Search

The geomagnetic field is typically about 50 μT (range 20–90 μT). Geomagnetic activity generally decreases by about 4% for the seven days leading up to a full moon, and increases by about 4% after the full moon, lasting for seven days. Animals can clearly detect the changes in magnetic field intensity that occur at full moon, as it has been shown that variations of just a few tens of nT are adequate to form a useful magnetic ‘map’. We think that moonlight increases the sensitivity of animals' magnetoreception because the radical pair model predicts that magnetoreception is light dependent. In fact, there have been some reports of changes in the sensitivity of magnetoreception with lunar phase. We propose a hypothesis that animals respond to the full moon because of changes in geomagnetic fields, and that the sensitivity of animals' magnetoreception increases at this time.

Reaction of microglial cells as well as DNA fragmentation in pyramidal cells was investigated using immunohisto-chemistry and in situ end-labeling method (TUNEL) in the hippocampus of rats after rapid kindling or kainic acid treatment. In intact rats, no or very little DNA fragmentation was detected in the hippocampus. Resting microglia distributed evenly throughout the hippocampus. Neither major histocompatibility complex antigens class I (MHC I) nor class II (MHC II) immunoreactivity was seen in the hippocampus. In the rapid-kindling model, no DNA fragmentation, reactive microglia or MHC antigen-positive cells were present in the hippocampus. In rats given an intraperitoneal injection of kainic acid (12 mg/kg), reactive microglial cells were seen around pyramidal neurons in the CA1 and CA3 field of the hippocampus as well as in the hilus of the dentate gyrus at 3 h. At that point in time, DNA fragmentation was not detected. DNA fragmentation was clearly observed, mainly in the CA1 region of the hippocampus, from 24 h to 4 weeks after the kainic acid injection. The number of reactive microglia was quickly increased and reached a maximum at 7 days after the injection, and continued until 8 weeks thereafter. During this period, many reactive microglia expressed MHC I and MHC II. The present study indicates that epileptic seizures do not depend on microglial activation and that microglial activation is closely related to the neuronal death process induced by kainic acid.

Kainic acid-induced seizures in rats represent an established animal model for human temporal lobe epilepsy. However, it is well-known that behavioral responses to the systemic administration of kainic acid are inconsistent between animals. In this study, we examined the relationship between expression of genes, neuropathological damage, and behavioral changes (seizure intensity and body temperature) in rats after systemic administration of kainic acid. The considerable differences in the response to kainic acid-induced seizures were observed in rats after a single administration of kainic acid (12 mg/kg i.p.). There was no detection of the expression of heat shock protein hsp-70 mRNA and HSP-70 protein in brain of vehicle-treated controls and in animals exhibiting weak behavioral changes (stage 1-2). A moderate expression of hsp-70 mRNA was detected throughout all regions (the pyramidal cell layers of CA1-3 and dentate gyrus) of the hippocampus, the basolateral, lateral, central and medial amygdala, the piriform cortex, and the central medial thalamic nucleus of rats that developed moderate seizures (stage 3-4). Marked expression of hsp-70 mRNA was detected in the all regions (cingulate, parietal, somatosensory, insular, entorhinal, piriform cortices) of cerebral cortex and all regions of hippocampus, and the central medial thalamic nucleus of the rats that developed severe seizures (stage 4-5). In addition, marked HSP-70 immunoreactivity was detected in the pyramidal cell layers of CA1 and CA3 regions of hippocampus, all regions (cingulate, parietal, somatosensory, insular, piriform cortices) of cerebral cortex, and the striatum of rats that developed severe seizures (stage 4-5). Furthermore, a marked expression of cyclooxygenase-2 (COX-2) mRNA and brain-derived neurotrophic factor (BDNF) mRNA levels by kainic acid-induced behavioral seizures (stage 3-4 or stage 4-5) was detected in all hippocampal pyramidal cell layers, granule layers of dentate gyrus, piriform cortex, neocortex, and amygdala. The present study suggest that the behavioral changes (seizure intensity and body temperature) and neuropathological damage after systemic administration of kainic acid are inconsistent between animals, and that these behavioral changes (severity of kainic acid-induced limbic seizures) might be correlated with gene expression of hsp-70 mRNA, COX-2 mRNA, and BDNF mRNA in rat brain.

In this study, we assessed the effects of the acute (a single injection) and repeated (once daily injections for 21 days) administration of the atypical antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) and the typical antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/kg, i.p.) on hippocampal partial seizures generated by low-frequency electrical stimulation in male Wistar rats. The seizure threshold and severity were determined by measuring the pulse number threshold (PNT) and the primary afterdischarge duration (ADD), respectively. A single injection of either 5 or 15 mg/kg of clozapine significantly decreased the PNT and significantly increased the primary ADD, indicating a proconvulsant action. The repeated administration of clozapine (1.5, 5, or 15 mg/kg, i.p.) produced dose-dependent, proconvulsant effects by significantly decreasing the PNT and by significantly increasing the primary ADD. In contrast to clozapine, the acute administration of haloperidol did not significantly alter the PNT or the primary ADD. The repeated administration of haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased the primary ADD, but did not alter the PNT. Overall, clozapine produces a greater proconvulsant action than haloperidol in an animal model of hippocampal seizures.

