2) increments, starting from 60 mg m(-2) (Days 1 and 8). ADP consisted of oral sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid, and was administered orally for 4 days with each dose of irinotecan. In the phase I portion, irinotecan pharmacokinetics was also examined. After the recommended dose of irinotecan with ADP was determined, a phase II study was conducted to evaluate the response. Maximum tolerated dose was reached at an irinotecan dose of 80 mg m(-2) (Grade 4 diarrhoea and neutropenia). Pharmacokinetic studies show that the maximum concentration and the area under the curve of both irinotecan and SN38 (active metabolite of irinotecan) tend to increase in the dose-dependent manner of irinotecan. The phase II portion of the study included 48 patients, who were treated with 75 mg m(-2) of irinotecan. Grade 3/4 toxicities included neutropenia in 65%, leucopenia in 33%, and late diarrhoea in 6% of the patients. During this treatment, PS did not change in 65% of patients. At the end of the chemotherapy, PS did not decline in 90% of patients. In the phase II portion, a response occurred in 63% (95% confidential interval (CI), 47-76%) of patients. Median time to progression was 19 weeks (95% CI, 15-22 weeks), and median survival was 52 weeks (95% CI, 39-64 weeks). This regimen of irinotecan and cisplatin with ADP resulted in promising efficacy with acceptable toxicity for patients with advanced NSCLC. This regimen is a candidate for the experimental arm towards future phase III studies.

Administration, Oral↗
PubMed2005

Calculation of nuclear magnetic shieldings using an analytically differentiated relativistic shielding formula.

Two expressions for nuclear-magnetic-shielding tensor components based on analytically differentiating the electronic energy of a system are presented. The first is based on a second-order Douglas-Kroll-Hess approach, in which the off-diagonal block terms of the transformed Dirac Hamiltonian are diminished to second order with respect to both the electrostatic nuclear attraction potential V and the magnetic vector potential A. The second expression is based on the method of Barysz-Sadlej-Snijders, in which the off-diagonal block terms in the transformed Dirac Hamiltonian are completely eliminated with respect to purely V terms, while they are diminished to second order with respect to terms including A. The two approaches are applied to the calculation of nuclear magnetic shieldings of HX (X=F, Cl, Br, I), H2X (X=O, S, Se, Te), and noble gas X (X =He,Ne,Ar,Kr,Xe) systems with common gauge origins. The results show that relativistic corrections of higher than second order are negligibly small, except for the paramagnetic parts of I, Te, and Xe shieldings. The present calculations yield very large positive values for the anisotropy of proton shielding, deltasigma(H) = sigmaparallel(H)-sigmaperpendicular(H), of HI compared to previous reports. Unfortunately, no experimental values for the anisotropy of proton shielding in HI are available for verification.

Journal Article↗
PubMed2004

Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale: a simple culture system using tetrameric HLA-peptide complexes.

BACKGROUND: Recipients of allogeneic stem cell transplants (SCT) are at risk of human CMV infection during their immunocompromised period. The increasing number of reports of CMV isolates resistant to ganciclovir after transplantation has led us to attempt to develop alternative strategies for preventing or treating CMV infection. This study describes a system for generating sufficient numbers of CMV-specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy after SCT. METHODS: CMV-specific CTL were isolated from a single blood draw of a CMV-seropositive donor using PE-labeled HLA-A*0201/pp65(495-503) tetramers and anti-PE magnetic beads. A mixture of a tetramer-positive population and CD4(+) T lymphocytes was expanded to sufficient numbers for clinical application with IL-2 and immobilized anti-CD3 stimulation. RESULT: Starting from 50 mL of blood, we generated >10(7)/m(2) tetramer-positive CTL within 2 weeks. Flow cytometric analysis of expanded lymphocytes showed that purity of CMV peptide-specific CTL was >75%. Upon stimulation of HLA-A*0201-restricted CMV peptide, expanded CD8 T lymphocytes produced intracellular IFN-gamma. Purified CTL exhibited cytotoxic activity against CMV peptide-pulsed T2 cells and CMV-infected HLA-A*0201-positive fibroblasts, but not against HLA mismatched or uninfected target cells. Alloreactivity could be excluded in MLC. DISCUSSION: This simple, rapid culture system can be useful for adoptive immunotherapy after allogeneic SCT. We are now trying to adapt our laboratory scale study to a clinical scale study under good manufacturing practices (GMP) conditions.

