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In this study, a system has been developed to draw three-dimensional coordinates of a catheter in real time using Unity for cerebral aneurysm coil embolization, which is one of the endovascular treatments. The system detects the tip of a catheter by binarization and delineation from X-ray images taken from two directions (frontal and lateral views) and calculates the tip coordinates of the catheter in the 3D model of blood vessels generated using VTK from DICOM images. In this system, surgeons can more effectively visualize the catheter tip in 3D by using an head-mounted display, a virtual reality device. In the evaluation experiment, we compared the catheter tip detection with conventional methods and found that it was faster and more accurate than conventional methods. Future tasks include accurate positioning of 2D images and 3D models and drawing catheters other than the tip.

In this study, we newly propose a generalized growth curve model of discrete type, which is based on the property of the Gompertz and logistic curve models. In particular, the bi-linearization technique is applied to the basic differential equation, and we discretize it to the difference equations so as to hold the property of integrable systems. These models can be used to predict the future behavior of the time series data by estimating the constant parameters included in the model. In the numerical examples, we analyze the actual data sets by using our model, and also we show the confidence intervals of the estimated growth curve via the bootstrap method.

The active components in cloves are eugenol and isoeugenol. Eugenol has recently become a focus of interest because of its potential role in alleviating and preventing chronic diseases such as cancer, inflammatory reactions, and other conditions. The radical-scavenging and anti-inflammatory activities of eugenol have been shown to modulate chronic diseases in vitro and in vivo, but in humans, the therapeutic use of eugenol still remains to be explored. Based on a review of the recent literature, the antioxidant, anti-proliferative, and anti-inflammatory activities of eugenol and its related compounds are discussed in relation to experimentally determined antioxidant activity (stoichiometric factor n and inhibition rate constant) and theoretical parameters [phenolic O-H bond dissociation enthalpy (BDE), ionization potential (IP according to Koopman's theorem), and electrophilicity (ω)], calculated using a density functional theory method. Dimers of eugenol and its related compounds showed large antioxidant activities and high ω values and also exerted efficient anti-inflammatory activities. Eugenol appears to possess multiple antioxidant activities (dimerization, recycling, and chelating effect) in one molecule, thus having the potential to alleviate and prevent chronic diseases.

Summary: The concern about the environmental impacts generated in the production of goods and services has increased last decades. The industry has used paints and varnishes in the manufacturing process have been pressed to improve air pollution prevention. Thus, the present work aims to identify the quantitative differences of VOC's and analyze the effect of VOC's in the burning rate, in a solvent and water-based paint, applied in the manufacture of automotive steering wheels. The results has showed that the solvent-based paint contains nine times more VOC's in your formulation in relation to water-based paint, when compared liquid and volatile organic compounds present in the solvent-based paint increase the speed of combustion of the polyurethanes samples. These data indicate that a discussion on the subject must be initiated in order to reduce these emissions that can harm society.

The fabrication of GaAs- and InP-based III-V semiconductor nanowires with axial/radial heterostructures by using selective-area metal-organic vapor-phase epitaxy is reviewed. Nanowires, with a diameter of 50–300 nm and with a length of up to 10 μm, have been grown along the〈111〉B or〈111〉A crystallographic orientation from lithography-defined SiO2mask openings on a group III-V semiconductor substrate surface. An InGaAs quantum well (QW) in GaAs/InGaAs nanowires and a GaAs QW in GaAs/AlGaAs or GaAs/GaAsP nanowires have been fabricated for the axial heterostructures to investigate photoluminescence spectra from QWs with various thicknesses. Transmission electron microscopy combined with energy dispersive X-ray spectroscopy measurements have been used to analyze the crystal structure and the atomic composition profile for the nanowires. GaAs/AlGaAs, InP/InAs/InP, and GaAs/GaAsP core-shell structures have been found to be effective for the radial heterostructures to increase photoluminescence intensity and have enabled laser emissions from a single GaAs/GaAsP nanowire waveguide. The results have indicated that the core-shell structure is indispensable for surface passivation and practical use of nanowire optoelectronics devices.

For the sensor probe of high frequency magnetic field in GHz region, films were prepared by liquid phase epitaxy technique and ferromagnetic resonances were investigated in high frequency region. Magneto-optical (MO) effect of magnetic garnet was utilized for the imaging sensor of the magnetic field distribution. However, for the application to the characterization of high frequency magnetic field in the GHz frequency region, usual MO measurements are difficult to detect the magnetic filed as the decreasing of the permeability of magnetic garnet. Magnetic resonance is an effective way to induce magnetic moment and enhance the magnetooptical effect in high frequency region of GHz order. In order to understand the possibility of magnetic field sensor of high frequency in detail, far-infrared magnetic resonances were measured at the high frequencies up to 315 GHz in pulsed high magnetic field. Taking account into sensitivity of MO signals and magnetic resonance intensities, magnetooptical method using a garnet film is effective at the frequencies below 100 GHz.

