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36Cl is a long-lived radioisotope, which, because it is created mainly through a thermal neutron capture process by 35Cl, may be used to estimate the strength of thermal neutron flux from A-bombs or nuclear fuel facilities. The 36Cl contents in granite samples from the Hiroshima A-bomb site have been measured by the Cl-36 accelerator mass spectrometry (AMS) system at the University of Tsukuba. The 36Cl/Cl ratios deduced from the 36Cl measurements are compared with independent evaluations based upon the Dosimetry System 2002 (DS02) of the radiation doses received by the survivors of the Hiroshima A-bomb. The measurements corresponded well up to a ground distance of 1100 m, which proved the effectiveness of the DS02. Measurements of the 36Cl/Cl ratio of unexposed granite samples were 1.92 × 10-13 on average, and because the measured ratio for samples at a ground distance of 1163 m was 2.50 × 10-13, the assessment of the neutron flux by the 36Cl measurements of samples beyond about 1100 m is not practical. This limitation arises from the inability to distinguish bomb-induced Cl-36 from activation due to ambient sources. [Copyright &y& Elsevier]

Abstract: We have measured the 36Cl/Cl ratio of uncultivated surface soil samples collected from 11 areas distributed throughout Japan to determine the undisturbed value of the ratio. The ratio was found to be on the order of 10−13 except for the Tokai-mura area, where four research reactors, two commercial nuclear power plants and a nuclear fuel reprocessing plant have been operated. The observed ratio in the Tokai-mura area was higher than 10−12. Notably, soil samples collected from a site of commercial BWR nuclear power plants in Fukushima prefecture showed no significant increase in 36Cl/Cl ratio. The 36Cl/Cl ratio depth profiles of soil samples collected at both of Makabe-town and Tokai-mura were also measured. Since Makabe-town is located about 50km apart from Tokai-mura, we do not expect it to be affected by the nuclear facilities. No large variations were observed in the Makabe depth profile; the measured ratios ranged from ∼3 to ∼5×10−13. The result obtained for Tokai-mura is significantly different in that from the surface to about 80cm depth, the measured ratios, ∼10−12, are much higher than any at Makabe. At depth below 80cm, the Tokai-mura ratios are lower and become indistinguishable from those at Makabe. The 36Cl/Cl ratio in unaffected areas of Japan is estimated to be 3–4×10−13. [Copyright &y& Elsevier]

Background: The high prevalence of underweight in young women has become a serious health problem in Japan. When and how young women reach a low body mass index (BMI) has not been clarified., Aim: To clarify the characteristics of BMI standard deviation scores (BMI SDS) trajectory of young Japanese women with underweight., Subjects and Methods: A total of 601 Japanese female university students aged 20 years were classified into underweight and healthy weight groups. Their school health check-up data were available from the ages of 6 to 20 years. We evaluated the estimated mean values of BMI SDS at each age and differences in BMI SDS (ΔBMI SDS) from 6 years to each age using a mixed-effects model and compared between the two groups at each age., Results: In the underweight group, the BMI SDS at every age (-1.67 to -0.91) and the ΔBMI SDS after 16 years of age (-0.76 to -0.38) were significantly lower than those in the healthy weight group (-0.41 to -0.13, -0.07 to 0.04), respectively., Conclusion: Young Japanese women with underweight have at least two characteristics of BMI SDS trajectory: being constitutionally underweight and shifting their weight status from baseline towards underweight in their late teens.

Objectives: The objective of the study was to analyze the outcomes of patients with renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) over a 40-year span., Methods: We retrospectively evaluated data of patients with ESRD-RCC diagnosed between 1979 and 2020 at two institutions. We assessed changes in stage, surgical approaches, and cancer-specific survival (CSS) following nephrectomy according to era between ESRD-RCC and sporadic RCC. Furthermore, perioperative outcomes in patients with ESRD-RCC were compared between laparoscopic and open surgery., Results: Patients with ESRD-RCC (n = 549) were diagnosed at an earlier stage (p = 0.0276), and the ratio of laparoscopic nephrectomy was increased (p < 0.0001) according to eras. Since 2000 (i.e., after implementation of laparoscopic nephrectomy), patients with ESRD-RCC (n = 305) had significantly shorter CSS (p = 0.0063) after nephrectomy than sporadic RCC (n = 2732). After adjustment by multivariate analysis and propensity score matching, ESRD status was independently associated with shorter CSS (p = 0.0055 and p = 0.0473, respectively). Improved CSS in sporadic RCC (p < 0.0001), but not ESRD-RCC (p = 0.904), according to era contributed to this difference. Laparoscopic nephrectomy showed favorable outcomes, including shorter surgery time, lower estimated bleeding volumes, transfusion rates, and readmission rates, and shorter postoperative hospitalization than open nephrectomy (p < 0.05)., Conclusions: Advances in diagnostic and treatment modalities potentially enable early diagnosis and minimally invasive surgery for patients with ESRD-RCC. As ESRD-RCC may not present indolently, careful post-operative monitoring is needed., (© 2023 The Japanese Urological Association.)

