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We propose a wireless power distribution system (WPDS) operating at 2.45 GHz CW in buildings instead of wired power distribution in order to reduce the initial cost of the building. Required technologies for the WPDS are (a) low-cost and low-loss deck plate waveguide, (b) variable microwave power distributor for the waveguide, and (c) high-power (>100 W) rectifier at the outlet. We developed and tested the deck plate waveguide, power distributor, and high-power rectenna consisting of 256 Si Schottky barrier diodes and newly developed GaN diodes. Finally, a test WPDS was built and microwave power transmission experiments were conducted. The total efficiency of the test WPDS was estimated to be 52%.

Ubc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear factor-κB signal transduction pathway in human diseases. The Shigella flexneri effector OspI affects inflammatory responses by catalyzing the deamidation of a specific glutamine residue at position 100 in Ubc13 during infection. This modification prevents the activation of the TNF (tumor necrosis factor) receptor-associated factor 6, leading to modulation of the diacylglycerol–CBM (CARD–Bcl10–Malt1) complex–TNF receptor-associated factor 6–nuclear factor-κB signaling pathway. To elucidate the structural basis of OspI function, we determined the crystal structures of the catalytically inert OspI C62A mutant and its complex with Ubc13 at resolutions of 3.0 and 2.96Å, respectively. The structure of the OspI–Ubc13 complex revealed that the interacting surfaces between OspI and Ubc13 are a hydrophobic surface and a complementary charged surface. Furthermore, we predict that the complementary charged surface of OspI plays a key role in substrate specificity determination.

Thin films of three types of fullerene derivatives were prepared through the electrospray deposition (ESD) method. The optimized conditions for the fabrication of the thin films were investigated for different types of fullerene derivatives: [6,6]-phenyl-C61-butyric acid methyl ester, [6,6]-phenyl-C71-butyric acid methyl ester, and indene-C60-monoadduct. The spray diameter during the ESD process was observed as a function of the supply rate achieved by changing the applied voltage. In all cases, the spray diameter increased with increasing applied voltage, reaching the maximum diameter (Dmax) in the voltage range 4 to 6 kV. It was clear that Dmax was influenced by the dipole moments of the fullerene derivatives (as calculated by density functional theory methods). Scanning electron microscopy observation of the fabricated thin films showed that imbricated structures were formed through the stacking of the fullerene-derivative sheets. Atomic force microscopy images revealed that the density of the imbricated structure was dependent on the spray diameter during the ESD process, and the root-mean-square roughness of the film surface decreased with increasing applied voltage. These findings suggest that the ESD method will be effective for the preparation of fullerene-derivative thin films for the production of organic devices.

p62/Sqstm1 is a multifunctional protein involved in cell survival, growth and death, that is degraded by autophagy. Amplification of the p62/Sqstm1 gene, and aberrant accumulation and phosphorylation of p62/Sqstm1, have been implicated in tumour development. Herein, we reveal the molecular mechanism of p62/Sqstm1-dependent malignant progression, and suggest that molecular targeting of p62/Sqstm1 represents a potential chemotherapeutic approach against hepatocellular carcinoma (HCC). Phosphorylation of p62/Sqstm1 at Ser349 directs glucose to the glucuronate pathway, and glutamine towards glutathione synthesis through activation of the transcription factor Nrf2. These changes provide HCC cells with tolerance to anti-cancer drugs and proliferation potency. Phosphorylated p62/Sqstm1 accumulates in tumour regions positive for hepatitis C virus (HCV). An inhibitor of phosphorylated p62-dependent Nrf2 activation suppresses the proliferation and anticancer agent tolerance of HCC. Our data indicate that this Nrf2 inhibitor could be used to make cancer cells less resistant to anticancer drugs, especially in HCV-positive HCC patients., Dysregulation of p62 has been implicated in tumorigenesis. Here, the authors show that p62 promotes hepatocellular carcinoma by reprogramming glucose and glutamine metabolism through Nrf2 and present a novel compound that can inhibit p62 action thus sensitizing cancer cells to chemotherapy.

An electromagnetic field leaked from WPT systems might cause a false operation of other electronic devices. We have measured and simulated it by using the WPT leakage emulator so far. In this paper, the electromagnetic field is evaluated on the assumption that several WPT systems are located in the residential house and operate simultaneously. It is shown that the simulated results coincide with the measured results approximately, and the validity of the simulation method is confirmed.