Epibatidine (exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane), an extract of frog skin, is a novel and highly potent agonist for the nicotinic acetylcholine (ACh) receptor. The present study was undertaken to examine the expression of Fos protein in several rat brain regions following an acute administration of epibatidine. Furthermore, we also studied the role of the dopamine D1 and D2 receptors and the N-methyl-d-aspartate (NMDA) receptor, and nicotinic ACh receptor in the expression of Fos protein by epibatidine. A single administration of epibatidine (5, 10, 50 microgram/kg) caused a marked induction of Fos-immunoreactivity in the prefrontal cortex, medial striatum, nucleus accumbens, amygdala and superior colliculus of rat brain. In these regions, pretreatment with SCH 23390 (1.0 mg/kg), a dopamine D1 receptor antagonist, MK-801 (1.0 mg/kg), a NMDA receptor antagonist, and mecamylamine (5. 0 mg/kg), a nicotinic Ach receptor antagonist, inhibited the induction of Fos protein by epibatidine (10 microgram/kg). Pretreatment with sulpiride, a dopamine D2 receptor antagonist, blocked the induction of Fos protein in the prefrontal cortex and the core region of accumbens nucleus, but not in the medial striatum and the shell division of nucleus accumbens of rat brain. These results suggest that epibatidine induced the expression of Fos protein in several regions of rat brain, and that dopamine D1 receptor, NMDA receptor, and nicotinic ACh receptor may play a role in the expression of Fos protein by epibatidine in rat brain. Furthermore, dopamine D2 receptor may, in part, play a role in epibatidine induced expression of Fos protein in the prefrontal cortex and the core region of nucleus accumbens, but not in the medial striatum and the shell division of nucleus accumbens of rat brain.

Hull and end-piece wastes generated from reprocessing plant operations are expected to be disposed of in a deep underground repository as Group 2 TRU wastes under the Japanese classification system. The activated metals that compose the spent fuel assemblies such as Zircaloy claddings and stainless steel nozzles are mixed and compressed after fuel dissolution, and then stuffed into stainless steel canisters. Carbon 14 is a typical activated product in the hulls and end-pieces and is mainly generated by the 14N(n,p)14C reaction. In the previous safety assessment of the TRU waste in Japan, the radionuclides inventory was calculated by ORIGEN-2 code. Some conservative assumptions and preliminary estimates were used in this calculation. For example, total radionuclides generated from a single type of fuel assembly (45 GWd/tU for a PWR unit), and the thickness of the Zircaloy oxide film on the hulls (80 μm) were both overestimated. The second assumption in particular has a large effect on exposure dose evaluation. Therefore, it is essential to have a realistic source term evaluation regarding such items as the C-14 inventory and its distribution to waste parts. In the present study, a C-14 inventory of the hull and end-piece wastes from the operation of a commercial reprocessing plant in Japan corresponding to 32,000 tU (16,000 tU in each BWR and PWR) was calculated. Analysis using individual irradiation conditions and fuel characteristics was conducted on 6 types of fuel assemblies for BWRs and 12 types for PWRs (4 pile types × 3 burnup limits). The oxide film thickness data for each fuel type cladding were obtained from the published literature. Activation calculations were performed by using ORIGEN-2 code. For the amount of spent assembly and other waste characteristics, representative values were assumed based on the published literature. As a preliminary experiment, C-14 in irradiated BWR claddings was measured and found to be consistent with the calculated activation. The total C-14 inventory was estimated as 4.46×1014 Bq, consisting of 2.58×1014 Bq for BWRs and 1.87×1014 Bq for PWRs, and is consistent with the safety assessment of 4.4×1014 Bq. However, the distribution of the C-14 inventory to hull oxide, which was estimated under the assumption of instantaneous radionuclide release in the safety assessment, decreased from 5.72×1013 Bq (13% of the total) in the previous assessment to 1.30×1013 Bq (2.9% of the total; consisting of 1.48×1012 for BWRs and 1.15×1013 for PWRs). In other words, the exposure dose peak is reduced to approximate 25% of its previous value due to the use of detailed oxide film data that the BWR cladding has a thin oxide film. Other instantaneous release components for C-14 such as the fuel residual were negligible.

Some previous studies have shown a positive relation between geomagnetic disturbances and an increased incidence of suicide. If such a relation exists, stronger geomagnetic fields may affect the number of suicides, because stronger geomagnetic fields generally cause larger geomagnetic field disturbances. Therefore, we here investigated the relation between local geomagnetic field magnetic flux density and the standardized morbidity ratios (SMR) for suicide by each prefecture in Japan.Monthly suicide data for each prefecture in the period January 1999 to December 2008 was obtained, and it was found that a total of 216 171 male individuals and 85 154 female individuals committed suicide during this period. A multiple linear regression analysis was carried out with a backward elimination procedure. The SMR for suicide by each prefecture was taken as the response variable and the explanatory variables were each prefecture's local geomagnetic field magnetic flux density (nT), north latitude (°), monthly mean unemployment rate (%), monthly mean air pressure (hPa), monthly mean air temperature (°C), monthly mean humidity (%), and monthly total day length (hours). Analyses were carried out separately for each sex.In the multiple linear regression analysis for male subjects, the local geomagnetic field magnetic flux density (nT), monthly mean unemployment rate (%), and monthly mean humidity (%) were associated with the incidence of suicide, but in the multiple linear regression analysis of female subjects, only north latitude was associated with that.In this study, we generated a hypothesis that stronger geomagnetic fields affect the number of cases of male suicide.

