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Background The most common causative pathogen of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was reported as HHV-6. Although excitotoxic injury with delayed neuronal death is considered to be a possible pathogenesis of AESD, the detailed pathophysiology remains unclear. Case presentation We present a twelve-month-old girl with AESD due to HHV-6 primary infection. She was successfully treated for AESD including targeted temperature management and the administration of vitamin B1, B6, and L-carnitine. Although the viral load of HHV-6 in her liquor was high (12,000 copies/mL), she fully recovered without antiviral agent use. Discussion There has been no study focusing on the HHV-6 viral load in patients with AESD, and only a few case reports have been published. We reviewed the clinical features and viral load in the liquor of our case and four reported infants with AESD due to HHV-6 primary infection who had real-time PCR tests results. Viral loads in the three patients with a poor prognosis were 31.5, negative, and 3,390 copies/mL, respectively. On the other hand, the copy numbers of HHV-6 DNA in the two patients with no sequelae were 12,000 and 106 copies/mL, respectively, and our case had the highest viral load among the five summarized patients.

Background Febrile neonates and young infants presenting with seizure require immediate evaluation and treatment. Herein we experienced two young infants with parechovirus-A3 (PeV-A3) encephalitis, initially presented with focal seizure suspecting herpes simplex virus (HSV) encephalitis. Cases We have experienced 2 infantile cases, initially presented with focal seizure. At presentation, HSV encephalitis was strongly suspected and empiric acyclovir therapy was started; however, serum and/or cerebrospinal fluid (CSF) PCR for HSV were negative. Instead, serum and/or CSF PCR for parechovirus-A was positive. PeV-A3 infection was confirmed by genetic sequence analyses. Both cases required multiple anticonvulsant therapy and intensive care for intractable seizure. Diffusion-weighted imaging of brain magnetic resonance imaging (MRI) showed distinct findings; high-intensity lesions in the gray matter of parietal and occipital lobes in Case 1, and bilateral decreased diffusion of the deep white matter and corpus callosum in Case 2. We have followed two cases more than four years; Case 1 developed epilepsy, has been on an anticonvulsant to control her seizure. Case 2 has significant neurodevelopmental delay, unable to stand or communicate with language. Conclusions PeV-A3 encephalitis needs to be in differential diagnosis when neonates and young infants present with focal seizure, mimicking HSV encephalitis. Special attention may be necessary in patients with PeV-A3 encephalitis given it could present with intractable seizure with high morbidity in a long-term.

Proton magnetic resonance spectroscopy (1H-MRS) has demonstrated that in vitro, lung cancer has higher lactate and choline signals than those of normal tissues. The detection of these metabolites in lung cancer in vivo by 1H-MRS would be useful for clinical diagnoses of lung cancer. We report the in vivo detection of lactate and choline in lung cancer by 1H-MRS in a 41-year-old Asian man who was diagnosed with pT4N0M0 ⅢA stage, right upper lobe lung adenocarcinoma. A lactate-lipid peak was observed near 1.33 ppm in the spectrum of lung cancer in vivo at TE = 30 ms, and it was inverted at TE = 135 ms, indicating that a lactate signal is contained in the lactate-lipid peak. A choline peak was also observed near 3.2 ppm in the spectrum with fat suppression at TE = 135 ms. An accumulation of similar cases will help determine the appropriate applications of 1H-MRS for lung cancer.

A 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20-30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B6, pyridoxal-5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4'-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B6 and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B6 in humans as a result of ginkgo seed poisoning.

Oxido-alcoholato- and oxido-thiolato-molybdenum(VI) complexes bearing two ene-1,2-dithiolate ligands (cyclohexene-1,2-dithiolate) are prepared as synthetic models of molybdenum(VI) reaction centers of dimethyl sulfoxide reductase family of molybdenum enzymes. These complexes are prepared by oxygen atom transfer from tertiary amine N-oxide (trimethylamine N-oxide and N,N-dimethylaniline N-oxide) to the five-coordinate alcoholato- and thiolato-molybdenum(IV) complexes, and are characterized by UV–vis, cold-spray-ionization mass, resonance Raman, and 1H NMR spectroscopies. The oxygen atom transfer reactions are studied kinetically at a low temperature (−40 °C) to demonstrate that the reactivity of the thiolato-molybdenum(IV) complex is higher than that of alcoholato-molybdenum(IV) complex by about 7 times, and that the oxygen atom transfer reactivity increases with increasing the electron withdrawing ability of the p-substituent of N,N-dimethylaniline N-oxide derivatives. Mechanistic details are discussed based on the reactivity studies.

