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Background Phosphoinositide lipids provide spatial landmarks during polarized cell growth and migration. Yet how phosphoinositide gradients are oriented in response to extracellular cues and environmental conditions is not well understood. Here, we elucidate an unexpected mode of phosphatidylinositol 4-phosphate (PI4P) regulation in the control of polarized secretion. Results We show that PI4P is highly enriched at the plasma membrane of growing daughter cells in budding yeast where polarized secretion occurs. However, upon heat stress conditions that redirect secretory traffic, PI4P rapidly increases at the plasma membrane in mother cells resulting in a more uniform PI4P distribution. Precise control of PI4P distribution is mediated through the Osh (oxysterol-binding protein homology) proteins that bind and present PI4P to a phosphoinositide phosphatase. Interestingly, Osh3 undergoes a phase transition upon heat stress conditions, resulting in intracellular aggregates and reduced cortical localization. Both the Osh3 GOLD and ORD domains are sufficient to form heat stress-induced aggregates, indicating that Osh3 is highly tuned to heat stress conditions. Upon loss of Osh3 function, the polarized distribution of both PI4P and the exocyst component Exo70 are impaired. Thus, an intrinsically heat stress-sensitive PI4P regulatory protein controls the spatial distribution of phosphoinositide lipid metabolism to direct secretory trafficking as needed. Conclusions Our results suggest that control of PI4P metabolism by Osh proteins is a key determinant in the control of polarized growth and secretion.

A psychological behaviour management programme with information and communications technology was developed that includes symbolic modelling, tell-show-do, positive reinforcement and distraction, and provides real-time treatment information. We hypothesised that the programme would help patients feel less stressed and show less uncooperative behaviours and subjective pain.Forty-eight paediatric patients were recruited from May 2016 to January 2017, and randomly divided into a control group and an experimental group. In the control, patients watched cartoon animations during the first and second treatments. The experimental group watched cartoon animations during the first treatment, and they used the programme during the second treatment. To measure stress, uncooperative behaviour and subjective pain, we recorded the heart rate, Procedure Behaviour Checklist (PBCL) and Wong and Baker's Faces Pain Rating Scale (FPRS).The experimental group resulted in a significantly lower mean heart rate, uncooperative behaviour and subjective pain in the second treatment than did the control group (p0.001). The differences in heart rate and uncooperative behaviour between the treatments were also significantly greater in the experimental group than in the control group (p0.001).The programme was effective in relieving fear and anxiety as well as learning cooperative behaviour.

Background Nomograms are statistics-based tools that provide the overall probability of a specific outcome. In our previous study, we developed a nomogram that predicts recurrence of early gastric cancer (EGC) after curative resection. We carried out this study to externally validate our EGC nomogram. Patients and methods The EGC nomogram was established from a retrospective EGC database that included 2923 consecutive patients. This nomogram was independently externally validated for a cohort of 1058 consecutive patients. For the EGC nomogram validation, we assessed both discrimination and calibration. Results Within the follow-up period (median 37 months), a total of 11 patients (1.1%) experienced recurrence. The concordance index (c-index) was 0.7 (P = 0.02) and the result of the overall C index was 0.82 [P = 0.006, 95% confidence interval (CI) 0.59–1.00]. The goodness of fit test showed that the EGC nomogram had significantly good fit for 1- and 2-year survival intervals (P = 0.998 and 0.879, respectively). The actual and predicted survival outcomes showed good agreement, suggesting that the survival predictions from the nomogram are well calibrated externally. Conclusions A preexisting nomogram for predicting disease-free survival (DFS) of EGC after surgery was externally validated. The nomogram is useful for accurate and individual prediction of DFS, patient prognostication, counseling, and follow-up planning.

Emerging digital image processing techniques demonstrate their potential applications in engineering mechanics, particularly in the area of system identification involving non-linear characteristics of mechanical and structural systems. The objective of this study is to demonstrate the proof-of-concept that the techniques permit the identification non-intrusively and remotely. First, the efficacy of the digital image processing method is shown by identifying the friction behavior between two solids that are assumed to be governed by the Coulomb friction model. The inverse analysis is carried out to validate the proposed method of identifying model parameters. Studies further illustrate that the digital imaging procedure and inverse analysis algorithms developed for the friction problem can be extended for identification of non-linear mechanical and structural characteristics. One illustration utilizes the second example, where relative motion between a model structure and a shaking table is measured by digitally processing the analogue image provided by a video tape recorded during a shaking table test of a model structure base isolated by a hybrid isolation device consisting of friction and elastomeric components. Third, constitutive relationship for a non-linear elastomeric membrane is identified by digitally processing images of its deformed states under tension. The relationship is postulated to follow the Mooney–Rivlin function. Schemes developed are verified with iterative non-linear finite-element program that is valid in the finite deformation range. Emerging cost-effective hardware and software systems for high-performance data acquisition and processing are quite promising to the implementation of the techniques by removing most, if not all, of its existing limitations.

Tube spinnability is defined as the maximum thickness reduction before either fracture or buckling under the given roller geometry, feed rate, and the speed of the mandrel during the tube spinning of a metal. There are two ways employed to experimentally determine the tube spinnability of the full-annealed and solution-treated AA 2024 and 7075 aluminum alloys. One is to reduce the thickness stepwise to the final thickness without failure the tube. The other is the one-path spinning with continuous reduction in wall thickness of preform from initial to the final thickness without buckling to determine the achieved maximum reduction. Using continuous reduction test, the determined macro-spinnability of full-annealed AA 2024 aluminum alloys is 75% and 7075 aluminum is 74%. Whereas, when examined by scanning electron microscope, the deformation tongue is visible on the outer surface as the thickness reduction higher above 50% for both full annealed 2024 and 7075 aluminum alloys. However, for both solution-treated 2024 and 7075 tubes, the spinnability is lower than that of full-annealed conditions. The discrepancy between the reduction test and microscopic spinnability will be discussed in terms of the microstructure and the mechanical properties.