Antigens, Viral↗
PubMed2004

Development of a fast neutron spectrometer composed of silicon-SSD and position-sensitive proportional counters.

A new fast neutron spectrometer has been developed. The spectrometer is composed of a silicon surface barrier detector and three position-sensitive proportional counters with methane gas working as counting gas and a radiator. A collimated incident neutron interacts with a hydrogen atom in the methane gas to generate a recoil proton. The position information on the path of the recoil proton obtained from the three position-sensitive proportional counters gives the recoil angle. In the meanwhile, the energy of the recoil protons is measured with the three proportional counters and the silicon surface barrier detector. The characteristics of the spectrometer were evaluated with a monoenergetic neutron beam. The best energy resolution was 1.8% for 5.0 MeV neutrons.

Computer Simulation↗
PubMed2004

Development of a tiny neutron probe with an optical fibre for BNCT.

We have developed a tiny neutron probe detector as a monitor of a thermal neutron flux for boron neutron capture therapy. The detector consists of an optical fibre and a small neutron probe. We have used a film-like ZnS(Ag) scintillator and a 6LiF neutron converter for the neutron probe. In order to improve the gamma-neutron discrimination ability, vacuum evaporation of 6LiF onto the ZnS(Ag) film has been done. In order to improve the neutron detection efficiency, we made use of a wavelength-shifting fibre as the probe material. The characteristics of the above two types of fibre probe detector have been evaluated experimentally.

Body Burden↗
PubMed2004

Construction of 144, 565 keV and 5.0 MeV monoenergetic neutron calibration fields at JAERI.

Monoenergetic neutron calibration fields of 144, 565 keV and 5.0 MeV have been developed at the Facility of Radiation Standards of JAERI using a 4 MV Pelletron accelerator. The 7Li(p,n)7Be and 2H(d,n)3He reactions are employed for neutron production. The neutron energy was measured by the time-of-flight method with a liquid scintillation detector and calculated with the MCNP-ANT code. A long counter is employed as a neutron monitor because of the flat response. The monitor is set up where the influence of inscattered neutrons from devices and their supporting materials at a calibration point is as small as possible. The calibration coefficients from the monitor counts to the neutron fluence at a calibration point were obtained from the reference fluence measured with the transfer instrument of the primary standard laboratory (AIST), a 24.13 cm phi Bonner sphere counter. The traceability of the fields to AIST was established through the calibration.

Algorithms↗
PubMed2004

Characterization of gamma rays existing in the NMIJ standard neutron field.

Our laboratory provides national standards on fast neutron fluence. Neutron fields are always accompanied by gamma rays produced in neutron sources and surroundings. We have characterised these gamma rays in the 5.0 MeV standard neutron field. Gamma ray measurement was performed using an NE213 liquid scintillator. Pulse shape discrimination was incorporated to separate the events induced by gamma rays from those by neutrons. The measured gamma ray spectra were unfolded with the HEPRO program package to obtain the spectral fluences using the response matrix prepared with the EGS4 code. Corrections were made for the gamma rays produced by neutrons in the detector assembly using the MCNP4C code. The effective dose equivalents were estimated to be of the order of 25 microSv at the neutron fluence of 10(7) neutrons cm(-2).

Algorithms↗
PubMed2003

Discovery of temperature-dependent phenomena of muon-catalyzed fusion in solid deuterium and tritium mixtures.

A systematic experimental study on muon-catalyzed fusion was conducted using a series of solid deuterium and tritium mixtures. A variety of conditions were investigated, i.e., tritium concentrations from 20% to 70%, and temperatures from 5 to 16 K. With decreasing temperature, we observed an unexpected decrease in the muon cycling rate (lambda(c)) and an increase in the muon loss probability (W). The origins of these observed changes were interpreted by the temperature-dependence in the dt mu formation process for lambda(c) and that in the muon reactivation process after muon-to-alpha sticking for W.

Journal Article↗
PubMed2003

Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus.

