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K Asakura

Publications and source records attributed to K Asakura.

At least 19 recordsLinked to original sources
PubMed2002

Gas6 rescues cortical neurons from amyloid beta protein-induced apoptosis.

Gas6, a product of the growth-arrest-specific gene 6, protects neurons from serum deprivation-induced apoptosis. Neuronal apoptosis is also caused by amyloid beta protein (Abeta), whose accumulation in the brain is a characteristic feature of Alzheimer's disease. Abeta induces Ca(2+) influx via L-type voltage-dependent calcium channels (L-VSCCs), leading to its neurotoxicity. In the present study, we investigated effects of Gas6 on Abeta-induced cell death in primary cultures of rat cortical neurons. Abeta caused neuronal cell death in a concentration- and time-dependent manner. Gas6 significantly prevented neurons from Abeta-induced cell death. Gas6 ameliorated Abeta-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Prior to cell death, Abeta increased influx of Ca(2+) into neurons through L-VSCCs. Gas6 significantly inhibited the Abeta-induced Ca(2+) influx. The inhibitor of L-VSCCs also suppressed Abeta-induced neuronal cell death. The present cortical cultures contained few non-neuronal cells, indicating that Gas6 affected the survival of neurons directly, but not indirectly via non-neuronal cells. In conclusion, we demonstrate that Gas6 rescues cortical neurons from Abeta-induced apoptosis. Furthermore, the present study indicates that inhibition of L-VSCC contributes to the neuroprotective effect of Gas6.

Amyloid beta-Peptides↗
PubMed2001

Deterioration of axotomy-induced neurodegeneration by group IIA secretory phospholipase A2.

Phospholipase A2 (PLA2) is proposed to play a role in the repair of the ruptured membrane after axotomy. In neonatal rats, we examined the effect of Group IIA secretory PLA2 (sPLA2-IIA) on axotomy-induced cell death of motoneurons. sPLA2-IIA significantly induced death of axotomized motoneurons. Indoxam, a specific inhibitor for sPLA2-IIA, protected motoneurons from the sPLA2-IIA-induced deterioration. The present study indicated that sPLA2-IIA possessed neurotoxic effect rather than neuroprotective effect against facial nerve.

Animals↗
PubMed2001

Association of L* protein of Theiler's murine encephalomyelitis virus with microtubules in infected cells.

We used an antibody raised against a synthetic peptide corresponding to amino acid residues 70-88 for characterizing the L* protein of Theiler's murine encephalomyelitis virus (TMEV), which is only synthesized in DA subgroup strains from an alternative AUG and is out of frame with the viral polyprotein; evidence suggests that L* protein is critical to viral persistence, demyelination, and growth in murine macrophage cell lines. It was synthesized with kinetics similar to that of other viral proteins, although less in amount. After synthesis, it remained stable in the cytoplasm and was not incorporated into virions. Immunofluorescent staining and immunoblotting of microtubule preparations demonstrated that it is associated with microtubules. Expression of L* protein also demonstrated that the 5' one third of the coding region may be responsible for the association. The association of L* protein with microtubules may be important in the disease-inducing and in vitro characters of L* protein.

Animals↗
PubMed2001

Time-resolved energy-dispersive XAFS study on the reduction process of Cu-ZSM-5 catalysts.

The time-resolved reduction process of copper cations in ZSM-5 during temperature-programmed reduction (300-700 K) was studied by energy dispersive X-ray absorption fine structure (DXAFS). The Cu K-edge DXAFS spectra for isolated Cu2+ species in the channels of ZSM-5 were recorded at an interval of 1 s during the reduction. The curve fitting analysis of the EXAFS data and the XANES analysis revealed that the isolated Cu2+ species in the channels were reduced stepwise. They were reduced to isolated Cu+ species at 400-450 K and the Cu+ species to Cu0 metallic clusters at 550-650 K. Small clusters like Cu4 were initially formed, followed by particle growth. A small part of them went out to the outer surfaces of ZSM-5 during the reduction.

Journal Article↗
PubMed2001

Three-dimensional analysis of the local structure of Cu on TiO2(110) by in situ polarization-dependent total-reflection fluorescence XAFS.

Cu K-edge XAFS of Cu/TiO2(110) was measured by polarization-dependent total-reflection fluorescence XAFS technique. XAFS of [001], [110], and [110] directions were measured to elucidate the three dimensional structure of Cu species on the TiO2(110) surface prepared by the deposition of Cu(DPM)2 followed by reduction with H2. Simulation of the EXAFS functions as well as conventional curve fitting analysis revealed that plane Cu3,4 small clusters with similar structure to Cu(111) plane were formed by the reduction at 363 K. The small clusters converted into spherical metallic Cu particles by the reduction at 473 K.