Background & aims The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants of these genes and the risk of developing hepatocellular carcinoma (HCC). Methods Nineteen tagging SNPs in base excision repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays; one significant SNP was found and confirmed in Japanese patients with chronic hepatitis C (CHC) (n = 38 HCC and 55 controls). The effects of modifying the intronic variants were determined by luciferase assays. MUTYH-null mice were used to examine the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis. Results Significant associations were found for a single intron SNP (rs3219487) in the MUTYH gene. The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (OR = 9.27, 95% CI = 2.39 −32.1, P = 0.0005). MUTYH mRNA levels in both peripheral mononuclear cells were significantly lower in G/A or A/A genotyped subjects (P = 0.0157 and 0.0108, respectively). We found that −2000 in the MUTYH promoter region is involved in enhanced expression of MUTYH by insertion of a major allele sequence of rs3219487. Liver tumors were observed in MUTYH-null mice after 12 months´ high iron diet, but no tumors developed when dietary anti-oxidant (N-Acetyl- L -cysteine) was also provided. Conclusions CHC patients with the rs3219487 adenine allele had a significantly increased risk of developing HCC. MUTYH-null mice with iron-associated oxidative stress were susceptible to development of liver tumors unless prevented by dietary anti-oxidants.

Purpose The accuracy of gated irradiation may decrease when treatment is performed with short “beam-on” times. Also, the dose is subject to variation between treatment sessions if the respiratory rate is irregular. We therefore evaluated the impact of the differences between gated and non-gated treatment on doses using a new online quality assurance (QA) system for respiratory-gated radiotherapy. Methods We generated dose estimation models to associate dose and pulse information using a 0.6 cc Farmer chamber and our QA system. During gated irradiation with each of seven regular and irregular respiratory patterns, with the Farmer chamber readings as references, we evaluated our QA system’s accuracy. We then used the QA system to assess the impact of respiratory patterns on dose distribution for three lung and three liver radiotherapy plans. Gated and non-gated plans were generated and compared. Results There was agreement within 1.7% between the ionization chamber and our system for several regular and irregular motion patterns. For dose distributions with measured errors, there were larger differences between gated and non-gated treatment for high-dose regions within the planned treatment volume (PTV). Compared with a non-gated plan, PTV D95% for a gated plan decreased by −1.5% to −2.6%. Doses to organs at risk were similar with both plans. Conclusions Our simple system estimated the radiation dose to the patient using only pulse information from the linac, even during irregular respiration. The quality of gated irradiation for each patient can be verified fraction by fraction.

Purpose It is unclear that spatial accuracy can reflect the impact of deformed dose distribution. In this study, we used dosimetric parameters to compare an in-house deformable image registration (DIR) system using NiftyReg, with two commercially available systems, MIM Maestro (MIM) and Velocity AI (Velocity). Methods For 19 non-small-cell lung cancer patients, the peak inspiration (0%)-4DCT images were deformed to the peak expiration (50%)-4DCT images using each of the three DIR systems, which included computation of the deformation vector fields (DVF). The 0%-gross tumor volume (GTV) and the 0%-dose distribution were also then deformed using the DVFs. The agreement in the dose distributions for the GTVs was evaluated using generalized equivalent uniform dose (gEUD), mean dose (Dmean), and three-dimensional (3D) gamma index (criteria: 3 mm/3%). Additionally, a Dice similarity coefficient (DSC) was used to measure the similarity of the GTV volumes. Results Dmean and gEUD demonstrated good agreement between the original and deformed dose distributions (differences were generally less than 3%) in 17 of the patients. In two other patients, the Velocity system resulted in differences in gEUD of 50.1% and 29.7% and in Dmean of 11.8% and 4.78%. The gamma index comparison showed statistically significant differences for the in-house DIR vs. MIM, and MIM vs. Velocity. Conclusions The finely tuned in-house DIR system could achieve similar spatial and dose accuracy to the commercial systems. Care must be taken, as we found errors of more than 5% for Dmean and 30% for gEUD, even with a commercially available DIR tool.

We previously isolated an IL-11–mimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitro and accumulates in IL-11R–expressing tumors in vivo . This synthetic peptide ligand was used as a tumor-targeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligand-targeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients ( n = 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues ( n = 36; P = 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes ( n = 301; P in vitro cell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications.

Background Staphylococcus lugdunensis ( S. lugdunensis ) is known as a common cause of clinically significant infections in adults although the clinical importance of S. lugdunensis isolates from pediatric samples is less known. The aim of this study is to assess the incidence, characteristics, and outcomes of S. lugdunensis bacteremia (SLB) in children. Methods From January 2009 to March 2014, all blood culture isolates were retrospectively screened for S. lugdunensis . We analyzed the isolates for antimicrobial susceptibility and patients who had developed SLB by reviewing the electronic medical records. Additionally, we identified mecA and blaZ for available isolates by polymerase chain reaction (PCR). Results Of the 647 positive blood cultures during the period, 277 (42.8%) yielded coagulase negative Staphylococcus (CoNS), and 10 of 277 CoNS were S. lugdunensis (3.6% of all CoNS isolates). Of eight SLB episodes identified, seven (87.5%) were considered to have clinically significant bacteremia. All patients had underlying diseases, and all SLB were either healthcare-associated or hospital acquired. There was no infectious endocarditis (IE) development. All patients were treated with antibiotics and recovered without sequelae. We found that the isolates in our study showed higher antibiotic resistance to penicillin (8/8: 100%) and oxacillin (6/8: 75.0%) than previously reported. Among isolates available, we detected mecA in all four isolates resistant to oxacillin and blaZ in 5 of 6 isolates resistant to penicillin. Conclusions S. lugdunensis is a rare but an important cause of bacteremia in children.