Background: Spinal cord stimulation (SCS) is one of the neuromodulation therapies for chronic neuropathic pain. The conventional paresthesia-based SCS involves the application of tonic stimulation that induces a sense of paresthesia. Recently, new SCS stimulation patterns without paresthesia have been developed. Differential target multiplexed (DTM) stimulation and fast-acting subperception therapy (FAST) stimulation are the latest paresthesia-free SCS patterns., Methods: A single-center, open-label, crossover, randomized clinical trial to investigate the superiority of SCS using the latest new stimulation patterns over conventional tonic stimulation for neuropathic pain is planned. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). In the SCS trial, participants will be randomly assigned to 4 groups receiving stimulation, including tonic, DTM, and FAST. Each stimulation will then be performed for 2 days, and a visual analog scale (VAS) for pain will be evaluated before and after each stimulation pattern. A stimulation-off period for 1 day is set between each stimulation pattern to wash out the residual previous stimulation effects. Pain improvement is defined as more than 33% reduction in the pain VAS. The primary analysis will compare pain improvement between the new stimulation patterns and the conventional tonic stimulation pattern in the SCS trial. The secondary outcomes will be evaluated as follows: (1) the relationships between causative disease and improvement rate by each stimulation pattern; (2) comparison of pain improvement between the DTM and FAST stimulation patterns in all cases and by causative disease; (3) changes in assessment items preoperatively to 24 months after the implantation; (4) preoperative factors associated with long-term effects defined as continuing for more than 12 months; and (5) adverse events related to this study 3 months after the implantation., Discussion: This study aims to clarify the effectiveness of the latest new stimulation patterns compared to the conventional tonic stimulation. In addition, which stimulation pattern is most effective for which kind of causative disease will be clarified., Trial Registration: Japan Registry of Clinical Trials (jRCT) 1,042,220,094. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is an approved member of the Primary Registry Network of WHO ICTRP., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To compare the utility of preoperative immunonutritional parameter measures for predicting postoperative mortality following palliative surgery (PS) for malignant bowel obstruction (MBO) in patients with late-stage cancer., Methods: The subjects of this retrospective study were 83 late-stage cancer patients with MBO who underwent PS between January, 2005 and December, 2018, at a single institution in Japan. We compared the modified Glasgow prognostic score (mGPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for predicting postoperative mortality following PS in these patients., Results: The most prevalent cancer in the patients who underwent PS was colorectal cancer (54.2%), followed by gastric cancer (24.1%). Postoperative complications of Clavien-Dindo classification grade ≥ 2 developed in 32 (38.6%) patients and stoma-related complications developed in 26 (31.3%) patients. There were 15 (18.1%) patients with 60-day mortality, 22 (26.5%) with 90-day mortality, and 4 (4.8%) with 30-day mortality. Multivariable analysis identified only mGPS as being associated with 60-day mortality (odds ratio, 9.387; 95% confidence interval, 0.001-4.478; p = 0.049). The overall survival of patients with a mGPS score of 2 was significantly worse than that of those with a mGPS score of < 2 (p = 0.013)., Conclusions: These results suggest that the mGPS is a good predictor not only of 60-day mortality, but also of the overall survival of patients with late-stage cancer and MBO., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: In rectal cancer (RC) surgery, the complexity of total mesorectal excision (TME) in laparoscopic sphincter-preserving surgery (lap-SPS) for RC near the anus has been a critical issue. Recently, technical assistance via the anus for complete TME has been receiving attention. This study aimed at clarifying the transanal down-to-up dissection viability for achieving TME in lap-SPS for RC near the anus., Methods: We evaluated surgical and oncological outcomes of a total of 123 consecutive patients undergoing either a transanal rectal dissection (TARD) under direct vision mobilizing the most difficult portion of TME via the anus or the transanal TME by using an endoscopic system (TaTME) for achieving TME in lap-SPS for RC near the anus between January 2006 and February 2021., Results: A total of 123 consecutive patients (83 men) with a median age of 66 years (range 33-86 years) were included. TARD and TaTME were performed for 50 (40.7%) and for 73 (59.3%) patients, respectively. Preoperative treatment was performed for 40 (32.5%) patients, resulting in a complete pathological response in 5 (12.5%) patients. Intersphincteric resection was performed significantly more in the TARD group (p<0.001). Although the TaTME group needed a longer operative time at the transanal portion (p<0.001), the median blood loss was lower (p<0.001). Postoperative complications with the Clavien-Dindo classification grade ≧2 developed in 52 (42.3%) patients. Urinary dysfunction and stoma-related complications were found most frequently. More patients needing medication for urinary dysfunction were found in the TARD group, but a significant difference was not observed (10.0% vs. 6.8%, p=0.526). The quality of TME was good for almost all patients. Recurrence developed in 18 (14.6%) patients. The 5-year overall survival (OS) and relapse-free survival (RFS) rates in 123 patients were 95.8% and 88.8%, respectively. The 5-year OS and RFS between the two groups were comparable., Conclusions: Our data suggested that a transanal down-to-up dissection of the distal rectum might be a viable approach in lap-SPS for RC near the anus. Further studies are needed to examine the differences between TARD and TaTME., (© 2022. The Author(s).)