It has been proposed that signaling pathways involved in adaptive neural plasticity are long-term targets for the action of electroconvulsive treatment (ECT), which is widely used in the treatment of drug-resistant depression. We have previously performed EST analysis to identify some molecular machinery responsible for antidepressant effect. One of the cDNA fragments identified as antidepressant related genes/ESTs was identified as kf-1 which has a RING-H2 finger motif at the carboxy-terminus. In the present study, we have demonstrated the induction of kf-1 in rat frontal cortex and hippocampus not only after chronic antidepressant treatment, but also after a single and repeated ECT. RING finger proteins are proposed to play some important roles in the ubiquitin-proteasome system. In conclusion, the current investigation has identified kf-1 as a novel molecular target for antidepressants and ECT.

Animals↗
PubMed2003

[Treatment of strategy for traumatic disruption of the thoracic aorta accompanied by multiple trauma].

Disruption of the thoracic aorta due to blunt chest trauma is often fatal and should generally be treated surgically as soon as possible. However, cases of disruption of the thoracic aorta due to blunt chest trauma are often complicated by damage to vital organs, making treatment difficult. Our policy is to treat other organs before treating the thoracic aorta in 1) cases in which fracture of the pelvic bone or bleeding from abdominal cavity organs is causing shock and 2) cases of severe cerebral contusion or intracranial hemorrhage that require emergency surgical treatment. The use of a stent for treatment of acute-stage cases should be considered prudently.

Accidents, Traffic↗
PubMed2002

Forensic significance of conduction system abnormalities as a precise cause of accidental death.

We examined the pathology findings of the cardiac conduction system in 42 human autopsies who were considered to have died an accidental death. Abnormalities in serial sections of the conduction system were found in seven and of these three had an accessory pathway in the conduction system. In one of these there was mild Ebstein's anomaly (ME), two had fibromuscular dysplasia of the atrioventricular node artery with mitral valve prolapse, and two others had abnormal routes showing fragmentation of the bundle of His with ME. A full investigation of the cardiac conduction system can therefore be useful for determining the precise cause in cases of accidental death.

Accidents↗
PubMed2002

Differential expression of VAMP2/synaptobrevin-2 after antidepressant and electroconvulsive treatment in rat frontal cortex.

The biological basis for the therapeutic mechanisms of depression is still unknown. We have previously performed expressed-sequence tag (EST) analysis to identify some molecular machinery responsible for antidepressant effect. Then, we developed our original cDNA microarray, on which cDNA fragments identified as antidepressant-related genes/ESTs were spotted. In this study, with this microarray followed by Western blot analysis, we have demonstrated the induction of vesicle-associated membrane protein 2(VAMP2/synaptobrevin-2) in rat frontal cortex not only after chronic antidepressant treatment, but also after repeated electroconvulsive treatment. On the other hand, expression of SNAP-25 and syntaxin-1 was not changed by these treatments. These components make a soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex with VAMP2 and mediate the synaptic vesicle docking/fusion machinery. In conclusion, it is suggested that VAMP2/synaptobrevin-2 plays important roles in the antidepressant effects. Our results may contribute to a novel model for the therapeutic mechanism of depression and new molecular targets for the development of therapeutic agents.

Animals↗
PubMed2001

Distribution of tetracaine and its metabolite in rabbits after high versus normal spinal anesthesia.

High spinal anesthesia is one cause of sudden death associated with the spinal anesthesia. We did animal experiments to verify high spinal anesthesia by analyzing tetracaine and its metabolite, p-butylaminobenzoic acid in tissue samples. Tetracaine (0.25% in 10% glucose solution) 0.21-0.28 mg/kg was administered to two groups of rabbits to induce high and normal spinal anesthesia. Tetracaine and the metabolite in rabbit tissues were analyzed by gas chromatography-mass spectrometry, as a free base for tetracaine and as tert-butyldimethylsilyl derivative for the metabolite. In the group given high spinal anesthesia, levels of the metabolite in the brain stem were higher than in the cerebrum, cerebellum and whole blood. On the other hand, in the group given normal spinal anesthesia, the opposite results were obtained. Therefore, high spinal anesthesia induced by tetracaine can be diagnosed by comparing the concentrations of metabolite in whole blood, cerebrum, cerebellum and brain stem.

Anesthesia, Spinal↗