The characteristics of a butane spray from pintle-type injector were studied by droplet velocity and diameter measurements and high speed photography. The accumulator type injector operated off a common rail fuel supply system operated at 13 MPa, and was controlled by a high-speed solenoid valve. Injection was carried out in a chamber at ambient temperature and at the pressure above (0.37 MPa) and below (0.15 MPa) the fuel vapor pressure. Two component phase/Doppler particle analyzer and traverser were used to obtain the droplet diameter and the velocity at numerous locations in the spray. The entire injection event was analyzed as a time-average and also subdivided into three temporal intervals. A, B, and C. The high-speed photographs showed a narrower cone angle during the quasi-steady spray period at the 0.37 MPa chamber pressure compared to the 0.15 MPa case.

The curing process is the final step in tire manufacturing where curing reactions of rubber compounds take place under elevated pressures and temperatures in a press. A simulator for the tire curing processes was developed, which implements numerical algorithms based on a finite element method to solve the rigorous model equations governing transient heat transfer and curing reactions. Extensive simulation has been carried out ranging from simple heat conduction problems to actual tire curing processes. The results have been verified through comparison with analytical solutions or actual thermocouple measurements. The simulator successfully describes the trends in temperature and the state of cure during the tire curing process. It also serves as the core module of an optimization algorithm, which is being developed for the curing processes.

Phosphoinositide kinases were characterized in membrane extracts of rat submandibular gland cells. Both phosphatidylinositol (PI) 4-kinase and phosphatidylinositol-4-phosphate (PI(4)P) 5-kinase phosphorylated endogenous substrates in reactions that were linear for up to 5 min, were activated by Mg2+ and showed maximal activity around neutral pH. PI 4-kinase was stimulated by Triton X-100 at an optimal concentration of 0.22%, but the detergent had an inhibitory effect on PI(4)P 5-kinase. Arachidonic acid (AA), at concentrations greater than 100 μM, inhibited the activity of both enzymes in a dose-dependent manner. The inhibitory effect was replicated by other unsaturated fatty acids, but not by a saturated fatty acid of the sn-20 series. The nature of AA inhibition of the kinases was examined in enzyme kinetic studies with exogenous phosphoinositide and adenosine 5′-triphosphate (ATP) substrates. Lineweaver-Burk plots of PI 4-kinase activity showed that AA had no effect on the apparent K m for either PI or ATP, but that the fatty acid significantly reduced V max (PI) from 331 to 177 pmol.mg−1.min−1 and V max (ATP) from 173 to 59 pmol.mg−1.min−1. This inhibitory action was consistent for PI(4)P 5-kinase kinetics, where again, AA did not alter apparent K m values, but lowered V max for both PI(4)P and ATP by around 50%. Since the combination of a reduced V max and an unchanged K m value indicates noncompetitive enzyme inhibition, it is proposed that AA regulates phosphoinositide cycle activity in submandibular gland cells by acting as a noncompetitive inhibitor of PI 4-kinase and PI(4)P 5-kinase.

In recent years, global warming leads rainfall intensity stronger than before. Therefore, bridge management requires a reliable monitoring platform in current, to monitoring of bridge piers based on the variations of safety and river erosion, can be timely warming of the bridge damage, achieving the maintenance of bridges safety in the flood. In view of bridge design and construction technology, the bridge engineering technology has matured, however monitoring and maintenance are important factors in the safety of the bridge. And increased with time, no matter how good engineering, high safety factor and then the bridge has aged, the incidence of deterioration, plus traffic overload, the role of erosion and earthquakes, needs more strengthen its safety monitoring and maintenance to ensure safety. Having this in mind, maintaining the safety of the bridge, this research focus on Chung Sha Bridge on Zhuo-shui River. This research installed accelerometer and inclinometer with the correction of the GPS function around substructure and superstructure of bridge, figured out the bridge scour monitoring technologies associated with natural frequency. And used wireless sensor network to monitor bridge disaster, in the end show whole monitor information on web-based system which developed by this research. This research also through long-term monitoring of scour erosion depth and model parameters such as vibration frequency to derive a similar formula. In addition, by way of remote monitoring management platform also improve the accuracy of the bridge monitor, it provide engineers, bridge maintenance unit a more efficient tool.

Wheat and soybean diets supplemented with either tallow or sunflower oil (SFO) were fed to broiler chicks. Variables examined included performance, incidence of sudden death syndrome (SDS), and cardiac sarcoplasmic reticular (SR) calcium transport. The phospholipid content of heart tissues was also determined. Birds fed the SFO diet gained significantly (P.05) more weight over the first 21 days of age and had a significantly better feed:gain ratio (P.01). The incidence of SDS mortality up to 39 days of age was also lower (P.05) for SFO-fed birds than for those fed the tallow diet. Calcium (45Ca2+) uptake and calcium-magnesium 5'-adenosinetriphosphatase (Ca2+ + Mg(2+)-ATPase) activity in cardiac SR vesicles did not differ due to diet (P.05). However, compared with similar weight pen-mates showing no disease signs, SDS birds had depressed 45Ca2+ uptake (P.01) and Ca2+ + Mg(2+)-ATPase (P.05) of cardiac SR vesicles. The phosphatidylcholine concentration in the cell membranes of heart tissue of tallow-fed birds was significantly higher (P.05) than in SFO-fed chicks. No differences were seen in other phospholipid constituents. The SDS birds, however, had significantly (P.05) lower phosphatidylethanolamine plus phosphatidylglycerol, sphingomyelin, and total phospholipid concentrations in the heart tissues than the pen-mate controls. The results support the hypotheses that SDS in broilers is a cardiac dysfunction associated with defective cardiac SR membrane function and that dietary fat type is implicated with the syndrome.

