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The experimental apparatus used for the first direct observation of the tau neutrino (the DONUT experiment) is described. Its main features consisted of a target system composed of nuclear emulsion targets and scintillation fiber trackers, a magnetic charged-particle spectrometer and detectors for lepton identification. This paper will concentrate on the description of the electronic detectors and their performance in selecting neutrino interactions, making the vertex predictions necessary for locating events in the emulsion target and lepton identification. © 2003 Elsevier B.V. All rights reserved.

A 27-year-old man with a traumatic direct dural arteriovenous fistula (DAVF) was treated using embolisation microcoils. He had suffered blunt trauma to the head while drunk and was aware of no neurological deficit. A few days after the accident, however, he noticed a bruit in the right temple. Angiography demonstrated a direct DAVF fed by the right middle meningeal artery and draining into a right temporal dural vein and the ipsilateral cavernous sinus. A Tracker-18 catheter was passed without difficulty through the fistula and the draining vein was then embolised from distal to proximal with microcoils, and finally the fistula was occluded with microcoils, resulting in total obliteration of the fistula. Immediately after the embolisation, the patient could no longer hear the bruit. Thus, when a microcatheter can be introduced into the draining vein, microcoils can be used as emboli in the treatment of direct DAVF.

The objective of this study was to investigate the presence of tumor necrosis factor-alpha (TNF-alpha) in the central nervous system and the effects of lipopolysaccharide on central and peripheral concentrations of TNF-alpha, behavioral conditions (standing or lying), elimination scores (defecation or urination), rectal temperature, and food intake (as-fed basis) in Chinese Meishan pigs. Intravenous injections of lipopolysaccharide resulted in increased (P0.05) plasma concentrations of TNF-alpha and cortisol. Although urination was not affected by the administration of lipopolysaccharide, defecation was stimulated (P0.05). Lipopolysaccharide increased (P0.05) rectal temperature and standing rate, and inhibited (P0.05) food intake in pigs. To determine whether TNF-alpha is present in the porcine central nervous system as well as in peripheral blood, TNF-alpha and its specific transcripts in brain tissues (hypothalamus, amygdala, or hippocampus) and the pituitary were determined. The abundance of TNF-alpha messenger RNA and immunoreactive TNF-alpha were observed in all tissues, and the concentrations of TNF-alpha were increased (P0.05) by the intramuscular injection of lipopolysaccharide. These results suggest that TNF-alpha is present in the central nervous system, and plays some roles in its biological regulation in Chinese Meishan pigs.

Presents an anthropomorphic robot hand called Gifu hand II that is a revised version of the Gifu hand I. The Gifu hand II has five fingers in which all joints are driven by servomotors built in the fingers and the palm. The thumb has 4 joints with 4 degrees of freedom (DOF), the other fingers have 4 joints with 3 DOF respectively, and two axes of joints near the palm cross orthogonally at one point like the human finger. It can be equipped with a 6 axes force sensor at each fingertip and a developed distributed tactile sensor with 624 detecting points on its surface. The design concepts and the specifications of the Gifu hand II, the basic characteristics of the tactile sensor, and the pressure distributions at object grasping are shown. These show that the Gifu hand II has a high potential to perform dexterous object manipulation like a human hand.

A compact SOI MOSFET model based on the Bsim3v3 bulk model with new features of effective substrate bias and transition voltage concepts to cover the transition behavior from partially-depleted to fully-depleted modes, R/sub out/ smoothing, enhanced models for impact ionization, L/sub eff/-dependent parasitic BJT and self-heating is proposed. Results obtained from this model are in excellent agreement with the experimental I-V, C-V and propagation-delay time data.

Previously we have addressed a 'man-machine system' as two agents and accomplished a certain degree of effectiveness. We extend the framework to a three agent model for a 'man-machine-man system'. This concept includes two humans and one artifact. When it was unacceptable to attain a target relationship for two humans, a support-agent which stands on mutual compensation could supplement their relationship. We suggest this method and construct a three agent model equivalent to a pair of humans and one machine which supports the communication between two humans. By the medium of computer simulation we observe and analyze this agent model. In our model, an agent which has incomplete information toward other agents can perform cooperative work. In the results of computer simulations, coupled triple agents show the effectiveness of our system.

