Use of TLR9 and TLR7/8 agonists in combination with d-galactosamine in exploring models for distinct severities of systemic inflammation relative to liver injury.

Challenges with various TLR ligands (TLRLs)in combination with D-galactosamine (GalN) in rodents may mimic diverse conditions of acute inflammation and organ failure. Here, we report that CpG (ODN1826, TLR9 agonist)/GalN induced a liver-specific injury with modest systemic effects, whereas R848 (resiquimod, TLR7/8 agonist)/GalN exhibited systemic and liver toxicity. We also observed the protective effect of Gr-1+ cells (the population containing neutrophils) against liver injury in both the R848/GalN and CpG/GalN models. In cytokine measurements, the intraperitoneal administration of antibodies showed a non-specific tolerance induction effect, which was more pronounced in the CpG/GalN than in the R848/GalN model. Cytokine analyses also suggested that the TLR9 agonist/GalN induced a limited degree of systemic inflammation compared to TLR7/8 agonist/GalN models. The relevance of this finding to the TLR9-mediated induction of stress tolerance (protective effect) in non-immune cells is discussed.

Downregulation of Ral GTPase-activating protein promotes tumor invasion and metastasis of bladder cancer.

The small GTPase Ral is known to be highly activated in several human cancers, such as bladder, colon and pancreas cancers. It is reported that activated Ral is involved in cell proliferation, migration and metastasis of bladder cancer. This protein is activated by Ral guanine nucleotide exchange factors (RalGEFs) and inactivated by Ral GTPase-activating proteins (RalGAPs), the latter of which consist of heterodimers containing a catalytic α1 or α2 subunit and a common ß subunit. In Ras-driven cancers, such as pancreas and colon cancers, constitutively active Ras mutant activates Ral through interaction with RalGEFs, which contain the Ras association domain. However, little is known with regard to the mechanism that governs aberrant activation of Ral in bladder cancer, in which Ras mutations are relatively infrequent. Here, we show that Ral was highly activated in invasive bladder cancer cells due to reduced expression of RalGAPα2, the dominant catalytic subunit in bladder, rather than increased expression of RalGEFs. Exogenous expression of wild-type RalGAPα2 in KU7 bladder cancer cells with invasive phenotype, but not mutant RalGAPα2-N1742K lacking RalGAP activity, resulted in attenuated cell migration in vitro and lung metastasis in vivo. Furthermore, genetic ablation of Ralgapa2 promoted tumor invasion in a chemically-induced murine bladder cancer model. Importantly, immunohistochemical analysis of human bladder cancer specimens revealed that lower expression of RalGAPα2 was associated with advanced clinical stage and poor survival of patients. Collectively, these results are highly indicative that attenuated expression of RalGAPα2 leads to disease progression of bladder cancer through enhancement of Ral activity.

Neural-activity mapping of memory-based dominance in the crow: neural networks integrating individual discrimination and social behaviour control.

Large-billed crows (Corvus macrorhynchos), highly social birds, form stable dominance relationships based on the memory of win/loss outcomes of first encounters and on individual discrimination. This socio-cognitive behaviour predicts the existence of neural mechanisms for integration of social behaviour control and individual discrimination. This study aimed to elucidate the neural substrates of memory-based dominance in crows. First, the formation of dominance relationships was confirmed between males in a dyadic encounter paradigm. Next, we examined whether neural activities in 22 focal nuclei of pallium and subpallium were correlated with social behaviour and stimulus familiarity after exposure to dominant/subordinate familiar individuals and unfamiliar conspecifics. Neural activity was determined by measuring expression level of the immediate-early-gene (IEG) protein Zenk. Crows displayed aggressive and/or submissive behaviour to opponents less frequently but more discriminatively in subsequent encounters, suggesting stable dominance based on memory, including win/loss outcomes of the first encounters and individual discrimination. Neural correlates of aggressive and submissive behaviour were found in limbic subpallium including septum, bed nucleus of the striae terminalis (BST), and nucleus taeniae of amygdala (TnA), but also those to familiarity factor in BST and TnA. Contrastingly, correlates of social behaviour were little in pallium and those of familiarity with exposed individuals were identified in hippocampus, medial meso-/nidopallium, and ventro-caudal nidopallium. Given the anatomical connection and neural response patterns of the focal nuclei, neural networks connecting pallium and limbic subpallium via hippocampus could be involved in the integration of individual discrimination and social behaviour control in memory-based dominance in the crow.