The present study proposes a simple numerical simulation technique for the split Hopkinson pressure bar (SHPB) and then investigates the experimental conditions for composite materials in a tensile-loading SHPB. The following issues were investigated through experiment and numerical simulation: (i) the effects of the cross section and acoustic mismatch between the jig with a slit and screw and the input/output bars on the loading condition and (ii) the effects of the duration time of the applied load and the acoustic impedance mismatch on the stress–strain curve obtained by SHPB testing. From the numerical simulation results, the following conclusions were found: (i) the proposed jig with a slit and screw can apply an ideal one-dimensional displacement to a specimen and (ii) the material characterization of a composite material by SHPB testing might be possible by optimizing a longer duration time if the acoustic mismatch is greater.

We examined depth perception effects on a moving automobile with static perspective method and dynamic perspective method by monocular HUD, WARP. Both methods have met the specification of within 70% accuracy. In addition, the dynamic perspective method provided stronger depth perception

The 26S proteasome is an ATP-dependent protease responsible for selective degradation of polyubiquitylated proteins. Recent studies have suggested that proteasome assembly is a highly ordered multi-step process assisted by specific chaperones. Rpn14, an assembly chaperone for ATPase-ring formation, specifically recognizes the ATPase subunit Rpt6. The structure of Rpn14 at 2.0 Å resolution in space group P6(4) has previously been reported, but the detailed mechanism of Rpn14 function remains unclear. Here, a new crystal structure of Rpn14 with an E384A mutation is presented in space group P2(1) at 1.6 Å resolution. This high-resolution structure provides a framework for understanding proteasome assembly.

Spontaneous intradural vertebral artery dissections may cause subarachnoid hemorrhage and often result in devastating damage. Increased use of noninvasive imaging studies has allowed larger numbers of patients to be diagnosed. In addition, intracranial vertebral artery dissection tends to induce multiple lesions affecting both intracranial vertebral arteries recurrently. Although unruptured dissections in this area usually have a benign nature, some authors have reported on the incidence of rupture from this lesion. Once hemorrhage from a dissecting vessel wall has occurred, it needs to be treated in the acute phase because of the high risk of rebleeding resulting in high morbidity and mortality. From December 2004 to July 2010, we managed 47 patients with spontaneous vertebral artery dissection, 31 patients were ruptured and 16 were unruptured. All patients who suffered from subarachnoid hemorrhage were treated with endovascular procedures. Most of the patients with unruptured dissection received medical therapy, but if the aneurysmal dilatation persisted or grew, surgical interventions were performed. Stenting with or without coils was deployed for 13 patients with posterior inferior cerebellar artery involvement at the site of dissection and/or were affected on the dominant side. In some patients, stenting was performed even if they were in the acute phase. For other ruptured patients, internal coil trappings were performed. Six patients died due to severe initial subarachnoid hemorrhage and one patient, who underwent stent deployment with coils for the dominant vertebral artery, with bilateral dissection continuing to the basilar artery died due to rerupture while the next additional coiling was planning. There were two cases of complications related to the intervention. During the follow-up period no bleeding occurred in any of the patients except for the previously mentioned patient. In conclusion, internal coil trapping or stent placement with or without coils was effective in preventing rebleeding of ruptured vertebral artery dissection. If the dissection is unruptured, it is necessary to detect the risk of bleeding with careful watching and when progress appears to be made, patients should be treated promptly. Stent-assisted therapy for preserving the patency of the parent artery and major branches is a promising treatment for vertebral artery dissection, even in the acute stage of subarachnoid hemorrhage. However, the risk of acute rerupture and recurrence remains even with the porous stent placement with or without coils.

We achieved the reduced the surface roughness of poly[9,9-dioctylfluorenyl-2,7-diyl]-co-1,4-benzo-(2,1,3)-thiadiazole (F8BT) thin film fabricated by the electrospray deposition technique, using two organic solvents. The root mean square (RMS) roughness of the F8BT thin film was reduced by the addition of dimethyl sulfoxide (DMSO) in tetrahydrofuran (THF). A minimum RMS roughness of 23 nm was obtained by optimizing the ratio of DMSO in THF. We found that the low evaporation pressure of the additional organic solvent is an important factor in attaining a smooth surface for F8BT thin film. The current density-voltage-luminance characteristics of the organic lightemitting diode was improved by reducing the surface roughness of the F8BT layer. A maximum luminance of 36.7 cd/cm2 was obtained, and it was more than 14 times higher than the reference device fabricated by the conventional single organic solvent technique., NOTICE: this is the author's version of a work that was accepted for publication in Thin Solid Films. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Thin Solid Films, [VOL 520, ISSUE 1, (2011)] DOI : 10.1016/j.tsf.2011.07.048.

We developed a compact, 2-liter, monocular head-up display that is WARP-mountable on an automobile. We proposed a novel depth-perception-controllable method and examined the depth perception enhancement characteristics under real space conditions. We confirmed depth perception was controlled as far as 60 meters and true AR was achieved.

