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Multidrug-resistant uropathogenic Escherichia coli (UPEC) is increasing gradually on a worldwide scale. We therefore examined the possibility of bacteriophage (phage) therapy for urinary tract infections (UTIs) caused by the UPEC strains as an alternative to chemotherapy. In addition to the well-known T4 phage, KEP10, which was newly isolated, was used as a therapeutic phage candidate. KEP10 showed a broader bacteriolytic spectrum (67%) for UPEC strains than T4 (14%). Morphological and genetic analyses showed that KEP10 resembles phage T4. Phages T4 and KEP10 injected into the peritoneal cavity of mice were distributed immediately to all organs examined and maintained a high titer for at least 24 h. They were stable in the urine of both mice and humans for 24 h at 37 degrees C. Administration of these phages into the peritoneal cavity caused a marked decrease in the mortality of mice inoculated transurethrally with a UPEC strain, whereas most of the control mice died within a few days of bacterial infection. Inoculation with phage alone produced no adverse effects attributable to the phage per se. The present study experimentally demonstrated the therapeutic potential of phage for E. coli-induced UTIs, and T-even-related phages may be suitable candidates with which to treat them.

An increase in the sheet resistance at small diffusion regions is caused by the formation of high resistivity phases of nickel silicide. The increase in the sheet resistance strongly depends on the size of diffusion region at which nickel silicide is formed. On the condition under which NiSi is formed at large diffusion regions, Ni3Si2 is formed at small N* diffusion regions and NiSi2 is formed at small N* diffusion regions. The uniformity of sheet resistance at small N* diffusion regions is improved by increasing the first anneal temperature. The uniformity of sheet resistance at small N* diffusion regions is not improved enough by increasing the first or second anneal temperature. It is considered that the transformation from Ni3Si2 to NiSi2 occurs at small N* diffusion region between 500degC and 550degC.

One of the major developments in recent years has been the increasing use of organotin reagents and intermediates in organic synthesis, exploiting both their radical and ionic reactivity. This chapter mainly describes the recent developments of reactive and activated organotin reagents used in organic synthesis. In particular, it focuses on tin hydrides, allylic, allenylic, and propargyl tins, tin enolates, tin-heteroarom bonds, and tin--metal bonds.

A MEMS-based methanol concentration sensor for monitoring and controlling the methanol to water ratio in a DMFC system is described. This sensor is based on a microfluidic chip that employs a resonant microtube and on-chip platinum temperature sensor to measure the density of a fluid. Using the density and temperature output the methanol concentration is determined. The performance of the sensor over temperature, concentration and in the presence of formic acid by-products is examined. Test comparisons between this sensing method and refractive index and speed-of-sound methanol concentration sensors are made. Additional biofuel applications for the sensor will be discussed.

Background: Although kyphosis and its mobility are reported to be associated with walking ability in elderly people, the causal relationship between them has not been clarified. Purpose:Toclarify the foot pressure pattern in individuals with kyphosis and examine the relationship between spinal kyphosis, mobility, foot pressure pattern, and walking ability. Methods: In 61participants, total inclination and thoracic, lumbar, and sacral anglesweremeasured by the SpinalMouse (IdiagAG,Switzerland). Forty-one of the 61participantswith total inclination >6 degrees and/or lumbar angle < 16 degrees were classified as the kyphosis group (6 men, 35 women; mean age, 78.5 years). The other 20 participants were classified as the control group (3 men, 17 women; 75.5 years). Spinal mobility of the total, thoracic, lumbar, and sacral spine was measured. Walking speed and step length at a comfortable walking speedweremeasured on a flat and straight 10-m course. Simultaneously, the foot pressure pattern was measured by the insole-type foot pressure measurement system (F-Scan II, Nitta, Japan). The anteroposterior length of the center of pressure (COP) path, expressed as the percentage of the foot length (%Long), the transverse width of the COP path, expressed as the percentage of maximum foot width (%Trans), and the partial foot pressure in the heel, central, metatarsal, hallux, and lateral toe area, expressed as the percentage of body weight (%PFP), were calculated. Results: Walking speed (0.8± 0.3 vs. 1.1± 0.3m/s, p= 0.031) and step length (0.4± 0.1 vs. 0.5± 0.1m, p= 0.042) in the kyphosis groupwere significantly lower than those in the control group. Total inclination in the kyphosis group was significantly higher than that in the control group (8.3± 8.2 vs. 1.0± 3.2 degrees, p= 0.007). Lumbar angle (−1.4± 17.2 vs. 24.9± 4.3 degrees, p= 0.008) and sacral inclination (−3.1± 9.3 vs. 9.9± 4.5 degrees, p= 0.008) in the kyphosis group were significantly lower than those in the control group. In the kyphosis group, mobility of the total, lumbar, and sacral spine was significantly lower than that of the control group. The %Long, %Trans, and %PFP of the hallux (4.4± 3.6 vs. 15.1± 6.4%, p= 0.034) and lateral toes (4.2± 3.2 vs. 9.7± 5.4%, p= 0.036) in the kyphosis groupwere significantly lower than those in the control group. A significant correlation was found between spinal inclination and %PFP of the hallux (r=−0.344) and lateral toes (r=−0.310). The %PFP of the hallux (r=0.560) and lateral toes (r= 0.437) also correlated with total spinal mobility. Conclusion(s): In individuals with spinal kyphosis, a decreased walking ability was evident, and severe kyphosis and low mobility of the spine were associated with low toe pressure. Thus, low toe pressure might induce insufficient driving forces, causing decreased walking ability. Implications:We should pay careful attention to the presence of low toe pressure in individuals with spinal kyphosis.