Tuberculosis (TB) continues to be a major global health problem. Extra-pulmonary TB (EPTB) manifests with protean symptoms, and establishing a diagnosis is more difficult than pulmonary TB (PTB).A university-affiliated hospital in southern Taiwan.To analyse the risk factors for EPTB compared with PTB.This retrospective study compared patients with EPTB and PTB in southern Taiwan by analysing their demographic data and clinical underlying diseases. Risk factors for EPTB were further analysed.A total of 766 TB patients were enrolled in this study, with 102 (13.3%) EPTB and 664 (86.7%) PTB cases. Of the 766 patients, 3% of PTB patients had EPTB, while 19.6% of EPTB patients also had PTB. The most frequently involved EPTB site was the bone and joints (24.5%). The incidence of EPTB vs. PTB decreased significantly for each decade increase in patient age. Multivariate logistic regression analysis showed that being female, not being diabetic, having end-stage renal disease and not smoking were independent risk factors for EPTB.This study defines the risk factors for EPTB compared with PTB. Awareness of these factors is essential for physicians to have a high index of suspicion for accurate and timely diagnosis.

N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolone-4-propionic acid (AMPA), and kainate (KA) receptors are members of the ionotropic glutamate receptor (iGluR) family and are increased in inflamed rat skin. These receptors contribute to inflammatory pain. In this study, we have examined whether there is a similar increase in iGluRs in inflamed human skin in the presence of inflammatory pain.Normal and inflamed-skin biopsies were obtained from eight patients undergoing elective wound-debridement surgery. Real-time-polymerase chain reaction (PCR) and western blot analysis were used for quantitation of iGluR mRNA and protein in normal and inflamed human skin.A significant increase in mRNA and protein for NMDA, AMPA, and KA receptor subunits was detected in inflamed compared with normal skin. The amounts of NMDA (NR1 subunit), AMPA (GluR2 subunit), and KA (GluR6 subunit) mRNA in inflamed skin were mean 6 (SD 1.6-fold), 2.5 (0.6-fold), and 3.8 (0.9-fold) (P0.05), respectively, greater than that measured in normal skin. The ratio of NR1, GluR2, and GluR6 protein in inflamed compared with normal skin was 5.7 (1.2), 2.4 (0.5), and 3.6 (0.9) (P0.05), respectively.These results, in human tissue, demonstrate that iGluR mRNA and protein expression are increased during persistent inflammation and that this increased activity may be involved in mediating clinical inflammatory pain in human skin.

Building inventory is a core input to risk and loss evaluation models, and as such, plays a key role in providing decision support for the disaster management community. This paper describes the extraction of detailed building inventory data, using optical remote sensing data within the new MIHEA (Mono Image Height Extraction Algorithm) tool. MIHEA is developed to extract building inventory information such as height, shape and square footage from single high-resolution remotely sensed images. Its pilot implementation in conjunction with QuickBird satellite imagery for London, United Kingdom and Long Beach, USA is described. A methodological protocol is proposed for integrating remote sensing-derived data into loss estimation tools, such as HAZUS® and INLET, to replace default datasets which offer limited accuracy at a census tract scale. The study suggests that when used in conjunction with MIHEA, remote sensing is a valuable source of building inventory information for locations around the World. Preliminary results for the integration of derived data into loss estimation tools are expected in Summer 2006.

Objective: Mental health impact of severe earthquakes on survivors has attracted considerable attention. Suicide represents a terminal outcome of the spectrum of potential major mental health issues spawned by severe earthquakes. This study used time-series analysis to examine the time trends of increased suicide rates after the Chi-Chi earthquake of 1999 in Taiwan in the affected counties. Method: Adult cause of death data were used to study monthly suicide rates per 100,000 adult population in the study and control counties, during January 1995 to December 2001. Box and Tiao's event intervention analysis was used to examine changes in monthly suicide rates before and after the Chi-Chi earthquake. Results: During the post-quake period, October 1999 to December 2001, the mean monthly suicide rate in the affected counties was 1.567 per 100,000, compared with the control counties' rate of 1.297 per 100,000. Mean monthly suicide rate among the high-exposure group was 42% higher during the 26 months following the earthquake than the average for the entire observation period. Examined by time trends, the increased suicide rate registered in the first month following the quake began a monthly gradual decline by 0.7/100,000 thereafter, accounting for a total reduction of 98% in quake-related suicides by the end of 10 months. Suicide rates fell to the baseline level after 10 months. Conclusion: We found that the mean monthly suicide rate for earthquake victims was higher while the low-exposure group remained stable and consistent throughout the observation period, indicating that the impact on the high-exposure group was attributable to the earthquake. This indicates the need for providing strengthened psychiatric services during the first year following major disasters.

PGE2, synthesized by cyclooxygenase-2 (COX-2)-overexpressing tumor, is known to contribute to cellular immune suppression in cancer patients, but the mechanism remains unclear. We report the mechanism of a CD4+ T regulatory type 1 (Tr1) induction by CD11c+ mature dendritic cells (DCs) that phagocytose allogeneic and autologous COX-2-overexpressing glioma. A human glioma cell line, U-87MG, and primary cultured glioblastoma cells (MG-377) overexpressed COX-2. We did not detect IL-10Rα expression in these gliomas, and rIL-10 did not suppress their COX-2 expression. Exposure to COX-2-overexpressing glioma induced mature DCs to overexpress IL-10 and decreased IL-12p70 production. These DCs induced a Tr1 response, which is characterized by robust secretion of IL-10 and TGF-β with negligible IL-4 secretion by CD4+ T cells, and an inhibitory effect on admixed lymphocytes. Peripheral CD4+ T cell populations isolated from an MG-377 patient also predominantly demonstrated a Tr1 response against MG-377 cells. Selective COX-2 inhibition in COX-2-overexpressing gliomas at the time of phagocytic uptake by DCs abrogated this regulatory response and instead elicited Th1 activity. COX-2 stable transfectants in LN-18 (LN-18-COX2) also induced a Tr1 response. The effect of a COX-2 inhibition in LN-18-COX2 is reversible after administration of PGE2. Taken together, robust levels of PGE2 from COX-2-overexpressing glioma, which is unresponsive to IL-10 within the local microenvironment, may cause DCs to secrete high levels of IL-10. These results indicate that COX-2-overexpressing tumors induce a Tr1 response, which is mediated by tumor-exposed, IL-10-enhanced DCs.