Dose measurement for medical staff with glass dosemeters and thermoluminescence dosemeters during 125I brachytherapy for prostate cancer.

Photoluminescence glass dosemeters (PLDs) and thermoluminescence dosemeters (TLDs) are commonly used as a personal monitoring dosemeter. PLDs and TLDs were used for surface dose monitoring of medical staff involved in (125)I brachytherapy for prostate cancer because these dosemeters have a wide dose-response linearity and high sensitivity for low photon energy. Surface doses measured with PLDs agreed with those with TLDs within ∼20 % except for a few cases. Surface doses at a surgeon's left hand and arm were higher than those at the other measuring points. A surgeon received a maximum dose of 650 µGy at the back of left hand. Surface doses to an assistant were <100 µGy. Surface doses to a nurse, a radiologist, an anaesthesiologist and a radiological technologist were <10 µGy. The occupational exposure to a surgeon could be reduced by the adjustment of fluoroscopic parameters and the use of lead gloves.

Evaluation of effective dose from a RANDO phantom in videofluorography diagnostic procedures for diagnosing dysphagia.

OBJECTIVES: Videofluorography (VF) is useful for diagnosing dysphagia; however, few reports have investigated appropriate effective doses for VF. The present study aimed to estimate the effective radiation dose in VF for diagnosis of dysphagia. METHODS: Radiation doses to tissues and organs were measured using the anthropomorphic RANDO woman phantom as an equivalent to the human body. Effective doses were estimated according to the recommendations of the International Commission on Radiological Protection (ICRP) 60 in 1990 and IRCP 103 in 2007. The tissues measured were those recommended by ICRP 60 and ICRP 103 including gonads (ovaries and testes), red bone marrow and tissues in which excessive radiation commonly causes malignant tumours including lung, thyroid gland, stomach, large intestine, liver, oesophagus, bladder, breast, bone marrow, skin, brain and salivary gland. Skin dose was also measured using thermoluminescent dosimeters. RESULTS: Using ICRP 103, the effective dose was estimated as 118.1 µSv at a tube voltage of 50 kV and 82.4 µSv at 45 kV. However, using ICRP 60 the effective dose for 1 min of VF was estimated at 62.4 µSv and 47.2 µSv under the same exposure conditions. CONCLUSIONS: Using ICRP 103, the effective dose for VF per examination at a total estimation time of 1 min was estimated as approximately 2.5-8.3 times that observed for digital panoramic radiography and 1/12 to 3 times depending on the measurement device for cone beam CT (CBCT). This value can be decreased in the future using a smaller irradiation field and decreased time for examination in VF in the future.

Radiation dose evaluation in 64-slice CT examinations with adult and paediatric anthropomorphic phantoms.