Corrosion tests of Zircaloy-4 were performed in a dilute NaOH solution (pH =12.5) at 303 K for 90 days using the gas flow system (oxygen; < 1 ppb) and a batch method (oxygen; < 0.1 ppm). The corrosion rate was determined by measuring gaseous hydrogen and the hydrogen absorbed into Zircaloy-4 assuming the following reaction:where x represents the Zircaloy-4 hydrogen absorption ratio. The initial hydrogen content in the Zircaloy-4 specimen was controlled to be below 10 ppm. The corrosion rate decreased with time (90-day values: 2.46×10-3 and 2.37×10-3 μm/y for the gas flow method and 6.72×10-2 μm/y for the batch test). The Zircaloy-4 hydrogen absorption ratio during corrosion was over 90%. The large amount of hydrogen absorbed in Zircaloy-4 will play an important role in the long-term safety for the disposal of irradiated Zircaloy materials.

Previous studies have shown a positive relationship between geomagnetic disturbances and an increased incidence of suicide. The Japanese suicide rate is the ninth highest in the world, but there have been no reports examining the relationship between geomagnetic disturbance and the number of suicides, and, therefore, this paper examines this relationship.The number of Japanese suicides per month from January 1999 to December 2010 was obtained, and it was found that a total of 262,596 males and 102,539 females committed suicide during this period. To adjust the other factors which affect the number of suicides, a multiple linear regression analysis with backward elimination was carried out, with the monthly number of suicides as the response variable and the monthly mean K index value, monthly mean number of sunspots, monthly mean unemployment rate, proportion of elderly people (%), monthly mean air pressure (hPa), monthly mean air temperature (°C), monthly mean humidity (%), and monthly mean day length (h) as the explanatory variables.In the multiple linear regression analysis for males, the monthly mean K index value was associated with the monthly number of suicides, but in females, the monthly mean K index value was not associated with the monthly number of suicides.In this study, we generated a hypothesis that geomagnetic disturbances may trigger male suicides.

The aim of this study was to investigate pigment degradation, chlorophyll fluorescence diminution, photosynthetic ability and growth reduction in two rice cultivars, in response to either iso-osmotic salt stress or water-deficit stress. Seedlings of rice cultivars RD6 and KDML105 were photo-autotrophically grown in MS media and subsequently exposed to –0.23 (control), –0.40 or –0.67 MPa iso-osmotic NaCl (salt stress) or mannitol (water-deficit stress) for 14 days. The survival percentage of the two rice cultivars reduced dramatically when subjected to –0.67 MPa NaCl treatment. Chlorophyll a (Chla), chlorophyll b (Chlb), total carotenoids (Cx+c), maximum quantum yield of PSII (Fv/Fm) and photon yield of PSII (ΦPSII) in the stressed seedlings were significantly lower when compared to seedlings in the control group (without mannitol or NaCl), leading to low net-photosynthetic rate (Pn) and growth reduction. In addition, the growth characters of plantlets in the salt stress conditions were more sharply reduced, and the physiological changes greater than those in water-deficit stress conditions. On the other hand, non-photochemical quenching in the leaves of stressed plantlets increased significantly, especially in response to iso-osmotic salt stress. In the present study, overall growth performance and physiological characters of KDML105 grown under iso-osmotic stress were better than those of RD6. El objetivo de este estudio fue investigar la degradación de pigmentos, la disminución de la fluorescencia de la clorofila, la capacidad fotosintética y la reducción en el crecimiento de dos cultivares de arroz, en respuesta al estrés salino iso-osmótico o hídrico. Se cultivaron de forma foto-autotrófica en medio MS plántulas de los cultivares RD6 y KDML105 y posteriormente se expusieron durante 14 días a NaCl (estrés salino) o manitol (estrés hídrico) iso-osmótico –0,23 (control), –0,40 ó –0,67 MPa. El porcentaje de supervivencia de los dos cultivares de arroz se redujo drásticamente con el tratamiento de NaCl 0,67 MPa. La clorofila a (Chla), clorofila b (Chlb), carotenoides totales (Cx+c), rendimiento cuántico máximo del PSII (Fv/Fm) y el rendimiento de fotones del PSII (ΦPSII) fueron significativamente menores en las plántulas estresadas respecto a las plántulas del grupo control (sin manitol o NaCl), lo que les llevó a una baja tasa de fotosíntesis neta (Pn) y a una reducción del crecimiento. Además, el crecimiento de las plántulas bajo estrés salino se redujo drásticamente y los cambios fisiológicos fueron mayores que bajo estrés hídrico. Por otra parte, el amortiguamiento no fotoquímico (NPQ) en las hojas de las plántulas estresadas aumentó considerablemente, especialmente en respuesta al estrés salino iso-osmótico. En este estudio, los caracteres de crecimiento y fisiológicos en conjunto de KDML105 cultivados bajo estrés iso-osmótico fueron mejores que los de RD6.

In breast cancer, the validity of surrogate endpoints for overall survival (OS) is a matter of controversy.In order to generate a hypothesis, we evaluated whether tumor response or progression-free survival (PFS) could be valid surrogates for OS in patients with metastatic breast cancer. Data from 30 patients were available from a phase II study of trastuzumab and capecitabine in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer resistant to both anthracyclines and taxanes. The proportional hazards (PH) model was applied to evaluate the relationship between OS and tumor response or PFS. In addition, to explore prognostic factors influencing OS or post-progression survival, the PH model with a stepwise regression procedure was applied.The relationship between tumor response and PFS was highly significant (P = 0.0036); however, there was no significant relationship between tumor response and OS or between PFS and OS. In the multivariate analysis, the sum of the longest diameter of target lesions (P = 0.0011), neutrophil count (P = 0.0033), and creatinine (P = 0.0085) were statistically significantly associated with OS.We generated a hypothesis that neither PFS nor tumor response were valid as surrogate endpoints for OS, at least in the phase II trial for metastatic breast cancer resistant to both anthracyclines and taxanes. We also found that the sum of the longest diameter of target lesions, neutrophil count, and creatinine were prognostic factors for OS.