A 15-year-old girl developed a rare case of subdural hygroma after foramen magnum decompression for Chiari type 1 malformation manifesting as rapid symptom deterioration around 10 days after uncomplicated operation with uneventful immediate postoperative course. Progressive enlargement of the subdural hygroma in both supra- and infratentorial spaces was followed by the development of hydrocephalus. Syringomyelia improved shortly after the first operation but then deteriorated with massive presyrinx formation. Reoperation with wide opening of the arachnoid membrane lead to a rapid resolution of the hydrocephalus and the presyrinx. The present case shows that wide opening of the arachnoid membrane is an effective therapeutic option.

症例1は直腸癌術後再発による神経障害性疼痛に対し緩和ケアチーム (palliative care team: 以下PCT) が介入した。オキシコドン徐放製剤の増量，鎮痛補助薬の変更，ベタメタゾン投与を行なった。またオキシコドン徐放製剤を1日2回投与から3回投与とし症状緩和が得られた。経過中cetuximab療法を2回施行した。症例2は乳癌術後再発による上肢痛と呼吸困難に対しPCTが介入した。モルヒネ硫酸塩水和物製剤と鎮痛補助薬を追加投与した。フェンタニル経皮吸収型製剤の貼付3日目に疼痛増強があったため3日毎交換から2日毎交換とした。経過中FEC100療法を2回施行した。この2症例ではPCTが積極的に介入し，速やかな症状緩和が得られたため，化学療法を問題なく施行することができた。PCTが積極的に介入するためには主治医の信頼を得ることが最も大切である。

Advanced Evolved Universal Terrestrial Radio Access (Advanced E-UTRA), called LTE-Advanced, has been standardized in the 3rd Generation Partnership Project (3GPP) as a candidate for IMT-Advanced. LTE-Advanced supports spatial orthogonal-resource transmit diversity (SORTD) [1], [2] for ACK/NACK signals and scheduling requests (SRs), which are used to control downlink hybrid automatic repeat requests (HARQs) and manage uplink radio resources based on uplink data traffic, respectively. Both ACK/NACK signals and SRs are carried via a physical uplink control channel (PUCCH) [3], and a common PUCCH format is used for both ACK/NACK signals and SRs. If SORTD is used, the base station assigns mutually orthogonal resources to each antenna included in the user equipment (UE) for ACK/NACK signals and SRs; hence, the number of required resources increases with the number of transmitting antennas in the UE. In this paper, we study the resource reduction method for ACK/NACK signal and SR in case of SORTD using the concept of common resource. In addition, we investigate a phase rotation scheme for common resources to improve the SR detection performance.

40歳，女性．平成19年4月頃から腹痛出現．貧血のみの指摘で，他に検査異常は認めなかったが，症状維持するため，精査目的で紹介となった．初診時Hb 7.9g/dl，腫瘍マーカーは基準値内であった．内視鏡検査で十二指腸水平部に全周性腫瘍を認め，生検結果はGroup Vであった．腹部CTで7cm×9cmの巨大腫瘍を認め，膵・左腎・上腸間膜動脈（SMA），大動脈壁に接していた．膨張性に発育していると考え，開腹手術を行った．十二指腸水平部に径7.2×5.7cmの巨大な腫瘍を認めた．周囲臓器へ接していたが剥離可能であり，膵鉤部合併切除にて，腫瘍を完全切除することができた．術後頻回の下痢を認めたが経過良好で第31病日に軽快退院となった．術後補助化学療法を施行．術後12カ月にリンパ節転移再発を認めた．十二指腸癌は稀で，切除しえても高率に再発を認める．生存期間の延長に期待できることから切除の可能性を検討すべきである．

長期透析患者の透析アミロイドーシスによる小腸穿孔のまれな1例を経験した．症例は79歳の女性で，17年間の血液透析歴がある．透析導入後，右手根幹症候群手術2回，S状結腸憩室出血手術を受け，狭心症，急性心不全，肺結核の治療を受けていた．外傷歴のない右大腿骨頸部骨折にて入院し，手術を受けた．術直後より腹痛と下痢を認め，術後2日目に腹痛が増強した．CT上，腹腔内の遊離ガス像と腹水貯留を認め緊急手術を施行した．小腸に穿孔部を2か所認めたため切除吻合を行った．病理学的に穿孔部周囲の粘膜下層の小血管壁にアミロイドの沈着を認めた．術後，創感染，深在性真菌症，難治性下痢，急性心不全を発症したが保存的治療で改善し，緊急術後78日目に軽快退院した．

The toxicokinetic characteristics of 3-phenoxybenzyl alcohol (3PBAlc) and 3-phenoxybenzaldehyde (3PBAld; metabolites of pyrethroid [PYR] after 25 mg/kg, single intravenous administration), were investigated in male and female rats. The systemic clearance (Cl) of 3PBAlc in females (0.403 ± 0.040 l/h/kg) was significantly larger than that of males (0.227 ± 0.036 l/h/kg). The plasma concentration-time curve of 3PBAld decreased gradually and then increased again 1 and 2 h after injection, suggesting the effect of enterohepatic circulation. The present study characterized the elimination and distribution of PYR metabolites and suggests that gender-related difference exists in the toxicokinetics of 3PBAlc and 3PBAld in rats.