For hydrogenated amorphous silicon oxide (a-SiO:H) layers applied to crystalline Si heterojunction solar cells, we have studied the correlations between the dielectric function and local bonding states using spectroscopic ellipsometry and high-sensitivity infrared spectroscopy. In particular, systematic characterizations have been made on both a-SiO:H and hydrogenated amorphous silicon carbide (a-SiC:H) layers prepared at similar conditions. In a-Si 1− x O x :H and a-Si 1− x C x :H layers, the increase in the alloy content x leads to the significant reduction in the amplitude of the dielectric functions due to microvoid formation. The infrared spectra reveal that the local bondings in the a-SiO:H are dominated by SiH 2 and SiH m (O 4−m ) (m ≤ 2) at high x , whereas the local bonding states of the a-SiC:H alloy can be interpreted as a mixture of SiH 2 and CH n (n = 2, 3). The amplitude of the a-SiO:H dielectric functions shows a clear relationship with a total amount of SiH m (O 4−m ) in the network, indicating that the significant microvoid formation in a-SiO:H layers is most likely triggered by the generation of SiH 2 (O 2 ) and SiH(O 3 ). Our results indicate that, compared with the C atom, the O atom increases the band gap of a-Si:H more effectively while suppressing the H incorporation in the amorphous network.

We have investigated acid- and base-induced conformational alterations of N -aryl- N -troponyl amides containing an electron-donating group on the phenyl ring. NMR spectral studies indicated that the E / Z conformational preferences of these amides can be reversibly controlled by pH-dependent protonation or deprotonation of the tropolone moiety. Thus, these compounds have potential applications as acid/base-controllable molecular switches.

Skeletal muscle regeneration requires migration, proliferation and fusion of myoblasts to form multinucleated myotubes. In our previous study, we showed that insulin-like growth factor (IGF)-I gene delivery stimulates the proliferation and differentiation of mouse myoblast C2C12 cells and promotes the contractile force generated by tissue-engineered skeletal muscles. The aim of this study was to investigate the effects of the extracellular matrix on IGF-I gene-engineered C2C12 cells in vitro. Retroviral vectors for doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into C2C12 cells. When cultured on a type IV collagen-coated surface, we observed significant increases in the migration speed and number of IGF-I gene-engineered C2C12 cells with Dox addition, designated as C2C12/IGF (+) cells. Co-culture of C2C12/IGF (+) cells and parental C2C12 cells, which had been cultured in differentiation medium for 3 days, greatly enhanced myotube formation. Moreover, type IV collagen supplementation promoted the fusion of C2C12/IGF (+) cells with differentiated C2C12 cells and increased the number of myotubes with striations. Myotubes formed by C2C12/IGF (+) cells cultured on type IV collagen showed a dynamic contractile activity in response to electrical pulse stimulation. These findings indicate that type IV collagen promotes skeletal muscle regeneration mediated by IGF-I-expressing myoblasts, which may have important clinical implications in the design of myoblast-based therapies.

Purpose We previously reported early efficacy results from a phase I/II study of definitive chemoradiotherapy using docetaxel, nedaplatin and 5-fluorouracil (DNF-R), and confirmed strong antitumor activity with an acceptable early toxicity profile for patients with esophageal cancer. Here, we present the long-term results of the study including late toxicity and survival. Methods Thirty-one patients were enrolled. Patients received 5-fluorouracil (400 mg/m2 civ, d1-5 and d8-12), nedaplatin (50 mg/m2 on d1 and 8), and docetaxel (20-30 mg/m2 on d1 and 8), repeated twice every 5 weeks with concurrent radiotherapy (59.4Gy/33fr). Study objectives in the phase II part included the CR rate, progression-free survival (PFS), overall survival (OS), and safety. Results Between December 2008 and February 2014, a total of 28 patients were registered. Grade 3/4 acute toxicities included neutropenia (43%), febrile neutropenia (7%), thrombocytopenia (18%), and esophagitis (21%). Grade 3/4 late toxicity included esophagostenosis (11%) and pleural effusion (7%), though these resolved with dilation and thoracic drainage, respectively. All patients achieved a response, with 23 (82.1%) CR cases (stege II/III 89%, T4/M1LYM 67%). With a median follow-up time of 69.8 months, the 3-/5-year PFS and OS were 68.4/68.4% and 71.5/66.8%, respectively. 5-year OS for stage II/III (nonT4) and T4/M1LYM were 68.4% and 28.6%, respectively. Conclusions The long-term results show that efficacy was maintained with high rate of PFS and OS compared with those of historical control, with durable responses and acceptable safety profile. DNF-R might be a promising regimen for definitive CRT for esophageal cancer.