The determination method of total arsenic (As) and the speciation method of inorganic As for non-glutinous rice reported in our preceding paper were applied to several varieties of rice under optimized experimental conditions. In the determination of total As with ICP-MS, acetic acid was added to increase the sensitivity and an internal reference method with germanium was adopted to increase the precision. The extraction temperature in the partial-digestion method with nitric acid to speciate inorganic As was raised to 100 degrees C, because extraction efficiency over 90% was obtained from glutinous rice and colored rice at this temperature. In the investigation of polished and unpolished forms of non-glutinous, glutinous, and colored rice, the amounts of total and inorganic As were 0.04-0.54 mg/kg and 0.02-0.41 mg/kg, respectively. The color of rice was not related to total or inorganic As content. These results indicate that the inorganic As content in commercial rice should be carefully monitored.

Structural change of OH-free fused quartz tube by blowing with hydrogen-oxygen flame was investigated by optical adsorption. The blowing increased the OH content within _??_500μm from the surface. The maximum OH content was ca. 1100ppm.

Background In Japan, high incidences of interstitial lung disease (ILD) and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC). We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0). ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%), of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

Backgrounds Prognostic factors are defined as biological or clinical measurement associated with overall survival and/or disease-free survival. Previous studies have shown that patients with estrogen receptor (ER) positive cancers have a better prognosis than patients whose cancers do not have these receptors. Methods This study investigated the assessment of variables in defining prognosis of 742 breast cancer women with pathological stage (pTNM) I-III diagnosed between 1980 and 2005 at the Kyoto University Hospital in Japan, by age, clinical stage (cTNM), pTNM, the numbers of positive lymph nodes (pN), and ER status. Results Multivariate analysis demonstrated that pTNM and ER status were the independent prognostic factors for overall survival, and that pTNM and pN were the independent prognostic factors for disease-free survival. For the 0- to 2-year interval, the hazard of recurrence was higher for the ER-negative patients than the ER-positive patients, and beyond 3 years the hazard was higher for ER-positive patients. Conclusion The present study confirmed the previous reports which showed favorable prognosis of the patients with lesser pTNM or positive ER status. A reversal of recurrence hazard rate between ER positive and negative breast cancer patients beyond 3 years after operation was detected. The fact may indicate the importance of long term adjuvant hormone therapy for ER positive cancer patients.

This study was designed to quantitatively assess the effectiveness of self-practiced qigong for treatment of essential hypertension.Six major electronic databases were searched up to July 2006 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of self-practiced qigong for essential hypertension reported in any language, with main outcome measures as systolic blood pressure (SBP) and diastolic blood pressure (DBP). The quality of included studies were assessed with the Jadad Scale and a customized standard quality assessment scale.Ninety-two (92) studies were identified. Nine (9) of these studies qualified for meta-analysis, comprising a total of 908 cases. Results were as follows: (1) The mean decrease of SBP in those practicing qigong was a 17.03 mm Hg reduction (95% confidence interval (CI) 11.53-22.52) compared with nonspecific intervention controls, but not superior to that in drug controls (1.19 mm Hg, 95% CI -5.40-7.79) and conventional exercise controls (-1.51 mm Hg, 95% CI -6.98-3.95). (2) Mean decrease of DBP in those practicing qigong was 9.98 mm Hg (95% CI 2.55-17.41) compared with nonspecific intervention controls, but not superior to that in drug controls (2.49 mm Hg, 95% CI -0.16-5.13) and conventional exercise controls (-1.59 mm Hg, 95% CI -4.91-1.74). (3) No obvious side effects were identified.Self-practiced qigong for less than 1 year is better in decreasing BP in patients with essential hypertension than in no-treatment controls, but is not superior to that in active controls. More methodologically strict studies are needed to prove real clinical benefits of qigong, and to explore its potential mechanism.

Iodine-129 collected from a reprocessing plant is regarded as the dominant nuclide in terms of safety for TRU wastes disposal in Japan. AgI vitrification (AgI-Ag2O-P2O5) is a potential iodine immobilization technique, which has the advantages of less iodine volatilization (low-temperature vitrification) and high volume reduction efficiency (approx. 1/25 the original waste volume). The iodine immobilization property can be evaluated by examining the surface condition of the AgI glass immersed in water. In this study, immersion tests have been performed on AgI glass in pure water in a 3% H2-N2 atmosphere at room temperature, and the surface characteristics have been examined. The thin layer (

We studied the effects of a micro-Tesla extremely low frequency magnetic field (microT ELFMF) on blood pressure. A 1-muT magnetic field was generated by Helmholtz coils (L, 3.0 meters; H, 1.7 meters) with 8/6-Hz alternating current. This study was carried out between March 2004 and March 2005, and data from a total of 30 volunteers were analyzed. The subjects' blood pressure was measured before and after exposure, at baseline, and 1, 2 and 3 months after the first ELFMF session. The mean age of the subjects was 46.5 years (range, 28-72 years). The median number of ELFMF sessions was 31.5, and the median duration of each session was 10.0 min (range, 2.0-120.0 minutes). In the hypertensive and normotensive subgroups, the difference between the baseline and 3-month pre-exposure systolic blood pressure (SBP) measurements was statistically significant (p0.001, p=0.013, respectively; paired t-test). The SBP of the hypertensive subgroup decreased more than that of the normotensive subgroup. These data suggest that the microT ELFMF may have a hypotensive effect on subjects, particularly hypertensive subjects.