Background:Many studies have demonstrated that thoracoscopic lobectomy is superior to open thoracotomy in terms of short-termoutcomes in patientswith early-stage non-small cell lung cancer. However, few studies have analyzed the predictor of the postoperative deteriorationof performance status or complication in patients undergoing thoracoscopic lobectomy, despite considerable research in open thoracotomy. Besides, those studies did not cover the physical functions such as a muscle strength or an exercise capacity. Purpose: The purposes of this study were to identify predictors of short-term outcomes including the postoperative deterioration of the performance status and cardiopulmonary complications and to determine whether preoperative physical function including the lower-limb muscle strength and exercise capacity is associated with the short-term outcomes. Methods: Between June 2005 and October 2012, we retrospectively reviewed 188 consecutive patients who underwent thoracoscopic lobectomy and the perioperative pulmonary rehabilitation for preoperative stage I non-small cell lung cancer. Demographic, lung and physical functions, surgical, and oncologic data were initially analyzed by using univariate analysis. Those with a P value of less than 0.2 of univariate analyses were used as independent variables in themultivariate logistic regression analyses. Pulmonary rehabilitation that consisted of postoperative early mobilization and progressive exercise training was administered during the patients’ hospitalization. Results: The incidences of postoperative deterioration of performance status and cardiopulmonary complication were 13.8% (n= 26) and 19.1% (n= 36), respectively. Multivariate analyses showed that percent of predicted diffusion capacity of the lung for carbon monoxide (

Human skin shows various morphological characteristics, depending on the body site. As these distinct phenotypes have been explained on the basis of the variance in epidermal keratinocytes and the presence of skin appendages, the spatial distinction of the dermal components has not been fully elucidated.To identify and characterize the profiles of mRNAs that are abundantly or specifically expressed by fibroblasts derived from trunk skin, but not from palmoplantar skin or oral mucosa.In order to identify the distinct mRNA expression by trunk skin fibroblasts, a subtraction cDNA screening was performed first, followed by Northern blotting, Western blotting and immunohistochemistry for cultured human and rat dermal fibroblasts and those skin tissues. Finally, whole mount in situ hybridization (WISH) was performed to examine the differences in the expression of the corresponding gene during the developmental stage of mouse embryos.We identified three cDNA clones encoding fibronectin (FN), pregnancy-specific beta1-glycoprotein 5 and beta-actin, respectively, whose mRNAs were abundantly or specifically expressed by trunk skin fibroblasts. FN and some integrins were further confirmed to be expressed more selectively in human and rat trunk skin fibroblasts, both in terms of the RNA and the protein levels, compared with the fibroblasts derived from plamoplantar skin and oral mucosa. WISH demonstrated that FN was localized around the hair follicles of mouse embryos.FN, one of most potent extracellular matrix molecules, was demonstrated to be spatially transcribed depending on the body sites. The distinct expression of FN was suggestive of the essential commitment in the process of cutaneous development and morphogenesis of appendages originated from hair germ. The paucity of FN in palmoplantar skin and oral mucosa might explain the characteristics of these skin phenotypes.

A light source using sum-frequency generation is developed for the ytterbium clock transition at 578 nm. Doppler-free spectroscopy of iodine lines near the Yb clock transition and frequency stabilization are demonstrated with the light source.

