Search

The incidence of rash caused by darolutamide in the ARAMIS trial was very low (2.9%).9 The rash types included combined dermatitis, erythema, rash, macular rash, maculopapular rash, papular rash and pustular rash, although the details of these cases have not been published. Several second-generation novel selective inhibitors of androgen receptor (AR), including apalutamide and darolutamide, are used to treat prostate cancers (PC).1 Some cases of apalutamide-caused drug eruption have been reported.2 However, cases of darolutamide-induced drug eruption have never been reported. The longer interval of darolutamide- and apalutamide-induced rash, as well as the negative LTT and absence of skin rash on the recommencement of darolutamide, suggest the presence of an unknown mechanism of drug eruption that is different from the canonical T-cell-mediated allergic reaction. [Extracted from the article]

Maculopapular-type drug eruptions caused by apalutamide: case series and a review of the literature Apalutamide may cause drug eruptions by a different mechanism than T-cell-mediated drug eruptions. In addition to the three cases presented here, five other cases of apalutamide-induced drug eruption have been reported in the English or Japanese literature (Table 1).4-7 All of our three cases exhibited maculopapular-type drug eruption accompanied by vacuolar dermatitis. [Extracted from the article]

In the Kumano forearc basin, offshore SW Japan, the potential occurrence of hydrocarbons has been inferred from both geophysical surveys which point to the presence of natural gas hydrates, and geochemical analyses of gas samples recovered from boreholes and submarine mud volcanoes. The forearc basin is located in the inner part of the Nankai Trough where the Philippine Sea plate is subducting northwards beneath SW Japan. The basin succession unconformably overlies a deformed accretionary prism complex. Hydrocarbons with both microbial and thermogenic origins have been recorded in the Kumano Basin, but the thermogenic petroleum potential is poorly constrained because the regional‐scale geological architecture of the Nankai subduction zone is not well understood. In this paper, the regional‐scale petroleum potential of the Nankai Trough is investigated based on the geological interpretation of new seismic reflection images. The images were derived from legacy seismic survey data using advanced processing techniques such as reverse time migration, which make use of both primary and multiple reflections in wide‐angle seismic data collected with ocean‐bottom seismographs. In the study area, a seaward‐dipping reflector was identified which terminates at the plate boundary décollement and which is interpreted as part of the boundary between previously‐identified older (>14 Ma) and younger (<6 Ma) accretionary prisms. A triangle body at the base of the younger accretionary prism is interpreted to consist of underthrusted sediments including thick hemipelagic mudstones with source rock potential which were scraped off the down‐going oceanic plate. These tentatively identified, deeply‐buried mudstones may have the potential to generate thermogenic hydrocarbons which may then migrate upwards along dipping carrier beds or faults and fractures to the unconformity at the base of the Kumano forearc basin succession. The presence of hydrocarbons in the accretionary prism may be inferred from positive amplitude anomalies which have been identified in the reprocessed multi‐channel seismic data. The new reflection interpretations therefore allow the potential for thermogenic petroleum to be proposed in the study area. The hydrocarbon potential at this subduction margin may therefore rely not only on shallow microbial methane, but may also involve deeper, thermogenic petroleum generated within the underlying accretionary prism. [ABSTRACT FROM AUTHOR]

Extreme El Niño events affect the number of intense tropical cyclones (ITCs) over the western North Pacific (WNP). In 1997 and 2015, both extreme El Niño years, ITC numbers were above normal in the WNP. In order to clarify how, and to what extent, sea surface temperature anomaly (SSTA) distributions control the ITCs genesis, the authors conducted 50‐member ensemble simulations using a high‐resolution global nonhydrostatic model that explicitly simulates ITCs. The ensemble simulations showed a clear relationship between the number of ITCs and their genesis locations in the WNP. However, the authors found that the simulated numbers of ITCs in the WNP were also closely related to the strength of the monsoon trough, which varies under given SSTA conditions. This indicates that reliable seasonal forecasting of ITCs depends on our ability to accurately reproduce the monsoon trough, whose strength is modulated mainly by internal atmospheric variability but also by SSTA. Plain Language Summary: Tropical cyclone has a potential to cause great loss of life and damage to infrastructure. Accurate prediction of tropical cyclone activity can reduce these loss and damage. However, deterministic prediction of tropical cyclone is difficult. Development of tropical cyclones is affected by sea surface temperature and its geographical distribution (e.g., El Niño). To evaluate variability of intense tropical cyclone activity, we conducted 50‐member simulations under an identical sea surface temperature condition. Although the simulation shows the number of intense tropical cyclones differs among members despite the identical sea surface condition, the number is strongly related to the atmospheric response to the sea surface temperature. Over the western North Pacific, the monsoon trough is strongly contributing to tropical cyclone genesis and its genesis location. The simulated number was correlated with the strength of westerly wind associated with the monsoon trough. The response of the monsoon trough to the sea surface temperature itself also shows variations. However, the response was partially predictable by the sea surface temperature. This study shows that the reproducibility of the monsoon trough plays a key role in reliable seasonal forecasting of intense tropical cyclones. Key Points: Fifty‐member ensemble simulations of 1997 and 2015 assessed the impact of El Niño on intense tropical cyclones in the western North PacificThe intense tropical cyclone numbers substantially varied among ensemble members, despite their use of identical sea surface temperatureThe strength of westerly wind associated with the monsoon trough played a key role in predicting the number of intense tropical cyclones [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour‐infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)‐positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3‐positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3‐positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types. [ABSTRACT FROM AUTHOR]