The objective of this study was to evaluate the organ dose and effective dose to patients undergoing routine adult and paediatric CT examinations with 64-slice CT scanners and to compare the doses with those from 4-, 8- and 16-multislice CT scanners. Patient doses were measured with small (<7 mm wide) silicon photodiode dosemeters (34 in total), which were implanted at various tissue and organ positions within adult and 6-year-old child anthropomorphic phantoms. Output signals from photodiode dosemeters were read on a personal computer, from which organ and effective doses were computed. For the adult phantom, organ doses (for organs within the scan range) and effective doses were 8-35 mGy and 7-18 mSv, respectively, for chest CT, and 12-33 mGy and 10-21 mSv, respectively, for abdominopelvic CT. For the paediatric phantom, organ and effective doses were 4-17 mGy and 3-7 mSv, respectively, for chest CT, and 5-14 mGy and 3-9 mSv, respectively, for abdominopelvic CT. Doses to organs at the boundaries of the scan length were higher for 64-slice CT scanners using large beam widths and/or a large pitch because of the larger extent of over-ranging. The CT dose index (CTDI(vol)), dose-length product (DLP) and the effective dose values using 64-slice CT for the adult and paediatric phantoms were the same as those obtained using 4-, 8- and 16-slice CT. Conversion factors of DLP to the effective dose by International Commission on Radiological Protection 103 were 0.024 mSvmGy(-1)cm(-1) and 0.019 mSvmGy(-1)cm(-1) for adult chest and abdominopelvic CT scans, respectively.

Carbon-ion radiotherapy: clinical aspects and related dosimetry.

The features of relativistic carbon-ion beams are attractive from the viewpoint of radiotherapy. They exhibit not only a superior physical dose distribution but also an increase in biological efficiency with depth, because energy loss of the beams increases as they penetrate the body. This paper reviews clinical aspects of carbon-beam radiotherapy using the experience at the National Institute of Radiological Sciences. The paper also outlines the dosimetry related to carbon-beam radiotherapy, including absolute dosimetry of the carbon beam, neutron measurements and radiation protection measurements.

Dose measurement on both patients and operators during neurointerventional procedures using photoluminescence glass dosimeters.

BACKGROUND AND PURPOSE: Although radiation skin injuries associated with interventional radiology have been known as a critical issue, there are few reports mentioning direct measurement of the entrance skin dose (ESD). Thus, the purpose of this study was to clarify the regional distributions of ESDs in neurointervention. MATERIALS AND METHODS: Using photoluminescence glass dosimeters (PLDs), we measured the ESDs in 32 patients with a median age of 61.5 years. Angiographic parameters, including exposure time, dose-area product (DAP), and the number of digital subtraction angiography (DSA) studies and frames, were recorded. The ESDs of operators were analyzed by the same method. RESULTS: The maximum ESD of 28 therapeutic procedures was 1.8 +/- 1.3 Gy. Although the averaged ESD on the right temporo-occipital region was higher than that in other regions, disease-specific patterns were not observed. Statistically positive correlations were found between the maximum ESD and exposure time (r = 0.5283, P = .005), DAP (r = 0.7917, P < .001), the number of DSA studies (r = 0.5636, P = .002), and the number of DSA frames (r = 0.8583, P < .001). As for operators, ESDs to the left upper extremity were significantly higher than those to other regions. However, most of the ESDs were <0.2 mGy. Lead protective garments reduced the exposure doses to approximately one half to one tenth. CONCLUSION: It was shown that the regional ESD could be measured by applying the PLD. This method should contribute to reducing the dose accumulation in patients as well as in operators.

Surface dose measurement in patients and physicians and effective dose estimation in patients during uterine artery embolisation.

Surface dose monitoring in patients and physicians during 29 uterine artery embolisation (UAE) procedures was performed using photoluminescence dosemeters and thermo-luminescence dosemeters. Organ or tissue doses were measured with an anthropomorphic phantom using UAE exposure conditions averaged from the 29 cases, and effective doses were estimated for the patient. Entrance surface dose of the patients at the maximum dose position ranged from 121.5 to 1650 mGy. Estimated doses ranged from 3.16 to 43 mGy for the ovary and from 3.8 to 51.8 mGy for the uterus. The effective dose was 1.09-14.8 mSv. Monitored doses on the body surface of physicians were relatively high in the upper arm (5.41+/-1.52 to 163+/-17.25 microGy) and the hand and fingers (0.85+/-1.18 to 222+/-16.4 microGy).