The active components in cloves are eugenol and isoeugenol. Eugenol has recently become a focus of interest because of its potential role in alleviating and preventing chronic diseases such as cancer, inflammatory reactions, and other conditions. The radical-scavenging and anti-inflammatory activities of eugenol have been shown to modulate chronic diseases in vitro and in vivo, but in humans, the therapeutic use of eugenol still remains to be explored. Based on a review of the recent literature, the antioxidant, anti-proliferative, and anti-inflammatory activities of eugenol and its related compounds are discussed in relation to experimentally determined antioxidant activity (stoichiometric factor n and inhibition rate constant) and theoretical parameters [phenolic O-H bond dissociation enthalpy (BDE), ionization potential (IP according to Koopman's theorem), and electrophilicity (ω)], calculated using a density functional theory method. Dimers of eugenol and its related compounds showed large antioxidant activities and high ω values and also exerted efficient anti-inflammatory activities. Eugenol appears to possess multiple antioxidant activities (dimerization, recycling, and chelating effect) in one molecule, thus having the potential to alleviate and prevent chronic diseases.

To elucidate the mechanism of the stabilization of pitches by iodine vapor below the melting temperatures of the pitches, the sorption or effect of introducing iodine into pitches and model-compounds was investigated using iodine sorption, Raman spectroscopy, 127I Mossbauer spectroscopy and gel permeation chromatography. Introduced/sorbed iodine was, at least, in two forms in the pitches: one formed charge-transfer complexes having strong interaction with molecules in pitches and the other weakly associated with the iodine in the complexes. The latter iodine seemed to be in a condensed state. Cata-condensed polycyclic molecules were polymerized with dehydrogenation and became larger molecules before forming charge-transfer complexes. On the contrary, peri-condensed polycyclic molecules easily produced charge-transfer complexes but showed no remarkable increase in their molecular weight. These increased the stability of the pitches even below their melting temperature.

When the lateral displacement of an AFM tip due to friction is comparable to or larger than the scan size, for example during atomic-scale friction measurement, the interpretation of the friction image is different from the situation where the scan size is much larger than the lateral displacement of the tip and the image is a simple direct mapping of the friction value. This is because, due to the lateral displacement of the tip, the tip is not at the position where the scan indicates, as can be clearly observed by an in-situ TEM/AFM combined microscopy and atomic-scale friction analysis. This lateral displacement of the tip at the nanometer scale affects the shape of the force-distance curve. We discuss the effect of the tip lateral displacement in AFM data and its normal load dependence.

Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells.

Pepsin-solubilized collagen (PSC) prepared from the skin of 3 fish species—common horse mackerel, yellow sea bream, and tiger puffer—were separated into 2 fractions, major and minor, by ammonium sulfate precipitation. These collagen fractions were further purified by phosphocellulose column chromatography. From the results of SDS-PAGE, peptide mapping, and amino-acid analysis, the purified major and minor collagens were identified to be type I and V collagens, respectively. These results suggest that type V collagen might be widely present in fish skin as a minor collagen.

Although regional lymph nodes (LN) have been extensively studied as rich sources of effector T cells in contact hypersensitivity (CH), it remains unknown whether T cell responses in the LN reflect those in effector skin sites. We previously showed that repeated elicitation of CH results in a shift in the time course of Ag-specific CH from a delayed-type hypersensitivity response to an early-type response, a reflection of a shift in cutaneous cytokine expression from a type 1 to a type 2 profile. To investigate whether repeated elicitation of CH could also drive T cell development to the type 2 phenotype in the regional draining LN, sequential cytokine gene expression after hapten application was assessed during both the acute and the chronic phase of CH. In the draining LN the shift to type 2 cytokine production was also observed, but more mixed patterns of responses were induced than in the corresponding skin sites. The chronic LN cells (LNC), when stimulated in vitro, produced markedly lower levels of type 1 cytokines and higher levels of type 2 cytokines than the acute LNC. A successful passive transfer of an early-type response by the LNC was only induced in the recipient mice when the skin sites chronically treated with hapten were elicited. These results indicate that an early-type response by regional LNC would take place only in a milieu with sufficient levels of type 2 cytokines.

To clarify the mechanism of the hemolytic activity of 4-META− (4-methacryloyloxyethyl trimellitate anhydride), an evaluation of the interaction of 4-META and its related compounds (4-MET; phthalic anhydride, PAN; and phthalic acid, PA) with DPPC liposomes using a DSC and NMR spectroscopy is presented.

The largest superconducting fusion machine, Large Helical Device (LHD), is now under construction in Japan and will begin operation in 1997. Design and construction of related R&D programs are now being carried out. The major radius of this machine is 3.9 m and the magnetic field on the plasma center is 3 T. The NbTi superconducting conductors are used in both helical coils and poloidal coils to produce this field. This will be upgraded in the second phase a using superfluid coil cooling technique. A negative ion source is being successfully developed for the NBI heating of LHD. This paper describes the present status and progress in its experimental planning and theoretical analysis on LHD, and the design and construction of LHD torus, heating, and diagnostics equipments.