The authors propose a novel scheme of vector quantization with memory, named vector quantization with short-time memory (VQ-STM). The VQ-STM has two types of codebooks, a fixed-structure codebook whose codewords are kept unchanged, and a variable-structure codebook, which is defined as a subset of the fixed-structure codebook and whose structure is continually updated depending on the past behavior of the coder. The VQ-STM coder chooses the proper codebook between two codebooks for every input vector. The update of the variable-structure codebook is easily performed only by simple heuristics for maintaining a finite-length self-organizing sequential list which stores past coder outputs. The results of experimental simulations conducted on monochrome images demonstrate that significant compression gains can be achieved by enhancing the vector-quantization approach with the concept of short-time memory. >

Some research institutes are elaborating plans to develop very high definition (VHD) visual media beyond the HDTV. Although a CCD camera with two million pixels has been developed for HDTV, the spatial resolution should be increased further to acquire VHD images. Reducing the pixel size is the most straightforward way to increase the spatial resolution, which makes a CCD imager much more sensitive to shot noise. To keep shot noise invisible on a monitor, there needs to be a limitation in the pixel size reduction. The current CCD technology has almost reached this limit. Therefore, a new approach is required to enhance the spatial resolution further beyond this limit. The authors present a new method for acquiring VHD images by processing and integrating multiple images taken simultaneously with different cameras. >

Considering the development of an efficient coding technique for high-fidelity compression of very high resolution images, the authors first compare three different scalar quantization schemes and improved permutation codes from the aspect of quantization performance for a memory-less probability distribution that well approximates the real statistical properties of high frequency sub-band signals, and demonstrate that at low coding rates the improved permutation codes algorithm is the most suitable quantization scheme. Furthermore, the authors develop a rate-adaptive quantization technique that chooses the proper quantization scheme from among different types of quantization schemes according to the number of bits allocated to each subblock, and apply it to the high-fidelity encoding of sub-band signals. The results of simulations conducted on very high resolution images demonstrate that the proposed rate-adaptive quantization technique is very useful as a means for quantizing sub-band signals of very high resolution images. >

We determine the number of solutions of the equation $a_1 x_1+a_2 x_2+cdots+a_m x_m=b$ in non-negative integers $x_1$, $x_2$, $dots$, $x_n$. If $m=2$, then the largest $b$ for which no solution exists is $a_1 a_2-a_1-a_2$, and an explicit formula for the number of solutions is known. In this paper we give the method for computing the desired number. The method is illustrated with several examples.

Diffusion processes in the soil water and air phases often govern transport and fate of nutrients, pesticides, and toxic chemicals in the vadose zone. This final paper in a 10-part series on diffusion-reaction processes in soils concerns the development of a unifying model platform for predicting so

We present a new stabilized zero-crossing representation with a salient feature that the signal reconstruction problem reduces to a typical minimum-norm optimization problem, the solution of which is formulated as a linear simultaneous equation, and develop an iterative algorithm for signal reconstruction. Moreover, we extend them to the two-dimensional case. With the extended two-dimensional reconstruction algorithm we can almost perfectly reconstruct an original image from the stabilized two-dimensional zero-crossing representation, and after some dozens of iterations the algorithm provides a reconstructed image with subjectively high picture quality. Furthermore, we introduce a threshold operation based on edge intensity to reduce the amount of information in the stabilized zero-crossing representation, and experimentally demonstrate that the threshold operation works well.

We present image processing algorithms for the generic temporal-integration video-enhancement approach based on the global segmentation representation of motion, and demonstrate their usefulness by experimental simulations. As a specific case, here we take up the interlaced-to-progressive scan conversion problem, form the interlaced-to-progressive transform along the line of the temporal integration, and then experimentally evaluate it. The experimental simulations demonstrate that the temporal-integration approach is very promising as a basic means of video enhancement.

We present image processing algorithms for the generic temporal integration video enhancement approach based on the global segmentation representation of the motion, and demonstrate their usefulness by experimental simulations. As a specific case, here we take up the interlace-to progressive scan conversion problem, from the interlaced-to-progressive transform along the line of the temporal integration and then experimentally evaluate it. The experimental simulations demonstrate that the temporal integration approach is very promising as a basic means of video enhancement.

By restricting object tracking, we form a robust object-specified active contour model which adapts itself to the properties of the specified object, that is to say, the objective smoothly deformable line-feature. The proposed model allows us to track the objective deformable line-feature throughout the entire observed noisy moving image sequence automatically. Furthermore we apply it to the surveillance image processing task that suspended power-transmission wires swinging due to strong winds are automatically tracked in an observed outdoor noisy moving image sequence. The experimental results demonstrate that the proposed method is considerably robust to noise.

We present a simple cue-based method for camera calibration aimed at 3-D shape measurement with a single domestic camera. This method performs both camera calibration and measurement of the 3-D shape simultaneously by projecting objects of measurement along with a cue object having feature points onto one image plane while moving the single camera by hand. Our proposed method requires only four coplanar points, and hence the use of a simple geometrical structure such as A4 size paper as the cue object allows us to perform measurement of the 3-D shape easily without special equipment. Furthermore, the method modifies the observed feature points' coordinates with the optimization method which formulates the orthogonality constraint between coordinate axes given by the camera calibration.