The ubiquitin-proteasome pathway is a major proteolytic system in eukaryotic cells and regulates various cellular processes. The 26 S proteasome, the central enzyme of this pathway, consists of a proteolytic core particle and two 19 S regulatory particles (RPs) composed of ATPase (Rpt) and non-ATPase (Rpn) subunits. Growing evidence indicates that proteasome assembly is assisted by a variety of chaperones. In particular, it has been reported recently that Nas2, Nas6, Rpn14, and Hsm3 bind specific Rpt subunits, thereby contributing to the formation of 19 S RP. Rpn14 transiently binds to the C-terminal domain of the Rpt6 subunit (Rpt6-C) during maturation of the ATPase ring of 19 S RP. In this study, we determined the crystal structure of yeast Rpn14 at 2.0 A resolution, which revealed that this chaperone consists of a unique N-terminal domain with unknown function and a C-terminal domain assuming a canonical seven-bladed beta-propeller fold. The Rpt6-binding site on Rpn14 was predicted based on structural comparison with the complex formed between Nas6 and Rpt3-C. The top face of Rpn14 exhibits a highly acidic surface area, whereas the putative interacting surface of Rpt6-C is basic. By inspection of structural data along with genetic and biochemical data, we determined the specific residues of Rpn14 and Rpt6 for complementary charge interactions that are required for 19 S RP assembly.

Acetylcholinesterase and butyrylcholinesterase (BChE) activities in blood are widely used as the biomarkers for organophosphorus insecticide (OP) exposure. In the present study, we conducted a cross-sectional study to evaluate plasma beta-glucuronidase (BG), a sensitive biomarker candidate for OP exposure, BChE activities and urinary dialkyl phosphates (DAPs), OP metabolites. We assessed the relationship between these biomarker levels in the following groups: 32 controls (control), 21 pest control operators and their co-workers who had not sprayed OPs within 3 days prior to sample collection (PCO1), and 21 pest control operators who sprayed OPs within those 3 days (PCO2). Logarithmically transformed age-adjusted means of DAPs were 3.88, 5.62 and 6.45 nmol/g creatinine for control, PCO1 and PCO2, respectively (P0.001 for difference, P0.001 for trend). Logarithmically transformed age-adjusted means of BG were 1.40, 1.52 and 1.85 micromol/L/h for control, PCO1 and PCO2, respectively. BG activity, but not BChE, was increased according to their OP exposure level (P=0.038 for difference, P=0.026 for trend). It was concluded that plasma BG activity is more sensitive biomarker as well as urinary OP metabolites than BChE for low-level exposure in humans.

Objectives: Recent reports have shown significant associations between organopshophorus pesticide (OP) exposure and decreased sperm motility in workers and laboratory animals. However, the notion that OPs possess spermatotoxicity has yet to be established. The aim of this study was to clarify the effects of OP exposure on detailed sperm toxicity markers, i.e., motility, morphology and sperm adenine nucleotide contents, and the histopathology of the testis and epididymis. Methods: Ten-week-old Wistar rats were divided into 4 groups (n=10) and orally administered corn oil, dichlorvos (DDVP; 5, 10 mg/kg) or diazinon (DZN; 3 mg/kg) 6 days a week for 9 wk. Sperm motility and morphology markers were analyzed with a computer-assisted sperm analysis (CASA) system. Results: In addition to a significant decrease in acetylcholinesterase (AChE) activities and a significant increase in urinary OP metabolites, DDVP and DZN significantly reduced sperm motility, but they did not influence sperm adenine nucleotide contents. The OPs also significantly increased the percentage of broken sperm, and DDVP significantly increased the percentage of cytoplasmic droplets. Importantly, both OPs significantly increased cytoplasmic vacuolation and nuclear shrinkage in the epithelial cells of the ductus epididymis, whereas the testes did not show significant histopathological changes. Conclusions: The broken sperm and cytoplasmic droplets as well as reduced sperm motility were the relevant spermatotoxicity makers of DDVP and DZN. To our knowledge, this is the first report to suggest that the above-mentioned OP-induced spermatotoxicity is related to histopathological impairment of the caput epididymis.