Journal Article↗
PubMed2001

Development of an in situ polarization-dependent total-reflection fluorescence XAFS measurement system.

An in situ polarization-dependent total-reflection fluorescence X-ray absorption fine structure (PTRF-XAFS) spectroscopy system has been developed, which enables PTRF-XAFS experiments to be performed in three different orientations at various temperatures (273-600 K) and pressures (10(-10) approximately 760 torr). The system consists of a measurement chamber and a preparation chamber. The measurement chamber has a high-precision six-axis goniometer and a multielement solid-state detector. Using a transfer chamber, also operated under ultra-high-vacuum conditions, the sample can be transferred to the measurement chamber from the preparation chamber, which possesses low-energy electron diffraction, Auger electron spectroscopy and X-ray photoelectron spectroscopy facilities, as well as a sputtering gun and an annealing system. The in situ PTRF-EXAFS for Cu species on TiO2 (110) has been measured in three different orientations, revealing anisotropic growth of Cu under the influence of the TiO2 (110) surface.

Journal Article↗
PubMed2001

DXAFS study on the decarbonylation process of Mo(CO)6 in NaY supercages.

The decarbonylation process of Mo(CO)6 in the NaY supercages was studied by means of a time resolved dispersive XAFS method during temperature programmed decarbonylation. XANES analysis demonstrated that the decarbonylation proceeded through two steps and that a stable intermediate existed between 440-490 K. The curve fitting analysis revealed that the intermediate was a molybdenum monomer subcarbonyl species coordinated by three CO ligands and three oxygen atoms of zeolite framework. Molybdenum dimer subcarbonyl species were not observed. This study demonstrated that DXAFS technique is a powerful method to study the dynamic behaviour of the Mo carbonyl species during decarbonylation process.

Journal Article↗
PubMed2001

Conditions for chiral asymmetry generation in the preparation of the chiral octahedral cobalt complex.

We have reported that the random chiral asymmetry generation, which is a spontaneous preferential generation of one enantiomer, was observed in the synthesis of a chiral octahedral cobalt complex, cis-[CoBr(NH(3))(en)(2)]Br(2). In this article, we review our studies to explain in this system the autocatalytic growth of small enantiomeric excess that arises due to statistical fluctuations. One important experimental finding was that the rate of chiral autocatalysis increased with increasing the degree of supersaturation. Furthermore, our numerical simulation indicates that even small inhomogeneities in the reaction system may play a significant role because their effect is amplified by the autocatalytic reaction under appropriate conditions. In a small volume, fluctuations in concentration can grow if the autocatalytic growth overcomes the diffusional loss of the excess concentration from this volume. This may makes the enantiomeric excess of the chiral complex randomly fluctuate from run to run.

Journal Article↗
PubMed2001

Synthesis and structure-activity relationships of potent and orally active sulfonamide ETB selective antagonists.

The synthesis and structure activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a, previously reported, (1) was selected as a lead compound, and isosteric replacement of the isoxazole ring of 1a with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation.

Aldehydes↗
PubMed2001

Chiral autocatalysis, spontaneous symmetry breaking, and stochastic behavior.

During the past decade, chirally autocatalytic systems that exhibit unusual and interesting phenomena, such as spontaneous chiral symmetry breaking and stochastic behavior, have been identified. In this Account we outline the context in which chiral autocatalysis is of interest, summarize recent advances, and discuss our current understanding of the underlying kinetics and mechanisms. In addition, we note some fundamental aspects of amplification of enantiomeric excess and sensitivity of symmetry breaking transitions to asymmetric factors.

Biopolymers↗
PubMed2001

Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid beta protein-induced neuronal cell death.