Expression and localisation of calbindin D28k in all intestinal segments of the laying hen.

1. The aim of the present study was to investigate expression and localisation of a 28-kDa calcium-binding protein (CaBP-D28k) related to active calcium (Ca) absorption, in the entire intestine of egg-laying hens. 2. Western blotting analysis showed that the entire intestine expressed CaBP-D28k to the following degree: duodenum > jejunum > caecum > ileum > colon. Immunohistochemistry showed strong CaBP-D28k localisation in enterocytes along the villus tip-crypt axis in the duodenum and in villus tips in the caecum and colon. The jejunum and ileum had moderate localisation with respect to the number of immunoreactive cells and staining intensity. 3. These results suggest that laying hens actively absorb Ca in both the large and small intestines.

Development of a portable system for checking radioactive sources using long wave radio frequency identification.

A portable system for automatically checking radioactive sources stored in lead containers at low temperatures was developed in order to prevent the discharging of orphan sources and contaminated materials from a controlled area to the general public. A radio frequency identification (RFID) system using a long wave in a frequency range of 125 kHz was composed of identification tags, a reader, a notebook computer, and software. ID tags without batteries were devised by using integrated circuits with an electrically erasable programmable read-only memory of 250 bytes and antennas. This software consisted of operating and maintenance functions. The read range of the ID tags was adjusted to around 5 cm in order to avoid accidental contamination and for discriminating the multiple sources. A water layer of 6.9 cm had no influence on communication between the ID tags and the reader. The data of the ID tags stored at +4, -20, and -80 degrees C were precisely read 4 mo later. The influence of lead was completely removed by separating the ID tags more than 1.6 cm from the lead. A reader can exactly identify the data of the ID tags within 6.0 cm at a velocity less than 9.0 cm s(-1). Performance of the software was verified using mock data. Nine lists concerning registered, disposed, and missing sources, etc., were displayed on the computer monitor and printed out. An RFID system using long waves proved to be applicable for routinely checking radioactive sources.

Characterization of a proteolytic enzyme derived from a Bacillus strain that effectively degrades prion protein.

AIMS: The purpose of this paper was to screen candidate bacterial strains for the production of proteases suitable for application to the degradation of pathogenic forms of prion protein (PrP(Sc)). This paper describes the biochemical characteristics and proteolytic activity of the isolated protease. METHODS AND RESULTS: After screening more than 200 bacterial proteases for keratinolytic activity, we identified a Bacillus stain that produced a protease exhibiting high-degradation activity against a scrapie PrP(Sc). Sequence analysis indicated that this serine-protease belonged to the Subtilisin family and had optimum pH and temperature ranges of 9-10 and 60-70 degrees C. Western blotting analysis revealed that the protease was also capable of decomposing bovine spongiform encephalopathy-infected brain homogenate. In addition, the protease was demonstrated to degrade dried PrP(Sc) that had become firmly attached to a plastic surface considerably more effectively than proteinase K or PWD-1, a previously reported keratinase. CONCLUSIONS: These results indicate that the isolated protease exhibited higher activity for PrP(Sc) degradation compared with other proteases examined. SIGNIFICANCE AND IMPACT OF THE STUDY: This protease could be used under moderate conditions for the decontamination of precision instruments that are susceptible to PrP(Sc) contamination.

Conversion factor for CT dosimetry to assess patient dose using a 256-slice CT scanner.

Recent rapid progress in CT technology has yielded equipment with large numbers of detector rows and standard computed tomography dose index (CTDI) is therefore no longer an adequate integration range. An integration range of 300 mm is necessary to accurately measure dose under a nominal beam width of 128 mm due to scattered radiation. However, such a long phantom is inconvenient to use routinely in cone-beam CT patient dose checking. To assess patient dose accurately with standard dosimetry methods, we determined a conversion factor (CF) which was calculated from the weighted dose profile integral (DPI(w)) for the 300 mm integration range with a 300 mm long CTDI phantom using a 300 mm long ionization chamber divided by that for the 100 mm integration range with a standard CTDI phantom (140 mm long) with a 100 mm long chamber. CF values increase with increasing nominal beam width and effective energy in the range from 1.5 to 2.0. CF values can also be adapted for use with other CT systems as their dose profiles are thought to be analogous to those for the 300 mm phantom and are useful in any hospital situation to assess accurate patient doses using standard dosimetry methods.