The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcgamma receptor (FcgammaR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcgammaRIIA) and 176F/F (FcgammaRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcgammaRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcgammaR polymorphisms.

The purpose of this study is to determine the levels of urinary 3-phenoxybenzoic acid (3-PBA) among general populations in rural and suburban areas and employees of pest control firms to evaluate the differences in the level of environmental or occupational pyrethroid (PYR) pesticides to which those populations are exposed.Spot urine specimens were collected from male residents in a rural area (n = 143) and male residents in a suburban area (n = 66) in August of 2005 and 2007, respectively. Male employees of pest control firms, who also provided their urine specimens at the time of a health-checkup in August 2007, were classified either as sprayers (n = 14) or as non-sprayers (n = 16) according to the presence of spraying during the pre-checkup week. Urinary concentrations of 3-PBA were determined using gas chromatography-mass spectrometry and corrected for the urinary creatinine concentrations. An analysis of covariance was used to examine the statistical difference in 3-PBA concentrations between these four groups after adjustment for age, body mass index, and current smoking/drinking habits.Multiple comparisons indicated no differences in adjusted 3-PBA concentrations between the groups of general residents from the rural areas (0.33 microg/g cre in geometric mean) and suburban area (0.51 microg/g cre). The group of sprayers showed a much higher level of 3-PBA concentrations (25.0 microg/g cre) than the other three groups. A statistically significant difference, though to a lesser extent, was also exhibited in 3-PBA concentrations between the group of non-sprayers (5.6 microg/g cre) and that of general residents.The results indicated that the levels of background low-dose exposure to PYRs are not likely to differ evidently among general populations according to the area of residence. Moreover, employees of pest control firms, who have been away from PYR spraying operations for a week or more, still retain much higher urinary 3-PBA concentrations than general populations.

Ursodeoxycholic acid (UDCA) is widely recognized as an effective compound in the treatment of chronic hepatitis and is known to modulate the redox state of the liver accompanied by an increase of GSH. In the present study, to access the antioxidative effect of UDCA and to clarify the molecular basis of the action on GSH level, we evaluated its effects in HepG2 cells exposed to excessive iron. UDCA inhibited both a decrease in the GSH level and an increase in the reactive oxygen species caused by excessive iron in the cells. UDCA increased the gene expression of the catalytic- and modifier-units of glutamine-cysteine ligase (GCL), which is a key enzyme in GSH synthesis. We further investigated the effect of UDCA on the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and obtained results showing that UDCA-induced increase in the GSH level was prevented by LY294002, a PI3K inhibitor. In addition, Western blot analysis of Akt showed that, while the total Akt level remained unchanged, the phosphorylated Akt level was increased by UDCA, and this increase was also prevented by LY294002. Moreover, UDCA promoted the translocation of a transcription factor, nuclear factor-E2-related factor-2 (Nrf2), into the nucleus, and this action was inhibited by LY294002. From these results, it was indicated that UDCA increased the GSH synthesis through an activation of the PI3K/Akt/Nrf2 pathway. This may be a primary mechanism of antioxidative action of UDCA concerned with its therapeutic effectiveness in chronic hepatitis.

Nagoya University, Department of Medical Technology, 金沢大学附属病院薬剤部, Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5±9.8 years of age, mean±S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 μg/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n=87) and the remaining general group without occupational exposure (n=448) were 0.38 and 0.29 μg/l, respectively, ranging from

肛門周囲膿瘍は，日常診療で比較的よく遭遇するが，鼠径部に膿瘍を形成することは非常に稀な病態であり，検索したかぎり1例も認めない．症例は45歳の男性で，既往は特に認めない．肛門痛を主訴に来院し，肛門周囲膿瘍の診断で同日切開排膿を施行した．切開後，痛みは一時軽快したが，発熱が持続し，切開排膿から12日目に右鼠径部痛を自覚するようになった．骨盤部造影CTでは右鼠径部にガスを含んだ液体貯留を認め，前立腺や膀胱の左側の瘻孔の存在を疑わせるガス像と連続していた．注腸造影X線検査では，肛門管から瘻孔が造影され，膿瘍も造影された．以上から，肛門周囲膿瘍から鼠径部膿瘍を形成したと診断し，膿瘍切開，人工肛門造設を施行した．術後経過は良好で入院から49日目に退院した．6カ月後の注腸造影X線検査で瘻孔は消失していたため，人工肛門を閉鎖した．その後2年経過するが，再発は認めない．