The aim of this study was to investigate whether insulin-like growth factor (IGF)-I gene delivery to myoblast cells promotes the contractile force generated by hydrogel-based tissue-engineered skeletal muscles in vitro. Two retroviral vectors allowing doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into mouse myoblast C2C12 cells to evaluate the effects of IGF-I gene expression on these cells. IGF-I gene expression stimulated the proliferation of C2C12 cells, and a significant increase in the growth rate was observed for IGF-I-transduced C2C12 cells with Dox addition, designated C2C12/IGF (Dox+) cells. Quantitative morphometric analyses showed that the myotubes induced from C2C12/IGF (Dox+) cells had a larger area and a greater width than control myotubes induced from normal C2C12 cells. Artificial skeletal muscle tissues were prepared from the respective cells using hydrogels composed of type I collagen and Matrigel. Western blot analyses revealed that the C2C12/IGF (Dox+) tissue constructs showed activation of a skeletal muscle hypertrophy marker (Akt) and enhanced expression of muscle-specific markers (myogenin, myosin heavy chain and tropomyosin). Moreover, the creatine kinase activity was increased in the C2C12/IGF (Dox+) tissue constructs. The C2C12/IGF (Dox+) tissue constructs contracted in response to electrical pulses, and generated a significantly higher physical force than the control C2C12 tissue constructs. These findings indicate that IGF-I gene transfer has the potential to yield functional skeletal muscle substitutes that are capable of in vivo restoration of the load-bearing function of injured muscle or acting as in vitro electrically-controlled bio-actuators.

Several procedures for conservation treatment were comparatively studied for degraded “ Suga- fibres” made of raw silk fibres dyed black. Two traditional methods, (1) neutralization with magnesium bicarbonate, and (2) antioxidant treatment with phytic acid, originally used for paper preservation, were tried for the conservation of Suga -fibres. The influences of a single treatment, or a combination of neutralization and antioxidant treatments, for the model fibres on their tensile strength were investigated under conditions of high humidity at high temperature before and after the accelerated aging test. The effect of the novel antioxidant cysteine on the fibre degradation was also examined. For the single treatments, the neutralization with magnesium bicarbonate retarded the degradation of higher iron-content iron (20%)/tannate-silk fibre, while the antioxidant with phytic acid treatment most effectively prevented the degradation of lower iron-content iron (2%)/tannate-silk fibre. This may be due to the different acidity in iron/tannate-silk fibres, and thus the degradation of iron (2%)/tannate-silk fibre would be caused by iron-catalyzed oxidation rather than acid-catalyzed hydrolysis because of its lower acidity. Among antioxidant treatments, cysteine more effectively retarded the degradation of the iron (20%)/tannate-silk fibre, while in the case of the iron (2%)/tannate-silk fibre, phytic acid more effectively conserved its strength and breaking strain. The result suggests that the thiol group of cysteine coordinates with an excess of ferrous ions in the iron (20%)/tannate-silk fibre and quenches the production of hydrogen peroxide. This study demonstrated that phytic acid, cysteine and magnesium bicarbonate treatments are useful as effective reagents for the conservation treatment of black-dyed textiles.

Fatigue experiments were carried out in laboratory air using an extruded magnesium alloy, AZ31, to investigate the effect of load ratio on the fatigue life and crack propagation behavior. The crack propagation behavior was analyzed using a modified linear elastic fracture mechanics parameter, M. The relation crack propagation rate vs. M parameter was found to be useful in predicting fatigue lives at different R ratios. Good agreement between the estimated and the experimental results at each stress ratio was obtained.

Compact tension (CT) specimens, 6 mm thick, of the aluminum alloy 6061-T6 were subjected to 100–300% overloads at R values ranging from 0.1 to 0.9. Both experimental and analytical results show that the delay phenomenon is found at all R values. For a given overload ratio, the number of delay cycles, Nd, at high R values was found to be specimen-type dependent. In tests using compact specimens, Nd increased with R, whereas in tests using center-cracked specimens Nd decreased with R. Over the complete range of R values, the delay phenomenon is shown to be caused by overload-induced crack closure.

Polystyrene-bound diethanolamine (PS-DEAM) work-up for a newly developed Pd(PPh3)4-catalyzed cleavage of allylic alkyl ethers using phenylboronic acid can effectively release Pd-free parent alcohols. Furthermore, chromatography-free deallylation can be conducted by using vinylboronic anhydride pyridine complex as an allyl scavenger with a catalytic amount of Pd(OAc)2 and 4-(diphenylphosphino)benzoic acid instead of Pd(PPh3)4 to yield the desired products in high purities and yields after removal of volatile byproducts and the phosphine-derived contaminants by evaporation and sequestration through acid–base interaction with PS-DEAM, respectively.

Wheel type mobile systems are the most popular transportation mechanisms because the energy efficiency is high, the mechanism is simple and the control system is well investigated. On the other hand, the wheel type mobile robots have difficulties in rough terrain movement. In previous research, a six-wheeled mobile robot employing a linkage mechanism, “Zaurus”, was developed to extend maneuverability. In this paper, a neural network controller and PID-controller are applied to Zaurus, and the performances of the two controllers are evaluated.