Aim: During the coronavirus disease 2019 pandemic, the governments of many countries responded to high levels of infection with lockdowns. As a result, some children were reported to experience weight gain. The aim of the present study was to examine the impact of school closures on body mass index (BMI) in Japanese children., Methods: This was a retrospective study of students enrolled in the participating schools (6- to 11-year-old elementary school students and 12- to 14-year-old junior high school students) between 2015 and 2020. Using school health check-up data, annual changes in the BMI standard deviation score (ΔBMI-SDS) were calculated. We compared ΔBMI-SDS in 2019-2020 with the corresponding control years., Results: 19 565 children with complete data were included in the analysis. Median ΔBMI-SDS in 2019-2020 were 0.24-0.35 in elementary school boys, 0.10-0.13 in junior high school boys, -0.02 to 0.15 in elementary school girls and -0.14 to -0.10 in junior high school girls. In comparison with every control year, ΔBMI-SDS in 2019-2020 were significantly higher in elementary school boys (control years: -0.07 to 0.14) and junior high school boys (control years: -0.04 to 0.06), and significantly lower in junior high school girls (control years: -0.06 to 0.09)., Conclusion: BMI-SDS increased significantly in elementary and junior high school boys, but decreased significantly in junior high school girls. The pandemic appears to have had an impact on Japanese children that was different from other countries., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Purpose: The choice of surgical procedure for rectal prolapse (RP) is challenging because of the high recurrence and morbidity rates. We aimed to clarify whether laparoscopic suture rectopexy (lap-rectopexy) is suitable for Japanese patients with recurrent RP., Methods: We retrospectively evaluated 77 recurrent RP patients who had been treated on average 1.5 times between June 2008 and April 2016. Forty-one patients underwent lap-rectopexy and 36 underwent perineal procedures. We compared surgical outcomes and recurrence rate following surgery between the two groups. The multivariable logistic regression analysis was performed to determine risk factors of recurrent RP., Results: In patients' characteristics, significant differences were observed in the type of anesthesia (p < 0.01) and length of recurrent RP (p = 0.030). The mean operative time was significantly longer in the lap-rectopexy group (p < 0.001). Blood loss, length of hospitalization, and postoperative complications were similar. The recurrence rate was significantly lower in the lap-rectopexy group (17.1% vs. 38.9%, p = 0.032). Multivariate analysis showed that only the laparoscopic approach was significantly associated with a low recurrence following surgery (odds ratio 0.273, 95% CI - 2.568 to - 0.032)., Conclusion: Lap-rectopexy is recommended for recurrent RP because its low recurrence rate and safety profile are similar to those of perineal procedures.

Tetramine (tetramethyl ammonium ion), a neurotoxin, is present at high levels in the salivary glands of buccinid gastropods and is responsible for human intoxication due to consumption of the gastropods. We used LC-MS/MS to examine the tetramine contents of salivary glands from 16 species of carnivorous gastropods collected along Japanese coasts. Tetramine was detected in all specimens except for Babylonia japonica. High levels of tetramine were detected in whelks, Neptunea lamellosa (1,380-9,410 μg/g of salivary gland) and N. purpurea (1,190-7,400 μg/g of salivary gland). Although consumption of N. lamellosa is well-known cause of foodborne tetramine poisoning, it was newly discovered that N. purpurea has tetramine. In addition, we found 7 other species of gastropods containing tetramine: Siphonalia cassidariaeformis (117-135 μg/g), S. fusoides (204 μg/g), Buccinum inclytum (2.94-3.40 μg/g), and B. aniwanum (0.700 μg/g) of the family Buccinidae, and Fusinus perplexus (397 μg/g), F. ferrugineus (105 μg/g), and F. forceps salisburyi (67.5 μg/g) of the family Fasciolariidae. The present study, together with previous studies, shows that gastropods with salivary glands containing more than 1,000 μg tetramine/g of salivary gland, including the genus Neptunea as well as Fusitriton oregonesis and Hemifusus tuba, carry a high risk of tetramine poisoning, and their salivary glands should be removed before consumption to prevent food poisoning.