Using the two-dimensional frictional force microscope, we observed two-dimensional discrete friction on the NaF(100) surface with its lattice periodicity, which is explained by the two-dimensional stick-slip model quantitatively. By the raster scan, such a discrete friction composes the lattice periodicity image of the NaF surface. This means that one of the AFM contrast mechanisms of the lattice periodicity of the ionic crystal is the discrete friction. On the other hand, with a normal load of 14 nN the discrete friction disappeared, so the number of contact atoms is estimated as a few atoms. Thus, even under a near single-atom friction regime the atomic scale friction is explained by the two-dimensional stick-slip model quantitatively.

SUMMARY Mitogen-activated protein kinases (MAPKs) play pivotal roles in the signal transduction pathway of plant defence responses against pathogens. A search for MAPK-interacting proteins revealed an interaction between a Nicotiana benthamiana MAPK, SIPK (NbSIPK) and cytosolic Hsp90 (NbHsp90c-1) in yeast two-hybrid assay. To study the function of Hsp90 in disease resistance, we silenced NbHsp90c-1 in N. benthamiana by virus-induced gene silencing (VIGS) with Potato virus X (PVX). NbHsp90c-1 silenced plants exhibited: (1) a stunted phenotype, (2) no hypersensitive response (HR) development after infiltration with the Phytophthora infestans protein INF1 and a non-host pathogen Pseudomonas cichorii that normally triggers HR in N. benthamiana, (3) compromised non-host resistance to P. cichorii, and (4) consistently reduced transcription levels of PR (pathogenesis related) protein genes. Similar phenotypes were observed also for plants in which a cytosolic Hsp70 (NbHsp70c-1), a gene for another class of molecular chaperon, was silenced. Hsp90 was isolated as a MAPK-interacting protein in yeast two-hybrid assay, therefore we tested the effect of NbHsp90c-1 silencing as well as NbHsp70c-1 silencing on the HR development caused by infiltration of a hyperactive potato MAPKK (StMEK1(DD)). No difference in the timing or extent of HR was found among NbHsp90c-1 silenced, NbHsp70c-1 silenced and control plants. This result indicates that observed impairment of INF1- and P. cichorii-mediated HR development in NbHsp90c-1 silenced and NbHsp70c-1 silenced plants was not caused by the abrogation in MAPK function downstream of active MAPKK that leads to HR. These findings suggest essential roles of Hsp90 and Hsp70 in plant defence signal transduction pathway upstream or independent of the MAPK cascade.

PKI (public key infrastructure) provides security functions on network, such as encryption of data, assurance that data are complete and user authentication, by public key encryption and so on. PKI begins to be built as an authentication base on a network by governments and universities. In Japan, UPKI (University Public Key Infrastructure) national academic authentication and authorization infrastructure project has started. Opengate is an user authentication gateway system for network in the environment opened to public. This system has been operating for controlling the campus-wide open network in Saga University since 2001. In this research, we implemented PKI authentication functions for Opengate, and we enabled the certificate-based authentication via a Web browser.

This paper points out a key issue related to the integration between cultural ontology based metadata management services and content management of digital resources. A multi-facet resource categorization approach is applied to metadata sets, allowing the metadata optimization of the description of cultural resources. It is part of the cultural ontology based metadata management system which supports interoperable semantic management.

We conducted a multi-center phase I/II trial of nonmyeloablative stem cell transplantation for patients with hematologic malignancies. The aim of this trial was to assess the safety and feasibility of this treatment modality for older or younger patients with significant organ dysfunction, who could not be treated with conventional high dose chemoradiotherapy. Twelve patients were treated with a conditioning regimen consisting of fludarabine and cyclophosphamide, followed by peripheral blood stem cell transplantation from human leukocyte antigen (HLA) identical siblings. Nonhematologic toxicities were mild. Median time to absolute neutrophils above 0.5 x 10(9)/l, 1.0 x 10(9)/l and platelets above 50 x 10(9)/l were 8, 10 and 12 days, respectively. Donor dominant hematopoiesis was achieved in all patients, with or without donor leukocyte infusion. The cumulative incidence of acute and chronic graft-versus-host disease (GVHD) was 75 and 56%, respectively. Only one patient experienced early death within 100 days, caused by acute GVHD complicated by fungal infection. All patients except one achieved complete remission. With a median follow-up of 330 days, expected progression-free survival is 75%. Overall survival is 76%. Our study confirms that nonmyeloablative stem cell transplantation with cyclophosphamide and fludarabine conditioning is a safe and promising treatment for elderly patients with hematologic malignancies. A further study in large-scale setting is warranted.