In this paper, we describe a highly integrated, quad-band (UGSM/EGSM/DCS/PCS), transmit, front-end module (TX-FEM) integrating power amplifiers, a PA controller, T/R switches, a switch controller, a dual-band directional detector/coupler, a diplexer, matching networks and harmonic filters in a single, 50 /spl Omega/ input and output, 9/spl times/10/spl times/1.5mm package. The module employs InGaP/GaAs HBT, AlGaAs/InGaAs/AlGaAs PHEMT, GaAs Schottky/passive, and Si Schottky/bipolar/CMOS semiconductor technologies and to the authors' best knowledge demonstrates the highest level of integration for a TX-FEM ever reported The module utilizes the excellent performance and ruggedness characteristics of the Skyworks fourth generation HBT process and features 34dBm Pout with 45% PAE GSM and 31dBm Pout and 36% PAE DCS/PCS performance, while meeting a VSWR>20:1 open loop ruggedness spec.

Current therapies for gliomas fail to address their highly infiltrative nature. Standard treatments often leave behind microscopic neoplastic reservoirs, resulting in eventual tumor recurrence. Neural stem cells (NSCs) are capable of tracking disseminating glioma cells. To exploit this tropism to develop a therapeutic strategy that targeted tumor satellites, we inoculated human glioblastoma xenografts with tumor necrosis factor-related apoptosis-inducing ligand-secreting NSCs. This resulted in the dramatic induction of apoptosis in treated tumors and tumor satellites and was associated with significant inhibition of tumor growth. These results add credence to the potential of NSCs as therapeutically effective delivery vehicles for the treatment of intracranial glioma.

This study presents a novel time-domain characterization method for the first time, to reveal dynamic charge behavior of HBTs. The charge model plays an important role in power InGaP-GaAs HBT amplifiers designed with self-biasing. It is shown that charge-storage and extraction from the base of the HBT at a high-power drive cannot be described by the conventional quasi-static model. A new collector-base charge model is proposed to account for the time-response of the devices.

Thoracoscopic approach to sympathetic surgery has gained its popularity and emerged as the main stream in the treatment of hyperhidrosis palmaris in Taiwan. Different kinds of anesthesia have been practiced and reported in these surgeries. We made a survey of anesthetic methods in twelve medical centers and regional hospitals of the island. It was found out that the choice of the anesthesia was mainly dependent on the mutual trust and the full communication between the anesthesiologist and the surgeon, both based on their skills and the operative methods chosen by the surgeon. Single-lumen endotracheal tube with general inhalation anesthesia is practiced in most of the hospitals surveyed. Sevoflurane and desflurane are the choices of the inhalational anesthetic agents. In short, the anesthesiologists tend to practice the type of anesthesia that is simple but safe enough to secure the airway of the patient throughout the thoracoscopic sympathetic surgery.

The objectives of this study were to establish a correlation between granzyme B expression and the clinicopathologic characteristics of patients with angiocentric lymphomas of the head and neck and to determine whether the expression of granzyme B had any influence on the treatment outcomes of such patients.Fifty-seven patients with angiocentric lymphoma of the head and neck who were treated between 1987 and 1996 were divided into two groups according to whether their tumors were immunoreactive for granzyme B: the granzyme B negative group (n = 22 patients) and the granzyme B positive group (n = 35 patients). The clinicopathologic features, immunohistochemical findings, patterns of disease failure, and survival data for the granzyme B positive group were compared with those for the granzyme B negative group.Greater than 60% of patients with angiocentric lymphoma of the head and neck were shown to have granzyme B positive tumors. All tumors that expressed granzyme B also consistently coexpressed CD56, indicating that they probably are the neoplastic equivalent of either natural killer (NK) cells or activated cytotoxic T cells. Although there were no significant differences in histopathologic features or expression of CD45RO and polyclonal CD3-epsilon between the groups, the Epstein-Barr virus genomes were detected more frequently in the granzyme B positive group compared with the granzyme B negative group. Despite a similar rate of complete remission after initial treatment, the locoregional recurrence rate of patients in the granzyme B positive group was much higher compared with patients in the granzyme B negative group. In addition, compared with patients in the granzyme B negative group, patients in the granzyme B positive group also had an increased risk of systemic disease recurrence and a decreased overall survival rate.The data indicate that the cytotoxic granule-associated protein, granzyme B, may be used as an additional marker for identifying NK/T-cell lymphoma and as a prognostic indicator for risk assessment in patients with angiocentric lymphoma of the head and neck.

Endotracheal tube (ETT) fire is a catastrophic disaster that may occur during laser surgery of the upper airway. Several means are available for protection of polyvinyl chloride (PVC) tube from fire, but they are not perfect in prevention of fires caused by laser beam. The PVC tube is hazardous for carbon dioxide (CO2) laser surgery if it is not well wrapped with metallized foil tape. We report a case that a PVC ETT wrapped with aluminum foil ignited during CO2 laser surgery of the larynx. In this report, we emphasize the shaft of the PVC tube must be completely wrapped with aluminum foil to prevent exposure of any surface if it is used in CO2 laser surgery of the upper aero digestive tract.