A 3.3 V 1 W 240 Mb/s EPRML read/write channel LSI for hard disk drives uses 0.4 /spl mu/m CMOS technology. Analog implementation of the entire channel has lower power consumption, because it eliminates the power-consuming A/D converter. It requires a BiCMOS process for precise analog circuits. The digital approach uses an A/D converter that provides precise digital signal processing. Here, the CMOS digital approach is used because it has potential for advanced signal processing. Two important issues are 1) reduction of the power consumption of extensive digital circuits and the A/D converter, and 2) breaking the speed bottleneck of the A/D converter. To reduce power consumption, a 0.4 /spl mu/m CMOS process with 3.3 V supply voltage is used. In addition, 3.3 V analog CMOS circuits are used, such as a gain controlled integrator for 7th-order equiripple active filters and an analog PLL.

This paper proposed a bilateral controller of a flexible master-slave manipulator (FMSM). A FMSM consists of a conventional compact rigid master arm and a flexible slave arm, and will be used in outer space in the future. This controller realizes stable compliance control and vibration control. The key idea is that this controller has dual compliance models.

The film material of old movies is often corrupted by blotches. We present a practical simple easy-implementable method for removing blotches and restoring their missing data. To cope with the motion, instead of estimating an optical flow directly, we take up the robust approach of a local analysis of spatiotemporal anisotropic gray-level continuity. The approach uses simple first-order directional derivatives to select the most smooth direction for each examined pixel, and puts out the incorruption probability that the examined pixel may not be corrupted by blotches. As the restoration filter, we employ a spatiotemporal fuzzy filter whose response is adaptively controlled according to a fuzzy rule with incorruption probability. We design the fuzzy rule in advance by some training method. Computer simulations are presented.

Concerns the automatic generation by computer of moving crowd graphics. Motion of animal flocks has been studied, but seldom human crowds. We are concerned with modeling and generation of a crowd in a 3D virtual city to increase reality. Virtual cities often have few inhabitants, and those are controlled by the users or only repeat behavior based on strict rules. For a more natural atmosphere, many data and rules are needed. A general view of a crowd reveals significant characteristics. Though the behavior of each figure is independent, the crowd, as a huge mass of it, has a pattern as a whole. Chaos is very convenient to represent such features. It is controlled by a few parameters. For instance, since chaos is influenced quite sensitively by initial value, it can produce various nonmutual values that decide the next actions of the figures. Moreover, these values form themselves into an attractor. As the attractor is transformed by changing a parameter, we can easily control the shape of the crowd. Although random numbers are often applied to such purposes, it is difficult to create and control such patterns. Utilizing these characteristics of chaos, we constructed the models of the crowd in the street and the folk dance. The prototype system was developed for evaluation and it was confirmed that users felt easy to generate and control the crowd.

A new digital servo signal processing architecture with 8.8 bit resolution of position error signal for disk drives is presented. It achieves an 8.8 bit resolution of the position error signal by use of a 6 bit ADC (analog to digital converter) for the data channel. This new architecture uses only a full wave rectifier and a divider. The burst signal is rectified in the analog domain before being sampled by the clock, which has a higher frequency than the servo frequency, in the ADC.

In shallow waters, water motion is one of the most important environmental factors for marine organisms. This is particularly true in coral reefs, where the effect of flow is important for growth processes and spawning settlements of coral inhabiting the area. However, it is very difficult to measure the water motion in these areas with conventional current meters (propeller type and electromagnetic current meters etc.) due to the meter size and bottom topography. For sessile organisms such as coral and oysters, the maximum instantaneous current velocity rather than the intensity of the averaged flow is important. Therefore, to measure water motion in coral reefs, a plaster ball technique has been developed and used. However, plaster balls are usable for only 2 or 3 days. In the case of measuring with plaster balls, such as for spawning settlement and diffusion of coral larvae, it is necessary to examine a large number of points over a long time period. Previously, we presented a way to improve the material of the plaster balls to make them usable for longer periods. In this study, we examined measurements of water motion around coral reefs using a large number of normal plaster balls and improved plaster balls, including plaster for dentistry, cement, and other types. The results of our experiment in a patch reef in the Sekisei Lagoon (Okinawa Prefecture, Japan) clearly showed that the intensity of the flow varied with depth and position, and that a small vortex had been generated around the patch reef. We consider the effect of such differential water motion and small vortices on the growth processes and spawning settlement of coral.

Doubly-fed adjustable-speed pumped storage generating systems of large capacity have been newly installed in power systems with technologies of power electronics. These new generating systems contribute not only to frequency regulation of power system at nights by means of input power change as results of rotor speed control, but also to enhancement of power system stability by fast control of voltage and power. New analytical method based on extended Heffron-Phillips model was developed in order to support design of a power system stabilizer which is used to improve dynamic stability of the synchronous generators located in the vicinity of the doubly-fed generating system. A systematic approach based on the new analytical method is shown with numerical examples, explaining how to design the additional power system stabilizing controller of the doubly-fed generating system.