SUMMARY: For the demonstration of feasibility and loss‐reduction effect of the larger‐capacity amorphous core transformers (AMT), this paper proposed the support structure and design method of the iron‐loss reduced amorphous wound cores with a weight of 7 tons. We designed and manufactured 10 MVA single‐phase test model with the cores inserted in a support cage having structures of the stress‐buffered core support, the proof electromagnetic force from the windings, and the stray loss‐reducing shields. The 50%‐loaded total loss of the test model estimated from the calculated and measured results has been reduced by 35% compared with a conventional silicon‐steel core transformer (SST) with the same power capacity. [ABSTRACT FROM AUTHOR]

We experienced a rare case of lymphatic effusion and skin metastasis at a TIVAP site in a patient with pancreatic cancer. The patients in this manuscript have given written informed consent to the publication of their case details. Aggressive, progressive or poorly differentiated tumours are more likely to be associated with tumour dissemination to the insertion site than localised or well-differentiated tumours. [Extracted from the article]

Background In highly invasive diseases, metabolism commonly changes. Hypercatabolism is frequent in acute stroke, and nitrogen balance tends to be negative. However, there has been no study describing nitrogen balance in subacute and chronic stroke patients. The present study aimed to examine nitrogen balance in the subacute and chronic phases and to identify the factors related to it. Methods Nitrogen balance was calculated from the collected urine of 56 patients with subacute stroke [mean (SD) 53.8 (18.4) days post-stroke] who were admitted for rehabilitation for their first-ever ischaemic or nonsurgical haemorrhagic stroke. In the first experiment, their nitrogen balance was measured during the rehabilitation phase, and factors (type, severity of hemiparesis, activities of daily living, dysphagia and malnutrition status) related to it were evaluated. The second experiment was performed to describe the time course of nitrogen balance in 31 consecutive patients, with assessments made at admission and at discharge. Results Nitrogen balance was positive in all patients in the subacute phase. A significant difference was seen in nitrogen balance between high and low fat-free mass in male patients. In the chronic phase, nitrogen balance was positive in 96% of the patients. There was no significant difference in nitrogen balance between discharge and admission. Conclusions In the subacute and chronic phases of stroke, it was confirmed that hypercatabolism had resolved and that intensive rehabilitation is possible in the convalescent period of stroke. [ABSTRACT FROM AUTHOR]

Diffuse optical tomography using near-infrared light in a wavelength range from 700 to 1000 nm has the potential to enable non-invasive diagnoses of thyroid cancers; some of which are difficult to detect by conventional methods such as ultrasound tomography. Diffuse optical tomography needs to be based on a physically accurate model of light propagation in the neck, because it reconstructs tomographic images of the optical properties in the human neck by inverse analysis. Our objective here was to investigate the effects of three factors on light propagation in the neck using the 2D time-dependent radiative transfer equation: (1) the presence of the trachea, (2) the refractive-index mismatch at the trachea-tissue interface, and (3) the effect of neck organs other than the trachea (spine, spinal cord, and blood vessels). There was a significant influence of reflection and refraction at the trachea-tissue interface on the light intensities in the region between the trachea and the front of the neck surface. Organs other than the trachea showed little effect on the light intensities measured at the front of the neck surface although these organs affected the light intensities locally. These results indicated the necessity of modeling the refractive-index mismatch at the trachea-tissue interface and the possibility of modeling other neck organs simply as a homogeneous medium when the source and detectors were far from large blood vessels. [ABSTRACT FROM AUTHOR]

The embryonic development of the Japanese eel Anguilla japonica and pike eel Muraenesox cinereus was morphologically investigated with laboratory-reared specimens to clarify the characteristics of somitogenesis. In A. japonica, somites were first observed at 18 h post fertilization (hpf) when epiboly reached 90%. Somitogenesis progressed at a rate of 1·6 h−1 at mean ± s.d. 22·6 ± 0·7° C and completed at 107 hpf (3 days post hatching; dph) when total number of somites ( ST) reached 114, which corresponds to the species' number of vertebrae (112-119). In M. cinereus, somites were first observed at 14 hpf when epiboly completed. Somitogenesis progressed at a rate of 1·9 h−1 at mean ± s.d. 24·4 ± 0·2° C and completed at 90 hpf (2 dph) with 149 ± 4 ST, which corresponds to the species' number of vertebrae (142-158). Both species hatched before somitogenesis was completed, at 37 hpf with 47 ST and 42 hpf with 82 ± 4 ST, respectively. The formation of other organs such as the heart, mouth and pectoral fin bud occurred during somitogenesis. Comparison with the development of zebrafish Danio rerio indicates a prolongation of somitogenesis in A. japonica and M. cinereus. Their somitogenesis rates, however, correspond well with that of D. rerio estimated at the same temperature and their developmental stages at hatching are almost equivalent to other fishes having similar yolk sizes. Therefore, the prolongation of somitogenesis in A. japonica and M. cinereus may be accounted for solely by the increased numbers of somites to be formed, not by a slow somitogenesis rate or an acceleration in organogenesis. [ABSTRACT FROM AUTHOR]