Marine pufferfish Takifugu exascurus is not approved for human consumption due to the lack of information on its toxicity. To clarify the toxicity of T. exascurus, ten live specimens were collected from the Sea of Kumano, Japan, and the toxicity and tetrodotoxin (TTX) concentration were determined using mouse bioassay and high performance liquid chromatography-fluorescence detection (HPLC-FLD), respectively. Toxicity was observed in the skin, liver, and ovaries, but the testes and muscle were non-toxic (<10 MU/g). On the other hand, HPLC-FLD revealed that TTX was detected in the muscle in two of the 10 specimens (1.4 and 1.5 MU/g). Based on the results, TTX is the main toxic component contributing to toxicity in T. exascurus.

Objectives: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC., Methods: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features., Results: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years., Conclusion: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC., Patients and Methods: This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed., Results: Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016)., Conclusion: Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We describe a new wound management technique using a soft dressing material to stabilize the areola skin graft and protect the nipple after nipple-areola reconstruction at the final stage of breast reconstruction. We introduced a center-fenestrated multilayered hydrocellular polyurethane foam dressing material that provides adequate pressure and retains a moist environment for a smooth skin graft "take." Moreover, the reconstructed nipple can be monitored at any time through the fenestrated window for adequate blood circulation. Altogether, this simple and inexpensive wound dressing technique improves the clinical outcome. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: Chronic total occlusion (CTO) lesions are a challenging issue. When dealing with complex CTO lesions in patients undergoing percutaneous coronary intervention (PCI), it is important to evaluate not only the CTO lesion itself but also atherosclerotic lesions of the whole coronary artery tree. The utility of the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Trial) score in patients with CTO undergoing PCI is unclear., Methods: This retrospective study included 304 consecutive patients with CTO lesions who underwent PCI. Primary endpoints were procedural failure and major adverse cardiac events (MACE) within 30 days. The SYNTAX and J-CTO (Multicenter CTO Registry in Japan) scores were assessed before the procedures, and patients were divided into two groups according to SYNTAX criteria: high (> 22; n = 158) and low (≤ 22; n = 146) SYNTAX scores., Results: Procedural success was achieved in 252 patients (82.9 %). Patients with a high SYNTAX score had significantly lower procedural success than those with a low SYNTAX score (74.7 % versus 91.8 %, p < 0.0001). There were 13 MACE (8.2 %) in patients with high SYNTAX scores and two MACE (1.4 %) in those with low scores. The SYNTAX and J-CTO scores had odds ratios of 3.33 (95 %CI, 1.44-7.74) and 3.64 (95 %CI, 1.24-10.66) for procedural failure. A higher SYNTAX score (> 22) was also an independent predictor of 30-day MACE after PCI (odds ratio = 4.80, 95 %Cl 1.03-22.42)., Conclusion: The SYNTAX score is predictive of procedural failure, as is the J-CTO score. Furthermore, a higher SYNTAX score is strongly associated with an increased risk of 30-day MACE. The SYNTAX score is useful for clinical decision making when treating patients with complex CTO lesions.

Purpose: To determine the predictive value of skin perfusion pressure (SPP) for wound healing after endovascular therapy (EVT)., Methods: Between May 2004 and March 2011, 113 consecutive patients (84 men; mean age 71.5±12.5 years) with CLI (123 limbs) underwent successful balloon angioplasty ± stenting (flow from >1 vessel to the foot without bypass) and were physically able to undergo SPP measurement before and within 48 hours after EVT. The status of wound healing was recorded over a mean follow-up of 17.4±12.4 months., Results: The wound healing rate was 78.9% (97 limbs of 89 patients). SPP values after EVT were significantly higher in these patients than in the 24 patients (26 limbs) without wound healing (44.2±15.6 mmHg vs. 27.5±10.4 mmHg, p<0.001). Receiver operating characteristics analysis of SPP after EVT to predict wound healing had an area under the curve of 0.81 (95% CI 0.723 to 0.899, p<0.001). The optimal cutoff for predicting wound healing was 30 mmHg, with a sensitivity of 81.4% and a specificity of 69.2%. Binary logistic regression analysis demonstrated SPP after EVT to be an independent predictor of wound healing (p<0.001). The probability of wound healing with SPP values >30 mmHg, 40 mmHg, and 50 mmHg were 69.8%, 86.3%, and 94.5%, respectively., Conclusion: SPP after EVT is an independent predictor of wound healing in patients with CLI. In our study, an SPP value of 30 mmHg was shown to be the best cutoff for prediction of wound healing after EVT.