1. The accumulation of amyloid beta protein (Abeta) in the brain is a characteristic feature of Alzheimer's disease (AD). Clinical trials of AD patients with nonsteroidal anti-inflammatory drugs (NSAIDs) indicate a clinical benefit. NSAIDs are presumed to act by suppressing inhibiting chronic inflammation in the brain of AD patients. 2. In the present study, we investigated effects of S-2474 on Abeta-induced cell death in primary cultures of rat cortical neurons. 3. S-2474 is a novel NSAID, which inhibits cyclo-oxygenase-2 (COX-2) and contains the di-tert-butylphenol antioxidant moiety. S-2474 significantly prevented neurons from Abeta(25 - 35)- and Abeta(1 - 40)-induced cell death. S-2474 ameliorated Abeta-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA completely. 4. Prior to cell death, Abeta(25 - 35) generated prostaglandin D(2) (PGD(2)) and free radicals from neurons. PGD(2) is a product of cyclo-oxygenase (COX), and caused neuronal cell death. 5. S-2474 significantly inhibited the Abeta(25 - 35)-induced generation of PGD(2) and free radicals. 6. The present cortical cultures contained little non-neuronal cells, indicating that S-2474 affected neuronal survival directly, but not indirectly via non-neuronal cells. Both an inhibitory effect of COX-2 and an antioxidant effect might contribute to the neuroprotective effects of S-2474. 7. In conclusion, S-2474 exhibits protective effects against neurotoxicity of Abeta. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for AD via ameliorating degeneration in neurons as well as suppressing chronic inflammation in non-neuronal cells.

Amyloid beta-Peptides↗
PubMed2001

Effects of JPEG and wavelet compression of spiral low-dose ct images on detection of small lung cancers.

PURPOSE: To compare the effect of compression of spiral low-dose CT images by the Joint Photographic Experts Group (JPEG) and wavelet algorithms on detection of small lung cancers. MATERIAL AND METHODS: Low-dose spiral CT images of 104 individuals (52 with peripheral lung cancers smaller than 20 mm and 52 control subjects) were used. The original images were compressed using JPEG or wavelet algorithms at a ratio of 10:1 or 20:1. Five radiologists interpreted these images and evaluated the image quality on a high-resolution CRT monitor. Observer performance was studied by receiver operating characteristic (ROC) analysis. RESULTS: There was no significant difference in the detection of cancers measuring 6 to 15 mm in uncompressed images and in those compressed by either of the algorithms, although the quality of images compressed at 20:1 with the wavelet algorithm was somewhat inferior. A lower diagnostic accuracy was noted using images compressed by the JPEG or wavelet algorithms at 20:1 in detecting lung cancers measuring 6 to 10 mm and cancers measuring from 6 to 15 mm with ground-glass opacity. CONCLUSION: Compression of low-dose CT images at a ratio of 10:1 using JPEG and wavelet algorithms does not compromise the detection rate of small lung cancers.

Algorithms↗
PubMed2001

Telemedicine system using computed tomography van of high-speed telecommunication vehicle.

The current medical system provides medical services to patients who visit hospitals. However, medical services can be provided at or close to the home of the patient using fully equipped mobile telemedicine systems. Such a system can identify the disease at an early stage, improve quality of life and prognosis through early diagnosis and treatment, and reduce the costs of medical service. Furthermore, the unit can provide mass screenings of the population, as well as full medical service to remote areas. The Telecommunications Advanced Organization of Japan, Matsumoto, Japan, and Shinshu University Hospital, Matsumoto, Japan, established a research center for a unique telemedicine project using a mobile system. The mobile unit consists of a van that houses a spiral computed-tomography (CT) machine and various telecommunications equipment. The unit allows medical examination, CT scanning, and on-line two-way transfer of image data/teleconferencing to a medical center for consultation with various specialists. We have used the system thus far for the early detection of lung cancer through mass screenings over a four-year period in 29 administrative districts. Mass screenings of 19117 residents resulted in the identification of 75 cases of early lung cancer who were later treated by partial pneumonectomy at Shinshu University Hospital and affiliated hospitals. We have also used the system to provide medical services to rural areas, as telemedicine support at remote areas, wintertime telemedicine support to an international sports competition, and various medical services to a home-care facility.

Humans↗
PubMed2000

Mercury emissions from a coal-fired power plant in Japan

The emissions study for mercury was conducted at a 700 MW coal-fired plant for the combustion of three types of coal with mercury concentrations of 0.0063, 0.0367 and 0.065 mg/kg. The power plant is equipped with a cold-side electrostatic precipitator and wet type flue gas desulfurization system. During full load operation of the boilers, samples of the input and output streams such as coal, coal ash, ESP ash and post-ESP particulates and flue gas were collected. The Hg concentrations in solid were measured by cold-vapor atomic absorption spectrometry (AAS) after appropriate preparation and acid digestion. Gaseous Hg was collected using a mixed solution of potassium permanganate and sulfuric acid and the Hg concentrations in the samples were measured using cold-vapor AAS. The results were used to examine: (1) overall mass balances; (2) relative distribution in the power plant; (3) equilibrium of Hg species using MALT-2 calculation program; and (4) Hg concentrations in stack emissions. The mass balances estimated in this study were 100, 138 and 89%, respectively, for the coals. Total Hg concentrations in stack gas were 1.113, 0.422 and 0.712 microg(m3N), respectively, for the coals. More than 99.5% of the Hg in the stack emissions were in gaseous form and the proportion in particulate form was extremely low. The relative distribution of Hg in ESP, FGD and Stack ranged from 8.3 to 55.2%, 13.3 to 69.2% and 12.2% to 44.4%, respectively. The results indicated that factors other than the Hg concentration of coals and efficiency of pollution control devices might affect Hg emissions from coal-fired plant. The calculated equilibrium of the distribution of Hg species using the MALT2 program suggest that it is necessary to consider condensation mechanism to interpret the affect of Hg species on the variations of the removal efficiencies of Hg in the ESP.