The advantages and disadvantages of oxidative permanent and acid-type semi-permanent hair colors are evident. The former provides a longlasting "permanent" color, while the latter imparts less damage to the hair. We developed a novel acid-type hair color technology that can allow an acid dye and a metal ion to form a complex inside the hair similar to the oxidative hair color. It is well known that acid dye diffuses into the hair and creates an ionic bond with the positively charged amino acid residues of hair protein. However, the dye can be extracted easily from the hair by daily shampooing due to the weakness of the bond. In order to strengthen this bond and to prevent the extraction of the dye by shampooing, an aluminum chloride ion was chosen as the metal ion component to form the dye-metal complex. A proper composition of penetration enhancers, benzyl alcohol and ethyl alcohol, was required to allow acid dyes to interact with the aluminum chloride ion after each component penetrates deeply into the hair to form a complex inside the hair. To provide color brightness and a color longevity effect to hair color, glycolic acid was also selected due to the observation that a weak acid with a small molecular weight would enhance those effects.

This paper presents a mathematical model for dynamic decision making with an objective function induced from fuzzy preferences. The fuzzy preference is related to decision making in artificial intelligence, and this paper models human behaviour based on his/her aggregated fuzzy preferences. To deal with fuzzy preferences in dynamic decision making brings us difficulty which is different from static one since the value criterion of fuzzy preferences in dynamic behavior transforms together with time and it is formulated gradually. A reasonable criterion based on fuzzy preferences is formulated for the dynamic decision making, and an optimality equation for this model is derived by dynamic programming. Mathematical models simulating human behavior with his/her decision making are applicable to various fields: robotics, customers' behavior analysis in marketing, linguistic learning modeling, multi-agent systems and so on.

Although adherence clearly influences response to antiretroviral therapy (ART), accurate assessment of adherence is problematic. The objective of this analysis was to assess the independent predictive value of protease inhibitor (PI) concentrations as a supplement to self-report as markers of medication adherence.This retrospective analysis was conducted from a prospective clinical trial designed to compare the outcomes of frequent versus infrequent HIV RNA measurement used to manage antiretroviral therapy. For 131 patients, self-reported medication adherence, HIV RNA levels, CD4 counts and PI concentrations (unannounced, random samples) were measured at baseline (when patients changed to a new regimen) and every 2 months thereafter. The change in HIV RNA from baseline to month 6 (area-based measure) was used to evaluate overall response. The proportion of measured PI concentrations below the detection limit was used as an alternative marker of adherence. An undetectable concentration would be expected after missing a single dose.The mean baseline CD4 count was 125 cells/mm3 and the mean HIV RNA level was 4.7 log10 copies/ml. The mean change in log10 HIV RNA was -0.73 copies/ml. The mean percentage of self-reported adherence was 91% (range: 15-100%) and the mean proportion of undetectable PI concentrations was 27% (range: 0-100%, mean 2.5 samples/patient). The correlation between the two measures was -0.23 (P=0.009). In a multivariate model, percentage of visits with undetectable PI concentrations (P=0.02), percentage of medication adherence (P=0.02), baseline HIV RNA level (P=0.005), prior PI use (P=0.0004), prior lamivudine (3TC) use (P=0.0009) and randomization to the frequent HIV RNA measurement group (P0.0001) were all related to change in HIV RNA. After accounting for adherence, patients who always had detectable PI concentrations had an average of 0.4 log10 additional HIV RNA reduction compared with those who had no detectable concentrations.Repeated, random PI concentration values are independently predictive of virological response and may add to self-report of adherence in understanding the response to ART.

Through this research, we have developed a "human sensory sensor" that takes real-time measurements of peripheral skin temperature, pulse, and galvanic skin response (GSR) - information that changes depending on human sensations - and analyzes this information to estimate the sensations being experienced. We have confirmed that by using these sensors, it is possible to estimate the sensations experienced by an individual during a massage. Furthermore, we have developed a massage control in accordance with the user's sensations as estimated by these sensors, and have confirmed the effectiveness of this method.

This paper newly proposes an accurate modeling method of the copper interconnect cross-section in which the width and thickness dependence on layout patterns and density are fully incorporated and universally expressed. In addition, we have developed specific test patterns for the model parameters extraction, and an efficient extraction flow which features correlating cross-section observation and resistance measurement to obtain the parameter values. We have extracted the model parameters for 0.15 /spl mu/m CMOS using this method and confirmed that 10% /spl tau/pd error normally observed with conventional LPE (Layout Parameters Extraction) was completely dissolved. This is the first time that the practical and accurate modeling methodology for layout pattern sensitive Cu Interconnect is ever reported.

Background and aim: The diagnosis of submucosal fundal varices is challenging. Currently, endoscopy and endoscopic ultrasound (EUS) are considered most useful for this purpose. The aim of this study was to evaluate if multi-detector row CT (MDCT) angiography contributes to the diagnosis of submucosal fundal varices.