In shallow waters, such as coral reef or seagrass regions, the water motion is one very important factor for the surrounding marine organisms. In these areas it is very difficult to measure the water current with conventional current meters due to the sensor size and topography. To measure currents in shallow waters, a plaster ball technique has been already used. A plaster ball is constituted of a sphere made of plaster (diameter of about 4.0 cm), and a steel bar (length of about 30 cm). Thus, it can be set up not only at many points in the patch reef, but also in coastal regions. This technique to measure time-averaged intensity of water motion is already well known, and could be also valid to measure the water motion in seagrass, seaweed beds and coral reef regions. However, plaster balls are usable only for 2 or 3 consecutive days. The purpose of this study is to improve the material of plaster balls to make them usable for longer periods. The authors tested six different types of plaster balls: viz. plaster for dental use type 1, 2, and 3, polymer type, cement type, and paint type. They estimated the resolution rate using each plaster ball and normal plaster balls in the coral reef region by corroborating the measurements with those observed by electromagnetic current meters. Their experimental results in a patch reef in the Sekisei lagoon (Okinawa prefecture, Japan) indicated that the measurements could be possible for about one-week or ten days when using a sensor with cement in the plaster.

Recycling of Municipal Solid Waste is vigorously promoted in Japan and the necessity of energy recovery from organic waste is increasing. An anaerobic digestion demonstration plant for organic waste in Kyoto City, Japan has been operated for about two years. Three kinds of wastes (garbage and leftovers from hotels, yard waste and used paper) mixed at various ratios are used. The plant has maintained stable operations with each mixture, generating biogas by the decomposition of VS at the rate of about 820 m3N/ton-VS.

A Japanese patient with Weber-Christian disease (WCD) presenting with ocular symptoms is reported. Panniculitis in the retrobulbar fat was diagnosed according to the histological findings from biopsy specimens, and improved over a month under steroid administration. Only three patients showing ocular manifestations have previously been reported. Panniculitis was in the late stage and a medium dose of prednisolone was effective in this patient. A biopsy of the orbital fat was useful for diagnosis. However, it is important to recognise that the stage of inflammation varies according to the fat tissue involved by WCD.

Orbital MALT lymphoma is a relatively rare malignant disease, for which radiation therapy is effective. However, the optimal dose has not been determined. We experienced two cases of orbital MALT lymphoma. One patient was successfully treated, but the other developed a severe complication. We conclude that for safe treatment of orbital MALT lymphoma, a dose in excess of 40 Gy must not be delivered.

The DONUT experiment used an emulsion/counter-hybrid-detector, which succeeded in detecting tau-neutrino charged-current interactions. A new method of emulsion analysis, NETSCAN, was used to locate neutrino events and detect tau decays. It is based on a fully automated emulsion readout system (Ultra Track Selector) developed at Nagoya University. The achieved plate-to-plate alignment accuracy of ∼0.2 μm over an area of 2.6 mm×2.6 mm permitted an efficient and systematic tau decay search using emulsion data. Moreover, this accuracy allowed measurement of particle momenta by multiple Coulomb scattering, and contributed to the efficient background rejection for the ν τ candidates. This paper describes details of our emulsion analysis methods. © 2002 Elsevier Science B.V. All rights reserved.

The gamma-ray-detected blazar 3C 454.3 exhibits dramatic flux and polarization variations in the optical and near-infrared bands. In December 2010, the object emitted a very bright outburst. We monitored it for approximately four years (including the 2010 outburst) by optical and near-infrared photopolarimetry. During the 2010 outburst, the object emitted two rapid, redder brightenings, at which the polarization degrees (PDs) in both bands increased significantly and the bands exhibited a frequency-dependent polarization. The observed frequency-dependent polarization leads us to propose that the polarization vector is composed of two vectors. Therefore, we separate the observed polarization vectors into short and long-term components that we attribute to the emissions of the rapid brightenings and the outburst that varied the timescale of days and months, respectively. The estimated PD of the short-term component is greater than the maximum observed PD and is close to the theoretical maximum PD. We constrain the bulk Lorentz factors and inclination angles between the jet axis and the line of sight from the estimated PDs. In this case, the inclination angle of the emitting region of short-term component from the first rapid brightening should be equal to 90$^{\circ}$, because the estimated PD of the short-term component was approximately equal to the theoretical maximum PD. Thus, the Doppler factor at the emitting region of the first rapid brightening should be equal to the bulk Lorentz factor., 8 pages, 6 figures, accepted for publication in ApJ

