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Rugosin G, an ellagitannin trimer, was isolated from the water-soluble fraction of red rose petals, and its inhibitory activity against recombinant human histidine decarboxylase was investigated. Rugosin G showed potent inhibition compared to ellagitannin monomers and a dimer with macrocyclic structure (oenothein B), suggesting the potent inhibition of rugosin G was attributed to its linear oligomeric conformation. Abbreviations: HDC, histidine decarboxylase; Me2CO, acetone; EtOAc, ethyl acetate

Clinical and subclinical ketosis are associated with low productivity and poor well-being of dairy cattle. Dietary supplementation of gluconeogenic precursors during the transition period is a strategy to prevent the occurrence of these diseases. However, there is a lack of information regarding the effect of feeding mixed gluconeogenic precursors on intake, and systemic and hepatic metabolism of transition dairy cows. Our objective was to examine the effect of supplementing a mixture of gluconeogenic precursors (Glucose Booster, GB) on intake, milk yield and composition, blood metabolites, and hepatic gene expression in transition dairy cows. Twenty-nine multiparous Holstein cows blocked by previous 305-d mature-equivalent milk yield were randomly assigned to one of the two treatments: GB supplementation or not (CTL). Cows received their respective dietary treatments from 28 d before expected calving to 21 d after parturition. Then, all cows were fed the CTL diet until d 56 of the lactation. Ambient temperature and relative humidity in the barn were assessed hourly. Vaginal temperature was determined weekly during the prepartum period from a subset of cows. Dry matter intake was recorded daily, and body condition score and body weight assessed every two weeks during the experiment. Milk yield was recorded daily and composition measured weekly in early lactation. Plasma samples were collected on d 28 and 10 before expected calving, calving, and 3, 7, 14, 21, 28 and 42 d after calving for analysis of metabolites and insulin. Liver biopsies were collected at 28 d before the expected calving and 14 d after calving to measure mRNA expression of genes related to gluconeogenesis, ketogenesis, and fatty acid oxidation. Data were analyzed using the PROC GLM or MIXED procedures of SAS. The temperature-humidity index averaged 74 and 65 in the pen for dry and lactating cows, and the vaginal temperature averaged 39.2 ○C before calving and was not different between treatments, suggesting that dry cows were exposed to heat stress. Treatment had no impact on intake, lactation performance, blood metabolites and insulin and hepatic gene expression. In conclusion, supplementation of GB did not affect performance or metabolism of transition dairy cows, indicating that exposure to heat stress may diminish the benefits of feeding gluconeogenic precursors during the transition period.

Histidine decarboxylase (HDC) catalyses the formation of histamine, a bioactive amine. Agents that control HDC activity are beneficial for treating histamine-mediated symptoms, such as allergies and stomach ulceration. We searched for inhibitors of HDC from the ethyl acetate extract of the petal of Filipendula ulmaria, also called meadowsweet. Rugosin D, rugosin A, rugosin A methyl ester (a novel compound), and tellimagrandin II were the main components; these 4 ellagitannins exhibited a non-competitive type of inhibition, with K(i) values of approximately 0.35-1 μM. These K(i) values are nearly equal to that of histidine methyl ester (K(i)=0.46 μM), an existing substrate analogue inhibitor. Our results show that food products contain potent HDC inhibitors and that these active food constituents might be useful for designing clinically available HDC inhibitors.

We identified an age effect on biopterin and biogenic amine metabolites in the cerebrospinal fluid from 56 neurologically normal patients, aged 1 mo to 80 y. The levels of total and reduced forms of biopterin, homovanillic acid, and 5-hydroxyindoleacetic acid were found to peak during the first year of life. The levels of these metabolites then gradually decreased, plateauing at the age of 20 y. We found significant correlations between biopterin, homovanillic acid, and 5-hydroxy-indoleacetic acid.