It is known that protein kinase C (PKC) signal transduction is enhanced in a diabetic state, and that PKC activator phorbol esters increase the gene expression of MDR1 in human tumor cells. To clarify the expression of the liver transporters under diabetic conditions and the roles of PKCalpha and the transcription factor NF-kappaB, we investigated the expression levels of Mdr1a, Mdr1b, Mdr2, Mrp2, Bcrp, Bsep, Oct1, Oat2, and Oat3 transporters, PKCalpha, IkappaB, and NF-kappaB in the liver of rats with STZ-induced hyperglycemia. A selective increase in the gene expression of Mdr1b was detected by RT-PCR. Western blotting with C219 antibody revealed an increase in P-glycoprotein. Although the mRNA level of PKCalpha was not affected, translocation of PKCalpha to the microsomal fraction was detected. NF-kappaB p65, IkappaBalpha and IkappaBbeta mRNA levels were increased as was the level of nuclear NF-kappaB p65. From these findings, it was suggested that STZ-induced hyperglycemia caused the upregulation of Mdr1b P-gp expression through the activation of PKCalpha and NF-kappaB.

Eukaryotic 20S proteasomes are composed of two alpha-rings and two beta-rings, which form an alphabetabetaalpha stacked structure. Here we describe a proteasome-specific chaperone complex, designated Dmp1-Dmp2, in budding yeast. Dmp1-Dmp2 directly bound to the alpha5 subunit to facilitate alpha-ring formation. In Deltadmp1 cells, alpha-rings lacking alpha4 and decreased formation of 20S proteasomes were observed. Dmp1-Dmp2 interacted with proteasome precursors early during proteasome assembly and dissociated from the precursors before the formation of half-proteasomes. Notably, the crystallographic structures of Dmp1 and Dmp2 closely resemble that of PAC3-a mammalian proteasome-assembling chaperone; nonetheless, neither Dmp1 nor Dmp2 showed obvious sequence similarity to PAC3. The structure of the Dmp1-Dmp2-alpha5 complex reveals how this chaperone functions in proteasome assembly and why it dissociates from proteasome precursors before the beta-rings are assembled.

Organic cation transporter-3 (OCT3) is expressed in several tissues including the brain. We have previously demonstrated that rats with behavioral sensitization to methamphetamine (METH) increased the brain penetration of METH with decreased expression of OCT3 in brain. Considering the earlier in vitro studies demonstrating that 1) OCT3 could transport dopamine (DA) and 2) the specific transport via OCT3 could be inhibited by METH, these results suggest that decreased OCT3 might decrease the efflux of METH and/or DA from brain, subsequently causing the development of behavioral sensitization. Thus, in the present study, behavioral task related to DA and pharmacokinetic experiment were performed using rats treated with antisense against OCT3 (OCT3-AS) since no specific ligands for OCT3 are still available. The continuous infusion of OCT3-AS into the third ventricle significantly decreased the expression of OCT3 in choroid plexus (CP) epithelial cells. Both METH-induced hyperlocomotion and METH-induced extracellular DA levels in nucleus accumbens and prefrontal cortex were significantly increased in OCT3-AS-treated rats. Moreover, the concentrations of METH were significantly increased in cerebrospinal fluid as well as extracellular areas at the nucleus accumbens in OCT3-AS-treated rats. These results suggested that decreased OCT3 elevated the concentration of METH and/or DA in brain, subsequently enhancing dopaminergic neuronal transmission and increasing METH-induced hyperlocomotion. In summary, OCT3 at the CP could regulate the effect of METH by controlling the levels of METH and/or DA in brain. Thus, these results suggest that OCT3 may be a new molecular target to treat METH-related disorders such as drug abuse and schizophrenia.

When pancreatic duct dilatation is found in the patient having undergone pancreatoduodenectomy (PD), observation is chosen in most cases. Similarly, recurrent tumor in the remnant pancreas of invasive ductal carcinoma (IDC) of the pancreas is seldom indicated for resection. We have aggressively performed repeated pancreatectomy for these cases and obtained good results. Repeated pancreatectomy after PD was performed for three types of circumstances: (1) pancreatodigestive anastomotic stricture; (2) neoplasm after intraductal papillary mucinous neoplasm (IPMN); and (3) recurrence of IDC of the pancreas. Resection of anastomosis and reanastomosis was performed for pancreatodigestive stricture in four patients. Symptoms derived from pancreatitis in three patients resolved by the second operation and did not recur during follow-up. None of the four patients required pancreatic enzyme substitution because of clinically overt malabsorption, and the defecation frequency of the four patients was within twice a day. Mild diabetes mellitus has been identified in only one patient who had diabetes mellitus before the second surgery. Completion pancreatectomy and pancreatic tail resection was performed for recurrence in two patients and IDC in one patient, respectively, after PD for IPMN. Intrapancreatic recurrences of IPMN in two patients existed in the main pancreatic ducts. As CT revealed pancreatic duct dilatation but not intraductal tumors, recurrences were not correctly diagnosed before the second operation. Completion pancreatectomy was performed for recurrence of IDC in two patients. One patient who underwent completion pancreatectomy for recurrence of IDC survived 66/44 months after the first/second operation. Repeated pancreatectomy should be performed for patients with pancreatodigestive anastomotic stricture to preserve remnant pancreatic function and for patients with neoplasm or pancreatic duct dilatation after PD for IPMN, and repeated pancreatectomy for recurrence of IDC might be indicated for selected patients.