The first advanced boiling water reactor (ABWR)—Kashiwazaki-Kariwa Nuclear Power Station Unit 6 (K6)—was built in Japan by Tokyo Electric Power Corporation (TEPCO) in 1996. Subsequently, Kashiwazaki-Kariwa Nuclear Power Station Unit 7 (K7) was constructed (completed in 1997). The K6 and K7 have been operating safely for more than 6 years. Presently, four additional ABWRs are under construction (two in Japan and two in Taiwan), with an additional nine ABWRs in Japan that are currently in the planning stage. One of the ABWRs now under construction is Hamaoka Unit 5 (H5), owned by Chubu Electric Power Co., Inc. The H5 has an estimated completion date of January 2005. The latest technologies have been applied to H5, which will result in improved economics, ease of maintenance, increased reliability, and a reduction in radiation exposure. Below, you will find the latest major technologies applied to H5 in terms of the history of development and verification of manufacturing stages: (1) Sealless Fine-Motion Control Rod Drive (S-FMCRD): S-FMCRD provides fine-motion control by the electric motor for normal operation and hydraulic pressure for scram insertion. This redundancy of power supply is similar to the conventional FMCRD. Additionally, S-FMCRD experiences excellent performance due to its magnetic coupling. As a result, S-FMCRD provides improved operation, ease of maintenance, increased reliability, and reduced occupational radiation exposure. (2) Multi-drive configuration of Reactor Internal Pump (RIP) Adjustable Speed Drive (ASD): Under a conventional configuration, one ASD drives one RIP. Under a multi-drive configuration, one ASD drives two or three RIPs. As a result, four ASDs would drive ten RIPs resulting in improved economics, ease of maintenance, and a smaller footprint. (3) Debris Filter Integrated Fuel Support (DFFS): In order to eliminate the risk of debris causing a fuel leak, debris filters have been developed that will be attached at the core-support orifice. DFFS enhances reliability and improves economics.Copyright © 2004 by ASME

A newly devised mouth-opening exerciser is presented. It is made of a 5-mm thick acrylic resin plate and is wedge-shaped with a cut tip. The exerciser has 3-mm long stairs so that patients can notice improvement in mouth-opening during exercise. Every stair has an extremely gentle slope so that it permits gradual mouth opening without severe pain. This exerciser was very effective for postoperative mouth opening exercises in patients with severe trismus due to temporomandibular joint ankylosis and fibrosis after maxillectomy.

We have been developing exoskeletal robots in order to support the motion of physically weak persons such as elderly persons or handicapped persons. In our previous research, the 2-DOF exoskeletal robots for shoulder motion support and its control method have been developed since the shoulder motion is especially important for people to take care of themselves in everyday life. In this paper, we propose intelligent interface, which realizes the fuzzy-neuro controller adjustment in accordance with the human subject's arm posture, in order to effectively control the 2-DOF exoskeletal robot for shoulder motion support. The intelligent interface is realized by applying a neural network. The effectiveness of the proposed intelligent interface of the exoskeletal robot has been evaluated by experiment.

The exoskeletal robots are expected to support the daily activities of physically weak persons such as elderly persons or handicapped persons in these days. In our previous research, the exoskeletal robots for elbow or shoulder motion support have been developed since the elbow and shoulder motion is especially important for people to perform tasks in everyday life. In this paper, we present a mechanism of the moving center of rotation of the shoulder joint of the exoskeletal robot for human shoulder motion support in order to fit the center of rotation of the robot shoulder joint to that of the physiological human shoulder joint during the shoulder motion. The effectiveness of the proposed mechanism of the robot has been evaluated by experiment.

The authors found that the inactive Zn in GaInP/(Al/sub 0.7/Ga/sub 0.3/)InP quantum well structures peculiarly degraded the carrier life time which strongly affected the laser's performance and reliability. The novel cap layer of n-(Al/sub 0.7/Ga/sub 0.3/)InP realized almost 100% activation of Zn in the p-(Al/sub 0.7/Ga/sub 0.3/)InP layer. The same temperature dependence on the threshold current density of visible lasers was obtained by introducing the novel n-cap layer. The kink level of 160 mW and the maximum light output power of 204 mW at 25/spl deg/C were realized by introducing the novel cap layer of the n-(Al/sub 0.7/Ga/sub 0.3/)InP for the window structured visible laser. This visible laser could achieve the finest reliability under stable continuous wave operation over 2600 hrs under 50 mW at 50/spl deg/C. >

A number of methods to control the phenomenon of chaos in nonlinear dynamical systems have been reported. Of these, the technique known as the OGY method, devised by Ott, Grebogi and Yorke (1990) has attracted attention as one which can confine the desired periodic motion with the application of a small external force. In our research, we have applied the OGY method to a forced pendulum with a cyclic external force applied in the horizontal direction, as a nonlinear dynamical system with a more complex structure than that of the Lorentz attractor. We first investigate in detail using bifurcation diagrams and Lyapunov exponents, the regions in which chaos occurs in a forced pendulum. We then present some issues related to the target focal point of the periodic orbit, which is needed in particular to execute control using the OGY method.