Interspecific hybrids between Rakkyo (Allium chinense G. Don) and its relative species, A. thunbergii G. Don and A. virgunculae var. kiiense Murata, were produced by an ovary culture. Among these hybrids, two cultivars being suitable for cut flowers and one cultivar for pot flowers were selected. The cultivars for cut flowers bloomed from late October to early November. They had solid stems between 50 and 70 cm in length with little tight spherical umbels from 5 to 6 cm in diameter consisting of more than 80 florets with six reddish purple petals. They produced two to three bulbs from one plant per year. The pot-flower cultivar also bloomed in October and had thin but solid stems of about 25 cm in length with small and spherical umbels of 3 cm in diameter consisting of more than 40 florets with six reddish purple petals. They produced three bulbs from one plant per year. In addition, all these cultivars were easy to cultivate. The new cultivars from interspecific hybrids of Allium reported here can create a new demand for cut flowers and pot flowers because of their autumn-flowering character without competing with other ornamental Allium species which flower in spring to early summer. INTRODUCTION There are a lot of commercial varieties of ornamental Allium species, but many of them are selected from wild types. Limited breeding of ornamental Allium species has been conducted. Most of the ornamental Allium bloom from spring to summer (Stearn, 1986). However, A. chninense, which is grown in Japan as a vegetable and some wild types of the species bloom in autumn. Though A. chinense does not have seed fertility because of autopolyploidy (Nishitani, 1980), some other Allium species in Japan are fertile. The Allium species in Japan are too small or too poor in quality to be used as cut flowers as they are. That is why we tried the first interspecific hybridization between commercial ornamental Allium and autumn-flowering Japanese Allium species. Consequently, some hybrids were obtained but all of them bloomed in summer (Nomura et al., 2002). On the other hand, Dubouzet et al. (1993) reported that hybrid plants between A. chinense and A. thunbergii were suitable for ornamental cut flowers. So next we tried a hybridization between A. chinense and A. thunbergii. It made a new cultivar of autumn-flowering Allium named ‘Autumn Violet’ (Nomura et al., 2001). This cultivar was between 50 and 60 cm tall and had reddish purple spherical umbels of 6 cm in diameter. It started to bloom in late October. However, this cultivar had a fault in that the flowers bloomed simultaneously. Because of this the harvest did not last. That is why we tried to make varieties which flowered both earlier and later than this cultivar. Additionally, we hoped that the subsequent cultivars would have taller and thicker stem with richer umbel. In this study, we made two cut-flower cultivars, which bloomed at different times respectively and were of a higher quality than ‘Autumn Violet’. Moreover a small and pretty pot-flower cultivar was also made. MATERIALS AND METHODS Cross Combinations and Ovary Cultures In making the cut-flower cultivars, ‘Autumn Violet’ was used as a maternal plant Proc. IX Intl. Symp. on Flower Bulbs Eds.: H. Okubo, W.B. Miller and G.A. Chastagner Acta Hort. 673, ISHS 2005 142 and was hybridized with A. thunbergii in October of 1996. The maternal plant was emasculated before the crossing. In making the pot-flower cultivar, A. chinense was used as a maternal plant and was hybridized with A. virgunculae var. kiiense in October of 1997. The emasculation of the maternal plant was not needed because of the pollen sterility of A. chinense. The ovaries of the maternal plants were cultured five days after pollination to preserve the hybrid embryos. After removing petals and pistils, the ovaries were collected and sterilized in 70% (v/v) ethanol for a few seconds and then in 1% (v/v) sodium hypochlorite solution for 10 minutes. Then they were rinsed three times in sterile distilled water. After rinsing, they were placed vertically on an MS (Murashige and Skoog, 1962) medium supplemented with 5% sucrose and solidified with 0.8% agar. The pH of the culture medium was adjusted to 5.8, and the media were autoclaved. The culture was kept at 25°C under white fluorescent light (2000 lx) with a 16-hour photoperiod for two months. The seedlings germinated from the ovaries on the MS medium were transferred to an MS medium containing 3% sucrose and 0.8% agar, which was adjusted to pH 5.8 before autoclaving. Morphological Characteristics of Hybrid Plants The hybrid plantlets were planted in pots from in vitro cultures in the following March and were grown in a greenhouse. In August, the bulbs of the hybrid plants were transplanted into a sand field and were vegetatively propagated. Each year in August, the bulbs were harvested, divided individually and then replanted in the same sand field for propagation. After the propagation, the multiplied bulbs were divided individually and were replanted in the sand field with 30 cm row spacing and 15 cm distance between each bulb in August of 2002. During the next year, the morphological characteristics and growth of each hybrid were investigated in June when the growth was most vigorous. The characteristics of the flowers were examined in October. Twenty plants per cultivar were examined in each stage. RESULTS Cut flower types were selected from the hybrids of ‘Autumn Violet’ and A. thunbergii. ‘Autumn Violet’ was a commercial variety which had already been made from the hybrid of A. chinense and A. thunbergii. A pot-flower type was selected from the hybrids of A. chinense and A. virgunculae var. kiiense. The appearance of these cultivars was similar to that of A. caeruleum or A. cowanii in that they had reddish purple umbels. They were also bulb forming plants. Their important characteristic was their ability to flower in autumn. The early-flowering type of the new cultivars for cut flowers was named ‘Autumn Violet 2’ (Fig. 1 and 2) and the late-flowering type was named ‘Autumn Violet 3’ (Fig. 3). On the whole the plant posture of the new cultivars was similar to that of ‘Autumn Violet’. The plant height, number of leaves and leaf width of ‘Autumn Violet 2’ were respectively 30 cm, 10.6 leaves and 6.4 mm. They were almost the same as those of ‘Autumn Violet’ but the leaf length of ‘Autumn Violet 2’ was 51 cm, which was about 10 cm longer than that of ‘Autumn Violet’ (Table 1). That is why ‘Autumn Violet 2’ looked larger than ‘Autumn Violet’. As for ‘Autumn Violet 3’, the plant height, number of leaves and leaf length were respectively 24 cm, 8.3 leaves and 43 cm. All of these measurements were a little smaller than those of ‘Autumn Violet’. However, the leaf width of ‘Autumn Violet 3’ was 7.1 mm, which was wider than that of ‘Autumn Violet’. The pot-flower was named ‘Autumn Violet Mini’ (Fig. 4) and the plant posture was similar to that of A. virgunculae var. kiiense on the whole. The plant height, leaf length and leaf width of ‘Autumn Violet Mini’ were respectively 20 cm, 28 cm and 3.0 mm which were less than those of ‘Autumn Violet’. But the number of leaves of the ‘Autumn Violet Mini’ was 12.2, which was more than that of ‘Autumn Violet’. That is why the ‘Autumn Violet Mini’ looked smaller than the ‘Autumn Violet’. Concerning the bulb formation of ‘Autumn Violet 2’, it multiplied at a rate of three times each year which was the same as that of ‘Autumn Violet’ (Table 2). The weight of all