The purpose of this study was to evaluate whether the carotid intima-media thickness (cIMT) and intima-media thickness variability (IMTV) along the artery are correlated to the ankle-brachial index (ABI) in Japanese coronary artery disease patients. Five hundred consecutive patients (312 males; median age 69 ± 11 years) who underwent carotid ultrasonography and first coronary angiography were prospectively analyzed. By using automated software (AtheroEdge™, AtheroPoint, Roseville, CA, USA), we obtained the cIMT and IMTV. Pearson correlation analysis was performed to calculate the association between ABI, automatically measured cIMT, automatically measured IMTV, and the SYNTAX score. The mean cIMT was 0.881 ± 0.334 mm and the mean IMTV was 0.141 ± 0.112. IMTV was negatively and significantly correlated to ABI (ρ = -0.147; p = 0.001), whereas cIMT was not (ρ = -0.075; p = 0.097). IMTV and cIMT had the same significant correlation with the SYNTAX score. When we considered patients with a higher risk factor (ABI ≤ 0.9), we found higher values of IMTV and the SYNTAX score, but not higher values of cIMT. Logistic regression analysis showed that IMTV was independently associated with the complexity of the coronary artery disease (as assessed by the SYNTAX score). In conclusion, we show that IMTV automatically measured using AtheroEdge™ was correlated with ABI, whereas cIMT was not. IMTV could be integrated with cIMT measurement to improve the assessment of cardiovascular disease.

Pufferfish accumulate tetrodotoxin (TTX) at high levels in liver and ovary through the food chain. However, the mechanisms underlying TTX toxification in pufferfish have been poorly understood. In order to search gene candidates involved in TTX accumulation in the torafugu pufferfish Takifugu rubripes, a custom 4x44k oligonucleotide microarray slide was designed by the Agilent eArray program using oligonucleotide probes of 60 bp in length referring to 42,724 predicted transcripts in the publicly available Fugu genome database. DNA microarray analysis was performed with total RNA samples from the livers of two toxic wild specimens in comparison with those from a nontoxic wild specimen and two nontoxic cultured specimens. The mRNA levels of 1108 transcripts were more than 2-fold higher in the toxic specimens than in the nontoxic specimens. The levels of 613 transcripts were remarkably high, and 16 transcripts encoded by 9 genes were up-regulated more than 10-fold. These genes included those encoding forming structural filaments (keratins) and those related to vitamin D metabolism and immunity. It was also noted that the levels of the transcripts encoding serpin peptidase inhibitor clade C member 1, coagulation factor X precursor, complement C2, C3, C5, C8 precursors, and interleukin-6 receptor were high in the toxic liver samples., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Although copy number variations (CNVs) are expected to affect various diseases, little is known about the association between CNVs and breast cancer susceptibility. Therefore, we investigated this relation. Array comparative genomic hybridization was performed to search for candidate CNVs related to breast cancer susceptibility. Subsequent quantitative real-time polymerase chain reaction was carried out for confirmation. We found seven CNV markers associated with breast cancer risk. The means of the relative copy numbers of patients with a history of breast cancer and women in the control group were 0.8 and 1.8 for Hs06535529&#95;cn on 1p36.12 (P < 0.0001), 2.9 and 2.2 for Hs03103056&#95;cn on 3q26.1 (P < 0.0001), 1.2 and 1.8 for Hs03899300&#95;cn on 15q26.3 (P < 0.0001), 1.0 and 1.5 for Hs03908783&#95;cn on 15q26.3 (P < 0.0001), and 1.1 and 1.7 for Hs03898338&#95;cn on 15q26.3 (P < 0.0001), respectively. Interestingly, nine or more copies of Hs04093415&#95;cn on 22q12.3 were found only in 8/193 (4.1 %) patients with a history of breast cancer and in none of the controls (P = 0.0081). Similarly, 12 or more copies of Hs040908898&#95;cn on 22q12.3 were found only in 7/193 (3.6 %) patients with a history of breast cancer and in none of the controls (P = 0.016). A combination of two CNVs resulted in 80.3 % sensitivity, 80.6 % specificity, 82.4 % positive predictive value, and 78.3 % negative predictive value for the prediction of breast cancer susceptibility. These findings may lead to a new means of risk assessment for breast cancer. Confirmatory studies using independent data sets are needed to support our findings.

Essential parameters for the applications of (36)Cl as a tracer in groundwater studies include the initial (36)Cl/Cl ratio, at the time of recharge, and/or the natural background deposition flux of (36)Cl in the recharge area. To facilitate the hydrological use of (36)Cl in central Japan, this study aimed to obtain a precise estimate of the long-term average local (36)Cl flux and to characterize its seasonal variability. The (36)Cl in precipitation was continuously monitored in Tsukuba, central Japan over a period of >5 years. The (36)Cl flux showed a clear seasonal variation with an annual peak during the spring, which was attributed to the seasonal variability of tropopause height. The long-term average (36)Cl flux (32±2atoms m(-2)s(-1)), estimated from the measured data, was consistent with the prediction from the (36)Cl latitudinal fallout model scaled using the global mean production rate of 20atoms m(-2)s(-1). The initial (36)Cl/Cl ratio was estimated to be (41±6)×10(-15), which is similar to that of pre-bomb groundwater in the Tsukuba Upland. An observation period covering an 11-year solar cycle would yield more accurate estimates of the values, given the increased (36)Cl flux during the solar minimum., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Salmonid fish is one of the allergenic items that are recommended to be labeled in the Japanese allergen-labeling system. This study develops a salmonid-specific polymerase chain reaction (PCR) method. A new primer pair, SKE-F/SKE-R, was designed to specifically detect the salmonid fish gene encoding mitochondrial DNA cytochrome b. Genomic DNAs extracted from 58 kinds of seafood and 11 kinds of processed food were individually subjected to PCR by using the primer pair, and a salmonid-specific fragment of 212 bp was only amplified in the salmonid samples and salmonid-containing processed foods. The detection limit of the PCR method was as low as 0.02 fg/µL of salmonid fish DNA (corresponding to 10 copies). There is no ELISA method for salmonid fish, making our PCR method the only reliable measure for detecting salmonid fish in processed foods.