Anemia in cancer patients has been under-recognized and little studied in Japan. To gain some insight into cancer-related anemia in Japanese patients undergoing outpatient chemotherapy, we performed a single-center retrospective study of the prevalence and incidence of anemia in 148 patients with solid tumors treated at the Kyoto University Hospital Outpatient Oncology Unit. We classified the cases of anemia in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Of 148 patients, 65 (44%) were anemic at the start of chemotherapy, 19 (13%) of whom had anemia of grade 2 or higher. Chemotherapy further increased the number of anemic patients, with 125 (84%) being anemic at some point during chemotherapy, and 61 (41%) of these having anemia of grade 2 or higher. Among the 83 patients without anemia at the start of chemotherapy, 60 (72%) developed anemia during chemotherapy, 15 (18%) of whom had anemia of grade 2 or higher. This is the first report showing a high prevalence and incidence of anemia in Japanese patients undergoing outpatient chemotherapy. Better recognition and management of cancer-related anemia are required in Japan. To this end, randomized controlled trials evaluating the effects of erythropoietic agents on patients' survival and quality of life are necessary.

This paper describes low temperature vitrification process with BiPbO2 I (BPI) as a promising immobilization technique in which Iodine-129 reacts with BiPbO2 NO3 (BPN) to form BPI, which is then solidified into a lead-boron-zinc glass matrix (PbO-B2 O3 -ZnO) using a low temperature vitrification process. Studies with EPMA, STEM-EDS and XRD found that iodine, lead and zinc were homogeneously dispersed in the waste form, and that there were no residual crystalline minerals in the amorphous glass matrix. Leaching tests conducted under typical geological disposal conditions show that iodine dissolves congruently with the BPI glass matrix in simulated seawater, whereas it dissolves incongruently in alkaline Ca(OH)2 solutions. This is due to retention within an altered surface layer.Copyright © 2007 by ASME

It has been found that metallic TRU waste releases considerable portions of C-14 in the form of organic molecules such as lower molecular weight organic acids, alcohols and aldehydes. Due to the low sorption ability of organic C-14, it is important to clarify the long-term behavior of organic forms under waste disposal conditions. From investigations on radiolytic decomposition of organic carbon molecules into inorganic carbonic acid, it is expected that radiation from TRU waste will decompose organic C-14 into inorganic carbonic acid that has higher adsorption ability into the engineering barriers. Hence we have studied the decomposition behavior of organic C-14 by gamma irradiation experiments under simulated disposal conditions. The results showed that organic C-14 reacted with OH radicals formed by radiolysis of water, to produce inorganic carbonic acid. We introduced the concept of “decomposition efficiency” which expresses the percentage of OH radicals consumed for the decomposition reaction of organic molecules in order to analyze the experimental results. We estimated the effect of radiolytic decomposition on the concentration of organic C-14 in the simulated conditions of the TRU disposal system using the decomposition efficiency, and found that the concentration of organic C-14 in the waste package will be lowered when the decomposition of organic C-14 by radiolysis was taken into account, in comparison with the concentration of organic C-14 without radiolysis. Our prediction suggested that some amount of organic C-14 can be expected to be transformed into the inorganic form in the waste package in an actual system.Copyright © 2007 by ASME

Objective: The objective of this study was to identify problems in the approval, pharmacovigilance, and post-approval regulatory decision-making procedures involving gefitinib and to propose countermeasures to prevent further drug-induced suffering in Japan in the future. Methods: We comprehensively reviewed reports regarding gefitinib published during the period from 2000 to 2006 by regulatory agencies, the manufacturer of the gefitinib-containing drug, cancer clinical study groups, and a scientific society. Results: We identified the following major problems in the approval, pharmacovigilance, and regulatory decision-making procedures: 1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly reflected in the label; 2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and 3) despite many serious cases of interstitial lung disease (ILD) being spontaneously reported, well-designed post-marketing surveillance was not immediately performed. Conclusions: We propose a mandatory total registry of all drug users and surveillance (i.e. a prospective outcome study) as one of the rational solutions for preventing further drug-induced suffering in Japan. Objetivo: Identificar los problemas en el registro, farmacovigilancia y toma de decisiones post-registro relativas al gefitinib y proponer contramedidas para prevenir futuros problemas producidos por medicamentos en Japón. Métodos: Revisamos intensamente los informes sobre gefitinib publicados durante el periodo 2000 a 2006 por las agencias reguladoras, el fabricante de medicamentos que contenían gefitinib, grupos de ensayos clínicos sobre medicamentos anti-cáncer, y una sociedad científica. Resultados: Identificamos los siguientes problemas principales en la aprobación, farmacovigilancia y proceso de toma de decisiones reguladoras: 1) los resultados de los estudios en animales y los ensayos clínicos pre-comercialización y los informes de reacciones adversas de otros países no se reflejaron correctamente en las fichas técnicas; 2) se expandieron las indicaciones del medicamento sin una estricta evaluación de la validez externa de los ensayos clínicos pre-comercialización; y 3) a pesar de que se comunicaron espontáneamente reacciones adversas graves de ILD, no se realizó inmediatamente una vigilancia post-comercialización bien diseñada. Conclusiones: Proponemos un registro obligatorio de todos los usuarios de medicamentos y vigilancia (p.e. un estudio retrospectivo de resultados) como una de las soluciones racionales para evitar futuros sufrimientos producidos por medicamentos en Japón.