The change of shape and elemental concentration of cellular samples in In-Air micro PIXE analysis was investigated. Cultured bovine aortic endothelial cells were analyzed in the atmosphere by using 2.6 MeV proton micro-beams. The shape of cross-sections of cells was not so much distorted by beam irradiation and the concentrations of trace elements did not change too, except for S. The concentration of S changed with strongly depending on the temperature rise due to beam irradiation.

We developed mini step samplers with low manufacturing and running costs for application in multi-site air-pollution monitoring. The miniaturization of the sampler was achieved by reducing the suction nozzle size. We tested the samplers with suction nozzle diameters of 2 and 4 mm through simultaneous exposure in the same site. Elemental concentrations of aerosol collected by these samplers were consistent within ±20% during comparison and the sample uniformity did not differ significantly. Sampling with small suction nozzle did not adversely affect aerosol collection. Aerosol samples were collected simultaneously at two sites in our laboratory and in the hall outside for 3 days and analyzed subsequently by PIXE. The time variation of elemental concentrations was high during daytime and low at night time and also during the weekend. Elemental concentrations in the hall were always higher than those in the laboratory. In our laboratory, we change shoes at the entrance and therefore, elemental concentrations inside the lab are lower than in the hall. In a second field experiment, we carried out simultaneous multi-site aerosol sampling during two periods in correlation with meteorological data (wind direction and velocity). It was observed that elemental concentrations of some soil origin elements changed periodically. On the other hand, the concentration of Cu and Zn showed irregular concentration spikes whose pattern showed a variation with the sites. Analysis using the data of wind directions showed that Cu had been transported to the sites from northeasterly direction and that the concentration of Zn was influenced by two big factories nearby. In conclusion, it has been demonstrated that the multi-site sampling system combined with meteorological data is well suited to identify sources of pollution.

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between 132Te and 137Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.

It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p < 0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly.

Intense photostimulated luminescence (PSL) is observed, for the first time, in X-ray-irradiated KBr:Eu and KCl/sub x/Br/sub 1-x/Eu phosphor ceramics. The peak in the stimulation spectrum for the PSL red-shifted with increasing the Br content of KCl/sub x/Br/sub 1-x/:Eu phosphor ceramics. The intensity of the PSL with a peak of about 420 nm increases linearly with increasing X-ray irradiation dose over a wide range. The KBr:Eu phosphor exhibites better fading characteristics at room temperature (RT) in the dark, comparing with that of BaFBr:Eu phosphor. The mechanism of fading of the PSL is also discussed.

In this work, our objective was to study the hydrogen bonding of alcohols in aqueous solutions and alcohol dipole relaxation by measuring the complex permittivity. Alcohols chosen for study were methanol, ethanol and propanol over the full composition range and from 297–363 K. Measurements were made with a frequency domain technique from 100 MHZ to 20 GHz. All of the alcohol–water mixtures studied had a negative excess permittivity that was skewed towards higher water mole fractions. The composition dependence of the dielectric relaxation showed remarkable behavior. At water concentrations of xwater 0.85 or so, the relaxation time had a sharp slope. Our data show that there is a distinct curvature between the pure component time constants, which indicates a gradual, nonlinear change of the relaxation time with composition. From the dielectric data, it would seem that there are three subtle but distinct regions of hydrogen-bonding environments.

Introduction: Cold stress, secondary to heat loss, can compromise infants in transport incubators during interfacility transfer. With current incubator designs, considerable radiant heat loss occurs. The use of additional external thermal insulation to reduce heat loss has been recommended for infant transports in cold environments. Method: A laboratory experiment was done to compare the rate of heat loss from a transport incubator with and without a commercially available, thermal insulating cover in place. The environment was a commercial freezer simulating subzero environmental temperatures. Measurements included air temperature inside the incubator and freezer, patterns of heater action and duration of battery power output. The significance of the different rates of cooling was compared using Pearson's r . Suboptimal battery performance was excluded by repeating one arm of the study with an external battery in place of the internal unit. Results: The rate of heat loss from the incubator was: 1) significantly slower when the covered and uncovered incubators were compared ( r 2 = 0.52), and 2) essentially identical for the uncovered incubator with either the internal or the external battery ( r 2 = 0.96). Conclusion: In the laboratory setting, external thermal insulation slows transport incubator radiant heat loss. Clinically, this effect likely would benefit infants at risk of cold stress during interfacility transports.