Journal Article↗
PubMed2000

Neurotrophin-4/5 promotes proliferation of oligodendrocyte-type-2 astrocytes (O-2A).

In this study, the ability of neurotrophin-5 (NT-4/5) to promote the proliferation of oligodendrocyte precursor (O-2A) cells has been examined. This has been accomplished by the addition of exogenous NT-4/5 to purified cultures of O-2A cells maintained in an undifferentiated state by the addition of the mitogens platelet derived growth factor (PDGF-AA) and basic fibroblast growth factor (bFGF). Counts of cells incorporating bromodeoxyuridine (BrdU) showed that the addition of NT-4/5 for 24 h increased O-2A cell proliferation by 1.8-fold above that seen in PDGF-AA and bFGF alone. These data demonstrate a previously unidentified role for the neurotrophin NT-4/5 in oligodendrocyte biology.

Animals↗
PubMed2000

alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic vasodilation and extravasation following electrical stimulation of trigeminal ganglion.

In this study, we investigated the effect of alpha-eudesmol, which potently inhibits the presynaptic omega-agatoxin IVA-sensitive (P/Q-type) Ca(2+) channel, on neurogenic inflammation following electrical stimulation of rat trigeminal ganglion. Treatment with alpha-eudesmol (0.1-1 mg/kg. i.v.) dose-dependently attenuated neurogenic vasodilation in facial skin monitored by a laser Doppler flowmetry. In addition, alpha-eudesmol (1 mg/kg. i.v.) significantly decreased dural plasma extravasation in analysis using Evans blue as a plasma marker. On the other hand, alpha-eudesmol (1 mg/kg, i.v.) did not affect mean arterial blood pressure in rats. The calcitonin gene-related peptide (CGRP) and substance P (SP) released from activated sensory nerves have recently been suggested to be associated with the neurogenic inflammation. In this study, we also showed that alpha-eudesmol (0.45-45 microM) concentration-dependently inhibits the depolarization-evoked CGRP and SP release from sensory nerve terminals in spinal cord slices. These results indicate that the anti-neurogenic inflammation action of alpha-eudesmol, which does not affect the cardiovascular system, may be due to its presynaptic inhibition of the neuropeptide release from perivascular trigeminal terminals. We also suggest that the omega-agatoxin IVA-sensitive Ca(2+) channel blocker, alpha-eudesmol, may become useful for the treatment of the neurogenic inflammation in the trigemino-vascular system such as migraine.

Animals↗
PubMed2000

Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis.

Promoting remyelination, a major goal of an effective treatment for demyelinating diseases, has the potential to protect vulnerable axons, increase conduction velocity, and improve neurologic deficits. Strategies to promote remyelination have focused on transplanting oligodendrocytes (OLs) or recruiting endogenous myelinating cells with trophic factors. Ig-based therapies, routinely used to treat a variety of neurological and autoimmune diseases, underlie our approach to enhance remyelination. We isolated two human mAbs directed against OL surface antigens that promoted significant remyelination in a virus-mediated model of multiple sclerosis. Four additional OL-binding human mAbs did not promote remyelination. Both human mAbs were as effective as human i.v. Ig, a treatment shown to have efficacy in multiple sclerosis, and bound to the surface of human OLs suggesting a direct effect of the mAbs on the cells responsible for myelination. Alternatively, targeting human mAbs to areas of central nervous system (CNS) pathology may facilitate the opsonization of myelin debris, allowing repair to proceed. Human mAbs were isolated from the sera of individuals with a form of monoclonal gammopathy. These individuals carry a high level of monoclonal protein in their blood without detriment, lending support to the belief that administration of these mAbs as a therapy would be safe. Our results are (i) consistent with the hypothesis that CNS-reactive mAbs, part of the normal Ig repertoire in humans, may help repair and protect the CNS from pathogenic immune injury, and (ii) further challenge the premise that Abs that bind OLs are necessarily pathogenic.

Antibodies, Monoclonal↗