The authors evaluated the efficacy of adjuvant chemotherapy with 5-fluorouracil (5-FU) plus doxorubicin in gastric carcinoma after D2-3 curative resection. They also evaluated the effect of dose-related factors (delivered total dose/m(2), actual dose intensity [ADI], relative dose intensity [RDI]) of this regimen on patient survival.A total of 301 patients with Stage II to IV (en bloc resected T4b; 1984 American Joint Committee on Cancer staging) were accrued between 1984 and 1996. Chemotherapy was started within 4 weeks of surgery according to the following schedule: intravenous bolus injection of doxorubicin 40 mg/m2 every 3 weeks for 12 cycles and 5-FU 400 mg/m2 weekly for 60 weeks. The toxicity and survival were evaluated.The median follow-up duration was 58 months. Sixty-four percent of the total patients and 71.7% of the patients who did not experience recurrence during the chemotherapy finished the protocol completely with acceptable toxicities. The 5- and 10-year disease free survival rates of total 301 patients were 58.4% and 46.5%, and the overall survival rates were 62.1% and 50.5%, respectively. Treatment completion group showed survival benefit over the early termination group in 5-year survival (75.2% vs. 52.9%; P = 0.0005). The median ADI of 5-FU and doxorubicin were 349 and 11 mg/m2/week, and the median RDIs of 5-FU and doxorubicin were 0.87 and 0.83, respectively. Multivariate analysis demonstrated that completion of chemotherapy is an independent prognostic factor of both disease free and overall survival. However, ADI and RDI did now show any effect on survival.Adjuvant chemotherapy with 5-FU plus doxorubicin for 60 weeks after D2-3 dissection induced promising survival duration with acceptable toxicities. Full administration of the planned dosage of the combined drugs is recommendable as opposed to early termination of the chemotherapy in gastric carcinoma.

Prolonged paralysis is a rare complication of succinylcholine. We report a case of palmar hyperhidrosis who underwent transthoracic endoscopic sympathetic ganglionectomy under general anesthesia with a facemask developed prolonged paralysis following the operation. The prolonged paralysis supposedly caused by intraoperative use of succinylcholine was recognized and confirmed by laboratory examination which showed low pseudocholinesterase activity. In this report, we describe the course of the event and discuss the causes of delayed awakening associated with anesthesia and its management.

Starvation potentiates the hepatotoxicity of a variety of small molecules, including chlorinated hydrocarbons and nitrosamines, through the induction of CYP2E1. A change in CYP2E1 expression during starvation may also alter the pharmacokinetic profiles of xenobiotics. Northern blot and Western blot analyses revealed that hepatic CYP2E1 was not induced during starvation in rats placed in metabolic or wire-bottom cages in contrast to the induction of CYP2E1 in animals housed in solid-bottom cages. We studied the effect of coprophagy on the expression of hepatic CYP2E1 during starvation. The extent of coprophagy was 24% in fed rats. Fecal matter of starving rats was reduced to 14% of control and starving rats re-ingested ~1.6 g of feces per day. The effect of fecal matter on CYP2E1 expression (i.e., 1.6 g/kg/day for 3 days) was assessed in fed or starving rats. Starving rats gavaged with fecal matter for 3 days resulted in a 3.5-fold increase in the level of CYP2E1 mRNA, while fed rats gavaged with feces failed to show an increase in the mRNA. The increase in the CYP2E1 mRNA level accompanied the induction of CYP2E1. Starving rats gavaged with methanol extract of feces (500 mg/kg/day for 3 days) showed a 3.3-fold increase in CYP2E1 mRNA level in the liver. These results provide evidence that CYP2E1 is not induced by starvation without coprophagy, raising the contention that the mechanistic basis for CYP2E1 induction by starvation should be reevaluated.

A 19-year-old female was scheduled for elective surgery of repair of ventricular septal defect (VSD). She had no known previous food or drug allergy history. She was not previously exposed to protamine and did not have any of the risk factors pointing to protamine hypersensitivity reaction. Unfortunately there were two anaphylactoid shocks occurring during this surgery. One was caused by intravenous (i.v.) administration of antibiotics, and the other happened following i.v. drip of protamine sulfate for reversal of systemic heparinization. She had none of the risk factors suggestive of hypersensitivity to drugs and was therefore considered not at risk for such severe adverse reactions which happened. This article was to discuss the anaphylactoid shock induced by antibiotics and protamine during anesthesia, and the prevention and management of such a reaction.

Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factors such as uPAR and growth factors. Thus, we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg cytosol protein and 4.8+/-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between the T stages (p0.05), nor in nodal stage, in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesterone receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.002) and TNM stage (p=0.0004) were significant. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.

Gene therapy, using cytokine gene transduction, aims to increase the antigenicity of tumor cells, and to activate the immune effector cells, and thereby inducing tumor regression. With regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity we compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus. IL-2 secretion was 186 pg/10(6) cells/24 h in SK-Hep1 cell line and 147 pg/106 cells/24 h in Hep-3B cell line with N2A/IL-2 retroviral vector and was 55,000 pg/10(6) cells/24 h in Hep-3B cell line with LNC/IL-2 retroviral vector. in vitro sensitivity to peripheral blood monocytes was increased by 163.8-254% in IL-2 transduced hepatoma cell lines (Hep-3B/LNC/IL-2, Hep-G2/LNC/IL-2) compared to those of the parent cell lines. The tumor was formed in 1 of 3 BALB/c mice and all 3 nude mice with the injection of 1x107 cells. Simultaneous injection of 1x10(7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5x10(5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. After injection of 1x10(7) cells into five other nude mice, the tumor of the IL-2 transduced hepatoma cells (Hep-3B/LNC/IL-2) gradually disappeared, however, the tumor of the parent hepatoma cell line initially decreased and then gradually regrew 20 days later. In conclusion, IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes. IL-2 secretion by LNC/IL-2 retrovirus from the hepatoma cell lines was more prominent compared with that by N2A/IL-2 retrovirus. IL-2 transduction into the hepatoma cells resulted in increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, which leads the regression of the tumors. However, the higher the tumor burden, the less efficient tumor regression by IL-2 transduction into the hepatoma cell line in nude mice was observed.