We developed an application specific multi-processor generation system intended for realtime applications. In this system, we adopted a distributed memory type multi-processor architecture with hierarchical tree network as a configurable multiprocessor which can be adapted to various scale systems flexibly. We have also developed a configurable multi-processor prototype as LSI chips with the 0.18 /spl mu/m CMOS standard cell technology.

The aim of this study was to investigate the outcomes of gemcitabine-treated patients with inoperable biliary tract cancers.We conducted a retrospective study of consecutively treated 22 inoperable biliary tract cancer patients with gemcitabine (500-1,000 mg/m(2) on days 1, 8, 15 every 4 weeks) as first-line, and 17 patients as second- or third-line treatment.The response rate of patients treated with gemcitabine as first-line and second- or third-line treatment was 5.3 and 28.5%, respectively. The median overall survival time in the first-, and second- or third-line treatment groups was 8.3 and 17.0 months, and the 1-year survival rate was 44.0 and 50.9%, respectively. The present study also suggests the possibility that the prognosis of patients with high levels of C-reactive protein and total bilirubin, or a low level of albumin might be worse.Our results indicate that the treatment of inoperable biliary tract cancers with gemcitabine is feasible. There was no difference in the response rate and overall survival between biliary tract cancer patients in the first- and second- or third-line treatment groups. We also present the systematic review of literature of the recent treatment results of biliary tract cancers treated with gemcitabine.

Aqueous dissolution tests of AgI were performed in Na2S solutions in order to evaluate, empirically, dissolution of AgI to release iodine under reducing conditions with sulfide. The results indicated that AgI dissolves to release iodine being controlled by mainly precipitation of Ag2S. However, the dissolution of AgI can be depressed to proceed, and the thermodynamic equilibrium cannot be attained easily. Solid phase analysis for the reacted AgI suggested that a thin layer of solid silver forming at AgI surface may evolve to be protective against transportation of reactant species, which can lead to the depression in the dissolution of AgI.

Various field observations suggested that rice plants with a deep and sound root system showed a relatively small yield loss due to spikelet sterility caused by the cool injury. The role of the vertical root distribution in susceptibility to a cool injury, however, has rarely been tested experimentally under field conditions. Three cultivars with different sensitivity to sterile-type cool injury were provided for the experiments. Roots were pruned at the panicle initiation and booting stages in 1998, and the root zone restriction treatment was imposed by placing unwoven cloth horizontally in a shallow soil layer (8–9 cm) before flooding in 1999 and 2000. Two levels of water temperature (Tw) were set during the reproductive periods (high, 23–24 °C; low, 19–20 °C). Low Tw substantially decreased spikelet fertility by 10–78% for all cultivars, and its magnitude differed largely between cultivars according to the cold tolerance ranks of the cultivars tested. Root pruning at the panicle initiation and booting stages did not decrease spikelet fertility of any cultivars under either Tw regime. The root zone restriction treatment gave no negative influence on spikelet fertility under both Tw regimes in both years. Bleeding rates were decreased by low Tw, but no difference was found between cultivars with largely different sensitivity to the sterile-type cool injury. The bleeding rate was not significantly affected by the root zone restriction treatment, suggesting that the limited root zone had a small influence on root activity. The results did not support an association between vertical root distribution and spikelet fertility under cool temperatures.

The winter wheat variety Kitahonami shows a superior flour yield in comparison to other Japanese soft wheat varieties. To map the quantitative trait loci (QTL) associated with this trait, association mapping was performed using a panel of lines from Kitahonami's pedigree, along with leading Japanese varieties and advanced breeding lines. Using a mixed linear model corrected for kernel types and familial relatedness, 62 marker-trait associations for flour yield were identified and classified into 21 QTLs. In eighteen of these, Kitahonami alleles showed positive effects. Pedigree analysis demonstrated that a continuous pyramiding of QTLs had occurred throughout the breeding history of Kitahonami. Linkage analyses using three sets of doubled haploid populations from crosses in which Kitahonami was used as a parent were performed, leading to the validation of five of the eight QTLs tested. Among these, QTLs on chromosomes 3B and 7A showed highly significant and consistent effects across the three populations. This study shows that pedigree-based association mapping using breeding materials can be a useful method for QTL identification at the early stages of breeding programs.

Trimethyltin (TMT), an organic metal, has been known to induce behavioral abnormalities including seizures and aggression. We administered TMT to rats, then, behavioral changes as well as the changes of dynorphin and Met-enkephalin mRNA were observed with or without phenobarbital treatment in order to reveal the role of neuropeptides in seizure-generating mechanisms. Met-enkephalin mRNA was significantly increased at the 2nd to 6th day after TMT administration when seizure was frequently observed. Meanwhile, dynorphin mRNA was decreased significantly from the 2nd day to 16th day during aggression score remained high. Phenobarbital abolished not only seizures and aggression, but also the changes of neuropeptide expressions. These results suggest that the changes of dynorphin mRNA are more strongly associated with aggression than seizures, while Met-enkephalin changes correlate more with seizures.