Food poisoning due to ingestion of a puffer fish occurred in Nagasaki Prefecture, Japan, in October 2008, causing neurotoxic symptoms similar to those of tetrodotoxin (TTX) poisoning. In the present study, we identified the species, toxicity, and toxins using the remaining samples of the causative puffer fish. The puffer fish was identified as smooth-backed blowfish Lagocephalus inermis by nucleotide sequence analysis of the 16S rRNA and cytochrome b gene fragments of muscle mitochondrial DNA. The residual liver sample showed toxicity as high as 1,230 mouse unit (MU)/g by bioassay and TTX was detected by liquid chromatography/mass spectrometry analysis. We therefore concluded that the food poisoning was due to TTX caused by consumption of the toxic liver of L. inermis. This is the first report that the liver of L. inermis caught in Japanese waters is strongly toxic, with levels exceeding 1,000 MU/g. In this context, we re-examined the toxicity of L. inermis collected off the coast of Japan. Of 13 specimens assayed, 12 were toxic, although the toxicity varied markedly among individuals and tissues. Because the intestine and ovary of L. inermis have been considered non-toxic, it is particularly noteworthy that these organs were determined to be toxic, with a maximum toxicity of 43.6 MU/g and 10.0 MU/g, respectively. Furthermore, kidney, gallbladder, and spleen, whose toxicity has been unknown, were frequently found to be weakly toxic with levels ranging from 10 to 99 MU/g. Therefore, further study is needed to re-examine the toxicity of smooth-backed blowfish L. inermis in the coastal waters of Japan.

We propose a methodology for estimating the residence time of groundwater based on bomb-produced (36)Cl. Water samples were collected from 28 springs and 2 flowing wells located around Mt. Fuji, Central Japan. (36)Cl/Cl ratios in the water samples, determined by accelerator mass spectrometry (AMS), were between 43 × 10(-15) and 412 × 10(-15). A reference time series of the above-background (i.e., bomb-derived) (36)Cl concentration was constructed by linearly scaling the background-corrected Dye-3 data according to the estimated total bomb-produced (36)Cl fallout in the Mt. Fuji area. Assuming piston flow transport, estimates of residence time were obtained by comparing the measured bomb-derived (36)Cl concentrations in spring water with the reference curve. The distribution of (36)Cl-based residence times is basically consistent with that of tritium-based estimates calculated from data presented in previous studies, although the estimated residence times differ between the two tracers. This discrepancy may reflect chlorine recycling via vegetation or the relatively small change in fallout rate, approximately since 1975, which would give rise to large uncertainties in (36)Cl-based estimates of recharge for the period, approximately since 1975. Given the estimated ages for groundwater from flowing wells, dating based on a (36)Cl bomb pulse may be more reliable and sensitive for groundwater recharged before 1975, back as far as the mid-1950s., (© 2011, The Author(s). Ground Water © 2011, National Ground Water Association.)

From September 2007 to January 2008, a total of 66 specimens of 7 gastropod species, Nassarius (Alectrion) glans (n=22), Bufonaria rana (n=11), Ficus subintermedia (n=10), Stellaria (Onustus) exutus (n=8), Tonna luteostoma (n=7), Hemifusus tuba (n=4) and Semicassis bisulcata persimilis (n=4), were collected from Tachibana Bay, Nagasaki Prefecture, Japan, and their toxicity was determined by mouse bioassay. Among the gastropods tested, all N. glans specimens were toxic, whereas no other species showed toxicity of more than 5 MU/g. The toxicity scores of N. glans were very high; 48-2,730 MU/g(775+/-615 MU/g)in the muscle, and 16-10,200 MU/g(1,490+/-2,530 MU/g)in the viscera, including digestive gland. Interestingly, toxin was localized in the muscle in 13 of 22 specimens, where the total toxicity of the muscle (725-9,860 MU/individual) was 5.9-110 times higher than that of the viscera. LC/MS analysis demonstrated that the toxin of N. glans consisted mainly of TTX, which accounting for about 60-65% of the total toxicity. As for the remaining toxicity, participation of 11-oxoTTX was suggested. No paralytic shellfish poison was detected in HPLC-FLD analysis.