In spectral analysis of temporally varying signals, constant Q-value filter banks using the short time spectral analysis method is known to be effective because the frame length can be changed freely with the method depending on the frequency. We have already reported an analysis with the LMS algorithm. But, the constant Q-value filter banks couldn't be constructed by this method because the parameters to control the stability and convergence factor of systems were scalar values. In order to realize the constant Q-value filter banks with this spectral analysis method, it is necessary to change the parameters of the stability and convergence factor from scalar to diagonal matrix. We first derive a LMS algorithm for this method. Then the characteristics of this spectral analysis method were found by extending the discussion to stability conditions of the method. Furthermore, the effectiveness of the proposed method for transfer performance was experimentally demonstrated by applying it to the analysis of human voices and acoustic waves generated by musical instruments.

The mouse for a personal computer is now replacing the keyboard for computer input devices, due to it's ease of use and the progress of operation systems. A mouse is easy for a nondisabled person to operate, however not so easy for a handicapped person. In particular, a cerebral paralyzed person and a proximal spine injured person often have much difficulty in dealing with a mouse or can't use it at all. However, a person with a C4 injured spinal nerve is able to bend, stretch and rotate his neck and also able to raise his shoulders because the functions of his sternodeidomastoid and trapezius muscles remain. For those people, the authors have developed an input system using neck and shoulder motions instead of manual input by a mouse. In this study, two kinds of devices using limit switches and linear potentiometers were developed and both of the results were compared. As operability has to be improved, practical usefulness for the handicapped person was confirmed. Finally, the feasibility of such systems being used for the driving wheel-chairs was examined.

Over the past sixteen years, newspaper PCSs (Production Control Systems) have been developed to support newspaper production, so that newspaper publishers can offer the most up to date information to the greatest possible number of readers in a timely manner while keeping production costs low. Up to now, the chief goal has been to produce a predetermined number of copies of a stylized newspaper (using a set layout and set number of pages) as efficiently and accurately as possible. However, in today's information-oriented society, readers and advertising clients have come to expect low cost newspapers that reflect their various interests and demands. To satisfy these, a PCS should aim at providing a reliable and flexible production system that allows immediate changes in format and circulation volume according to article contents, as well as coordinated production (printing and delivery) between locally distributed printing plants. In this paper, a new newspaper PCS architecture and data-processing and networking techniques are discussed based on an autonomous decentralized system (ADS). The architecture provides a system that allows flexible change of the production schedule, while ensuring reliability, because it has autonomous filtering functions that distinguish between different kinds of data, namely control data and man-machine data. The Asahi Shimbun newspaper company currently uses this highly effective system in its Setagaya printing plant.

A total of 23 newly-synthesized 2-aminomethylene-3(2H)-benzofuranone and structurally-related compounds were compared for their cytotoxic activity against both normal (human gingival fibroblast HGF) and tumor cells (human oral squamous cell lines HSC-2, HSC-3 and human salivary gland tumor cells HSG). There was a significant variability of drug sensitivity among the oral tumor cell lines. In general, HSC-2 cells were the most sensitive, followed by HSG cells, while HSC-3 cells were the most resistant. HGF normal cells were highly resistant to all compounds, suggesting their tumor-specific cytotoxic action. The cytotoxic activity of the compounds with morpholine, 1-methylpiperazine or piperidine structure was generally elevated by the introduction of fluorine, but not chlorine and methoxy functional groups, to the benzofuranone structure, whereas that of compounds attached by 1-phenylpiperazine or 1-(2-pyridyl)piperazine was rather reduced. The most active compounds induced internucleosomal DNA fragmentation in human promyelocytic leukemia HL-60 cells, but not in HSG, further confirming that oral tumor cell lines are resistant to DNase digestion.

We report a Japanese family with Sebastian platelet syndrome. Twenty-one thrombocytopenic patients exhibited giant platelets and inclusion bodies in their granulocytes. They were thought to be related because they bore the same surname and lived within a localized area. None of them had additional clinical findings peculiar to Fechtner syndrome. Ultrastructural studies of the granulocytes were performed on four patients. The inclusion bodies in the granulocytes were different from those found in May-Hegglin anomaly, and consisted of ribosome clusters and rough endoplasmic reticula.

A total of 11 newly synthesized benzothiepins and structurally-related compounds were investigated for cytotoxic activity against both normal and tumor cells. All these compounds showed higher cytotoxic activity against three human oral tumor cell lines (HSC-2, HSC-3, HSG) than against normal human gingival fibroblast (HGF), suggesting tumor-specific cytotoxic action. In general, 3,4-dihydro-1-benzothiepin-5(2H)-ones [1-6] showed higher cytotoxic activity than 2,3-dihydro-1-benzothiepins [7-11]. Compounds 4 (4-bromo-3,4-dihydro-2-(2-oxo-2-phenylethyl)-1-benzothiepin-5(2H)-one), 5 (4-bromo-3,4-dihydro-2-(2-oxopropyl)-1-benzothiepin-5(2H)-one) and 6 (4-bromo-3,4-dihydro-2-[1-(methoxycarbonyl)-1-methylethyl]-1-benzothiepin-5(2H)-one), showed higher cytotoxic activity than compounds 1, 2 and 3, respectively, which had Cl instead of Br at C-4 position. Agarose gel electrophoresis demonstrated that these compounds induced large DNA fragments in oral tumor cells, whereas they produced smear pattern of smaller DNA fragments in human promyelocytic leukemia cells HL-60. These data suggest the medicinal efficacy of benzothiepins.