We developed a barometer applicable to a small space, to assess oral and pharyngeal functions. Negative oral pressure during rest and pressure changes during swallowing were measured in a space between the palate and tongue ( STP). Twenty volunteers were asked to sit in a chair in a relaxed upright position. A sensor was placed on the posterior midline of hard palate. Recording commenced just before subjects closed their lips and continued. Subjects were asked to swallow saliva and keep the apposition. Finally, subjects were asked to open their mouth. Recordings were performed five times, and 5 s of continuous data in each phase was averaged. To verify the reliability of the system, the same procedure was accomplished with twin sensors. When the jaw and lips were closed, the pressure slightly decreased from atmospheric pressure (−0·17 ± 0·24- kPa). After swallowing, the pressure in STP showed more negative value (−0·50 ± 0·59- kPa). There is a significant difference between the values in open condition and after swallowing ( P < 0·001) and between values after swallowing and final open condition ( P < 0·05). Twin sensor showed almost the same trajectories of pressure changes for all the recordings. Obtained negative pressure might generate about 0·71-N of force and would be enough to keep the tongue in the palatal fossa at rest. The system detected large negative/positive pressure changes during swallowing. We conclude this system may be a tool to evaluate oral functions. [ABSTRACT FROM AUTHOR]

Objectives Plumbagin ( PL), a naturally occurring quinoid, exerts antitumoral effects in diverse types of cancer cells. However, the effect of PL on tumor cell proliferation in oral squamous cell carcinoma ( OSCC) remains poorly understood. In this study, we assessed the efficacy of PL, in human OSCC cells. Methods The effect of PL on the cell growth and apoptosis of OSCC cell lines was evaluated using MTT and Annexin V assays, respectively. The effect of PL on mitochondrial membrane potential loss and reactive oxygen species ( ROS) generation was evaluated using flow cytometry analysis. Results MTT assay showed that PL dose-dependently suppressed OSCC cell growth, with IC50 values ranging from 3.87 to 14.6 μM. Flow cytometry analysis revealed that PL treatment resulted in a significant decrease in mitochondrial membrane potential and an increase in the number of apoptotic cells. Notably, ROS generation was significantly elevated after PL treatment. Furthermore, a ROS scavenger, N-acetylcysteine ( NAC), clearly suppressed the decrease in mitochondrial membrane potential, increase of caspase-3/7 activity, and apoptosis after PL treatment. Conclusion This study provides the considerable evidence of the tumor-suppressive effect of PL, thereby highlighting its therapeutic potential for OSCC treatment. [ABSTRACT FROM AUTHOR]

Schoenoplectus juncoides is one of the most harmful weeds found in East Asian paddy fields. Recent emergence of biotypes that are resistant to the herbicide sulfonylurea ( SU) has made weed control difficult. To examine the effect of the evolution of this herbicide resistance on genetic diversity within local populations, we investigated microsatellite variability within and among paddy field populations of S. juncoides in Kinki, Japan. In vivo assay of acetolactate synthase activity and root elongation assay in the presence of SU revealed that of 21 populations, five were sulfonylurea-susceptible ( SU- S) and eight were completely sulfonylurea-resistant ( SU- R). The remaining eight populations were a mixture of SU- S and SU- R individuals. The average gene diversity for SU- R populations ( H S = 0.168) was lower than those for SU- S ( H S = 0.256) and mixed ( H S = 0.209) populations, but the difference was not significant. This indicates that positive selection for SU- R phenotype did not cause a genome-wide reduction in genetic diversity. Genetic differentiation among S. juncoides populations was higher than that observed for most weed species studied previously. Although populations in neighbouring paddy fields showed a high level of differentiation, Bayesian clustering analyses suggested that some level of gene flow occurs among them and that the genetic exchange or colonisation between neighbouring populations could contribute to the geographical expansion of the resistant allele. [ABSTRACT FROM AUTHOR]

The oral appliance ( OA) is considered to be an effective treatment modality for obstructive sleep apnoea ( OSA). Upper airway enlargement during OA therapy is critical, and lateral cephalometry has been used for the two-dimensional evaluation of upper airway form during this therapy. However, this method cannot provide an accurate three-dimensional (3D) view of upper airway form. To confirm the effects of OA on the upper airway in patients with OSAS, we performed CT in the presence and absence of OA in 15 Japanese patients (12 males, 3 females) who responded to OA therapy. CT in the presence and absence of OA was consecutively performed for each patient, and upper airway cross-sectional area in six arbitrary planes parallel to the palatal plane was measured. Next, 3D image reconstruction was performed; morphological changes in upper airway form were evaluated, and upper airway volume at three levels from the palatal plane to the deepest point of the epiglottis was measured. The cross-sectional area of two planes in the posterior soft palate region significantly increased in the presence of OA compared with that in the absence of OA. In the presence of OA, upper airway cross-sectional area and volume significantly increased in the posterior soft palate region compared with those in the posterior tongue region. 3D CT image reconstruction accurately confirmed morphological changes in the upper airway during OA therapy. Continued use of this 3D evaluation is expected to improve the results of OA therapy in the future. [ABSTRACT FROM AUTHOR]