Protein C is a vitamin K-dependent anticoagulant and homozygous protein C deficiency is a rare fatal thrombotic disease. This report describes the perioperative management of homozygous protein C deficiency in a patient who underwent a total of three surgical procedures under general anesthesia and the successful use of activated protein C concentrate.A female baby, who developed disseminated intravascular coagulation and purpura fulminans shortly after birth, was diagnosed as purpura fulminans syndrome due to homozygous protein C deficiency. At one month of age, she suffered bilateral retinal detachment and glaucoma due to retinal hemorrhage. After marked improvement of her condition after administration of activated protein C concentrate, she underwent a left iridectomy and implantation of a Broviak catheter under general anesthesia. Her intraoperative course was uncomplicated but, on postoperative day four, she presented another episode of massive cutaneous necrosis and gangrene. Activated protein C concentrate was administered again, with good results. She underwent replacement of a Broviak catheter at four months of age, and right iridectomy for glaucoma at eight months. Both were uneventful.The perioperative management of homozygous protein C deficiency and purpura fulminans requires appropriate measures for thromboembolic prophylaxis. Sufficient iv fluid administration is necessary. Attention should be paid to decrease the risk of tissue compression such as that associated with positioning, blood pressure cuff, and endotracheal intubation, which may cause necrosis over pressure points. Replacement therapy with activated protein C concentrate appears safe and effective. The anesthetic management is reviewed and discussed.

This study evaluated the efficacy of long-term pilsicainide therapy to maintain sinus rhythm in patients with paroxysmal atrial fibrillation in terms of the time of onset.A total of 81 patients (57 men, 24 women, mean age 65 +/- 11 years) were given pilsicainide (150 mg/day) after cardioversion. Paroxysmal atrial fibrillation was divided into three types by the time of onset: the day type (AM 7:00-PM 5:00, n = 13), the night type (PM 5:00-AM 7:00, n = 12) and the mixed type (n = 56). Mean follow-up period was 35.4 +/- 16.1 months.There was a higher incidence of hypertension in the day type (38.5%) and the mixed type (48.2%) than in the night type (8.3%) (p0.05). The periods for maintenance of sinus rhythm in the day type, the night type and the mixed type were 15.7 +/- 5.0, 9.9 +/- 2.7 and 5.7 +/- 1.3 months, respectively, with a significant difference between the day type and the mixed type (p0.01). Actuarial event free-rates at 1, 3, 6, 9 and 12 months were 76.9%, 69.2%, 61.5%, 53.8% and 53.8% respectively, in the day type, 83.3%, 66.7%, 58.3%, 33.3% and 33.3%, respectively, in the night type and 58.9%, 37.5%, 26.8%, 25.0% and 21.4%, respectively, in the mixed type. There was a significant difference in the rate at 12 months between the day type and the mixed type (p0.05).These results suggest that pilsicainide has a high degree of efficacy for maintaining normal sinus rhythm in patients with the day type onset of paroxysmal atrial fibrillation.

We examined changes in the concentrations of serum progesterone (P4), estradiol-17beta (E2), FSH, LH, prolactin (PRL), and inhibin to determine their interaction and their effect on the reproductive endocrine controls of pregnant and nonpregnant female Japanese black bears. Fourteen female bears were used in this study over a 2-yr period. In the first year, six of the bears were divided into two groups; a pseudopregnant group and a nonpregnant group. In the second year, the remaining eight bears were also divided into two groups; a pregnant group and a nonpregnant group. Pregnant and pseudopregnant bears had similar P4 trends with both groups exhibiting a significant increase in December, which is the suspected time of implantation in pregnant bears. These trends correlated with an increase in PRL levels, whereas low levels of LH were maintained throughout the year. Nonpregnant bears maintained low concentrations of P4, and compared with pregnant and pseudopregnant bears, they also exhibited a delayed elevation in PRL. Luteinizing hormone activity varied among individual animals, but regardless of reproductive status, fluctuation patterns of E2, FSH, and inhibin did not differ among bears. Our results suggest that PRL may play a luteotropic role in both pregnant and pseudopregnant bears, and is possibly responsible for inducing reactivation of the dormant corpus luteum that precedes implantation in the Japanese black bear.

Ovulation accompanied by tissue damage can cause an increase in the level of tissue factor (TF) in the follicular fluid, triggering the extrinsic coagulation pathway. However, follicular fluid must block fibrin formation and maintain fluidity until the release of the oocyte at ovulation. The combination of sulfated proteoglycan, antithrombin, and TF pathway inhibitor (TFPI) appears to play a critical role in the hypocoagulability of human follicular fluid. When compared with plasma, folicular fluid differs markedly in the levels of a number of important coagulation proteins. Principal among these are 15-fold, 13-fold, and 3.7-fold increases in free TFPI, thrombin-antithrombin complex, and TF, respectively. The excessively prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT) of human ovarian follicular fluid appear to be primarily due to high concentrations of sulfated proteoglycans, which accelerate the inactivation of thrombin and the anti-Xa activity of TFPI. Thus, heparitinase treatment shortened the clotting times of follicular fluid and reduced the inhibition of thrombin by the proteoglycan fraction combined with a fraction containing antithrombin. The remaining prolongation of APTT and PT may be caused by high levels of free TFPI in follicular fluid, which were confirmed by Northern blotting analysis, demonstrating TFPI mRNA expression by granulosa cells.