Twenty patients with advanced hematological malignancies at high risk of relapse who had each received a bone marrow transplant from a matched sibling were registered between October 1996 and January 2000. Cyclosporine (CSP) was tapered on day 40 and stopped on day 50 in 10 patients without prior grade II-IV acute graft-versus-host disease (GVHD), relapse or active infection. These patients were eligible for early tapering of CSP. Although grade II/III acute GVHD was observed in three patients and chronic GVHD in eight patients after CSP tapering, no patients died of GVHD. Three patients died due to disease relapse and one patient died of idiopathic interstitial pneumonia while in remission. The probability of event-free survival at 2 years was 60%. These result indicate that early tapering and withdrawal of CSP is feasible and may provide a graft-versus-leukemia effect in patients with advanced leukemia.

We report a patient with chronic myelogenous leukemia who received a second transplant from a one-locus HLA-mismatched unrelated donor after rejection of an initial bone marrow graft. For the first transplant, HLAs were fully matched, conditioning with busulfan + cyclophosphamide (CY) was applied, and cyclosporin A + short-term methotrexate (sMTX) was used for prophylaxis against GVHD. A complete chimera was not obtained, and the graft was rejected on day 122. For the second transplant, there was a one-HLA locus (DR) mismatch, conditioning was done with total body irradiation + cytarabine + CY, and GVHD prophylaxis consisted of FK506 + sMTX. Engraftment was obtained on day 27, and no graft failure was occurred at the time of writing. This case suggests that strong immunosuppression may have prevented rejection of the second bone marrow graft.

The relationship between the polyol pathway and sugar cataracts has been studied extensively using streptozotocin-induced diabetic rats and galactose fed rats as animal models for insulin-dependent diabetes mellitus (IDDM). In these models, sugar cataracts progress quickly, leading to rapid lenticular polyol accumulation in the early stages of cataract formation. In 1992, a new animal model of non-insulin-dependent diabetes mellitus (NIDDM), the Otsuka Long–Evans Tokushima Fatty (OLETF) rat, was established. In the present study, we examined both biochemical and morphological changes in the lenses of the OLETF rats to determine whether these changes reflect those associated with diabetic cataract formation and to clarify their relationship with the polyol pathway. For the biochemical analysis, we measured the enzyme activity of aldose reductase (AR) and sorbitol dehydrogenase (SDH) and the sorbitol levels using 20, 40 and 60 week old OLETF or control Long–Evans Tokushima Otsuka (LETO) rats. Enzyme activities of AR and SDH, which were lower in 20 week old OLETF rats than in LETO rats, were increased in 60 week old OLETF rats. The lenticular sorbitol level of the OLETF rats was similar to the control level at 20 weeks of age, but it was markedly increased at 40 weeks of age, and slightly decreased at 60 weeks of age compared with rats at 40 weeks but not compared with controls. Slight lens fiber swelling was observed in the anterior and/or posterior subcapsular regions of 40 week old OLETF rats, accompanying elevated sorbitol level and slightly increased SDH activity in the lens. Swelling and liquefaction of lens fibers were observed in the subcapsular and supranuclear region of 60 week old OLETF rats, as well as decreased lenticular sorbitol, and markedly increased SDH activity compared with rats at 40 weeks. AR activity was also increased causing the elevation of sorbitol in lenses of OLETF rats during the early stages of cataract formation. Despite differences in the etiology of diabetes mellitus, the strain of rat and the rate of disease progression in the OLETF rat model compared with other diabetic models, the present results support the theory that the polyol pathway via AR is a factor in the development of sugar cataracts.

A 35-year-old man with chronic myeloid leukemia (CML) in blastic crisis (BC) received an allogeneic bone marrow transplant from an unrelated donor in October 1998 after three cycles of chemotherapy. BC relapse developed on day 349 after transplantation. After one cycle of chemotherapy and treatment with interferon, the patient received donor lymphocyte infusion (DLI), and this resulted in a complete cytogenetic response 21 days later. Grade III acute graft-versus-host disease developed on day 25 after DLI, but this was resolved after administration of prednisolone. Disease relapse occurred at extramedullary sites on day 162 after DLI, and the patient died of sepsis after receiving chemotherapy. This case illustrates that unrelated DLI can induce remission successfully in patients with relapse of CML in BC through a graft-versus-leukemia effect.