For precision machines, it is very important to attenuate microvibrations caused by various sources. In order to suppress the transmission of vibration from the floor, it is standard to employ a rigid platform supported by air springs and install a precision machine on it. However, because of high compliance, such a vibration isolation system is easily disturbed by movements of the machine on the platform. To suppress this direct disturbances, feedback control such as PID and LQR has been extensively used, which however cannot satisfy severe specifications required, for example, in recent semiconductor manufacturing processes. This paper proposes a new feedforward control scheme for suppression of the direct disturbance. The feedforward control signal is not generated online, but computed in advance from the data of a response to the direct disturbance and the transfer function from the control input to the controlled output, which are obtained by a test. An experimental result shows that the proposed feedforward control works very well to improve the response to the direct disturbance.

The plastic ball grid array (PBGA), which can increase the I/O pin counts by arranging the solder balls on the package back side, is advantageous in surface mount type IC packages. However, this package seems to have problems such as warpage and reflow crack resistance depending on the package structure and material combination. We studied the influence of material properties on the warpage and reflow crack resistance of PBGAs in order to optimize the properties of each material and material combination. It was found that PBGA warpage is closely correlated with the properties of the molding compound, i.e. polymerization shrinkage and the coefficient of thermal expansion, rather than those of the substrate and the die attach material, and that the warpage was drastically reduced by using a molding compound with low polymerization shrinkage. On the other hand, reflow crack resistance was heavily influenced by the existence of voids in the die attach layer, which are produced by vapor from the water absorbed by the substrate during the die bonding process. Hardening the die attach material before the vapor penetrates the die attach layer can reduce voids and is effective in improving reflow crack resistance. By using a molding compound with low polymerization shrinkage by introducing a rigid molecular structure such as naphthol hardener and an acrylic type die attach material, it was found that the warpage is less than 60 /spl mu/m and the reflow crack resistance meets JEDEC level 2 (85/spl deg/C/60%RH/168 hr) for the 352 I/O model PBGA package.

We propose a top-down hardware/software co-simulation method for embedded systems and introduce a component logical bus architecture as an interface between software components and hardware components. Co-simulation using a component logical bus architecture is possible in the same environment from the stage at which the processor is not yet determined to the stage at which the processor is modeled in register transfer language. A model whose design is based on a component logical bus architecture is replaceable and reusable. By combining such replaceable models, it is possible to quickly realize seamless co-simulation. We further describe experimental results of our approach.

In distributed applications, multiple objects cooperate to achieve some objectives. Each object is manipulated through an operation supported by the object and then the operation may further invoke operations of other objects, i.e. nested operations. Purpose-oriented access rules indicate what operation in each object can invoke operations of other objects. Information flow among the objects occurs if the requests and responses of the operations carry data. Only the purpose-oriented access rules which imply legal information flow are allowed. In this paper, we discuss how to specify the access rules so that the information flow occurring in the nested invocation of the operations is legal.

In distributed applications, a group of multiple objects are cooperating to achieve some objectives. An object is modeled as a pair of data structures and operations. Each object is manipulated through an operation supported by the object and then the operation may further invoke operations of other objects, i.e., nested operations. The purpose-oriented access rules indicate which operation on each object can invoke operations of other objects. The information flow among the objects occur if the requests and responses of the operations carry some data. Only the purpose-oriented access rules which imply the legal information flow are allowed. We discuss how to test the access rules if the information flow occurring in the nested invocation of the operations is legal.

The optimization problem for a stopped Markov decision process is considered to be taken over stopping times /spl tau/ constrained so that E/sub /spl tau///spl les//spl alpha/ for some fixed /spl alpha/>0. We introduce the concept of a randomized stationary stopping time which is a mixed extension of the entry time of a stopping region and prove the existence of an optimal constrained pair of stationary policy and stopping time by utilizing a Lagrange multiplier approach. Also, applying the idea of the one-step look ahead (OLA) policy the optimal constrained pair is sought concretely. As an example, constrained Markov deteriorating system is explained.