Tegafur, an anticancer prodrug, is reported to be bioactivated to 5-fluorouracil (5-FU) by cytochrome P450 (P450) enzymes. Liver microsomal P450 enzymes involved in the biotransformation of tegafur into 5-FU in rats and the effect of tegafur in vivo on P450 levels in rats were investigated. Of 12 cDNA-expressed rat P450 enzymes tested, CYP1A2, CYP3A1, and CYP2C11 had high 5-FU formation rates from 100 microM and 1.0 mM tegafur concentrations. The contributions of CYP1A, CYP2C, and CYP3A enzymes to 5-FU formation in male rat liver microsomes were supported by immunoinhibition studies. 5-FU formation from tegafur, at substrate concentrations of 100 microM and 1.0 mM, was increased by intraperitoneal treatment of tegafur (50 mg/kg for 5 days) as well as by beta-naphthoflavone, phenobarbital, and dexamethasone. Orally administered tegafur (100 mg/kg daily for 20 days) caused the induction of CYP2B (5-fold) and of CYP1A and CYP3A (approximately 2-fold) and of 5-FU formation (approximately 2-fold) in rat liver microsomes. These results suggest that CYP1A and CYP3A enzymes, autoinduced by tegafur, have important roles in 5-FU formation from tegafur in rat liver microsomes. Coadministration of tegafur and P450-inducing drugs could markedly enhance the biotransformation of tegafur into 5-FU via P450 induction.

Recently, we have reported that tegafur, an anticancer agent, is biotransformed into active drug 5-fluorouracil (5-FU) by cytochromes P450 1A2, 2A6, and 2C8 in human liver microsomes (T. Komatsu et al., Drug Metab. Dispos, 28: 1457-1463, 2000). Because the conversion of tegafur into 5-FU has also been reported to be catalyzed by cytosolic thymidine phosphorylase (dThdPase), the involvement of human liver microsomes and cytosol and individual differences in 5-FU formation from tegafur were investigated. In 14 human samples, the mean rates of 5-FU formation in liver microsomes were 5-fold and 2-fold higher than those in liver cytosol at substrate concentrations of 100 microM and 1 mM tegafur, respectively. In the presence of 5-chloro-2,4-dihydroxypyridine, a dihydropyrimidine dehydrogenase inhibitor, the rates of 5-FU formation by the combination of liver microsomes and cytosol showed 5- and 3-fold interindividual differences at 100 microM and 1 mM tegafur, respectively. Kinetic analysis of human liver cytosolic 5-FU formation indicated an apparent higher Km value (16 +/- 4 mM) than that of liver microsomes (1.8 +/- 0.3 mM) with similar Vmax values. Human liver cytosolic 5-FU formation was confirmed to be catalyzed by dThdPase with correlation and chemical inhibition studies. These results suggested that 5-FU formation from tegafur in human liver was mainly catalyzed by microsomal P450 at low concentrations of tegafur, but the contribution of cytosolic 5-FU formation by dThdPase would be important at high concentrations.

Blood loss during treatment carries a potential risk for the transmission of blood-borne pathogens in hospital patients. To determine whether nosocomial transmission of hepatitis C virus (HCV) occurs in surgical wards and dental hospitals, we tested anti-HCV antibodies and HCV RNA in sera from these patients and analysed the hypervariable region 1 (HVR1) sequence of HCV phylogenetically in the HCV RNA-positive patients. Five of 83 patients from a surgical ward were positive for HCV RNA, and six patients from one dental hospital and nine patients from a second were found to be positive for HCV RNA during the examination period. The HVR1 sequences were amplified from these patients' serum, and after subcloning, multiple clones of the HVR1 sequence from each patient were determined. The phylogenetic analysis of these sequences showed that HVR1 species from each patient could be classified into one to three genetic clusters of HVR1 quasi-species and that these clusters were independent of each other among patients. Thus, there was no evidence of HCV transmission in our study, and unrecognized transmission of HCV may be a rare event in surgical and dental patients at university hospitals.