To clarify the possible link between radicals and cytotoxicity of eugenol-related compounds, dimeric compounds were synthesized from eugenol (4-allyl-2-methoxy-phenol), butylated hydroxyanisole (BHA) (2-t-butyl-4-methoxyphenol) or MMP (2 methoxy-4-methylphenol); bis-EUG (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol), bis-BHA (3,3'-di-t-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol), and bis-MMP (3,3'-di-methoxy-5,5'-dimethyl-1,1'-biphenyl-2,2'-diol). The cytotoxic activity of these compounds was determined using a salivary gland tumor cell line (HSG), oral squamous cell carcinoma cell line (HSC-2) and human promyelocytic leukemia cell line (HL-60). A parabolic relationship between the cytotoxicity and log P (the octanol-water partition coefficient) was observed, showing that both BHA and bis-MMP, with a log P of 3-4, were the most cytotoxic. The cytotoxic activity of the 2-methoxy derivatives, eugenol, MMP and bis-MMP, against HSG cells was significantly enhanced by visible-light irradiation, possibly due to their high redox potential. Electron spin resonance (ESR) spectroscopy indicated that eugenol and BHA alone produced radicals under alkaline conditions (pH9.5), and eugenol most efficiently scavenges reactive oxygen species (O2-). Antioxidative reactivity of eugenol-related compounds was determined by measuring the inhibiting periods of the AIBN (2,2'-azobisisobutyronitrile)/MMA (methyl methacrylate) polymerization system, and the number of moles of peroxy radical trapped by moles of the relevant phenols (stoichiometric factor, n). It was found that the n values of eugenol and MMP were approximately 1, whereas those of BHA2, suggesting that eugenol and MMP undergo dimerization through radical-radical couplings through quinone methides, whereas BHA undergoes the competitive interaction with poly-MMA radicals after oxidation by AIBN-peroxy radicals. BHA was an efficient peroxy radical-scavenger, but possibly reacted with polymer radicals of the lipid, thus mediating the cytotoxicity. The n value of bis-BHA was two, whereas those of bis-EUG and bis-MMP were 1.6-1.7, suggesting that the latter were further oxidized. The enthalpies of phenoxyl radical formation were determined using the semi-empirical PM3 quantum-mechanical method and the possible link to redox potential was discussed.

In patients with both p210-bcr-abl (p210) and p190-bcr-abl (p190)-positive acute lymphoblastic leukemia, the number of p190 transcripts is lower than that of p210 transcripts. It is speculated that the p190 transcript occurs as a consequence of alternative splicing or missplicing events in the BCR gene. Four patients with both p210- and p190-positive acute lymphoblastic leukemia were studied for expression of p210 and p190 by RT-PCR before and after allogeneic bone marrow transplantation. p190 negativity was documented in all four patients, followed by p210 negativity one to two months later in three patients. These results suggest that negativity for p190 indicates an ongoing decrease in the small number of residual leukemic cells. In one patient p190 appeared transiently in spite of prolonged negativity for p210 18 months after bone marrow transplantation. We conclude that analysis of p210 and p190 is useful for following up patients with both p210- and p190-positive acute lymphoblastic leukemia.

The atomic force / lateral force microscope (AFM/LFM) using the optical lever method works as a two-dimensional frictional-force microscope (2D-FFM) in case of the atomically flat sample surface. On an atomic scale, the sliding body cannot be approximated to a uniform one but becomes a periodic one. As a result, the friction motion shows a lattice periodicity and becomes two-dimensional, because of the symmetry breaking of the stick-point distribution along the sliding (scanning) direction. Using a 2D-FFM, we can investigate the elementary process of the friction under the elastic deformation region, i.e., the two-dimensional nature of the atomic-scale friction with a lattice periodicity. Here, we show how to analyze the experimentally obtained 2D-FFM image patterns and how to deduce the load dependence of the effective adhesive region and also the stick-point distributions.

The inhibitory effects of six phenolic compounds and two analogues on the polymerization of methyl methacrylate (MMA) by azobisisobutyronitrile (AIBM) were examined. Differential scanning calorimetry was used to determine the induction period (IP) and initial rate of polymerization (IRP). The IP values (minutes) decreased in the order: eugenol>thymol>hydroquinone>cresol>quaiacol> phenol>>>ssafrole> methol. The IRP values of all compounds tested ranged from 0.8 to 1.2 percent per minute, except for hydroquinone (0.2 percent per minute). Phenolic compoundsinhibited the polymerization of MMA by scavenging radicals, and eugenol was the most potent inhibitor.

Hydroquinone (HQ) dose-dependently reduced the viable cell number of oral tumor cell lines (HSC-2, HSG). HQ induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 nor HSG cells. Cytotoxic activity of HQ was slightly reduced by catalase, but was enhanced by superoxide dismutase, suggesting the possible involvement of hydrogen peroxide in HQ-induced cytotoxicity. This was supported by slight increase or decrease of cytotoxicity of HQ in the presence of Cu2+ and Fe3+, respectively. Lower concentrations of sodium ascorbate, ascorbic acid and ascorbic acid 6-palmitate reduced both the radical intensity and cytotoxic activity of HQ, more efficiently than ascorbic acid 2,6-dipalmitate, in contrast to the cytotoxic action of these ascorbates at higher (millimolar) concentrations. Popular antioxidants such as N-acetyl-L-cysteine and cysteine also reduced the radical intensity and cytotoxic activity of HQ. The present study suggests that cytotoxic activity of HQ is generated by radical-mediated oxidation mechanism.