Aim To assess the glucose-lowering effects of monotherapy with the glucokinase activator AZD1656 in Japanese patients with type 2 diabetes mellitus. Methods This was a randomized, double-blind, placebo-controlled study performed in Japan (NCT01152385). Patients (n = 224) were randomized to AZD1656 (40–200, 20–140 or 10–80 mg titrated doses) or placebo. The primary variable was the placebo-corrected change from baseline to 4 months in glycated haemoglobin (HbA1c). Effects on fasting plasma glucose (FPG) and safety were also assessed. Results HbA1c was reduced numerically from baseline by 0.3–0.8% with AZD1656 and by 0.1% with placebo over the first 2 months of treatment, after which effects of AZD1656 started to decline. The changes from baseline to 4 months in HbA1c were not significant for the AZD1656 40–200 mg group versus placebo [mean (95% CI) placebo-corrected change: −0.22 (−0.65, 0.20)%; p = 0.30]. Formal significance testing was not carried out for the other two AZD1656 dose groups. A higher percentage of patients on AZD1656 achieved HbA1c ≤ 7% after 4 months versus placebo, but responder rates were low. Results for FPG reflected those for HbA1c. Cases of hypoglycaemia were rare with AZD1656 (one patient) and no safety concerns were raised. Conclusions Although initially favourable plasma glucose reductions were observed, there was a loss of effect over time with sustained AZD1656 treatment. The study design did not allow an evaluation of the reasons for this lack of long-term efficacy.

The ablation dynamics of tin micro-droplet target irradiated by double pulses was investigated for extreme ultraviolet lithography source. Debris from Sn droplet target was visualized by the laser-induced fluorescence imaging and shadowgraph imaging.

A method for detecting strange-quark matter is discussed. In order to confirm the existence of strange-quark matter in the cosmic radiation, a new instrument under construction for a balloon experiment is presented.

At the Neutrino 98 conference the Super Kamiokande collaboration presented a reduction of up-going μ-like events compared to down-going μ -like events by a factor of 0.54 −0.05 +0.06 for an exposure of 33 kton-years. Also, the zenith angle distribution observed by MACRO for -1 ≤ cos Θ ≤ −0.1 does not fit well for the no oscillation expectation. On the basis of x 2 tested results (shape, absolute value), however, their claim for neutrino oscillations cannot be considered to be firmly established from the standpoint of statistical evidence.

As the pixel size of CMOS image sensors (CIS) shrink, problems associated with crosstalk become more severe for devices built using mainstream CMOS processing. This high crosstalk increases the amount of noise added to the final image (via an increase of the off-diagonal terms in the color correction matrix (CCM)) and degrades the modulation transfer function (MTF). Reducing dark current has also been challenging for such CIS imagers. At present, the solution to these problems has been to switch to n-type substrates since they have been used for interline charge-coupled devices (CCDs) for decades.

A major technical challenge of an extreme ultraviolet (EUV) light source for microlithography at 13.5 nm is the in-band power requirement of more than 115 W at the intermediate focus. The solution for HVM EUV lithography is a laser produced plasma light source with a cost effective CO2 drive laser and a high conversion efficiency Sn target. To demonstrate this, a LPP source is developed for high volume manufacturing EUV lithography which is based on a high power CO2 MOPA (Master Oscillator Power Amplifier) system and a tin target. It is concluded that the CO2 laser driven Sn light source is the most promising candidate for HVM EUVL due to its scalability, high efficiency and long collector mirror lifetime.

Summary form only given. Extreme Ultraviolet Lithography (EUVL) is a major candidate of next generation lithography (NGL) technology for the fabrication of 45 nm node and below. In this paper, we report the laser produced plasma EUV light source development status.

We have developed a programmable DSP for MPEG4, H.263, H.261 and wavelet based sub-band codec algorithms. This DSP has the capability of processing these algorithms in real-time and has excellent flexibility, so that it can, for instance, perform video codec at 15 CIF frames/sec or video/speech (G.723.1) codec at 30 QCIF frames/sec. This chip includes a video pre/post-processing engine and needs only one 16 Mbit SDRAM as an external memory to perform the above algorithms, making it possible to realize low-cost systems. This chip is fabricated using 0.25 um CMOS technology and contains 7.7 M transistors on 9.41 mm/spl times/9.22 mm die.

We describe a new architecture and protocol that we have developed to meet the requirements of workflow systems that are used for electronic commerce systems among enterprises. We developed practical electronic commerce systems using XML-based workflow systems among enterprises. We found that the requirements are greatly different from traditional workflow systems in some points; such as process management, server communication protocol, history log management, data conversion, and external application calls. In this paper, we illustrate the new requirements and problems when EC systems are developed using traditional workflow architecture and protocols, then we propose our new architecture and protocol that provide solutions for these requirements and problems. In this architecture based on XML, servers have the server communication module and the external-call module. The server commutation module provides a way to make a batch request. The external-call module provides a reliable way to call business applications. We also presented a retrying algorithm that maintains consistency between a workflow engine and an external application. The logging server provides a stable and fast way to query logs by collecting events from workflow servers. Our new protocol is being proposed of WfMC (WorkFlow Management Coalition) as an extension of Wf-XML.