Comparison of patient doses in 256-slice CT and 16-slice CT scanners.

The 256-slice CT-scanner has been developed at the National Institute of Radiological Sciences. Nominal beam width was 128 mm in the longitudinal direction. When scanning continuously at the same position to obtain four-dimensional (4D) images, the effective dose is increased in proportion to the scan time. Our purpose in this work was to measure the dose for the 256-slice CT, to compare it with that of the 16-slice CT-scanner, and to make a preliminary assessment of dose for dynamic 3D imaging (volumetric cine imaging). Our group reported previously that the phantom length and integration range for dosimetry needed to be at least 300 mm to represent more than 90% of the line integral dose with the beam width between 20 mm and 138 mm. In order to obtain good estimates of the dose, we measured the line-integral dose over a 300 mm range in PMMA (polymethylmethacrylate) phantoms of 160 mm or 320 mm diameter and 300 mm length. Doses for both CT systems were compared for a clinical protocol. The results showed that the 256-slice CT generates a smaller dose than the 16-slice CT in all examinations. For volumetric cine imaging, we found an acceptable scan time would be 6 s to 11 s, depending on examinations, if dose must be limited to the same values as routine examinations with a conventional multidetector CT. Finally, we discussed the studies necessary to make full use of volumetric cine imaging.

Application of artificial neural network modelling to identify severely ill patients whose aminoglycoside concentrations are likely to fall below therapeutic concentrations.

OBJECTIVE: Identification of ICU patients whose concentrations are likely to fall below therapeutic concentrations using artificial neural network (ANN) modelling and individual patient physiologic data. METHOD: Data on indicators of disease severity and some physiologic data were collected from 89 ICU patients who received arbekacin (ABK) and 61 who received amikacin (AMK). Three-layer ANN modelling and multivariate logistic regression analysis were used to predict the plasma concentrations of the aminoglycosides (ABK and AMK) in the severely ill patients. RESULTS: Predictive performance analysis showed that the sensitivity and specificity of ANN modelling was superior to multivariate logistic regression analysis. For accurate modelling, a predictable range should be inferred from the data structure before the analysis. Restriction of the predictable region, based on the data structure, increased predictive performance. CONCLUSION: ANN analysis was superior to multivariate logistic regression analysis in predicting which patients would have plasma concentrations lower than the minimum therapeutic concentration. To improve predictive performance, the predictable range should be inferred from the data structure before prediction. When applying ANN modelling in clinical settings, the predictive performance and predictable region should be investigated in detail to avoid the risk of harm to severely ill patients.

Dose measurement for patients and physicians using a glass dosemeter during endovascular treatment for brain disease.

It has been reported that exposure of patients and physicians to radiation from interventional radiological procedures cannot be disregarded. Direct measurement of patient exposure used to be difficult due to possible interference by the detector with the observation of X ray images. Recently, a dosemeter system consisting of small-sized glass chips and a reader which adopts pulsed UV laser stimulation has been developed. Owing to its small size, radiolucency and physical characteristics, direct monitoring of surface dose has become feasible. Dose measurement for patients and physicians during neurointervention was done using the photoluminescence glass dosemeter system. The dose-response of the dosemeter was almost linear over a broad dose range, but its energy dependency was rather high without a filter, the use of which is recommended by the manufacturer to compensate for energy dependency. Variation of sensitivity of about 20% was observed for effective energies of 45-60 keV which are used in neurointervention. In spite of this shortcoming, the photoluminescence glass dosemeter system was judged to be a convenient means for monitoring dose during neurointervention.