The ability of nine synthetic eugenol-related compounds to scavenge O2- (generated by the hypoxanthine-xanthine oxidase reaction) was compared with their radical generation and cytotoxic activity. ESR spectroscopy showed that eugenol (4-allyl-2-methoxyphenol), 2-allyl-4-methoxyphenol, 2-allyl-4-t-butylphenol and 2,4-dimethoxyphenol efficiently scavenged O2- and produced radicals under alkaline conditions. 2-allyl-4-t-butylphenol showed the highest cytotoxic activity and DNA-synthesis inhibitory activity, possibly due to the hydrophobic radical reactivity. 2-allyl-4-methoxyphenol and 2,4-dimethoxyphenol showed higher antioxidant activity than 3-t-butyl-4-hydroxyanisol (BHA), but all these compounds showed comparable cytotoxic activity with each other. These findings suggest a possible link between the cytotoxic activity and radical generation/scavenging activity in eugenol-related compounds.

To investigate the possible link between radicals and cytotoxicity of eugenol-related compounds, dimer compounds were synthesized from eugenol (4-allyl-2-methoxyphenol) or isoeugenol (4-propenyl-2-methoxyphenol): bis-eugenol (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol); dehydrodiisoeugenol (2-(3-methoxy-4-hydroxyphenyl)-3-methyl-5-(1-propenyl)-7-methoxy-2,3- dihydrobenzofuran) and alpha-di-isoeugenol (r-l-ethyl-5-hydroxy-t-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-c-2- methylindane). Both the cytotoxic activity and the DNA synthesis inhibitory activity of these compounds against a salivary gland tumor cell line (HSG) and normal human gingival fibroblast (HGF) were decreased in the order of: dehydrodiisoeugenol, alpha-di-isoeugenolisoeugenoleugenolbis-eugenol. Electron spin resonance (ESR) spectroscopy showed that dehydrodiisoeugenol, alpha-di-isoeugenol and eugenol, but not isoeugenol and bis-eugenol, produced phenoxyl radicals under alkaline condition (pH9.5). However, benzyl radicals were produced during the dimerization of isoeugenol to dehydrodiisoeugenol. The radical intensity of alpha-di- and dehydrodiisoeugenol appeared at relatively later incubation time than eugenol, suggesting that their phenoxyl radical was more stable than that of eugenol. Such a phenoxyl radical is produced by scavenging free radicals, during the inhibition of lipid peroxidation. Higher cytotoxic activity of isoeugenol dimers was thought to be induced by interaction with cell membranes via the lipophilic radical. The present study supports the notion that relative cytotoxicity of chemicals can be evaluated by measuring the radical intensity using ESR.

The interaction between hydroquinone (HQ) and ascorbic acid analogs was investigated. Semiquinone radicals (SQ.) generated by HQ were comparably scavenged by ascorbic acid, sodium ascorbate and ascorbate 6-palmitate, but much less efficiently by ascorbate 2,6-dipalmitate. Organic solvents, such as dimethysulfoxide (DMSO) or ethanol, which are utilized for solubilization of water-insoluble analogs, ascorbate 6-palmitate and ascorbate 2,6-dipalmitate, also scavenged SQ.. DMSO scavenged the SQ. more efficiently than ethanol. This suggests the importance of considering such a quenching effect of organic solvent in the study of the interaction between HQ and antioxidants. The involvement of the ascorbate radical for cytotoxicity induction is discussed.

Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.

We have investigated the stability of semiquinone radical (SQ .) produced from the mixture of hydroquinone (HQ) and bisphenol A (BPA) in the presence of various antioxidants, some of which induce apoptosis in tumor cell lines. BPA produced no detectable amount of ESR signal. The acceleration of HQ oxidation by BPA results in the production of SQ .. The BPA-enhanced SQ . production may occur through either SQ. regeneration by electron transfer from BPA working as an antioxidant or the O2- scavenging activity of BPA. SQ . intensity of HQ/BPA was reduced by lower concentrations of sodium ascorbate, epigallocatechin, gallate and quercetin, but significantly enhanced by gallic acid. The initial SQ . was replaced by the radicals of antioxidants except lignin and salicylic acid, at higher concentrations, due to their radical-radical coupling or dismutation process. Among these compounds, gallic acid enhanced the radical intensity of SQ . to the greatest extent. The results suggest that antioxidants from foods suppress the activity of xenobiotics such as HQ, however, they produce their own radical at higher concentrations, suggesting their bimodal actions. The present study demonstrates the usefulness of ESR spectroscopy for the interaction between HQ/BPA and antioxidants.