Mammalian cells have an activity of mutagenic repair for DNA double-strand breaks (DSBs), microhomology-mediated end joining (MMEJ), in which DNA ends are joined via microhomologous sequences flanking the breakpoint. MMEJ has been indicated to be undertaken without Ku proteins, which are essential factors for non-homologous end joining (NHEJ). On the other hand, recent studies with cell-free (in vitro) systems indicated the involvement of Ku proteins in MMEJ, suggesting that MMEJ could be also undertaken by a Ku-dependent pathway. To clarify whether Ku proteins are essential in MMEJ in vivo, linearized plasmid DNAs with microhomologous sequences of 10 bp at both ends were introduced as repair substrates into Ku80-proficient and Ku80-deficient CHO cells, and were subjected to MMEJ and NHEJ. Activities of MMEJ and NHEJ, respectively, of the cells were evaluated by mathematical modeling for the increase in fluorescence of GFP proteins produced from repaired products. The Ku80 deficiency caused approximately 75% reduction of the MMEJ activity in CHO cells, while it caused is ≥90% reduction of the NHEJ activity. Therefore, it was indicated that there is a Ku-dependent pathway for MMEJ; however, MMEJ is less dependent on Ku80 protein than NHEJ. The fraction of MMEJ products increased in proportion to the increase in the amounts of substrates. The results suggest that the increase in DSBs makes the cell more predominant for MMEJ. MMEJ might function as a salvage pathway for DSBs that cannot be repaired by NHEJ.

In this paper, the concept and design of a newly developed artistic robot “J2: Jumping Joe” are discussed. The main objective of the robot is to realize acrobatic motions such as jumping, rolling and somersault to extend the field of robot activity. In order to realize the artistic robot, four kinds of special actuators, Inertia Actuator, Parallel Hip Joint, Lever-crank Knee Joint and Cam Charger are installed. Each actuator is developed as a function module including micro-controllers for easy debugging.

The researches on swarm intelligence using many mobile robots have been investigated actively, and the possibilities of cooperative transportation, distributed sensing, survey, collision avoidance, etc., have been discussed. In this research, the concept and specification of a small mobile robot platform “With” aimed at realization of swarm intelligence have been discussed and examined through experiments.

The transportation using wheels is one of the most popular transportation mechanisms for mobile robots because of its high energy efficiency, simple mechanisms and well-investigated control systems. However, the wheel type mobile robots have the biggest weakness in the rough terrain movement. In the previous researches, a six-wheeled mobile robot employing a linkage mechanism, “Zaurus”, has been developed to extend maneuverability of the conventional wheel type mobile systems. The experiments to climb over single bumps with twice the height of diameter of the robot's wheel have been carried out and succeeded. In this paper, a neural network controller and PID controller are introduced as the control system, and their performances are compared by simulations. The neural network controller shows superior filtering and feature extraction capabilities.

A linearized plasmid DNA, in which tandem repeats of 400 bp flank the breakpoints, was transfected into vertebrate cells, and breakpoint junctions of plasmid DNA circularized in the cells were analyzed to assess the repair activities against DNA double-strand break (DSB) by non-homologous end joining and homology-directed repair (i.e., homologous recombinational repair and single-strand annealing). The circularization by non-homologous end joining repair of the breakpoints depended on the expression of DNA-PKcs, while that by homology-directed repair through the repeats depended on the length of the repeats, indicating that these two DSB repair activities can be rapidly assessed by this assay. Predominance in circularization by either non-homologous end joining or homology-directed repair differed among cells examined, and circularization was exclusively undertaken by homology-directed repair in DT40 cells known to show a high homologous recombination rate against gene-targeting vectors. Thus, this assay will be helpful in studies on mechanisms and inter-cellular variations of DSB repair.

The electrochemical system presented here is the oxidation of ferrocene in the hemispherical droplet of polydimethylsiloxane (PDS) at the ring shape of the oil|water|electrode interface. The PDS phase included ferrocene without supporting electrolyte, whereas the aqueous phase included an electrolyte such as NaBF 4 or NaClO 4 without electroactive species. The voltammogram showed the steady-state anodic wave for the oxidation of ferrocene, independent of potential sweep rate. The limiting current was proportional to the radius of the droplet. These facts indicate that the electrode reaction should occur at the thin annular part on the electrode into which the water and the oil phase merge. The ring width of the three-phase boundary was evaluated from the limiting current on the basis of the microband model to yield 18 and 9 μm for BF 4 − and ClO 4 − , respectively, much larger than the molecular length or thickness of a diffuse double layer predicted geometrically from the intersection of two planes. The large values suggest participation in the fluctuation of the three-phase boundary. The fluctuation is ascribed to the emulsion formed at the oil|water interface owing to forced dissolution of ferricenium ion in the oil phase. The emulsion was observed with a microscope and was detected chemically.