Phenytoin, 5,5-diphenylhydantoin, is a widely used anticonvulsant agent with a variety of toxicities, including drug interactions. The formation of four oxidative metabolites, 4'-hydroxylated (4'-HPPH), 3'-hydroxylated (3'-HPPH), a catechol (3',4'-diHPPH), and the 3',4'-dihydrodiol form of phenytoin was examined in rat liver microsomes. In 11 cDNA-expressed rat P450 enzymes tested, CYP2C6 had the highest activities in 4'- and 3'-HPPH formation from phenytoin, followed only by CYP2C11. In contrast, CYP2C11 had high activity for 3',4'-diHPPH formation from 4'-HPPH, followed by CYP2C6. The rates of 4'-HPPH and 3',4'-diHPPH formation from phenytoin in liver microsomes in the presence of NADPH were significantly decreased by oral administration of phenytoin (300 mg/kg for 20 days) to rats, despite the increase in P450 contents. However, the cumene hydroperoxide-supported formation of 3',4'-dihydrodiol and 4'-HPPH from phenytoin was induced by phenytoin administration. Hydrogen peroxide formation in reaction mixtures with NADPH was induced by the administration of phenytoin; however, the coupling ratio of phenytoin oxidation was decreased in phenytoin-induced liver microsomal P450 systems. These results suggested that phenytoin could not stimulate its own apparent oxidative metabolism by liver P450s induced with phenytoin administration. The increase of unmetabolized phenytoin and byproducts of oxygen generated in the phenytoin-induced liver microsomal P450 system may be involved in phenytoin-related drug toxicity.

The efficacy of cibenzoline was assessed in the termination and long-term prevention of paroxysmal atrial fibrillation in relation to the time of onset in a series of patients with paroxysmal atrial fibrillation.Study of the termination included 92 patients (63 males, 29 females, mean age 64 +/- 12 years) and study of long-term prevention included 106 patients (77 males, 29 females, mean age 64 +/- 11 years; mean follow-up 32.7 +/- 18.8 months). Paroxysmal atrial fibrillation was classified into 3 types based on the time of onset: day type (AM 7:00-PM 5:00), night type (PM 5:00-AM 7:00) and mixed type (anytime). Successful termination was defined as pharmacological cardioversion within 30 min of the intravenous administration of 70 mg cibenzoline and efficacy of long-term prevention was presented as the event-free ratio of patients after oral administration of 300 mg/day cibenzoline.Successful pharmacological termination was achieved in 66.7% of the day type (n = 24), 70.0% of the night type (n = 48), and 41.6% of the mixed type (n = 20). There was a significantly higher success in the day type (p0.05), and tendency to success in the night type (p = 0.079) compared to the mixed type. The event-free ratios at 1, 3, 6, 12, 24 months after oral administration were 84.6%, 76.9%, 73.1%, 65.4%, 61.5% in the day type (n = 26), 92.0%, 80.0%, 80.0%, 72.0%, 60.0% in the night type (n = 25), and 81.8%, 61.8%, 47.3%, 30.9%, 23.6% in the mixed type (n = 55), respectively. Significantly higher success was achieved at 24 months in the day type and the night type compared to the mixed type (p0.05).Termination and long-term prevention of paroxysmal atrial fibrillation by cibenzoline has a high degree of efficacy in patients with both day and night onset of paroxysmal atrial fibrillation.

This study characterized semen collected from the Japanese black bear, Ursus thibetanus aponicus, to provide information on semen cryopreservation for artificial breeding. Preliminary studies using a beagle dog as the model species showed that sperm concentration and total sperm count were lower in semen collected by electroejaculation than in semen collected by digital manipulation, but that sperm motility, viability and morphology were similar. Characterization of semen obtained from Japanese black bears by electroejaculation under general anesthesia revealed that semen volume and total number of spermatozoa collected were lower; but that sperm concentration, motility, viability and morphology were equivalent to those reported in other ursids. When semen was collected via a catheter inserted into the urethra during the stimulation for ejaculation, the sperm concentration, total sperm count and motility were relatively higher than when semen was collected directly in a test tube. Specific normal semen characteristics (mean +/- SEM) were pH, 7.6 +/- 0.0; volume, 0.212 +/- 0.038 mL; sperm concentration, 361 +/- 100 x 10(6)/mL; total sperm count, 84.0 +/- 32.2 x 106; +++ motility, 30 +/- 5%; motility, 77 +/- 3%; viability 77 +/- 2%; and abnormal morphology, 11+/- 2%. These results suggest that semen can be collected from Japanese black bears by electroejaculation.

Based on analysis of data from 10 patients newly diagnosed as having acute myelogenous leukemia (AML), we developed a critical pathway (CP) to prevent infection and thus shorten the period of hospitalization. This CP shows laboratory test results, vital signs, chemotherapy regimen, concomitant supportive care and oral medications, gargling with antiseptic mouthwash, other anti-infection measures, diet, room conditions, patient education in anti-infection measures, outcome, and variance on the vertical axis and time on the horizontal axis. After introduction of the CP, 9 of the newly diagnosed AML patients did not experience severe treatment-related complications during a mean hospitalization of 29 days until remission and 95 days until discharge. These results suggest that the present CP makes it possible to shorten the hospital stay, reduce treatment costs, and improve the quality of life of AML patients.