Consumption of raw or undercooked poultry products contaminated with Campylobacter has been identified as a risk factor for human campylobacteriosis. We determined whether slaughtering of Campylobacter-positive flocks was associated with contamination of chicken products derived from Campylobacter-negative flocks slaughtered at the same abattoir. The presence of Campylobacter was investigated in 22 broiler farms 1 week prior to slaughter and in one abattoir on nine separate slaughter days. A total of 600 bulk packed chicken products were tested, with 198 (33.0%) of the products found to be Campylobacter positive. Of the 350 chicken products originating from Campylobacter-positive flocks, 180 (51.1%) were contaminated with the bacteria. In contrast, only 18 (7.2%) of 250 chicken products derived from Campylobacter-negative flocks were contaminated. In 14 of these 18 products, the Campylobacter isolates were identical to isolates obtained from the flock slaughtered immediately prior to the Campylobacter-negative flock. Notably, on 4/6 slaughter days, Campylobacter-negative flocks were slaughtered prior to the positive flocks, and Campylobacter was absent from all chicken products originating from the negative flocks. These results suggest that implementation of logistic slaughter (where Campylobacter-negative flocks are slaughter first) significantly decreases the prevalence of Campylobacter-positive chicken products. [ABSTRACT FROM AUTHOR]

Campylobacter was isolated from 67 (47.2%) of 142 broiler flocks between September 2009 and February 2010. The prevalence of Campylobacter in broiler flocks was significantly lower during January and February than it was from September to December. Campylobacter colonization was more common in flocks that were not provided with a disinfected water supply, which was consistent with the findings of a previous study. The prevalence of antimicrobial drug-resistant Campylobacter spp. was investigated, and the minimum inhibitory concentrations of eight antimicrobial agents were determined for 122 Campylobacter jejuni isolates and 46 Campylobacter coli isolates from broiler flocks between 2007 and 2010. In this study, 29.5% (36/122) of C. jejuni isolates and 41.3% (19/46) of C. coli isolates were resistant to enrofloxacin (ERFX), whereas all isolates were susceptible to erythromycin. Furthermore, the ERFX-resistant isolates were tested for susceptibility to other classes of antimicrobial agents, and 55.6% (20/36) of ERFX-resistant C. jejuni isolates and 47.4% (9/19) of ERFX-resistant C. coli isolates were resistant to at least one of aminobenzyl penicillin, dihydrostreptomycin and oxytetracycline. To avoid an impact of antimicrobial drug-resistant Campylobacter spp. on the efficacy of antimicrobial treatment for human campylobacteriosis, prudent use of antimicrobial agents is a requisite. The use of antimicrobial agents should be accompanied by various approaches such as prevention of Campylobacter colonization in broiler flocks with the aim of lowering the occurrence of Campylobacter infection in humans. [ABSTRACT FROM AUTHOR]

AR-NW12A is an in-vacuum undulator beamline optimized for high-throughput macromolecular crystallography experiments as one of the five macromolecular crystallography (MX) beamlines at the Photon Factory. This report provides details of the beamline design, covering its optical specifications, hardware set-up, control software, and the latest developments for MX experiments. The experimental environment presents state-of-the-art instrumentation for high-throughput projects with a high-precision goniometer with an adaptable goniometer head, and a UV-light sample visualization system. Combined with an efficient automounting robot modified from the SSRL SAM system, a remote control system enables fully automated and remote-access X-ray diffraction experiments. [ABSTRACT FROM AUTHOR]

To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy. [ABSTRACT FROM AUTHOR]