Central venous catheterization (CVC) has become an important maneuver both for measuring the central venous pressure and for carrying out long-term intravenous alimentation. Furthermore, a central vein may be needed for the rapid restoration of blood volume in condition of acute hemorrhage with difficulties establishing of a peripheral cannulation. However, complications related to either the venipuncture or the presence of catheters in the central venous system were reported. The case we reported here had two ruptured catheter fragments retained in the great vessels, one in the right subclavian vein and the other one in the femoral vein during CVC. They migrated to the pulmonary artery and inferior vena cava, and were finally removed through open sternotomy with pulmonary arteriotomy and exploration of common iliac vein two weeks later. This was an unusual and possibly fatal complication.

Epidural butorphanol has been shown to produce effective analgesia with less side effects than that of morphine but relatively short duration. Clonidine, an alpha 2-adrenergic agonist, has been reported to provide [corrected] pain relief by epidural administration. Furthermore, epidural clonidine has been shown to potentiate the analgesic effect of epidural morphine. The present study was undertaken to evaluate the analgesic and side effects of epidural administration (Ep) of butorphanol and clonidine.After giving their consents, 60 adult patients scheduled for abdominal surgeries were enrolled in this study. Prior to anesthesia induction, indwelling lumbar epidural catheters were placed in all patients who then received general anesthesia with inhalation anesthetic without narcotic analgesics. In the postoperative period, when the patients first complained of pain, they were divided into 2 equal groups of 30 patients each in a randomized and double blinded fashion with Group I receiving Ep butorphanol 0.5 mg and Group II receiving Ep butorphanol 0.5 mg plus clonidine 75 micrograms. All patients were observed for pain relief, sedation, vital signs, arterial blood gas studies and adverse effects for 12 h.Onset of pain relief with epidural butorphanol began at 5 min and peaked at 20-30 min with a duration of action lasting 4-6 h. The combination of butorphanol and clonidine had numerically superior pain relief than that of butorphanol for the first 30 min but it did not attain statistical significant difference. The duration of action with the combination group was similar to that of butorphanol alone. Incidence of adverse effects were similar in both groups except that hypotension and more pronounced sedation were observed in Group II.Our study showed that the addition of clonidine to epidural butorphanol did not enhance its analgesic effect in any significant manner nor did it reduce the adverse effects. This combination does not seem to offer any advantage for clinical use.

Prognosis of gastric carcinoma is related to invasion and metastasis. Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membrane. The serine protease urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), appear to have a major function in these processes. Recent reports have demonstrated that expression of these proteolytic enzymes is elevated in breast and colon carcinoma and that it can be associated with invasiveness and poor prognosis. Therefore, the authors evaluated whether the expression and activation of uPA and PAI-1 might be of clinical value as a tumor/biologically defined risk factor in patients with gastric carcinoma.Enzyme-linked immunoadsorbent assays were used to test for uPA antigens and PAI-1 in tissue extracts of normal and cancerous tissue from 160 gastric carcinoma patients who were enrolled in the Yonsei Cancer Center Study Group.Both uPA and PAI-1 levels were significantly higher in cancerous tissues than in normal tissues (uPA: 9.4 +/- 8.7 vs. 5.3 +/- 3.1 ng/mg protein cytosol; PAI-1: 10.9 +/- 9.1 vs. 5.8 +/- 2.9 ng/mg protein cytosol), (P0.001, respectively). Both high uPA and PAI-1 levels were associated with differentiation of the tumor (P = 0.04 and P = 0.004, respectively), and a high PAI-1 level was associated with lymph node metastasis at an advanced stage (P = 0.003 and P = 0.04, respectively). There was a correlation between the levels of uPA and PAI-1 expression in cancerous tissues (correlation coefficient = 0.57). In univariate analysis, a high level of uPA or PAI-1 was associated with a short relapse free survival, but in multivariate analysis only a high level of uPA was an independent prognostic parameter for a short relapse free survival for gastric carcinoma patients.These data indicate that uPA is a new independent variable for the identification of high risk gastric carcinoma patients. Therefore, therapy targeting uPA can be applied as a new biologic treatment modality for these individuals.

Mutations at codons 12, 13, and 61 of the three ras genes, H-ras, K-ras, and N-ras, convert these genes into active oncogenes. It appears that ras gene mutations can be found in a variety of tumor types. The purpose of this study was to evaluate the clinical significance of K-ras gene mutation in nonsmall cell lung carcinoma (NSCLC).The authors analyzed 58 NSCLC patients for mutations at codons 12, 13, and 61 of the K-ras gene and correlated the findings with the tumor stage and patient survival. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and the direct nucleotide sequencing method were used to detect mutations after amplification of ras specific sequences by PCR.Fourteen mutations (24%) of ras genes were found, all at codon 12 of the K-ras gene. GGT to GAT transition was the predominant mutational pattern. There was a significant association between K-ras mutation and the tumor stage (i.e., the higher the stage, the higher the mutation rate) (P = 0.014). Using univariate analysis, the presence of K-ras mutation in paraffin embedded tissue from patients who received treatment with curative intent was associated with a shorter survival (P = 0.039). The median survival duration for patients with or without K-ras mutation was 9 and 30 months, respectively. The Cox proportional hazards model also predicted a higher risk for patients with K-ras mutations (P = 0.047).K-ras mutations, present in a subset of NSCLC, are associated with tumor progression and shortened patient survival.