Disturbances in the reservoir function of the stomach may cause epigastric fullness or early satiety, which are the main symptoms in patients with dysmotility-like functional dyspepsia. Gastric adaptive relaxation is involved in the reservoir function of the proximal stomach. Ecabet sodium, synthesized from abietic acid, is widely used in Japan as an antiulcer drug. The purpose of this study was to evaluate the effects of ecabet on gastric adaptive relaxation in isolated guinea-pig stomachs. Changes in intragastric volume and pressure were recorded in the presence of atropine and guanethidine. Gastric adaptive relaxation was triggered by luminal distention. Ecabet at the dose of 20 mmol/l in solutions at two pHs (pH 3.0 and 7.4) significantly lowered the threshold pressure needed for such relaxation and increased intragastric volume, but lower doses had little or no effect. The results suggested that this antiulcer drug might improve symptoms in patients with dysmotility-like functional dyspepsia.

CD44 is a principal cell surface receptor for hyaluronan, a major component of extracellular matrices. Cells are surrounded by and encounter matrix in vivo, which in turn serves a variety of cell functions through the direct adhesion via their receptors. CD44 communicates cell-matrix interactions into the cell via "outside-in signaling" and has an important role in biological activities. The interaction of CD44 with fragmented hyaluronan on rheumatoid synovial cells induces expression of VCAM-1 and Fas on the cells, which leads to Fas-mediated apoptosis of synovial cells by the interaction of T cells bearing FasL. On the other hand, engagement of CD44 on tumor cells derived from lung cancer reduces Fas expression and Fas-mediated apoptosis, resulting in less susceptibility of the cells to CTL-mediated cytotoxicity through Fas-FasL pathway. Thus, although the CD44-mediated signaling differs among cells and circumstances, we here propose the functional role of CD44 in inflammatory processes and tumor susceptibility and the rational design of future therapeutic strategies including the exploitation of CD44-mediated pathway in vivo.

A benthic toxic dinoflagellate identified as Prorocentrum lima (Syn. Exuviaella lima), and designated as strain PRL-1, was isolated from the coast of El Pardito (Coyote) Island in Baja California Sur, Mexico, after a fisherman poisoning incident involving consumption of liver from Lutjanus colorado, and Mycteroperca prionura fish. Purification and culturing was done in ES-Si medium, under 12:12 light/dark cycle (4 x 20 W cool-white fluorescent lamps), at 22 degrees C and constant stirring during 28 days. Whole cells were toxic to Artemia franciscana and its methanolic extract to mouse and to the marine yeast Debaryomyces hansenii. Chromatographic analysis (TLC and HPLC-MS) of such extract indicated an unusual proportion (1:2) okadaic acid (OA) and dinophysistoxin-1 (DTX-1). Estimated total toxin content by mouse bioassay (based on OA toxicity) was 19 pg/cell, a value significantly higher than that found by HPLC-MS (about 5.2 pg/cell, taking into account OA and DTX-1 only), suggesting that additional toxic components of unidentified nature are detected with the bioassay. This is the first report of a successful isolation and culturing of a toxic dinoflagellate from the Gulf of California, Mexico.

It is well known that the 5-year survival rate of advanced ovarian cancer patients greatly improved after the appearance of cisplatin. Recently, paclitaxel has been reported to be effective in the treatment of cisplatin-resistant ovarian cancer. However, control of intraperitoneal lesions is still the biggest problem in this treatment, and attention is focused on the development of effective approaches. Intraperitoneal chemotherapy is considered to be a mode of administration expected to have a direct effect on ovarian cancer by penetrating the tumor and an indirect effect via blood vessels. We examined the outcome and adverse drug reactions in 102 ovarian cancer patients who underwent repeated intraperitoneal administration of cisplatin in our hospital between April 1987 and April 1999. We confirmed that this method may greatly improve the five-year survival rate compared to intravenous administration.

We performed meta-analysis using the data in literatures of the clinical study related to pharmacotherapies for allergic rhinitis in Japan as evidences. We extracted double-blind studies which used first-generation antihistamines, early-stage second-generation antihistamines, late-stage second-generation antihistamines and arachidonic acid metabolite-receptor antagonists as investigational drugs. In meta-analysis of first-generation antihistamines and early-stage second-generation antihistamines, significant differences between them were detected in final overall improvement and usefulness. In meta-analysis of early-stage second-generation antihistamines and late-stage second-generation antihistamines, significant differences between them were detected in usefulness and sleepiness as an adverse effect. In meta-analysis of late-stage second-generation antihistamines and arachidonic acid metabolite-receptor antagonists, significant differences between them were detected in final overall improvement and usefulness. These results indicate a historical trend in the development of drugs including measures to deal with sleepiness as an adverse effect. The arachidonic acid metabolite antagonists appeared to be promising among the oral drugs for allergic rhinitis, although data related to the arachidonic acid metabolite antagonists are still few and further collection of them is necessary.