Diabet. Med. 28, 1381-1387 (2011) Abstract Aims We previously showed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. Given that diabetes mellitus is an important risk factor for myocardial infarction, the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to diabetes. The purpose of this study was to examine the relation of rs6929846 of BTN2A1 to Type 2 diabetes mellitus. Methods A total of 8650 Japanese individuals from two independent subject panels were examined: Panel A comprised 1141 individuals with Type 2 diabetes and 3161 control subjects and panel B comprised 1664 individuals with Type 2 diabetes and 2684 control subjects. Results The chi-square test revealed that rs6929846 of BTN2A1 was significantly related to the prevalence of Type 2 diabetes in subject panel A ( P = 0.0002) and subject panel B ( P = 0.006). Multivariable logistic regression analysis with adjustment for age, sex, body mass index and smoking status revealed that rs6929846 was significantly associated with Type 2 diabetes ( P = 0.0006; odds ratio 1.25) in all individuals, with the T allele representing a risk factor for this condition. Multiple regression analysis with adjustment for age, sex and body mass index revealed that rs6929846 was significantly ( P = 0.04) related to blood glycosylated haemoglobin content in control subjects. Conclusions BTN2A1 may be a susceptibility gene for Type 2 diabetes in Japanese individuals. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Activity patterns of the swallowing-related muscles were examined in normal subjects at different four body positions during swallowing of foods with different textural properties. Surface electromyograms were recorded from two muscle groups, the anterior tongue and suprahyoid muscles. The TP technique we developed was applied to the electromyograms for quantitative analysis of the activity patterns. Three test foods were prepared by dissolving 2·0% (low), 5·7% (middle) and 9·1% (high concentration) of a thickening agent into distilled water. Each subject was delivered randomly, one of the test foods to swallow at one of the four body positions i.e. horizontal supine, 30° inclined, 60° inclined and upright. In this study, T50 values were calculated in activity data of the two muscle groups, and the T50 values were statistically examined analysis of variance with a linear model including four fixed effects of ‘concentrations’, ‘body positions’, ‘subjects’ and ‘sessions’. Three major findings obtained were that (i) the activity pattern of the anterior tongue was altered from a decrementing discharge pattern to an incrementing discharge pattern by shifting from the upright to the horizontal supine position, (ii) the activity pattern of the suprahyoid muscles was altered from a decrementing discharge pattern to an incrementing discharge pattern by shifting from the low concentration food to the higher ones and (iii) two subgroups were detected in subjects with the significant effects of ‘concentrations’ and ‘body positions’. These findings lead a conclusion that activity patterns of the swallowing-related muscles are affected by food properties and body positions. [ABSTRACT FROM AUTHOR]

Background: Human thioredoxin (TRX) is one of redox-active proteins that regulate reactive oxidative metabolisms. In recent study, we found that serum levels of TRX were elevated in asthmatic patients with exacerbation; however, few details are known about the physiological role of TRX in allergic inflammation, involving eosinophil infiltration. Objective: In the present study, we examined whether TRX modulated C-C chemokine-induced chemotaxis of human eosinophils. Methods: Eosinophils were isolated from subjects with mild eosinophilia by modified CD16 negative selection. After incubation with or without recombinant TRX, chemotaxis of human eosinophils was measured using Boyden chamber. Results: Preincubation with TRX suppressed eotaxin- and regulated on activation, normal T-cell expressed and secreted (RANTES)-induced chemotaxis of eosinophils. Although, TRX had no effect on the expression of C-C chemokine receptor 3, which is a receptor of eotaxin and RANTES, we demonstrated that the activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases, which play an important role in eosinophil migration, was attenuated by the treatment with TRX. Conclusion: Our results suggest that the elicited TRX is beneficial to reduce allergic inflammation through negative regulation of eosinophil functions and has potential in the treatment of allergic diseases, such as asthma. [ABSTRACT FROM AUTHOR]

Despite the significant implication of apoptosis in tumorigenesis, there is no biomarker to assess the extent of ongoing apoptosis in vivo for hematological malignancies. We investigated the potential of serum cytochrome c (cyto-c) as a biomarker for apoptosis. Cyto-c and lactate dehydrogenase (LD) were released into the culture medium from apoptotic cells induced by tumor necrosis factor-related apoptosis-inducing ligand in a time-dependent manner in vitro, with different kinetic patterns. Only one-third of 153 patients with hematological malignancies showed high levels of serum cyto-c (>20 ng/ml). Although serum cyto-c level was roughly correlated to serum LD activity, their different kinetic patterns from serial measurements indicated that serum cyto-c rather than LD is a more sensitive indicator for tracking changes of tumor status. Furthermore, serum cyto-c level stratified patients with acute adult T-cell leukemia into favorable and unfavorable subgroups with 5-year survival rates of 67% vs. 11%. In conclusion, serum cyto-c may provide a fast real-time biomarker for tracking changes of tumor status involved in apoptotic cell death, but lacking disease or cell-type specificity. [ABSTRACT FROM AUTHOR]

The influences of water temperature and feeding regime on otolith growth in Anguilla japonica glass eels and elvers were investigated using individuals reared at 5, 10, 15, 20, 25 and 30° C and in fed or unfed conditions at salinity 32 after their otoliths were marked with alizarin complexone (ALC). To eliminate the difficulty of observing the edges of otoliths with optical (OM) or scanning electron (SEM) microscopes, three to 10 individuals were sampled from each tank at 10, 20 and 30 days during the experiment and reared for an additional 10 days at 25° C after their otoliths were marked a second time. Otolith growth and the number of increments were measured using both OM and SEM. Most A. japonica commenced feeding after 10 days at 20–30° C or after 20 days at 15° C, but no feeding occurred at 5 and 10° C. No otolith growth occurred at 5 and 10° C except in two individuals with minimal increment deposition at 10° C. Otolith growth was proportional to water temperature within 15–25° C and not different between 25 and 30° C. At 15, 25 and 30° C, the mean otolith growth rate in fed conditions was higher than in unfed conditions. The number of increments per day was significantly different among water temperatures (0·00–0·01 day−1 at 5 and 10° C, 0·43–0·48 day−1 at 15° C and 0·94–1·07 day−1 at 20–30° C). These results indicated that otolith growth in A. japonica glass eels and elvers was affected by temperature and ceased at ≤10° C under experimental conditions. Hence, future studies analysing the otoliths of wild-caught A. japonica glass eels and elvers need to carefully consider the water temperatures potentially experienced by the juveniles in the wild. [ABSTRACT FROM AUTHOR]