The wireless power transfer (WPT) system has been actively developed in recent years. Since the electromagnetic field leaked from the WPT system may cause a false operation of other electronic devices, an analysis of the leaked electromagnetic field is significant issue for its practical realization. This paper presents that the electromagnetic field leaked from the WPT system installed in a case-study house is evaluated in the measurement and simulation. The WPT leakage emulator that can generate the electromagnetic field leaked from the WPT system is used in the measurement. The suitable calculation algorithms with respect to three frequency bands that cover the high-harmonic component of the leaked electromagnetic field are applied for the simulation. Moreover, the significant improvement of the simulation speed is achieved using the supercomputer. The evaluation results of the leaked electromagnetic field distributions at four positions in the case-study house show the validity of the simulation compared with the measurement.

Much of the immune system is situated in the gastrointestinal tract.1–4 Disruption of gut barrier function and intestinal microbial imbalance can result in systemic inflammation and ultimately induce septic complications after surgery.5–7 Despite improvements in surgical techniques and refinements in perioperative care, the high incidence of postoperative infectious complications in patients undergoing hepatobiliary resection for biliary cancer remains a major problem.8–12 Enteral feeding is one effective treatment among several strategies aiming to minimize postoperative septic complications concerning bacterial translocation.13–15 A recently proposed refinement of enteral feeding suggests dietary supplements including probiotics and prebiotics as having have a potential to prevent bacterial translocation.16–19 Probiotics, viable bacteria that benefit the host by improving intestinal microbial balance, now are used widely in food supplements.20 Prebiotics are nondigestable food constituents that selectively alter growth or activity of one or a limited number of bacterial species in the colon in a manner that potentially improves the health of the host.20–22 Used in combination, probiotics and prebiotics are called synbiotics.22 While synbiotic combinations are considered to have beneficial effects on human health, their clinical value in surgical patients remains unclear given a paucity of applicable clinical studies.23–25 We recently assessed clinical usefulness of synbiotics in biliary cancer patients who underwent hepatobiliary resection, finding that postoperative synbiotic administration reduced infectious complications after hepatectomy, mainly by correcting an intestinal microbial imbalance.26 Based on this observation, we hypothesized that additional preoperative administration of synbiotics should reduce infectious complications still more effectively. The present prospective randomized study was designed to investigate the effect of preand postoperative administration of synbiotics on intestinal permeability, integrity, immune responses, systemic inflammatory responses, and microflora, as well as surgical outcome, in a clinical setting.

Background: Methamphetamine (MAP) is one of the most frequently used illegal substances in Japan, and family and twin studies have suggested that genetic factors contribute to psychostimulant dependence, including MAP dependence. Organic cation transporter 3 (OCT3) has been reported to be involved in the disposition of MAP as well as MAP-induced behavioral changes in animals. Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence. Methods: Using 96 healthy control subjects, linkage disequilibrium (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms (SNPs) were selected as haplotype tag SNPs to search for an association with MAP dependence. Single-marker analyses and haplotype analyses of these SNPs were performed in 213 subjects with MAP dependence and 443 healthy controls. Results: SLC22A3 polymorphisms were not significantly associated with MAP dependence in any of the single-marker and haplotype analyses. When subjects with MAP dependence were divided into polysubstance and single-MAP users, genotype and allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed significantly between groups. Conclusions: These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with MAP dependence.