Based on the previous report showing that mitochondrial (MT) alteration is associated with platinum (Pt) resistance, we have determined how the alternative MT function is involved in Pt cell cytotoxicity particularly in relation to the apoptosis. MT membrane potential (delta psi m) semi-quantitatively assessed by rhodamin 123 (Rh) sensitivity was significantly elevated in acquired Pt-resistant 2008/C13*5.25 cells (C13) established from its parental 2008 cells or known intrinsic Pt-resistant JHOC cells established from ovarian clear cell adenocarcinoma. Laser confocal microscopy of these cells stained with Rh revealed that MT in Pt-resistant cells were distributed in whole cytoplasm with relatively higher fluorescent intensity whereas MT in Pt-sensitive cells were localized in perinuclear space with lower fluorescent intensity. Electron microscopy showed the predominantly condensed MT in which crestal structure was not observed clearly in Pt-resistant cells. Western blot analysis using murine monoclonal anti-Bcl-2 antibody showed more than 5-fold Bcl-2 overexpression in Pt-resistant cells in response to cisplatin treatment. Cytochrome C (CytC) in MT was released from MT into cytoplasm in response to cisplatin treatment in Pt-sensitive cells, whereas up-regulation of CytC level in MT rather than CytC release from MT was observed in Pt-resistant cells. These data are strongly suggesting that changes at MT level would impact on the relative resistance of malignant cells to undergo drug-induced apoptosis.

The factors influencing the development of small intestinal obstruction following gastric surgery are controversial.Univariate and multivariate analyses were carried out on data from 48 patients with gastric cancer who underwent total gastrectomy and Roux-en-Y reconstruction for a potential cure.Of these 48 patients, 11 (22.9%) presented with mechanical obstruction in the small intestine postoperatively. There were no statistically significant differences with regard to age, sex, and the presenting pathology. The development of obstruction was not related to a longer operation time, a greater estimated blood loss during surgery, an extensive lymph node dissection and a combined resection of adjacent organs. The probability that the antecolic anastomosis would cause obstruction was significant when compared with findings in case of the retrocolic anastomosis (P0.05). In the multivariate logistic regression analysis, the significant risk factors related to the development of small intestinal obstruction proved to be reconstructive route of jejunal loop.In potentially curative patients undergoing total gastrectomy, retrocolic anastomosis should be attempted to prevent the development of postoperative intestinal obstruction.

We report a case of basal subarachnoid hemorrhage in a child. The etiology of this lesion was difficult to diagnose. The patient was a 9-year-old boy. He sustained minor head injury followed by loss of consciousness and cardiopulmonary arrest. He was brought to our emergency room by ambulance. On arrival, he presented with cardiopulmonary arrest and deep comatose state. Basal subarachnoid hemorrhage was revealed on CAT scan. 3D-CTA documented two bulging portions: one was at the junction between the left vertebral artery and the left posterior inferior cerebellar artery. The other one was shown at the basilar artery. He died on the 7th hospital day. The autopsy revealed a laceration of the left vertebral artery. Microscopically, the wall around the laceration showed a defect in the internal elastic membrane and a decrease of smooth muscle cells with moderate fibrosis in the tunica media. These findings were compatible with the structure of a congenital aneurysm. Hence, the patient was strongly suspected to have had a congenital aneurysm whose rupture was triggered by minor head injury.

Cell adhesion molecules are involved in a number of biological functions, such as cell survival, cell differentiation, tissue repair, and development. A novel molecule, POEM (preosteoblast epidermal growth factor-like repeat protein with meprin, A5 protein, and receptor protein-tyrosine phosphatase mu domain), was isolated by reverse transcription-polymerase chain reaction using a set of degenerate primers designed after other known epidermal growth factor (EGF)-like motifs. From its structure, POEM was suggested to be a novel adhesion molecule with five EGF-like domains, an Arg-Gly-Asp (RGD) cell binding motif, and a meprin, A5 protein, and receptor protein-tyrosine phosphatase mu (MAM) domain. By in situ hybridization using embryonic day 16.5 (E16.5) mouse embryos, strong expression of POEM mRNA was observed in developing kidney renal tubules, parathyroid and thyroid glands, developing bone, tooth germ, and endocrine organs of the brain. The inner ear, skeletal muscle, smooth muscle (except for the vascular system), and skin were also positive for POEM expression. Bacterial recombinant POEM protein containing the RGD sequence and MAM domain showed strong cell adhesion, spreading, and survival-promoting activities. By mutating the RGD sequence to RGE, the cell spreading and survival activities were significantly decreased, but the MAM domain was shown to contribute only to cell adhesion and not to cell spreading and survival-promoting activities. The distribution of POEM in several tissues was close to that of alpha(8)beta(1) integrin. Therefore, we conducted cell adhesion assays using KA8 cells, a K562 leukemia clone stably expressing alpha(8) integrin. Parental K562 cells, which expressed alpha(5)beta(1) integrin, bound to fibronectin but not to POEM. On the other hand, KA8 cells showed strong binding and spreading on both fibronectin and POEM. These results suggest that POEM is a novel ligand for alpha(8)beta(1) integrin and that POEM may be involved in the development and function of various tissues, such as kidney, bone, muscles, and endocrine organs.