A-57-year-old woman had suffered from high fever, general malaise, and loss of weight (6 kg) since January, 2000. She was admitted to our hospital in May, 2000, because of gait disturbance following to swelling of bilateral calves with severe pain beside the above symptoms. Laboratory data showed leukocytosis (WBC 10,000/microliter), high ESR (98 mm/hr), positive CRP (3.43 mg/dl), positive ANA (x160), high titer of RA (266 IU/l), and a low titer of MPO-ANCA (18 EU). T 2-weighted magnetic resonance image (MRI) showed intensity area of the M. gastrocnemius. Skin biopsy specimens of the right leg demonstrated necrotizing arteritis of small-sized arteries. These findings supported the diagnosis of limited type of polyarteritis nodosa (PN). In this report, we demonstrate a rare case of PN limited to both calves with characteristic MRI findings and a low titer of MPO-ANCA.

Angioplasty for the unprotected left main trunk remains controversial, but new procedures and devices such as directional coronary atherectomy and stenting have improved the results. We compared the results of angioplasty with the inflexible balloon and new devices.The procedures were performed in 239 consecutive lesions in 160 patients between April 1986 and March 2000. This study excluded emergency cases and repeat angioplasty cases, and included 120 initial and elective cases. Initial and long-term results were compared between the balloon group (n = 29) and the new device group (n = 91).Lesion success rate was lower in the balloon group (90% vs 100%, p0.05), but there were no significant differences in in-hospital results including cardiac death (0% vs 0%), noncardiac death (0% vs 3.3%), Q-wave myocardial infarction (0% vs 2.2%), non-Q wave myocardial infarction (3.4% vs 6.6%), bypass surgery (0% vs 0%) and repeat angioplasty (6.9% vs 1.1%). Quantitative angiography showed significant improvements in minimal lumen diameter (mean 2.17 vs 3.16 mm, p0.001) and percentage diameter stenosis (mean 31% vs 13%, p0.001) in the new device group after the procedures. The minimum lumen diameter remained larger at 3 (p0.001) and 6 months (p0.05) in the new device group. Therefore, angiographic restenosis rate was higher in the balloon group (55% vs 21%, p0.005). Five-year survival rate showed no significant difference between the groups (75.0% vs 83.8%).New devices significantly improved the minimal lumen diameter after angioplasty for unprotected left main trunk disease, and lead to significant improvement of restenosis rate at follow-up.

A 58-year-old female was admitted to the hospital complaining of dyspnea. The chest roentgenogram and CT scan revealed a large mediastinum tumor and massive pleural effusion in the right hemithorax. The diagnosis of lung cancer with carcinomatous pleulitis was performed through thoracocentesis an treatment of chemotherapy was chosen. After 6 years, she was admitted again to the hospital complaining of dull pain in the right leg. Chest CT scan and MRI showed a giant dumbbell shaped mass connected to the spinal canal. The tumor was larger than that of six years ago and diagnosed as schwannoma by CT-guided pericutaneous needle biopsy. At operation, hemilaminectomy of Th 1-3 was done first, and total tumor resection was performed through posterolateral thoracotomy. Intrathoracic adhesion was severe and it was difficult to control air leakage from the lung, thoracoplasty was performed.

The short-term and long-term predictors of outcome after coronary angioplasty in the unprotected left main coronary artery were investigated.The procedure was performed in 122 consecutive patients for de novo lesions without myocardial infarction in our hospital between April 1986 and October 1998, including 16 emergency cases. Procedures were directional coronary atherectomy (73 patients), balloon angioplasty (31 patients), and stent implantation (18 patients). There were 101 males and mean age was 68 +/- 10 years. Follow-up angiography was performed in 98% of discharged patients, and all patients were clinically followed up for more than 1 year. Clinical and angiographic predictors of in-hospital and long-term outcome were evaluated.The in-hospital mortality was 5.7% (7 of 122 patients). Multivariate analysis revealed that more patients were admitted as emergency cases (57% vs 10%, p = 0.0088), with left ventricular ejection fractionor = 35% (57% vs 22%, p = 0.029) and renal failure (43% vs 3%, p = 0.0004) finally died. Mean follow-up period was 3.5 years. Estimated survival rate was 77.1%, and cardiac-death free survival rate was 81.0% at 5 years by the Kaplan-Meier method. Univariate analysis showed that the predictors of cardiac death were emergency angioplasty, renal failure, decreased left ventricular ejection fraction, multivessel disease and unstable angina and/or congestive heart failure. Cox's regression model showed that renal failure (p = 0.0004) and multivessel disease (p = 0.0075) were significant predictors of long-term prognosis.Renal failure was the strongest predictor of outcome after unprotected left main coronary artery angioplasty.

We identified an age effect on biopterin and biogenic amine metabolites in the cerebrospinal fluid from 56 neurologically normal patients, aged 1 mo to 80 y. The levels of total and reduced forms of biopterin, homovanillic acid, and 5-hydroxyindoleacetic acid were found to peak during the first year of life. The levels of these metabolites then gradually decreased, plateauing at the age of 20 y. We found significant correlations between biopterin, homovanillic acid, and 5-hydroxy-indoleacetic acid.