In the process of developing a new dosimetry system for atomic bomb survivors in Hiroshima and Nagasaki (DS02), an intercomparison study between (152)Eu and (36)Cl measurements was proposed, to reconcile the discrepancy previously observed in the Hiroshima data between measurements and calculations of thermal neutron activation products. Nine granite samples, exposed to the atomic-bomb radiation in Hiroshima within 1,200 m of the hypocenter, as well as mixed standard solutions containing known amounts of europium and chlorine that were neutron-activated by a (252)Cf source, were used for the intercomparison. Gamma-ray spectrometry for (152)Eu was carried out with ultra low-background Ge detectors at the Ogoya Underground Laboratory, Kanazawa University, while three laboratories participated in the (36)Cl measurement using accelerator mass spectrometry (AMS): The Technical University of Munich, Germany, the Lawrence Livermore National Laboratory, USA and the University of Tsukuba, Japan. Measured values for the mixed standard solutions showed good agreement among the participant laboratories. They also agreed well with activation calculations, using the neutron fluences monitored during the (252)Cf irradiation, and the corresponding activation cross-sections taken from the JENDL-3.3 library. The measured-to-calculated ratios obtained were 1.02 for (152)Eu and 0.91-1.02 for (36)Cl, respectively. Similarly, the results of the granite intercomparison indicated good agreement with the DS02 calculation for these samples. An average measured-to-calculated ratio of 0.98 was obtained for all granite intercomparison measurements. The so-called neutron discrepancy that was previously observed and that which included increasing measured-to-calculated ratios for thermal neutron activation products for increasing distances beyond 1,000 m from the hypocenter was not seen in the results of the intercomparison study. The previously claimed discrepancy could be explained by insufficient understanding of the measured data.

About 10-40% of testicular germ cell tumours (TGCTs) have been reported to have activating c-kit gene mutations. A European study group has reported that most bilateral TGCTs from European patients have c-kit mutations at codon 816, although few unilateral cases harbour the mutations. This implies that the presence of a c-kit mutation in a unilateral TGCT predicts the development of TGCT in the contralateral testis (bilateral disease). However, since little is known about on c-kit gene mutational frequencies in bilateral TGCTs from patients of Asian origin, we examined 12 bilateral TGCTs from seven Japanese patients, along with 39 unilateral TGCTs from Japanese patients, for the presence of c-kit mutations. We analyzed c-kit exons 11 and 17 by PCR followed by direct sequencing, and also analyzed the hotspot mutations at codon 816 by loop-hybrid mobility shift assay, a sensitive PCR-based method. We found c-kit mutations in seven of 39 (18%) unilateral TGCTs: two of the seven mutations were in exon 11 and the others, including four point mutations at codon 816, were in exon 17. No mutations, however, were observed in bilateral TGCTs. Thus, the presence of c-kit gene mutations in TGCTs may not be associated with bilateral diseases, at least in Japan.

To clarify the influences of ethnic and regional characteristics, and differences in perception on the cedrol effect on autonomic nerve activity, we compared women in their 20s-40s in Norway, Thailand, and Japan. A questionnaire survey of sense of stress and sleep conditions was performed at the same time. The degree of perceived stress, using a 30-item checklist, was highest in Japanese women. The mean stress score exceeded 5.0 in Japanese women, significantly higher than in Thai women (p<0.05) and Norwegian women (p<0.01). Sleeping time was shortest in Japanese women in all generations among the three countries. As the index of autonomic nervous activity, the miosis rate (ratio of pupil-diameter variation after light stimulus to initial pupil diameter) in pupillary light reflex was measured before and after cedrol inhalation. The miosis rate significantly increased after cedrol exposure compared to that before exposure in all three countries, suggesting that the parasympathetic nervous system became dominant. These findings suggested that cedrol produces a sedative effect in people of the three countries despite differences in the ethnic and living environments.

Purpose: Collecting duct carcinoma, a rare type of renal cell carcinoma, remains poorly understood. To analyze the nature of collecting duct carcinoma a retrospective survey was performed in Japan., Materials and Methods: This survey was done from August 2001 to April 2003. A total of 281 institutions throughout Japan were requested to document all cases of collecting duct carcinoma. All pertinent clinical information was compiled, including patient age, sex, mode of presentation, evaluation modality, preoperative laboratory data, surgery type, macroscopic and microscopic findings, and survival data. Two urological pathologists reviewed microscopic slides of all tumor specimens to confirm collecting duct carcinoma., Results: Two pathologists confirmed collecting duct carcinoma in 81 of the 120 cases documented as collecting duct carcinoma. Mean patient age was 58.2 years and males comprised 71.6% of all patients. The mode of presentation was classified as symptomatic in 65.4% of cases, incidental in 24.7% and not available in 9.9%. Regional lymph node metastasis was histologically detected in 44.2% of patients who underwent lymph node dissection, while 32.1% of the population had distant metastasis at presentation. Although postoperative adjuvant therapy against metastasis or recurrence was performed in 25 patients, no obvious responses were identified except in 1 with lung metastases, who showed a partial response to combined gemcitabine and carboplatin therapy. At a median followup of 15 months 1, 3, 5 and 10-year disease specific survival was 69.0%, 45.3%, 34.3% and 13.7%, respectively., Conclusions: We report what is to our knowledge the largest known series of collecting duct carcinoma. Since advanced or recurrent collecting duct carcinoma is resistant to standard treatment modalities, new treatment strategies are needed for advanced collecting duct carcinoma.