The slowly activating delayed rectifier K(+) current (I(Ks)) was recorded in single myocytes dissociated from guinea-pig ventricles and the mechanism underlying the block of I(Ks) by a chromanol derivative, 293B, was investigated. In the presence of 1 - 100 microM 293B, activation phase of I(Ks) was followed by a slower decay during 10 s depolarizing pulses. Both the rate and extent of the decay were increased in a concentration-dependent manner. The relationship between the concentration of 293B and the block showed a Hill's coefficient of approximately 1. The half-inhibitory concentration was approximately 3.0 microM and did not differ significantly at various membrane potentials from +20 to +80 mV. A mathematical model for the 293B block was constructed on the basis of multiple closed and open states for the I(Ks) channels, and the blocking rate was calculated by fitting the model to the original current traces. The blocking rate constant showed a linear function with the 293B concentration, indicating 1 : 1 binding stoichiometry. At +80 mV the blocking rate was 4x10(4) M(-1) s(-1) and the unblocking rate was 0.2 s(-1). The results indicate that 293B is an open channel blocker with relatively smaller blocking rate than those reported so far for time-dependent blockade of various ionic channels.

This study was undertaken to identify the factors influencing pulmonary function in patients who underwent hematopoietic stem cell transplantation (HCT). Pulmonary function tests were evaluated before and after HCT in 51 adult patients who underwent HCT between 1993 and 1998. The patients with hematologic malignancies were given total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Six patients suffered from acute GVHD above grade II and 27 patients suffered from chronic GVHD. The post-transplant % diffusing capacity (%DLco) 100 days after HCT was significantly lower than pretransplant values (82 +/- 21% versus 71 +/- 15%, p0.01). The %DLco at 100 days was significantly lower in patients with chronic GVHD than in patients without chronic GVHD (66 +/- 16% versus 77 +/- 9%, p0.05). These findings suggested chronic GVHD is related to the decreased %DLco values observed 100 days after HCT.

The radical intensity of BHA (4-Hydroxy-3-t-butylanisole) and its dimer (3,3'-Di-t-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol, Bis-BHA) were compared with their cytotoxic activity. ESR spectroscopy showed that BHA produced characteristic five peaks of radicals under alkaline conditions (pH9.5). At higher pH, BHA radical rapidly disappeared, and progressively transformed into new radical species, as detected by the splitting of the ESR signal. BHA showed higher cytotoxic activity against salivary gland tumor cell line than against normal human gingival fibroblast. On the other hand, Bis-BHA did not produce any detectable amounts of radicals at wide ranges of pH, corresponding with its weaker cytotoxic activity as compared with BHA. BHA scavenged DPPH (1,1-Diphenyl-2-picrylhydrazyl) radical and superoxide anion, more efficiently than Bis-BHA. The present study demonstrated that BHA is more cytotoxic, produces higher amounts of radicals and more efficiently scavenges various radical species, as compared with Bis-BHA. This suggests the possible link between the cytotoxic activity and radical generation/scavenging activity in BHA-derived compounds.

A 22-year-old woman was admitted with purpura. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. On the 17th day after treatment with all-trans retinoic acid (ATRA), left subdural hematoma developed. Although coagulation abnormalities were still observed, emergency surgery was performed. Acute epidural hematoma was confirmed by computed tomographic scan after the operation. A second operation for drainage was successful. Post-operative intracranial hematoma may be caused by rapid decompression induced by surgery, but DIC could also be involved. This case underscored the need for careful consideration of the indications for surgical treatment of such DIC patients, with close follow-up monitoring for the postoperative development of neurological symptoms.

Precision and accuracy are important to assure the quality of clinical laboratory tests. We investigated the precision and accuracy of white blood cell (WBC) differentiation by automated blood cell analyzers. The coefficients of variation (CVs) of neutrophil, lymphocyte, monocyte, eosinophil and basophil differentiation by GEN.S (Coulter), based on a flow system and VCS technology, were 1.1%, 1.5%, 4.6%, 2.1%, and 33.3%, respectively. Between-run precision for neutrophil, lymphocyte, monocyte, eosinophil and basophil differentiation by GEN.S using cell control, 5C in 26 serial days was 2.0%, 2.8%, 6.5%, 9.2%, and 29.5%, respectively. The precision of WBC differentiation by blood cell analyzers based on the flow system was excellent except for basophil. We studied the accuracy of WBC differentiation by blood cell analyzers based on the flow system in contrast with eye-count. The correlations between neutrophil, lymphocyte, monocyte, eosinophil, and basophil percentages counted by GEN.S and by eye-count were r = 0.968, 0.971, 0.902, 0.940, and 0.391, respectively. The agreement rate between WBC differentiation by Microx, a blood cell analyzer based on pattern recognition, and eye-count cell by cell was good except for basophils. The accuracy of WBC differentiation by blood cell analyzers was also excellent excluding basophils.