We conducted a clinical investigation of 80 suicides who met the DSM-III-R criteria for schizophrenia. The results using this approach showed no significant difference with those of preceding studies, and general features regarding the phenomenology of suicide among schizophrenics worldwide were recognized. The present study, however, served to underscore the following points: (i) suicide of schizophrenics must be considered a concern at all stages of the disease; (ii) the subjective strength of the will to die may be more important for the committing suicides than the lethality of the methods employed; and (iii) a change in the environment, for example, a hospital admission or discharge, may trigger suicide. A control group of 80 living schizophrenics with no past attempted suicide was then matched to the suicide group with respect to sex and illness duration, in order to identify the predictors of suicide. In a logistic regression analysis, the presence of suicidal ideation, degree of anxiety estimated by positive and negative syndrome scale, and birth order were revealed as predictors of suicide. As to the birth order, the risk is higher in middle children.

e19642 Background: Gemcitabine is an active anticancer drug approved for various kinds of cancers and has relatively few adverse events except for bone marrow toxicity, but we have sometimes experienced vascular pain during intravenous administration of gemcitabine. In retrospective analysis, we reported that the use of 5% glucose solution for dissolution of gemcitabine decreased frequency of vascular pain compared with that of saline solution for. However, there were no reports which demonstrated the difference in frequencies of vascular pain between 5% glucose solution and saline for gemcitabine dissolution. Therefore, we conducted this double-blind randomized study to compare the frequency and degree of vascular pain during administration of gemcitabine between them. Methods: Ninety patients were enrolled in a double-blind, randomized, crossover, and multicenter study from July 2009 to June 2010. The primary endpoint was frequency of vascular pain, and the secondary endpoints were degree and duration o...

e15563 Background: Although sorafenib has been reported to prolong survival of patients with advanced hepatocellular carcinoma (HCC), the prognosis of those who did not respond to or are not candidate to transarterial chemoembolization (TACE) remains poor. The aim of this outcome analysis is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted injection port in the treatment of such patients. Methods: From the prospective cohot database of Outpatient Oncology Unit, Kyoto University Hospital, patients with HCC who had been treated with HAIC using low dose cisplatin and 5-FU (cisplatin 10mg and 5-FU 250mg for day 1–5, repeated serially for three or four weeks, then repeated once weekly) between October 2003 and December 2008 were searched for. All adverse events were assessed according to Common Terminology Criteria for Adverse Events v3.0. Survival analysis was performed by using Kaplan-Meier method. Prognostic factors were assessed using Log-rank test. Results: Forty-one patients were identified. The indications of HAIC were: (1) the presence of portal vein tumor thrombus (20/41 cases, 49%), (2) failure to TAE (19/41, 46%) or (3) not candidate for TAE due to the presence of extrahepatic disease (2/41 case, 5%). One complete response and 7 partial responses were observed, overall response rate being 19.5% (95%CI, 7.4–31.6%). Median overall survival was 26.1 month (95%CI: 9.6–45.6). Commonly observed grade 3/4 adverse events were thrombocytopenia (10 cases, 16.3%) and neutropenia (10 cases, 16.3%). There was a trend that fewer death occur in patients who responded to HAIC (1/8 cases, 12.5%) as compared to patients who did not (11/33, 33.3%), but log-rank test failed to detect a statistical significance (P=.145). Conclusions: HAIC for patients with advanced HCC who are not candidate for TACE warrants randomized controlled trial. No significant financial relationships to disclose.

17066 Background: The information generated in daily practices is critical to assure safety and efficacy of therapeutic interventions. Clinical investigators are faced with enormous amounts of data and a greater need to organize it in a meaningful and coherent manner than ever before. Computerization could offer many advantages that clinical data systematically accumulated in the course of routine medical care can provide researchers with the clues to resolve many medical questions. Methods: We developed a novel clinical database system, named CyberOncology, integrated in EMR of Kyoto University Hospital. It contained summarized treatment history, national cancer registry and consecutive clinical database. All adverse events according CTCAE ver.3, response to the treatment based on RECIST criteria and survival data were collected. The medical staffs have routinely used the CyberOncology since its starting on October 2003. The CyberOncology directly collected all data concerning oncology management of inpatient and outpatient care from EMR, and simultaneously analyzed clinical outcomes. Results: For three years since October 2003, consecutive 1,516 new cancer patients including 590 GI, 435 lung, 234 breast cancer, and 140 lymphoma with 19,767 chemotherapeutic administrations were registered in the CyberOncology. Main benefits are improvement of the quality of patient care and safety, practice standardization, and the quickness and the reliability of collecting the data. Moreover, it had the capability to serve a cross-sectional approach of cancer and drug-orientated analysis. For example, this system can easily provided with a review of clinical practice in a real time manner. Conclusions: The CyberOncology form integrated EMR successfully meets requirements of electronic case report. It has been useful in monitoring outcomes of care, effectiveness, efficiency and adherence to clinical trial. No significant financial relationships to disclose.