Iwojima volcano, located on the southernmost part of the Izu–Ogasawara arc, is characterized by a magma chemistry, which differs from that of the other volcanoes in the arc, suggesting a larger contribution of subducted component. In order to elucidate the behavior of volatile elements during the subduction process in generating this unusual magma, noble gas and carbon isotope ratios of volcanic volatiles were measured. The noble gas and carbon isotopic characteristics of Iwojima magma are quite distinct from other volcanoes in the Izu–Ogasawara–Mariana arc system: (1) a low 3 He/ 4 He ratio of 5.6 R A ; (2) enrichment in heavy noble gases; and (3) a heavy carbon isotope ratio (+1.5‰) almost equivalent to the highest value for marine carbonates. These unusual features strongly suggest the involvement of slab-derived volatiles in the magma, although the possibility of a shallow origin for the low 3 He/ 4 He ratio still remains. Based on a mixing calculation using helium–carbon isotope systematics, an extremely large contribution of slab-derived components (31% for 4 He and more than 95% for 12 C) is required to explain the unusual features of helium and carbon isotopes of Iwojima. This is in agreement with other petrological and geochemical features which imply a greater role of subducted materials, although the precise relative contributions of each source materials are somewhat different for several of the tracers. This difference is probably caused by different provenance in subducting materials carrying them to melt generation depth in the mantle wedge. The elevated carbon/helium ratio of the slab-derived component also suggests decoupling during the subduction process probably resulting from the preferential loss of helium from the subducting slab beneath the forearc region. Enhanced outputs of slab-derived carbon and helium (3.5×10 9 and 4.0×10 3 mol/year) indicate a large input of slab component to the mantle wedge and/or effective devolatilization of slab materials. As for its origin, we believe that the unusual tectonic setting around Iwojima may be responsible: (1) subduction of the Ogasawara Plateau, which brings a significant volume of thick crustal blocks into the mantle wedge beneath Iwojima; (2) flattened subduction as a consequence of the buoyancy of the subducting Ogasawara Plateau; and (3) propagation of the back-arc basin rift axes in the Mariana Trough. In contrast to large-scale subduction of overthickened oceanic crust associated with slab melting, the subduction of a relatively small oceanic plateau may be responsible for the characteristics of the Iwojima magma, in which slab material itself does not play an important role in magma genesis but slab-derived volatiles make a significant contribution.

The object of this study is to assess whether aneurysm surgery can be performed in patients with ruptured and unruptured cerebral aneurysms by using three-dimensional computerized tomography angiography (3D-CTA) alone, without conventional catheter angiography (CCA). We have operated on 153 consecutive patients with ruptured aneurysms and 89 patients with unruptured aneurysms based on 3D-CTA findings since December 1996 and February 1997, respectively. In the cases of ruptured aneurysm, 153 ruptured aneurysms including 62 associated unruptured aneurysms were detected by 3D-CTA. CCA was performed in 7 of 153 patients after they underwent 3D-CTA, which included four dissecting vertebral artery (VA) aneurysms, two basilar artery (BA) tip aneurysms, and one BA–superior cerebellar artery (SCA) aneurysm. In 89 patients with unruptured aneurysms, 101 unruptured aneurysms were detected by 3D-CTA. In 5 of 101 unruptured aneurysms, which included giant or large aneurysms and a case of an aneurysm associated with infarction, CCA was needed. All of the ruptured and unruptured aneurysms were confirmed during surgery and treated successfully. The authors stress that 3D-CTA could replace CCA in the diagnosis of saccular aneurysms and that surgery could be performed in almost all ruptured and unruptured aneurysms by using only 3D-CTA without CCA.

In our previous study, 60 cases of subarachnoid hemorrhage (SAH) from ruptured aneurysms were prospectively evaluated both by three-dimensional computerized tomography angiography (3D-CTA) and conventional catheter angiography (CCA), which resulted in a 100% accuracy for 3D-CTA in the diagnosis of ruptured aneurysms. Based on the results, we assessed whether the aneurysm surgery can be performed on patients with ruptured cerebral aneurysms using 3D-CTA without CCA. 3D-CTA was performed with a helical CT scanner. A total of 123 consequent patients with SAH who had undergone surgery in the acute stage on the basis of 3D-CTA findings were studied. One hundred and twenty-three ruptured aneurysms, including 49 associated unruptured aneurysms, were detected using 3D-CTA. In 7 of 123 ruptured aneurysms, 3D-CTA was followed by CCA to acquire the diagnostic confirmation or the information of the vein. All of the ruptured aneurysms were confirmed at the surgery and treated successfully. One hundred and sixteen patients who underwent the operation with the use of 3D-CTA only had no complications related to the lack of CCA information. 3D-CTA provided us with aneurysm location as well as the surgically important information on the configuration of its sac and neck, and its relationship to adjacent vessels and bone structures. 3D-CTA can replace CCA in the diagnosis of ruptured aneurysms and acute surgery can be performed in almost all acutely ruptured aneurysms by using only 3D-CTA without CCA.