In order to investigate a role of paraoxonase 1 (PON1) polymorphism in organophosphorus (OP)-induced 8-hydroxydeoxyguanosine (8-OHdG) levels, urinary metabolites of OP, PON1 genotypes, and 8-OHdG levels in leukocyte and urine were measured in OP indoor insecticide sprayers and controls in summer and winter. The study population contained 18 male sprayers and age-matched 18 male controls. Sprayers were primarily exposed to OP insecticides (mainly fenitrothion, dichlorvos, chlorpyrifos, and diazinon), and partially to pyrethroids (mainly permethrin) and carbamates (mainly propoxur). Urinary metabolites of OP were measured by gas chromatography-mass spectrometry. 8-OHdG levels in leukocyte and urine were measured by ELISA kit. PON1 genotype was identified using allele-specific fluorogenic TaqMan probes. The mean concentrations of urinary dimethyl phosphate (DMP) and total dialkyl phosphates (DAP) in summer and those of 8-OHdG in summer and winter were significantly higher in OP sprayers than controls. This resulted in a significant positive correlation between 8-OHdG levels and urinary DMP or DAP, suggesting a correlation between OP metabolites and production of oxidative stress. Of PON1 genotypes, incidences of Q/Q, Q/R, and R/R types were 17, 39, and 44% in OP sprayers and controls, respectively. Although PON1 polymorphism did not contribute to the leukocyte and urinary 8-OHdG levels, the urinary OP metabolite concentrations in summer showed a significant decrease as the number Q allele decreased. These results indicate that an increase in OP metabolites is associated with a high level of oxidative stress in OP sprayers, although the contribution of the PON1 polymorphism to the metabolism of OP is still unclear.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection causes severe clinical symptoms, due to its bacterial toxin, called Shiga-like toxin (SLT). However, little is known about the information to establish a safe and efficient prescription to treat for EHEC O157:H7 patients. Thus, we investigated the effect of SLT-II on intestinal function in rats by using the antibiotic norfloxacin (NFLX) as a model drug. The intestinal clearance (CLi) of NFLX, determined by loop method in the jejunum, was significantly decreased by SLT-II. In histopathological experiment, epithalaxia was observed in SLT-II-treated rats without structural changes of tight junction suggesting the deterioration of active transport systems by SLT-II. CLi of NFLX in normal rats was decreased by carnitine (CAR), suggesting the possible involvement of CAR-sensitive transporter in CLi of NFLX. Taken together, these results suggest that the EHEC O157:H7 infection might affect the intestinal disposition of NFLX due to the changing intestinal expression/function of drug transporters by SLT-II.

In 2003, an occurrence of the yessotoxin (YTX)-producing dinoflagellate, Protoceratium reticulatum, and resultant toxin concentration in scallops was monitored in Okkirai Bay, northern Japan. The occurrence peaked after 1 July and reached a maximum density (400 cells L -1 ) on 16 July. It occurred over a wide range of water temperature and inorganic nutrient concentrations and was tolerant of a broad range of environmental conditions. Hydrological parameters were monitored, and it was obvious that P. reticulatum flourished under low salinity (30.59-32.60) and occurred at highest density in the surface layer (0-5 m depth) where effects from rainfall were greatest. In addition, dinoflagellate density increase and decrease was well correlated with inflows of oceanic water into the bay. Thus, it can be assumed that the oceanic inflows may cause initial population increases (e.g. excystment or input of a 'seed population'), with resultant growth in rain-affected waters and subsequent spread throughout the entire bay via water movement. YTX and 45-OHYTX concentrations in scallops reached maximum levels (0.79 μg g -1 and 0.44 μg g -1 of digestive gland, respectively) 2 weeks after the maximum cell density of P. reticulatum, and high levels of the toxin continued for a month. Low levels of the toxin were detected even during periods when cells were not observed.

The present study aims to investigate the role of P glycoprotein and multidrug resistance-associated protein (Mrp2) in the transport of telithromycin, a newly developed ketolide antibiotic, in vitro and in vivo. The in vitro experiments revealed that the intracellular accumulation of telithromycin in adriamycin-resistant human chronic myelogenous leukemia cells (K562/ADR) overexpressing P glycoprotein was significantly lower than that in human chronic myelogenous leukemia cells (K562/S) not expressing P glycoprotein. Cyclosporine significantly increased the intracellular accumulation of telithromycin in K562/ADR cells. When telithromycin was coadministered intravenously with cyclosporine in Sprague-Dawley (SD) rats, cyclosporine significantly delayed the disappearance of telithromycin from plasma and decreased its systemic clearance to 60% of the corresponding control values. Hepatobiliary excretion experiments revealed that cyclosporine almost completely inhibited the biliary clearance of telithromycin, suggesting that telithromycin is a substrate of P glycoprotein and a potential substrate of Mrp2. Moreover, the biliary clearance of telithromycin was significantly decreased by 80% in Eisai hyperbilirubinemic mutant rats with a hereditary deficiency in Mrp2, indicating that Mrp2, as well as P glycoprotein, plays an important role in the biliary excretion of telithromycin. When the effect of telithromycin on the biliary excretion of doxorubicin, a substrate of P glycoprotein and Mrp2, was examined in SD rats, telithromycin significantly decreased the biliary clearance of doxorubicin by 80%. Results obtained from this study indicate that telithromycin is a substrate of both P glycoprotein and Mrp2, and these transporters are involved in the hepatobiliary transport of telithromycin.