7675 Background: Survival after progression (SAP) was longer (median: 8 months) than progression-free survival (median: 6 months) in a phase III randomized trial in patients with stage IIIB or IV NSCLC (SWOG-Japan Common Arm Trial, the Japan Multinational Trial Organization LC00–03, Kawahara, PASCO 2006, #7013). The overall survival in the trial was longer than that in the US populations (median: 14 months vs. 9 months in the paclitaxel/carboplatin arms, Crowley, PASCO 2006, #7050). The aims of this study were to identify predictors and to assess impacts of second-line chemotherapy on SAP of advanced NSCLC. Methods: To identify independent predictors and to estimate hazard ratios (HR) for SAP, we used the Cox proportional hazards model. We evaluated survival benefit of second-line chemotherapies after adjustment for baseline factors and regimens of first-line therapy, types of progression, and time to progression. Results: Out of 393 patients in the LC00–03 trial, 340 patients had progressive disease during the follow-up period. The identified independent significant predictors for SAP were PS (HR: 2.19, p [Table: see text]

Purpose: This study was conducted to assess the effect of NMDA receptor antagonists (MK-80 I and CPP) and a non-NMDA receptor antagonist (NBQX), administered into inferior colliculus (IC) or into the ambient cistern on audiogenic seizures i n rats neonatally exposed to propylthiourecil (PTU). Furthermore, the role of glutamatc rcceptor subtypes i n audiogenic seizures was cxanincd by analysis of behavioral manifcstations induced hy inttacisternal injection of NMDA or AMPA in naive rats. Methods: I. Rats were exposed to 0.02% PTU through the mother's milk from day 0 to day 19 (PTU rats). Those animals were tested for audiogcnic scizure susceptibility at the age of 10 wccks. PTU rats without generalized tonic-clonic scizurc (GTCS) after auditory stimulation wcrc excluded i n this study. MK-801 at doscs of 2, 20, 40 nmol/side (n = 2, I I, 5), CPP at doscs of 0.04, 0.4, 4 nmol/side (11 = I I, 5, 13), or NBQX at doscs of 2, 20 imnol/side (n = 3, 13) was bilatcrally;idministered into IC. Thiriy minutcs aftcr treatment of drugs, auditory stimulation wiis applied by ringing the emergency bell (1 12 dB) [or 80 scc. The latency to running fit (RF) and GTCS, and the duration 0 1 RF and GTCS wcrc observed i n each tested animal. MKX O I at doses of 0.02, 2, 40 nmol/brain (n = 6, 5, 5), CPP at doses of 0.04, 0.4, 4 nmol/hrain (n = 6, 6, h), or NBQX at doses of 0.5, 5 nmol/brain (n = 6, 6) was administered inio cisterna ambicncc of PTU rats. Five minutes after treatment of drugs, the audiogenic seizures wcrc obscrved as stated above. 2. Naive Spraguc-Dawlcy rats were used at 7 weeks of age. NMDA at doscs of 10, 20 pglbrain (n = 10, 5) or AMPA at doses of 3, 6 pg/brain (11 = 6, 7) was administcrcd into cisterna ambience. After trcatincnt of NMDA or AMPA, the behavioral changes wcrc observed for 30 minutes. Furthermore, aftcr trcatment of NMDA 5 pg/hrain (n = 4) or AMPA 3 @brain (n=6), the behavioral changes were obscrvcd i n cach tested animal during 80 seconds with auditory stimulation. AMPA 3 pg/brain was administered into cisterna arnbiencc after pre-trciitmcnt of systemic administration or MK-801 0.5 mg/kg. The behavioral changes of the prc-treated animals were comparcd with those of non pre-treated animals during 80 scconds with auditory stimulation. Results: I. In PTU rats the microinjection of CPP into 1C at 0.4, 4 nmol/side was found to exhibit significant blocking effects on both RF and GTCS. NBQX at 20 nmollside inhibited only GTCS. 2. intracisternal injection of MK-801, CPP, or NBQX showed significant block-ing effects on both RF and GTCS in PTU rats. 3. Thc intracistcrnal administration of NMDA or AMPA in naive rats dose-dependently elicitcd RF lollowcd by GTCS similar to audiogenic seizurcs in PTU rats. 4. Auditory stimulation augmented both RF and GTCS induced by subclinical dose of AMPA in naive rats but failed to affect the procon vulsant action of NMDA. This augmentative effect was inhibited by MK-80 I. Conclusion: These results suggest that both NMDA and AMPA receptor activation arc ncccssary to induce RF. In audiogcnic scizurcs, thc auditory stimulation probably is equivalent to the activation of NMDA receptors, and thc relay mcchanism from RF to GTCS is presumably related to NMDA receptors.

The structure of a new indole derivative, serotobenine (1), from sfflower meal (Carthamus tinctorius> L.) is proposed based on 1H- and 13C-NMR spectral data and X-ray crystallography. The known compounds N-feruloyltryptamine (2) and N-(p-coumaroyl)tryptamine (3) were also isolated and identified.

Operating conditions for the qualitative and quantitative determination of fatty acids and several phosphono-fatty acids were investigated by capillary-tube isotachophoresis using a potential gradient detector. Behenoic acid-NaOH (or Na-behenoate, or K-behenoate) in methanol as a terminal electrolyte and HCl-Tris in methanol as a leading electrolyte were effective for analysis of fatty acids. The potential unit (PU) values for capillary-tube isotachophoresis depended on the molecular weight of fatty acids. The isotachophoretic sensitivities of fatty acids decreased with increasing carbon chain length of the fatty acids. Isotachophoregrams of phosphono fatty acids showed only one zone coresponding to the secondary dissociated ion species. The results regarding phosphono-fatty acids are discussed in terms of charge.