Ocean Drilling Program (ODP) Leg 169, which was conducted in 1996 provided an opportunity to study the gas geochemistry in the deeper part of the sediment-rich hydrothermal system in Escanaba Trough. Gas void samples obtained from the core liner were analyzed and their results were compared with analytical data of vent fluid samples collected by a submersible dive program in 1988. The gas geochemistry of the pore fluids consisted mostly of a hydrothermal component and was basically the same as that of the vent fluids. The He isotope ratios (R/RA=5.6–6.6) indicated a significant mantle He contribution and the C isotopic compositions of the hydrocarbons [δ13C(CH4)=−43‰, δ13C(C2H6)=−20‰] were characterized as a thermogenic origin caused by hydrothermal activity. On the other hand, the pore fluids in sedimentary layers away from the hydrothermal fields showed profiles which reflected lateral migration of the hydrothermal hydrocarbons and abundant biogenic CH4. Helium and C isotope systematics were shown to represent a hydrothermal component and useful as indicators for their distribution beneath the seafloor. Similarities in He and hydrocarbon signatures to that of the Escanaba Trough hydrothermal system were found in some terrestrial natural gases, which suggested that seafloor hydrothermal activity in sediment-rich environments would be one of the possible petroleum hydrocarbon generation scenarios in unconventional geological settings.

A photo-stimulated luminescent (PSL) material, BaFBr 0.85 I 0.15 : Eu 2+ , was irradiated by 1 and 2 MeV He + ions. The radiation effects were compared with that of fission neutrons, 137 Cs and 60 Co gamma-rays. Deterioration of PSL signals was measured as a function of total fluence for ions and neutrons or dose for gamma-rays. Relative deteriorations for neutrons and gamma-rays were compared with that of 1 MeV He + ion irradiation. A self-generation of PSL signals depending on fluence and storage time was observed.

By water vapour plasma glow discharge treatment, microporous hydrophobic polypropylene film was modified to make it partially hydrophilic. The plasma-treated part was a spot 6 mm in diameter and permeable to water. After treatment with octamethylenediamine and glutaraldehyde, the plasma spot membrane served as a substrate to immobilize proteins such as antibodies or enzymes. Using this membrane, an amperometric enzyme immunoassay system was established to determine human serum albumin (HSA) in urine. The measurable range with this system was from 0.5 to 100 mg l −1 HSA in urine, which is suitable for the prognosis of diabetic nephritis. The HSA values in urine samples determined by the present system showed a linear correlation with those obtained by radioimmunoassay ( r = 0.974). After keeping the antibody-immobilized plasma spot membranes at 4°C for 6 months, the same calibration graph for HSA determination was obtained. In addition, a colour-producing reaction was also performed on the immunoreacted plasma spot membrane. Reflectance spectrometric analysis demonstrated that the colour on the plasma spot membrane itself corresponded to the HSA concentration. The difference in colour between 10 and 100 mg l −1 HSA could be visually discerned.

A partial modification was made to a microporous hydrophobic polypropylene film by water vapour plasma glow discharge treatment. The modified part, a spot 6 mm in diameter, became hydrophilic so that water could penetrate easily. By treating this “plasma spot membrane” with octamethylenediamine and glutaraldehyde, a membrane for immobilization of proteins was obtained. As immobilization of the antibody and the immunoreaction could be performed in the limited spot area, only small amounts (10 μl) of reagents and sample were required. Using this plasma spot membrane and a Pt-AgCl electrode, an amperometric enzyme immunoassay system was established for the measurement of urinary human serum albumin. In this system, non-specific adsorption of enzyme-labelled antigen to the membrane was only 4.4% of specific binding. The range of measurement was 0.5–200 mg l−1 of human serum albumin, which is satisfactory for the diagnosis of human kidney function.

A significant temperature effect on the new photochemical reactions of 9-α-bromopropionylanthracene has been noted. In comparison to the temperature effect on the fluorescence intensity of 9-propionylanthracene, it was suggested that the rotation of the carbonyl group on photo-excitation might operate as an enhancing factor in the intersystem crossing process.

Bronchodilating actions of 7-hydroxy(I), 5, 7-dihydroxy(II), 5, 6, 7-trihydroxy (III) and 6, 7.8-trihydroxy(IV)-()-I-(3, 4, 5-trimethoxybenzyl)-12, 3, 4-tetrahydroisoquinolinc (TMI) were investigated in anesthetized cats and results were compared to those of AQ-110 (6, 7-dih)droxy-TMI) and isoproterenol. TMI derivatives given intravenously suppressed the bronchoconstriction induced by serotonin. These compounds also caused an increase in heart rate and a decrease in diastolic pressure. All of these actions sere inhibited by pretreatment vvith propranolol, suggesting that they were classified as β-sympathominictics. Bronchodilating activities of AQ-110, I, II, III and IV were 1 2.6, 136, 1 4.0, 1 7.7 and 1 23 that of isoproterenol, respectively. When compared with isoproterenol, I and the other TMI derivatives were about 9 and 2 times more potent in producing bronchodilation than in increasing heart rate. On the other hand, the bronchodilating activities of I, II and AQ-110 were 2-3 times as great as their depressor activities, while III and IV had no selectivity. When administered into the duodenum, II was the most potent in producing bronchodilation and the potency was followed by these of AQ-110, I, III, isoproterenol and IV in decreasing order. Duration of the bronchodilating action of TMI derivatives administered via either intravenous or intraduodenal route was considerably longer than that of isoproternol; especially I and II were long-acting. These results suggest that I and II exhibits a greater absorption efficiency or intraduodenal bioavailability than the other compounds tested.