This study was designed to examine the effect of different food properties and body positions on electromyographic amplitudes of the anterior tongue (AT) and suprahyoid (SH) muscles during swallowing in normal subjects (six men and three women; 21–30 years old). Each subject was asked to swallow three foods (consisting of 2·0%, 5·7% or 9·1% of a thickening agent dissolved in water) with different textural properties in one of four body positions: upright, inclined at 60° or 30°, or supine. Surface electromyograms (EMG) were recorded from the anterior tongue and SH muscles, and the integrated and cumulated EMG were used to evaluate the amplitude changes. The increases in food hardness and adhesiveness elevated the integrated and cumulated EMGs of both the AT and SH muscles during swallowing in a stepwise manner ( P < 0·0001, one-wayanova) that was independent of the body position. There was a linear relationship between the concentrations of the thickening agent and the logarithmic values of the food hardness. There was also a parallel relationship between the logarithmic hardness values and the final logarithmic values of the cumulated muscle activity during swallowing. Unlike these simple amplitude responses of the AT and SH muscles to the different food properties, our previous studies have shown that the durational responses of these muscle activities to different food properties are more complicated. Possible neural mechanisms responsible for the amplitude responses observed are discussed. [ABSTRACT FROM AUTHOR]

Background: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that bind sialic acid and mostly contain immunoreceptor tyrosine-based inhibitory motifs, suggesting that these molecules possess inhibitory functions. We have recently identified Siglec-8 as an eosinophil-prominent Siglec, and cross-linking of Siglec-8 on human eosinophils induces apoptosis. In this article, we address the in vivo consequences of Siglec engagement. We and others have identified mouse Siglec-F as the closest functional paralog of human Siglec-8, based on shared ligand-binding and expression pattern. We therefore hypothesized that Siglec-F engagement would affect levels and viability of eosinophils in vivo. Methods: Wild type and hypereosinophilic mice were administered Siglec-F antibody and levels of eosinophils in peripheral blood and tissue were measured. Eosinophil apoptosis ( in vivo and in vitro) was determined by binding of Annexin-V. Results: Studies in IL-5 transgenic mice, displaying hypereosinophilia, show that administration of a single dose of Siglec-F antibody results in rapid reductions in quantum of eosinophils in the blood. This decrease was accompanied by reductions in tissue eosinophils. Quantum of eosinophils in blood was decreased using two separate antibodies, as well as in other mouse models (wild type mice and in a mouse model of chronic eosinophilic leukemia). Mechanistic studies demonstrated that Siglec-F antibody administration induced apoptosis of eosinophils in vivo and in vitro. Conclusion: These data demonstrate that activation of innate immune receptors, like Siglec-F, can significantly reduce mouse eosinophil viability. As such, targeting Siglec-8/F may be a therapeutic approach for eosinophilic disorders. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine (i) whether or not textural properties of foods and body positions affect the durations of anterior tongue and suprahyoid muscle activities during swallowing, and (ii) if such changes occur, is the 'pre-peak' or the 'post-peak' duration of integrated muscle activity responsible. We used two test foods with different proprieties of hardness and adhesiveness. We recorded electromyograms (EMGs) from the anterior tongue and suprahyoid muscles as well as the laryngeal movement associated with swallowing in normal subjects (six men and three women; 21-30-years old). The subjects swallowed the test foods in four randomly set postures: upright, two inclined (60 ° and 30 ° to horizontal), and supine. None of the measured durations for the anterior tongue and suprahyoid EMGs were different among the four positions during swallowing of either food. The 'total' duration, from the start to the end of the integrated EMG, of anterior tongue activity was significantly ( P < 0·001,anova) longer during the swallowing of the tougher and more adhesive food than during swallowing of the other food, but the 'total' duration of suprahyoid activity was unchanged. The 'post-peak' duration of anterior tongue activity, which stretched from the peak to the end of the integrated EMG, was also significantly longer ( P < 0·001,anova) during swallowing of the tougher and more adhesive food. The results indicate that tougher and more adhesive foods prolong the duration, especially the 'post-peak' duration, of anterior tongue activity during swallowing in the upright, inclined and supine positions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine (i) whether or not textural properties of foods and body positions affect the durations of anterior tongue and suprahyoid muscle activities during swallowing, and (ii) if such changes occur, is the ‘pre-peak’ or the ‘post-peak’ duration of integrated muscle activity responsible. We used two test foods with different proprieties of hardness and adhesiveness. We recorded electromyograms (EMGs) from the anterior tongue and suprahyoid muscles as well as the laryngeal movement associated with swallowing in normal subjects (six men and three women; 21–30-years old). The subjects swallowed the test foods in four randomly set postures: upright, two inclined (60 ° and 30 ° to horizontal), and supine. None of the measured durations for the anterior tongue and suprahyoid EMGs were different among the four positions during swallowing of either food. The ‘total’ duration, from the start to the end of the integrated EMG, of anterior tongue activity was significantly ( P < 0·001,anova) longer during the swallowing of the tougher and more adhesive food than during swallowing of the other food, but the ‘total’ duration of suprahyoid activity was unchanged. The ‘post-peak’ duration of anterior tongue activity, which stretched from the peak to the end of the integrated EMG, was also significantly longer ( P < 0·001,anova) during swallowing of the tougher and more adhesive food. The results indicate that tougher and more adhesive foods prolong the duration, especially the ‘post-peak’ duration, of anterior tongue activity during swallowing in the upright, inclined and supine positions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about the natural history of ovarian cancer with respect to the change of serum CA125 level. Methods: The Shizuoka Cohort Study on Ovarian Cancer Screening (SCSOCS) Trial contains approximately 100,000 data on serum tumor marker CA125 prospectively obtained from more than 70,000 women. We reviewed the clinical charts and collected serum samples 2 months to 9.4 years prior to the surgery were available. Results: In 396 (95%) of the 419 patients with ovarian cancer, one serum sample was present before the diagnosis (mean, 4.1 years). The change of CA125 level before the diagnosis of ovarian cancer could be clearly separated into two groups according to the length of the following intervals: 47% (107/228) of patients with non-serous-type ovarian cancers develop secondarily from slightly elevated CA125 level (35