The modulation of CCl4-induced hepatotoxicity in response to alkyl sulfides and alkyl ethers including allyl disulfide (ADS), allyl sulfide (AS), allyl ether (AE), propyl disulfide (PDS), propyl sulfide (PS), propyl ether (PE) and butyl sulfide (BS) was studied. Whereas pretreatment of rats with either ADS or AS (50 mg/kg, 7 days) blocked a CCl4-induced increase in plasma alanine aminotransferase (ALT) activity by 91 and 56%, respectively, AE, PDS, PS, PE or BS treatment enhanced CCl4-induced ALT activity by 52, 55, 238, 25 or 86%, respectively. Histochemical examinations supported the results of plasma ALT activity. Injection of GdCl3 to PS-pretreated rats failed to block the potentiated ALT increase, whereas GdCl3 completely prevented vitamin A-enhanced elevation of ALT activity. AS treatment completely blocked PS-potentiated CCl4 intoxication. Concomitant treatment of animals with both PS and vitamin A followed by a CCl4 insult resulted in super-potentiation of CCl4-induced hepatotoxicity, suggesting that the mechanism of PS-enhanced hepatotoxicity differs from that caused by vitamin A. Pyridine or phenobarbital potentiation of CCl4-induced increases in ALT activity implys that cytochrome P450 2E1 (P450 2E1) and P450 2B expression may be associated with the increased toxicity. P450 2E1 expression appeared to be associated with the alkyl sulfide-modulated hepatotoxicity, as evidenced by both immunoblot analyses and metabolic activity. P450 2B immunoblot analysis revealed that either AS or PS substantially induced hepatic P450 2B1/2 levels. Thus, PS-enhanced CCL4 hepatotoxicity may be related in part with P450 2B induction. ADS, AS or PS treatment caused increases in the glutathione S-transferase (GST) conjugating activity toward 1-chloro-2,4-dinitro-benzene. ADS, AS or PS induced Ya and Yb1 subunits by 2- to 3-fold. ADS or AS treatment also significantly elevated the levels of Yc subunits. PS failed to induce Yc expression, although this agent effectively increased Yb2 expression. Northern blot analyses revealed that ADS and AS concomitantly stimulated GST Ya, Yb1 and Yc2 gene expression, whereas PS increased the levels of Ya, Yb1, and Yb2 mRNA, but not Yc2 mRNA levels. The expression of GST subunit Yc2 in response to these compounds might be associated with hepatoprotective effects. These results demonstrate that ADS and AS have distinct capability of blocking CCl4-induced hepatotoxicity, whereas certain saturated alkyl sulfides rather potentiate CCl4-induced hepatotoxicity and that the underlying mechanism is associated with P450 2E1 and P450 2B expression, and possibly with certain GST expression.

The characteristics of muscarinic cholinergic-induced phospholipase D (PLD) activation, and the involvement of the enzyme in the release of arachidonic acid were examined in rat submandibular acinar cells. Carbachol produced a dose-related activation of PLD to around fivefold control values at 100 microM agonist concentration. This was associated with the appearance of free choline, phosphatidic acid and arachidonic acid, indicating that the PLD substrate was phosphatidylcholine. The response to carbachol was inhibited by 60% by U73122, a blocker of a phospholipase C (PLC) specific to phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], suggesting that the cleavage of phosphatidylcholine by PLD was, at least in part, secondary to agonist-coupled hydrolysis of PtdIns(4,5)P2 by PLC. Consistent with this, PLD was also activated to levels comparable to those induced by carbachol, by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), and the Ca2+ mobilizer, thapsigargin, two agents that respectively mimic the activation of protein kinase C (PKC) by diacylglycerol and the elevation of cytosolic Ca2+ by inositol 1,4,5-triphosphate [Ins(1,4,5)P3] in the phosphoinositide effect. The cell-permeant Ca2+ chelator 1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA/AM) abolished the thapsigargin-induced activation of PLD and inhibited the responses of PLD to carbachol and TPA by 60%. The PKC inhibitor, Ro-31-8220, also inhibited the activation of PLD by carbacol and TPA to a level of approximately double control values, but had no effect on the thapsigargin-induced elevation of PLD. A role for both the PKC-associated and Ca(2+)-mobilizing arms of the PtdIns(4,5)P2-PLC pathway in PLD regulation is thus suggested. Pretreatment of cells with the phosphatidate phosphohydrolase blocker, propranolol, significantly enhanced the carbachol-induced elevation of phosphatidic acid, but decreased agonist-stimulated production of diacylglycerol and arachidonic acid, indicating that phosphatidlycholine was the likely source of arachidonic acid. We therefore propose that, in submandibular mucous acinar cells, muscarinic activation of the PtdIns(4,5)P2-PLC pathway regulates phosphatidylcholine-specific PLD through both the PKC- and Ca(2+)-mobilizing arms of the phosphoinositide response, and that diacylglycerol, derived from phosphatidylcholine via phosphatidic acid, is a source of free arachidonic acid.

Acute hemorrhage leading to acute hypovolomic shock is a medical emergency carrying high mortality. It therefore requires prompt and effective treatment. We reported a case of lung tumor receiving lobectomy at our hospital. Repeated internal bleeding due to subclavian artery perforation occurred three times within three weeks after the surgery. During the period of resuscitation, the patient received emergently massive blood transfusion. Some complications of massive blood transfusion. Some complications of massive blood transfusion were noted later. A total of 89 units of whole blood, 34 units of fresh frozen plasma and 28 units of platelet was given.