The external granular layer (EGL) of the cerebellum thickens, thins and disappears in its developmental process. We examined the thickness of the EGL, both intralobule differences and interlobule differences, in the whole midline sections of mouse cerebella for the entire postnatal period up to disappearance. The thinnest site in each lobule was located at the outer apex throughout the observation period, the thickest site was the portion facing the inner apex during early period, and that facing the convexity where the EGL curved in the later period. The observed interlobular differences of the EGL thickness were statistically divided into three groups, referred to as the early developing group (EDG), the late developing group (LDG), and the mixed-type group (MTG). The EDG consisted of the whole anterior lobe and a site in lobule VI facing the fissura prima. These sites thickened earlier, and showed a similar thickness on each observation day. The LDG was composed of all sites in the posterior lobe, with the exception of two sites where lobules VIII and IX confronted each other as well as the site included in the EDG. The sites in the LDG thickened later. They demonstrated a similar thickness during thickening, but varied during thinning. The MTG, consisting of two sites where lobules VIII and IX facied each other, showed features similar to the EDG in the mitotic zone and the LDG in the premigratry zone. These data may serve as the basis for studies on regional differentiation of the cerebellum.

To present a case of fluoroquinolone treatment failure in urinary tract infection caused by Pseudomonas aeruginosa, accompanied by in vivo selection of the post-treatment isolate that showed decreased susceptibilities to fluoroquinolones, and to report fluoroquinolone resistance mechanisms in the post-treatment isolate.A patient with urinary tract infection was treated with a suboptimal dose of a fluorinated quinolone, gatifloxacin. P. aeruginosa strains were isolated before and after fluoroquinolone treatment. The pretreatment and post-treatment isolates were examined for relatedness by arbitrarily primed polymerase chain reaction. For these isolates, the minimum inhibitory concentration of antimicrobial agents was determined and mutations in the target genes (gyrA and parC) and regulatory genes (mexR and nfxB) for drug efflux pumps were analyzed.Failure of fluoroquinolone treatment of urinary tract infection was observed. The post-treatment isolate, which was assumed to be isogenic to the pretreatment isolate, exhibited fourfold to 16-fold increases in the MIC of fluoroquinolones. In this isolate, a new mutation, not observed in the pretreatment isolate, was found only in the gyrA gene, resulting in an amino acid change of aspartic acid to asparagine in codon 87 of GyrA.The P. aeruginosa isolate that was initially susceptible to fluoroquinolones showed decreased susceptibility to fluoroquinolones after treatment with a suboptimal dose of one fluoroquinolone. In the post-treatment isolate, the alteration of GyrA would be responsible for the decreased susceptibility to fluoroquinolones. We should be aware that inappropriate use of fluoroquinolones could select such a strain harboring a quinolone resistance-associated alteration of DNA gyrase.

Production of guanidinoacetic acid, a precursor of creatinine is known to be reduced by metabolic disturbance when kidney function is damaged, and thus it may be a sensitive marker of renal damage. Therefore, the urinary levels of guanidinoacetic acid, creatinine and creatine from patients with urinary tract neoplasm who received cisplatin treatment were measured by liquid chromatography-mass spectrometry. Following the administration of cisplatin, the urinary excretion of guanidinoacetic acid decreased significantly, and the low concentration was maintained for at least five days. The concentrations of creatinine and creatine gradually decreased until the third day after cisplatin administration, and slightly increased on the fifth day. As superoxide might be concerned in renal damage by cisplatin, the effect of cisplatin on superoxide generation was also investigated using human neutrophils. Cisplatin significantly enhanced phorbol 12-myristate 13-acetate-induced superoxide generation in a concentration-dependent manner, but had no effect on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine and arachidonic acid. The superoxide generation increased by cisplatin was inhibited by staurosporine, an inhibitor of protein kinase C, but was rather enhanced by genistein, an inhibitor of protein tyrosine kinase.

We experienced a case of paraurethral cyst in a 42-year-old woman. A paraurethral cyst, the diameter of which was about 2 cm, was observed in the septum between urethra and vagina. No communication between the cyst and urthra or vagina was detected. The resected cyst did not reveal malignant findings. Sixty-one cases of paraurethral cyst in the Japanese literature are also reviewed.