In vivo thyroid 131I monitoring system using an imaging plate.

The counting efficiency and detection limit of an in vivo thyroid 131I monitoring system using an imaging plate (IP) were estimated using an anthropomorphic thyroid neck phantom. The counting efficiency of the IP system was approximately constant for thyroid volumes between 11.7 and 20 ml and neck diameters between 10 and 14 cm. The detection limits were distributed from 288 to 451 Bq depending on the combination of neck diameter, thyroid volume and tissue thickness. The IP monitoring system gives a reliable counting efficiency notwithstanding the variation of thyroid volume and neck diameter. The IP system is a new option for thyroid 131I monitoring.

[Evaluation of central retinal sensitivity after vitrectomy with removal of choroidal neovascular membrane for age-related macular degeneration].

PURPOSE: To evaluate retinal sensitivity in patients with age-related macular degeneration (AMD) before and after surgery. METHODS: Seven consecutive patients with AMD underwent vitrectomy with removal of choroidal neovascular membrane(CNV). Static microperimetry using a scanning laser ophthalmoscope(SLO) was performed before and after surgery. Central dense scotoma size was measured. RESULTS: Retinal sensitivity improved in all cases. Mean size of the central dense scotoma was decreased by 42%(range 14-62%). CONCLUSION: The results suggest that vitrectomy with removal of CNV can improve the central retinal sensitivity.

The trimannosyl cores of N-glycans are important for the procoagulant protease-inhibitory activity of urinary protein C inhibitor.

We investigated the relationship between the procoagulant protease-inhibitory activity and the N-glycan structures in urinary protein C inhibitor (uPCI) by sequential exoglycosidase digestions based on the N-glycan structures elucidated in this report. uPCI was glycosylated on the three potential N-glycosylation sites, asparagines 230, 243 and 319 (N230, N243 and N319) in the molecule and had four biantennary complex type sugar chains. The inhibitory activities of uPCI toward thrombin and plasma kallikrein were little changed by the sequential removal of N-acetylneuraminic acid and galactose residues from the termini and N-acetylglucosamine residues from the branches of the N-glycans. However, the inhibitory activities were markedly decreased by further removing alpha-mannose residues from the trimannosyl cores of the N-glycans. These results suggest that the trimannosyl cores of N-glycans are important for uPCI to inhibit the procoagulant protease.

Paediatric absorbed doses from rotational panoramic radiography.

OBJECTIVES: To determine the paediatric doses in rotational panoramic radiography with film/screen and photostimulable phosphor receptors. STUDY DESIGN: A paediatric anthropomorphic head and neck phantom was used. Absorbed doses were measured for two panoramic systems, the Orthophos (Sirona Dental Systems, Bensheim, Germany) and the PM 2002 CC (Planmeca Oy, Helsinki, Finland), with and without programmable child settings, using both screen/film and photostimulable phosphor receptors. RESULTS: Absorbed doses to the eye ranged from 5 to 24 micro Gy. Doses to the dental arches with the Orthophos unit ranged from 50 to 555 micro Gy with the adult and from 27 to 436 micro Gy with the child program; using the PM 2002 CC unit, doses ranged from 56 to 1040 micro Gy using the adult settings, and from 60 to 890 micro Gy with the paediatric settings. The paediatric exposure settings reduced doses at most locations for both panoramic systems. The highest doses were measured near the rotational axes of the X-ray beam. Paediatric settings with the Orthophos P10 resulted in the dose reduction more than 50% to the thyroid but not with the PM 2002 CC. When lower kVcp or mA settings were used, absorbed doses were effectively reduced for all combinations of machines, programs and detectors. CONCLUSIONS: Specific program settings for children reduced the absorbed doses from panoramic radiography irrespective of the machine or receptor used.