A capacitance model for microwave Double Heterojunction Bipolar Transistors (DHBTs) is presented to account for their special behavior in small-signal S-parameters. A physical picture of barrier effects in DHBTs is described.

Background The prognosis of gastric cancer with peritoneal metastasis is extremely poor. Neither systemic chemotherapy nor surgery alone prolongs survival of patients significantly. Methods Patients diagnosed with advanced gastric cancer underwent staging laparoscopy and received chemotherapy when peritoneal dissemination and/or cancer cells on peritoneal cytology were confirmed. The chemotherapy regimen consisted of S-1, weekly intravenous and intraperitoneal paclitaxel, which was verified in our phase II trial (Ann Oncol 2009). S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. Clinical response of chemotherapy was assessed by computed tomography, gastroendoscopy, peritoneal cytology and second-look laparoscopy. Radical gastrectomy was carried out when macroscopic curative resection was made achievable by chemotherapy. Chemotherapy was restarted after operation as soon as possible. Overall survival, relapse free survival, morbidity and mortality of gastrectomy were evaluated. Results Out of 100 patients with peritoneal metastasis who received chemotherapy, 60 patients underwent gastrectomy after response to chemotherapy, including 54 with macroscopic metastasis and 6 with positive peritoneal cytology only. A median of three courses were administered preoperatively (range 1–16). Total or distal gastrectomy with lymphnode dissection was carried out in 54 or 6 patients, respectively. The median survival time was 34.5 months. The median relapse-free survival was 16.7 months. The first site of relapse was the peritoneum in 24 patients and the other organ site in 17 patients. Postoperative complications included anastomotic leakage and pancreatic fistula in two patients each, which were healed conservatively. There were no treatment-related deaths. Conclusions Gastrectomy combined with S-1, intravenous and intraperitoneal paclitaxel is safe and active for gastric cancer patients with peritoneal metastasis.

Basic fibroblast growth factor (bFGF) is a strong inducer of angiogenesis and thus may play an important role in the growth of solid tumors. However, bFGF is usually found immobilized on the extracellular matrix, and it is only partly understood how it is solubilized to reach and activate its extracellular receptors. We studied the potential contribution to this process by a secreted binding protein (BP) with high affinity for FGFs. An expression vector for BP was transfected into a human cell line (SW-13) that contains constitutively high levels of bFGF. The BP-expressing cells began to grow colonies in soft agar due to their autocrine stimulation by bFGF and released biologically active bFGF into their media. Furthermore, they grew into well vascularized tumors in athymic nude mice. In addition, we found the BP mRNA expressed at high levels in squamous cell carcinoma (SCC) tissues from patients and in SCC cell lines of different origin as well as in immortalized keratinocytes. However, we failed to detect BP mRNA in normal adult tissues or in a number of non-SCC tumor cell lines. Expression of the secreted BP appears to be a mechanism through which immobilized FGF can be activated to support tumor growth and angiogenesis.

LBA4002 Background: Surgical resection is a recommended treatment for operable gastric cancer (GC) in general, despite high recurrence rates (40%–80%). Adjuvant chemotherapy aims to reduce recurrences; however, there is currently no universally accepted adjuvant regimen for GC. Methods: CLASSIC is a randomized, open-label, multicenter, international (South Korea, China, and Taiwan) study of XELOX (capecitabine 1000mg/m2 bid, d1–14, q3w and oxaliplatin 130mg/m2, d1, q3w x 8 cycles) vs observation, following D2 gastrectomy. Eligible patients were chemotherapy- and radiotherapy-naive, with stage II (T2N1, T1N2, T3N0), IIIa (T3N1, T2N2, T4N0), or IIIb (T3N2) GC resected within 6 weeks prior to randomization. The primary endpoint is 3-year disease-free survival (DFS). A sample size of 512 patients per arm was planned to observe the 385 DFS events required to provide 80% power at a 5% significance level for the hypothesized treatment effect (hazard ratio [HR] 0.75). The Independent Data Monitoring Committee recommended full evaluation and reporting of results following a positive pre-planned interim analysis at 266 events. Results: The XELOX and observation arms (ITT populations of 520 and 515 patients, respectively) were well balanced for baseline characteristics. The median duration of follow-up was 34.4 (16–51) months. XELOX-related grade 3/4 adverse events (AEs) occurred in 244/496 patients (49%) of the safety population. Neutropenia was the only AE observed in >10% of patients (21%, n=106/496). Serious XELOX-related grade 3/4 AEs occurred in 34/496 patients (7%). There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of XELOX and observation arms, respectively, mostly due to disease progression. Efficacy results in the ITT population are summarized below. Conclusions: This study demonstrates the superior efficacy of adjuvant XELOX vs observation alone following D2 gastrectomy. Although OS data are still immature, there is a trend towards superiority of XELOX. These data support the use of adjuvant XELOX for GC. [Table: see text]

599 Background: Adjuvant! Online (AOL) is a web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy ( www.adjuvantonline.org ). AOL has never been validated for Asian colon cancer patients. Methods: Using the Yonsei Tumor Registry (YTR) database, we calculated the survival for the patients with T1-4, N0-2, M0 colon cancer who were treated at the Yonsei Cancer Center between 1990 and 2005. Observed and predicted 5-year survival was compared for each patient. Results: The median age of the study population was 60 years (range, 15-87 years) and the median follow-up duration was 7.9 years (range, 0.06-19.8 years) for all 1,431 patients. While AOL underestimate overall survival (OS) (predicted-observed=-1.02%, P=0.008), it overestimate colon cancer-specific survival (CCSS) (predicted-observed=3.8%, P Conclusions: KAOL model for Korean colon cancer patients is more suitable to predict 5-year outcomes compared to ALO model for Western patients. No significant financial relationships to disclose.