The analytical methods of Southern blot hybridization (SBH) and the polymerase chain reaction (PCR) for complementarity determining region-3 (CDR3) are fundamental for detecting IgH gene rearrangement. However, there are problems stemming from the characteristics of both methods; especially, the long turn around time (TAT) because of the complex process in the SBH, and the low analytical sensitivity for amplicons in the PCR. Thus, to improve the PCR procedure, we investigated the application of detecting the clonal amplicons based on the different melting Temperature ( Tm) in internal melting domains corresponding to the CDR3 hypervariable region. Our new protocol is based on the combination of a LightCycler Technology with high-speed amplification, and Idaho-Technology with rapid and high-resolution melting curve analysis (MCA), designated PCR-MCA. This method can provide the results within 3 h with an analytical sensitivity of 10−3. The diagnostic sensitivity and specificity relative to the results documented with the SBH analysis were 89.2% and 100%, respectively. This indicates that the new protocol of PCR-MCA is acceptable for clinical testing; especially, PCR-MCA is relevant in terms of the rapid and sensitive detection of IgH clonality within amplicons. [ABSTRACT FROM AUTHOR]

The primary purpose of this study was to determine whether body posture altered the duration of oral swallowing. To answer this question, we recorded electromyograms (EMGs) from the anterior tongue and suprahyoid (SH) muscles as well as laryngeal movement associated with swallowing in nine normal young subjects. The subjects swallowed a test food after receiving a signal while in four randomly set postures: upright, two inclined (60° and 30° to the horizontal), and supine positions. We measured the durations from the start to the peak and from the peak to the end of the integrated tongue and SH EMGs. We assumed that the duration from the start to the peak of the integrated SH EMG would correspond to the duration of oral swallowing. The average duration from the start to the peak of the integrated SH EMG decreased after moving from the upright to the inclined and supine positions. The decrease in the duration was statistically significant and consistent for three experimental sessions. The duration from the start to the peak of the integrated tongue EMG during swallowing tended to decrease after lying down, but not significantly. The postural changes did not affect the remaining four durations. The decrease in the duration of oral swallowing induced by lying down suggests that the gravitational force placed on the test food facilitates the swallowing reflex. Large variation in the tongue activity during swallowing among the subjects can probably be attributed to the lack of a significant decrease in the duration of the tongue activity. [ABSTRACT FROM AUTHOR]

As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks −1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms −1789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects. [ABSTRACT FROM AUTHOR]

The fate of cystic ovarian follicles that developed spontaneously during the early postpartum period of 50 lactating dairy cows was traced by ultrasonography to characterise the follicular dynamics in relation to the fertility of the cows. The absence of postpartum ovulations caused by repeated waves of anovulatory large follicles was also characterised and evaluated. Fifteen of the 50 cows developed cystic follicles, and these follicles became follicular cysts in five of the 15 cows. Most of the cystic follicles emerged before the first postpartum ovulation of the cows. The transition from cystic follicles to follicular cysts delayed the cows' first ovulation, oestrus and insemination, but had less influence on their fertility after they had recovered spontaneously. In addition to the 15 cows that developed cystic follicles or follicular cysts, six of the cows had five to 13 waves of follicles before their first ovulation. These repeated waves of follicles caused a more severe delay in the early postpartum reproductive events but did not affect the cows' fertility. [ABSTRACT FROM AUTHOR]