This study was intended to identify a high molecular weight allergen that had been detected in fish. Analyses by ELISA of five protein fractions prepared from bigeye tuna muscle showed that the high molecular weight allergen was contained in the myostromal protein fraction. Based on the results of SDS-PAGE, immunoblotting and amino acid analysis of the myostromal protein fraction, the high molecular weight allergen was judged to be collagen. Five of the eight patient sera used were found to react to the bigeye tuna collagen. In competitive ELISA inhibition experiments, the bigeye tuna collagen almost completely inhibited the IgE reactivity to the heated extracts from five species of fish, suggesting that collagen is commonly allergic regardless of fish species. However, no antigenic cross-reactivity was observed between collagens from fish and other animals.

Nurses have the most contact with patients in the clinical settings, and they play an important role in the guidance and education of patients. Nurses' basic knowledge of alcohol-related problems greatly influences early discovery of and early intervention against alcohol-related problems in general units (GU). In a study undertaken mainly to understand the status of nurses' knowledge in GU, a survey was performed to compare the knowledge and attitude of nurses working in GU and those with working in units specializing in the treatment of alcoholism (AU). For reference, we used the results of separate surveys performed previously on the general population. The results showed that, compared with nurses in AU, nurses in GU (1) were more tolerant of drinking, but (2) were more stigmatic concerning alcoholism, and (3) had little knowledge concerning alcohol-related problems. Nurses in GU tended to have less knowledge about alcohol-related problems than the general population. Moreover, the knowledge of nurses in AU could not be considered sufficient. This study suggested the need for basic education concerning alcohol-related problems and their treatment aimed at nurses.

The biosensor consisted of a sodium electrode and covered with the frog bladder membrane within a flow cell was tested for the estimation of tetrodotoxin (TTX) and saxitoxin (STX). This sensor was applied to detect very low amounts of the Na+ channel blockers, STX and TTX, in different shellfishes and swellfishes. A good agreement was obtained between TTX activities determined by mouse assay and amounts of Na+ channel blockers estimated by frog membrane sensor. The lowest level of TTX (fg) that can be determined by frog membrane sensor does not cause human poisoning. The channel blockers in short-necked clam, which was assumed to be STX, were monitored by this sensor continuously every week for one year. It was discovered that the STX content increased from July until September and then decreased from October until March. The biosensor proposed here may be used for the estimation of STX and TTX conventionally in the future.

Two protease inhibitors (AXPI-I and -II) were isolated from the sea anemone Anthopleura aff. xanthogrammica by a combination of acetone precipitation, gel filtration on Sephadex G-75, cation-exchange fast protein liquid chromatography (FPLC) on Mono S and reverse-phase HPLC on TSKgel ODS-120T. Both inhibitors are basic polypeptides, and their amino acid compositions are characterized by the presence of six half-Cys residues and the absence of Met and Trp. They are potently active against trypsin; inhibition of other serine proteases (alpha-chymotrypsin and elastase) is also displayed by only AXPI-I. However, the inhibitors show no affinity for metallo-proteases and cysteine proteases. Analyses of the N-terminal portion and enzymatic fragments established their complete amino acid sequences comprising 58 residues. The overall sequence homology and the conserved location of all half-Cys residues confirmed that the A. aff. xanthogrammica inhibitors belong to the Kunitz-type family.

This study was aimed at examining the effect of familial predisposition on cancer incidence in a cohort population. Family history (FH) of cancer and reproductive history were obtained by a simple questionnaire from about 40,000 participants in a cervical cancer screening program visiting screening clinics in 1977. Number and age structure of family members were not known. About 40% of subjects reported positive FH which was not medically verified. Comparing the observed and expected numbers of pair-wise combination of various cancers observed among the family members, we found more intense cluster of cancers of the same than different sites. This population was followed until 1987 by using the population-based cancer registry and 638 cancer cases were detected. By matching residence and birth year, the same number of nonaffected controls was chosen from the original cohorts. Positive effect of FH was detected for large bowel and breast cancers, but not for stomach and cervical cancers. Older age at marriage and lower parity were noted for breast cancer cases.