The positive inotropic effect of TA-064, (−)-(R)-1-(p-hydroxyphenyl)-2-[(3',4-dimethoxyphenethyl)ammo]ethanol, was studied in the anesthetized dog and isolated guinea pig heart. An intravenous administration of TA-064 dose-dependently increased the cardiac contractile force with little effect on blood pressure in dogs. The positive inotropic activity of TA-064 was 1/100 that of isoproterenol and similar to that of dobutamine. This effect of TA-064 was stereospecific, and it was blocked by practolol. Thus TA-064 has beta1-adrenoceptor agonistic action. The positive inotropic effect of TA-064 was more pronounced than the positive chronotropic effect, compared with those of isoproterenol. Similar effect of TA-064 was observed in the reserpinized dog and in the isolated perfused heart of the guinea pig as well. TA-064 administered intraduodenally at a dose of 0.1 mg/kg increased contractile force by 120% of the control, and the effect lasted for more than 150 min. TA-064 given in the femoral artery demonstrated a very weak vasodilating effect on the artery. TA-064 is an orally active, positive inotropic agent. The selective positive inotropic action of TA-064 may result from its beta1-adrenoceptor agonistic property.

A fine-structural study of sperm-egg interactions in the polychaete Neanthes japonica was carried out. Unfertilized eggs are surrounded by a chorion 0.6-0.7 micrometers thick. Oocyte microvilli are inserted into the inner layer of the chorion. The outer layers of the chorion are opened just above the tips of the microvilli, where a membrane vesicle (microvillus tip vesicle, about 0.2 micrometers in diameter) plugs the chorion's opening. During fertilization, the acrosomal process of the sperm fuses with an egg microvillus within 1 min of insemination. All the microvillus tip vesicles disappear from the chorion surface within 5 min of insemination. When eggs, which are prefixed with glutaraldehyde, are inseminated, numerous sperm undergoing the acrosome reactions attach to the eggs. In the majority of these sperm, the tip of acrosomal process which is coated with the acrosomal content, adhere to a microvillus tip vesicle. These findings suggest that the microvillus tip vesicle serves as a sperm receptor, which induces the acrosome reactions and adhere to the sperm acrosomal process. The adhesion of the acrosomal process to the microvillus tip vesicle seems to be a prerequisite event for its fusion with the microvillus.

Crude mitochondrial P2 fractions from bovine hypothalamus and substantia nigra, slices from rabbit spinal cord and mesencephalon and glial fractions from rabbit brain were incubated with [3H]-substance P and the uptake was measured and compared with those for 5-HT and GABA. Substance P was to some extent taken up into the fractions but this uptake was neither temperature nor time dependent and the pellet/ medium ratios were less than 1. Similar results were obtained in high potassium treated slices from rabbit mesencephalon. The rate of uptake for [3H]-substance P increased linearly in proportion to the medium concentration, suggesting a non-saturable binding. These results, together with our previous observations provide strong evidence that nerve terminals and glial cells lack a temperature sensitive, active uptake system capable of terminating transmitter action of substance P at the synapse.

The cardiovascular effects of trimetoquinol (AQL-208), the l-isomerof 1-(3,4,5-trimethoxybenzyl)-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline HCI (AQ-110), were investigated and compared with AQ-110 (racemate), AQD (d-isomer and (dl-isoproterenol. The compounds, except for AQD, produced hypotensive, positive inotropic and chronotropic effects as well as peripheral vasodilation. The d-isomer (AQD) of AQ-110 had little effect on the cardiovascular system. The results indicate that the cardiovascular effect of the racemate can be ascribed to the l-isomer. The potency of AQL-208 was about twice that of AQ-110, while it was approximately 1 2.5 that of isoproterenol. In this and preceding papers, it is suggested that the test compounds exert their pharmacological effects mainly by acting as β-sympathomimetics, whereas death caused by toxic doses of the compounds is due to respiratory paralysis.

In a previous report (1), it was shown that a new 1, 5-benzothiazepine derivative, 3-acetoxy-2, 3-dihydro-5-[2-(diethylamino) ethyl]-2-(p-methoxyphenyl)-l, 5-benzothiazepine-4 (5H)-one hydrochloride, produced a potent coronary vasodilator effect in anesthetized dogs. Among four Ttereoisomers of the compound, d- and l-isomers of cis- and transforms, the d-cis-isomer (CRD-401) exhibited the most powerful effect when injected into the femoral vein. Without increase in myocardial oxygen consumption, a significant increase in coronary blood flow resulted. The present report deals with the vasodilator action of d-cis-isomer of the new benzodiazepine derivative under the influence of various pharmacological blockers. The results are considered in relation to the mechanism of the compound. Effects of dl- and l-cis-isomers and dl-trans-isomer were also investigated and compared with the action of d-cis-isomer. Experiments were performed on the coronary and femoral arteries in anesthetized dogs and on the coronary vessels in isolated hearts of the guinea pig.