Transport models for sorbing organic chemicals in soil require accurate predictions of the diffusion and sorption processes in both the liquid and gaseous phases. In this study, the ability of recently-presented diffusivity models in combination with equilibrium sorption models to predict the effective (i.e., including sorption effects) diffusion coefficient, D eff , as a function of soil-water content, θ, is tested for different sorbing organic chemicals in different soils. The water-induced linear reduction (WLR) gas diffusivity model, combined with a two-component (hydrophobic and vapor) equilibrium sorption model, well described short-term ( 700 h. Consequently, an increasing K D value with time was required in the DATES model to obtain successful D eff (θ) predictions. Since chemical-soil contact time and adsorption-desorption history typically vary in each compartment of a soil profile, transport models, including sorption kinetics, will become very complex and DATES with a time-dependent K D relation may represent a useful model alternative.

Tegafur, an anticancer prodrug, is bioactivated to 5-fluorouracil (5-FU) mainly by cytochrome P450 (P450) enzymes. The conversion from tegafur into 5-FU catalyzed by human liver microsomal P450 enzymes was investigated. In fourteen cDNA-expressed human P450 enzymes having measurable activities, CYP1A2, CYP2A6, CYP2E1, and CYP3A5 were highly active in catalyzing 5-FU formation at a tegafur concentration of 100 microM. Kinetic analysis revealed that CYP1A2 had the highest V(max)/K(m) value and that the V(max) value of CYP2A6 was high in 5-FU formation. In human liver microsomes, the activities of 5-FU formation from 10 microM, 100 microM, and 1 mM tegafur were significantly correlated with both coumarin 7-hydroxylation (r = 0.83, 0.86, and 0.74) and paclitaxel 6 alpha-hydroxylation (r = 0.77, 0.62, and 0.85) activities, respectively. Coumarin efficiently inhibited the 5-FU formation activities from 100 microM and 1 mM tegafur catalyzed by human liver microsomes that had high coumarin 7-hydroxylation activity. On the other hand, furafylline, fluvoxamine, and quercetin, as well as coumarin, showed inhibitory effects in liver microsomes that had high catalytic activities of 5-FU formation. The other P450 inhibitors examined showed weak or no inhibition in human liver microsomes. Polyclonal anti-CYP1A2 antibody, monoclonal anti-CYP2A6, and anti-CYP2C8 antibodies inhibited 5-FU formation activities to different extents in those two microsomal samples. These results suggest that CYP1A2, CYP2A6, and CYP2C8 have important roles in human liver microsomal 5-FU formation and that the involvement of these three P450 forms differs among individual humans.

We studied the effect of various amino acid mixtures on nasal allergy induced by the intranasal application of toluene diisocyanate (TDI) in mice. In Experiment 1 (Exp. 1), mice were fed a 25% casein, soy protein isolate (SPI), egg white protein (EW) or gluten diet. In Experiment 2 (Exp. 2), mice were fed a 25% amino acid mixture diets patterned after casein (AA-casein), SPI (AA-SPI), EW protein (AA-EW) or gluten (AA-gluten). In Experiment 3 3 (Exp. 3) we modified the glutamine/glutamic acid (Gln/Glu) concentrations in the amino acid mixtures. Mice were fed a 25% AA-SPI, low Gln/Glu AA-SPI (LG-AA-SPI), AA-EW or high Gln/Glu AA-EW (HG-AA-EW) diet. At the 5th week, mice were divided into sensitized (sen-) and non-sensitized (ns-) groups. The mice in sensitized groups were treated with two courses of intranasal application of toluene diisocyanate (TDI) in ethyl acetate for 5 consecutive days, separated by 9 days rest. The non-sensitized groups of mice were treated with a vehicle. Nine days after the second sensitization, all mice were provoked by TDI. Nasal responses and serum IgE concentration were studied. The findings of Exp. 1 showed that the sen-EW group exhibited a lower body weight gain, higher nasal symptom score and higher IgE concentration than the other sensitized groups. The findings dings of Exp. 2 showed that the sen-EW group had a lower body weight gain, higher nasal symptom score and higher IgE concentration than the other sensitized groups. In Exp. 3, the AA-EW group showed a higher total nasal score and IgE concentration than the HG-AA-EW group, however, the findings of LG-AA-SPI and AA-SPI were similar. These findings demonstrated that amino acid mixtures affect nasal allergy induced by the intranasal application of TDI in mice.