We previously reported that ceramide released from glycosphingolipids (GSLs) by endoglycoceramidase was directly metabolized to GSLs, and thus the content of GSLs was constantly maintained in B16 melanoma cells (Ito, M., and Komori, H. (1996) J. Biol. Chem. 271, 12655-12660). In this study, the metabolism of ceramide released from sphingomyelin (SM) by bacterial sphingomyelinase (SMase) was examined using B16 cells and their GSL-deficient mutant counterpart GM95 cells. Treatment of B16 melanoma cells with bacterial SMase effectively hydrolyzed SM on the plasma membrane. Under these conditions, NeuAcalpha2,3Galbeta1, 4Glcbeta1,1ceramide was significantly increased. Interestingly, UDP-glucose:ceramide glucosyltransferase-1 (GlcT-1) activity and GSL synthesis, but not SM synthesis or sphingosine generation, were found to be up-regulated by SMase treatment. The up-regulation of GSL synthesis seemed to occur at both the transcriptional and post-translational steps of GlcT-1 synthesis. Accumulation of ceramide by bacterial SMase was much higher in GM95 cells than in the parental cells. When the enzyme was removed from the culture medium, the intracellular ceramide level in B16 cells, but not that in the mutant cells, normalized. No rapid restoration of SM in either of the cell lines was observed after removal of the enzyme. SMase treatment strongly inhibited DNA synthesis in GM95 cells but not that in B16 cells. In the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of GlcT-1, SMase treatment markedly increased the ceramide content and thus inhibited DNA synthesis in B16 cells. Our study provides the first evidence that GlcT-1 functions to regulate the level of intracellular ceramide by glycosylation of the ceramide when it is present in excess.

To evaluate the early age-related changes in neuropeptides, we have measured the cerebrospinal fluid (CSF) levels of beta-endorphin and substance P in young patients over a range of ages. Specimens of CSF were obtained from 39 neurologically normal children, aged 1 month to 10 years of age, and in 9 adult controls. CSF levels of both neuropeptides were observed to peak during the first year of life, and showed a negative correlation with increasing age. A significant positive correlation was observed between the CSF level of beta-endorphin and that of substance P.

We measured CSF levels of beta-endorphin, an opioid hormone, in 19 patients with infantile autism and in 3 patients with Rett syndrome, and compared them with control values. In infantile autism, CSF levels of beta-endorphin did not differ significantly from those of age-matched controls. There was no significant correlation between CSF levels and clinical symptoms, including self-injurious behavior, pain insensitivity, and stereotyped movement. However, CSF levels of beta-endorphin were significantly higher in the patients with Rett syndrome than in the control (p.05). Data suggest that neurons containing beta-endorphin may not be involved in patients with infantile autism. Thus, there is no relationship between dysfunction of brain opioid and autism.

Background Tocilizumab(TCZ) improves artrerial stiffeness. Sometime TCZ improves artrerial stiffness even at higher level of disease activity. There is no evidence that association of disease activity and arterial stiffness after TCZ treatment has not shown. Objectives To evaluate TCZ therapy improves arterial stiffness beyond its effects of disease activity. Methods We used only high disease activity data(simplified disease activity index(SDAI) at baseline from our several clinical trial data that were treated by TCZ therapy(n= 87). All 87 RA patients had no previous history of cardiovascular disease or steroid treatment. Patients were divided into low, moderate and high disease activity at one year of TCZ treatment by SDAI(low disease activity(LDA), moderate disease activity(MDA), and high disease activity(HDA)). Arterial stiffness was assessed by cardio-ankle vascular index(CAVI; CAVI is modified Pulse Wave Velocity), and aortic augmentation index normalized to a fixed heart rate of 75 beats per minute (AIx@75). Improvement of CAVI and AIx@75 were compared between LDA, MDA, and HAD at one year of treatment(Kruskal.Wallis). Results Charatceristics at baseline were similar among the groups(LDA, MDA, and HDA group at one year). Improvement of CAVI was -0.85±0.16, -0.89±0.22, and, -0.84±0.31, respectively(in LDA, MDA and HDA). Improvement of AIx@75 was -2.38±0.35, --1.85±0.32, and, -2.58±0.58, respectively(in LDA, MDA and HAD). Improvement of CAVI and AIx@75 were not correlated disease activity at one year of TCZ treatment(CAVI: p=0.87, AIx@75: p=0.78). Conclusions TCZ improves arterial stiffness independently of its effects on disease activity, since even in HDA is halted. This indicates that IL-6 inhibition therapy conveys profound anti- arterial stiffness effects and dissociates the link between disease activity and arterial damage. References: Kume K, Amano K, Yamada S, Hatta K, Ohta H, Kuwaba N. et al. Tocilizumab monotherapy reduces arterial stiffness as effectively as etanercept or adalimumab monotherapy in rheumatoid arthritis: an open-label randomized controlled trial. J Rheumatol. 2011 Oct;38(10):2169-71. Disclosure of Interest : None Declared