Background: The inhibition spectrum (IS) in solar urticaria was identified mainly in Japanese patients with solar urticaria, although the mechanism of action of the IS has not been elucidated. Methods: Because an intradermal injection of action spectrum (AS)-irradiated serum in a case of solar urticaria induced a wheal response, we studied the responsiveness of the intradermal injection after an IS irradiation. Results: An AS in this patient was composed of visible light shorter than 500 nm, while an IS was composed of visible light longer than 530 nm. When the IS was exposed immediately after the AS irradiation, the wheal response was inhibited. However, when the IS was exposed before the AS irradiation, the wheal response was not inhibited. An intradermal injection of her serum produced no reaction, whereas an intradermal injection of her serum pre-irradiated with visible light induced a wheal flare response. Further examination revealed that the in vivo wheal-inducing activity of her serum irradiated with visible light could be attenuated by post-IS irradiation at the injection site, while the wheal-inducing activity of her visible light-irradiated serum was not inhibited by irradiation of the activated serum with the IS. The wheal–flare response induced by compound 48/80 and histamine was not altered by IS irradiation at the site of skin tests. Conclusion: These findings indicate that photoallergens in the patient's serum that are activated by visible light irradiation are responsible for the development of her symptoms and that the IS may suppress the wheal response by inhibiting the binding of the photoallergens to mast cells, not by inactivating the photoallergens and stabilizing mast cells. [ABSTRACT FROM AUTHOR]

Background: Propofol is a widely used intravenous anesthetic although its injection pain is a common and unpleasant problem. Long-/medium-chain triglyceride (LCT/MCT) propofol has been introduced, as its low free propofol content is expected to reduce injection pain compared with LCT propofol. Target controlled infusion (TCI) differs from conventional induction in the initial infusion pattern. During induction using TCI, we investigated injection pain caused by two propofol solutions with different triglyceride compositions. Methods: Fifty patients, ASA I–II, with adequate communicative ability, were randomly assigned to two groups. TCI was conducted with Diprifusor for LCT and with BeComSim (custom-made software) for LCT/MCT. The target blood concentration was set at 4 μg/ml for both groups. At 30, 60, and 120 s after the infusion, patients were asked questions regarding the severity of pain on a 0–10 pain score. The total dose of propofol and the time required to induce anesthesia were also investigated. Results: The LCT/MCT propofol group had a larger number of pain-free patients and showed lower severity of pain than the LCT group [the number of pain-free patients being 11 and 3, respectively ( P < 0.05), and median maximum pain being 0 and 4.5, respectively ( P < 0.01)]. The dose and time required for induction were not significantly different between the groups (dose of 84 ± 27 and 80 ± 24 mg, respectively, and time of 119 ± 60 and 107 ± 55 s, respectively). Conclusion: Our study showed that the frequency and severity of pain during TCI induction with propofol could be significantly reduced using LCT/MCT propofol rather than LCT propofol. [ABSTRACT FROM AUTHOR]

Background Of the numerous adhesion molecules expressed by eosinophils, the α4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the α4β1-adhesion complex, but eosinophils also express the α4β7-integrin complex. Objective To investigate the role of α4β7, by assessing its membrane expression on eosinophils from different compartments using allergen-challenged mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the impact of β7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models. Results Evaluation of α4β7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue eosinophils revealed a down-regulation of this integrin as eosinophils migrate through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic mice had low expression of the α4β7-complex. While expression of the α4-chain remained unchanged, a significant decrease in β7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the α4β7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the α4β7-integrin. However, eosinophil trafficking into the lungs of β7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, β7-deficient mice had impaired eosinophil recruitment to the intestine. Conclusion Taken together, these results identify differential expression of the α4β7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells, but not in normal cells, and hence TRAIL has recently emerged as a novel anti-cancer agent. Adult T-cell leukaemia lymphoma (ATLL) is a neoplasm of T-lymphocyte origin aetiologically associated with human T-lymphotropic virus type 1 (HTLV-I), and is resistant to standard anti-cancer therapy. We thus characterized the sensitivity of ATLL cells to TRAIL in this study. Although most primary ATLL cells and cell lines expressed TRAIL death receptors on their surface, they showed only restricted sensitivity to TRAIL. Among the 10 ATLL cell lines examined, one was sensitive, but two had insufficient death-receptor expression, two had an unknown resistant mechanism with abrogation of the death signal upstream of caspase-8, and the remaining five showed attenuation of the signal in both extrinsic and intrinsic pathways by X-linked inhibitor of apoptosis and Bcl-2/Bcl-xL respectively. Furthermore, the level of HTLV-I tax expression was significantly correlated to TRAIL resistance. Interestingly, ATLL cells themselves expressed TRAIL on the cell surface. Constitutive production of TRAIL may offer resistance, thus allowing the development of TRAIL-resistant ATLL cells. Consequently, the resistant mechanism in ATLL cells against TRAIL was assigned to multiple factors and was not explained by a definitive single agent. [ABSTRACT FROM AUTHOR]