Background Urate-lowering therapy (uric acid Objectives To comparerecurrent gout attacks in chronic gout treated by US findings normalization strategy or ULT strategy. Methods We designed an open label, randomized controlled trial. We screened 74 chronic gout (uric acid>7.0 mg /ld., and double contour sign of US findings in any joint) for inclusion. 63 gout patients were randomly allocated either US strategy group (US group) or ULT group(C group). In both strategies febuxostat is used. US strategy is performed US by 4 weeks. Double contour sign or urate crystals were evaluated; febuxostat is intensified to dissolve it. ULT strategy is performed blood examination by 4 weeks. Febuxostat is intensified to target uric acid Results The characteristics of each group at baseline were not significantly different. There was no significant difference in the proportion of no recurrent attack within 52 weeks between the US strategy (87.6%) and ULT strategy (83.4%) groups. There was no significant difference in the occurrence of adverse events (AEs) between the US strategy and ULT strategy groups. Conclusions In chronic gout, if the patients were treated by febuxostat, US without blood examination might be equivalent to uric acid in blood. References A systematic review of ultrasonography in gout and asymptomatic hyperuricaemia. Chowalloor PV, et al. Ann Rheum Dis. 2013 Jan 3. [Epub ahead of print]2. EULAR evidence based recommendations for gout . Part II:Management. Report of a task force of the EULAR Standing Committee For International Clinical Studies Including Therapeutics (ESCISIT). Zhang W, et al. Ann Rheum Dis. 2006 Oct;65(10):1312-24. Epub 2006 May 17.3. Efficacy and Tolerability of Febuxostat in Hyperuricemic Patients With or Without Gout : A Systematic Review and Meta-Analysis. Ye P, et al. Clin Ther. 2013 Jan 15. doi:pii: S0149-2918(12)00723-0. 10.1016/j.clinthera.2012.12.011. Disclosure of Interest : None Declared

The roles of histone modifications in T cell activation and memory formation are poorly understood. Thus, we used RNAseq and ChIPseq in tandem to assess the impact of promoter H3K4 di- and trimethylation in naive vs memory human CD4 T cells at rest and 5 days after activation. Changes in H3K4me2 and me3 correlated strongly with changes in RNA expression when comparing naive and memory cells; e.g. increased H3K4 methylation with increased gene expression. These changes define unique signatures comprised of >200 genes at rest and >400 post-activation. Dramatically, activation of naïve CD4 resulted in differential H3K4 methylation of >4000 genes while only ~800 changed with activation of memory. In contrast, activation-induced changes in gene expression and methylation correlated nearly perfectly in memory but poorly for naïve CD4 T cells. These data suggest a higher level of H3K4 methylation-based commitment in the memory subset 5 days after activation. We are presently doing the same studies for days 1 and 14 after activation to understand how quickly activation-induced H3K4 methylation changes occur and how well H3K4 methylation signatures are reflected 14 days after activation of naive cells. In sum, naïve and memory CD4 T cells demonstrate specific H3K4 methylation signatures, T cell activation is clearly an epigenetically dynamic process, and profiling of H3K4 methylation provides important insight into the epigenetic mechanisms driving the commitment to memory.

The aim of the present study was to compare the safety of endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) in terms of liver and kidney functions in patients with liver cirrhosis.Forty-four patients admitted to Takatsuki General Hospital between February 1991 and March 1993 with esophageal varices due to liver cirrhosis were randomly assigned to receive either EVL or EIS. Serum levels of AST, ALT, total bilirubin (T-bil), direct bilirubin (D-bil), prothrombin time (PT), hepaplastin test (HPT), antithrombin III (ATIII), creatinine (Cr), and blood urea nitrogen (BUN) were measured before and 24 h, 3 days, 7 days, and 14 days after both forms of therapy.Significant elevations of serum T-bil, serum D-bil, and serum ALT and AST levels were observed in the EIS group but not in the EVL group. No significant increases of serum PT, HPT, ATIII, BUN, or Cr levels were observed after treatment in either group.EVL should be considered a first choice therapy for eradicating esophageal varices.

This paper describes the homeostasis of glycosphingolipid (GSL) on the cell surface as revealed for the first time by an application of endoglycoceramidase (EGCase) capable of hydrolyzing the linkage between the oligosaccharide and the ceramide of various GSLs. When cell-surface GSLs of B16 melanoma cells were hydrolyzed by the action of EGCase, the synthesis of GSLs was found to increase transiently, possibly due to activation of UDP-glucose:ceramide glucosyltransferase. As a result, the cell-surface GSL content was restored quickly to exactly the same level found without the EGCase treatment, if EGCase was removed from the cell culture. Treatment of erythrocytes with EGCase caused the suppression of de novo ceramide production, resulting in maintenance of the ceramide content of B16 cells at the same level even after EGCase treatment. The signal for homeostatic regulation could be the ceramide release found to mimic in part the action of EGCase; it suppressed de novo production of ceramide and was directly converted to GSL, NeuAc alpha 2,3GAl beta 1,4Glc beta 1,1 N-acetylsphingosine (C2-ceramide GM3). Our finding demonstrates a novel form homeostatic regulation coupled to the GSL-synthesizing system in mammalian cells for maintaining the contents of both cell-surface GSLs and free ceramide. Since many opportunistic pathogens were found to produce EGCase extracellularly, this restoration mechanism could also be present as a defense mechanism against microbial EGCase.

Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ or tissue obtained by carbon dioxide infusion into the supplying artery, was performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The hemodynamics of tumors observed with USAG were divided into three groups: hypovascular, isovascular, and hypervascular, compared with the adjacent pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%). Hypervascular cases included all of the mucin producing tumors and islet cell tumors but only one case of duct cell carcinoma. So you can almost exclude duct cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value 83.6%). These results were compared with those on conventional x-ray angiograms and incremental CT scans. Ultrasound angiography enabled us to detect more slight differences of tumor vascularity than the other modalities. Thus we conclude that USAG can be a useful diagnostic aid in small mass lesions of the pancreas.

γδ T cells represent a major T cell population in epithelial tissues where they function in maintenance of the epithelium and provide a crucial first line defence against epithelial insults. Despite their importance, little is known about the molecular mechanisms involved in their activation and function. γδ T cells resident in the epidermis are a prototypic epithelial γδ T cell population and are an essential component of the wound healing process in the skin. We have exploited this population to identify molecules involved in the complex cell-cell interactions between epithelial resident γδ T cells and the neighboring cells they support. In the skin, keratinocyte damage is a primary trigger of γδ T cell activation, however the molecular interactions regulating this activation are unknown. Here we confirm a vital role for TCR-ligand interactions in the initiation of the γδ T cell response to keratinocyte damage. In addition, we identify two receptor-ligand pairs crucial for an effective γδ T cell response both in vitro and in vivo. Interactions between JAML and CAR provide costimulatory signals for γδ T cell activation and signals through CD100 and plexin B2 are responsible for γδ T cell morphology changes in response to wounding. Disruption of these interactions delays the γδ T cell-mediated wound healing response. Our results provide insight into the molecular mechanisms of γδ T cell activation and describe two novel receptor-ligand pairs vital to this process.

Antihepatitis C virus (HCV) status was investigated in 100 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between 1980 and 1989. The clinicopathological findings and operative results, inpatients with or without HCV marker, were compared retrospectively. The positivity rate of anti-HCV was 51 per cent. In this group there was a higher mean age, fewer symptoms, raised alanine aminotransferase level, higher 15-min indocyanine green clearance rate and earlier tumour stage compared with the anti-HCV negative group. Positive tumour margins and vascular invasion were seen less frequently in the anti-HCV positive group. HCC with HCV marker showed characteristic features of chronic non-A non-B hepatitis and of HCC originating from liver cirrhosis. There was a better cumulative 1-year survival rate for anti-HCV positive patients, but 3- and 5-year survival rates after hepatectomy were similar in both groups. Although HCV-related HCC had typical features of chronic non-A non-B hepatitis and a relatively early stage of tumour, biological features and operative results were similar with or without the HCV marker.

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.

A high-multiplicity event detected by the Kolar Gold Field (KGF) detector is examined to determine whether or not it is an abnormal phenomenon, taking into account the cosmic-ray primary composition and ordinary interaction models. Our calculation shows that a proton-dominated primary composition around the knee'' is not consistent with measurements of the multiple-muon distributions. On the other hand, taking 15--40 % for the proton fraction and 25--50 % for iron nuclei, there is satisfactory agreement. We have estimated the frequency of multiple-muon events with muons in excess of 20 taking the above primary composition. From this result, one would expect such an event per 60--100 years of operation time, and therefore the probability of observing such an event becomes a few percent for the duration of KGF experiment. Thus, we would suppose that the KGF event is a natural phenomenon in spite of their argument that it is difficult to explain it in terms of a conventional muon production mechanism even if an extreme case of heavy chemical composition of primaries is assumed.

Tumor hemodynamics including arterial vascularity (AV) and portal perfusion (PP) were evaluated in histologically confirmed 55 hepatic nodules associated with cirrhosis using ultrasonographic (US) angiography during intraarterial carbon dioxide microbubbles injection and CT during arterial portography. Tumor hemodynamic patterns were classified into 6 types as follows: Type I (n = 10): PP (+), AV (hypo); Type I' (n = 2): PP (+), AV (iso); Type II (n = 5): PP (-), AV (hypo); Type III (n = 8): PP (-), AV (iso); Type IV (n = 25): PP (-), AV (hyper), Type V (n = 5): PP (partially +), AV (vascular spot in hypovascular). Eight nodules of Type I were diagnosed as benign nodules histologically including adenomatous hyperplasia (AH) (n = 6) and regenerative nodule (n = 2). Hundred percent (5/5) of Type II and 88% (7/8) of Type III nodules were well-differentiated HCC, in contrast to 8% (2/25) of Type IV nodules, typical HCCs. Fatty metamorphosis was observed in 75% (6/8) of Type III nodules, in contrast to 16% (4/25) of typical (classical) HCC nodules (Type IV). We concluded that at the malignant transformation from AH to HCC, reduction of portal blood flow in the nodule precedes the initiation of the increase of the arterial tumor vessel. Moreover, early stage HCC could exhibit hypovascular (Type I, II), isovascular (Type III), or vascular spot in hypovascular pattern (Type V) compared with a typical HCC (Type IV). It was also suggested that the more mature as a neoplasms the HCC becomes, the more the arterial tumor vessel in the nodule increases and fatty metamorphosis of well-differentiated HCC is highly related with tumor hemodynamic condition, i.e., hypoperfusion state from both arterial and portal vessel.