Search

Abstract: In Japan, absolute shortage of donors still continues even after the law allowing organ transplantation from deceased donors came into force in 1997. With the passage of the waiting period after registration for pancreas transplantation (PTx), both deaths and serious cases of diabetic complications necessitating withdrawal of the registration have undoubtedly increased. Therefore, so-called “marginal donor” (MD) has been considered as a potential solution for shortage of donors in Japan. The aim of the present study is to evaluate feasibility of MD in terms of post-PTx outcomes using data from Japan Organ Transplantation Network. A total of 148 PTx were performed from deceased donors in Japan from 2000 to 2012. MD was defined as follows: (1) >45 years old; (2) hemodynamically unstable at harvest using a high-dose dopamine or more than 2 vasopressors; or (3) non–heart-beating status. Postoperative outcomes after PTx were compared between the MD group and the non-MD group. Among the 148 PTx donors, 108 donors (73.0%) satisfied the criteria of MD. Early graft loss of pancreas graft during 3 months post-transplant was observed in 15 patients (10.1%), and the marginality (MD vs non-MD) was not significantly correlated with the early loss of pancreas graft. The overall patient survival of the MD group (1, 3, 5 years: 94.7%, 94.7%, 94.7%) was not significantly different from that of the non-MD group (1, 3, 5 years: 95.0%, 95.0%, 95.0%). Pancreas graft survival in the MD group (1, 3, 5 years: 80.9%, 73.2%, 66.0%) seemed to be slightly lower than that in the non-MD group (1, 3, 5 years: 92.5%, 85.2%, 77.4%), but no statistically significant differences were found between the 2 groups. These results suggest the feasibility of the use of MD for PTx. [Copyright &y& Elsevier]

Background Long-term immunosuppression is associated with an increased risk of cancer. Especially, the immunosuppression in pancreas transplantation is more intensive than that in other organ transplantation because of its strong immunogenicity. Therefore, it suggests that the risk of post-transplant de novo malignancy might increase in pancreas transplantation. However, there have been few studies of de novo malignancy after pancreas transplantation. The aim of this study was to analyze the incidence of de novo malignancy after pancreas transplantation in Japan. Methods Post-transplant patients with de novo malignancy were surveyed and characterized in Japan. Results Among 107 cases receiving pancreas transplantation in Japan between 2001 and 2010, de novo malignancy developed in 9 cases (8.4%): post-transplant lymphoproliferative disorders in 6 cases, colon cancer in 1 case, renal cancer in 1 case, and brain tumor in 1 case. Conclusions We clarified the incidence of de novo malignancy after pancreas transplantation in Japan. [ABSTRACT FROM AUTHOR]

Background: Limited crop production due to lower rainfall has a major impact on the supply and demand of food for the human population. In potato (Solanum tuberosum L.), one of the major crops, there is also concern about a lack of production due to drought stress. Especially the cultivar "Toyoshiro" suitable for processing, has significant reduction in drought yield. Therefore, it is necessary to understand the mechanism of gene expression changes that occur in potato "Toyoshiro" plants and tubers during drought., Methods and Results: Seed potatoes were split in half and one was used as a control plant (CT), and the other was used as a drought-stressed plant (DS). CT was watered daily, and DS watered off to mimic the weather conditions of the Tokachi-Obihiro region in 2021. These tubers were harvested at week 14 and the transcriptome was analyzed. DS plants showed 423 downregulated genes and 197 upregulated genes compared to CT. Factors related to cell wall modification, heat stress response, and phytosterol metabolism were detected among the genes whose expression changed. Moreover, the expression of "Abscisic acid and environmental stress-inducible protein TAS14 like (TAS14)," a molecule reported to be upregulated under drought stress, was also upregulated, and was upregulated expression in all strains that reproduced drought. The localization of this molecule in the nucleus and plasma membrane was confirmed in a mCherry-tagged TAS14 mutant line., Conclusions: Our findings contribute to understanding the survival strategy system of Japanese processing potatoes in response to drought stress., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes., Methods: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm., Results: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21). When comparing PTCL-TBX21 and PTCL-GATA3, PTCL-TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity-related genes, such as PD-L1, LAG3, and IDO1, in PTCL-TBX21 than in PTCL-GATA3. PTCL-GATA3 had significantly worse overall survival (OS) than those with PTCL-TBX21 (p = 0.047), although a similar tendency was observed for progression-free survival (PFS) (p = 0.064). PTCL-GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09-3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93-4.61; p = 0.074). In the PFS analysis, PTCL-GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08-3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07-5.11; p = 0.032)., Conclusion: The classification of PTCL-NOS into PTCL-TBX21 and PTCL-GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The East Asian-specific genetic diversity, the rs671 variant of aldehyde dehydrogenase 2, causes the "Asian flush" phenomenon following alcohol consumption, resulting in an alcohol avoidance phenotype. The variant is suggested as a risk factor for Alzheimer's disease; however, its association with mild cognitive impairment (MCI), an effective target for secondary prevention of dementia, remains unclear., Method: This cross-sectional study examined 430 individuals aged 60-80 years (251 women) without overt cognitive impairment in Yoshinogari, Japan. The effect of the rs671 variant on MCI, defined by scores <26 or <25 on the Japanese version of the Montreal Cognitive Assessment, was evaluated using multivariate logistic regression., Results: The models included APOEε4, sex, age, education, history of habitual drinking, Brinkman index, hypertension, diabetes, and subclinical magnetic resonance imaging findings and consistently estimated the risk of the rs671 variant. Subsequently, stratified analyses by history of habitual drinking were performed based on an interactive effect between rs671 and alcohol consumption, and the rs671 variant significantly influenced MCI in participants who did not drink habitually, with odds ratios ranging from 1.9 to 2.1 before and after adjusting for covariates, suggesting an association independent of hippocampal atrophy and small vessel dysfunction. Conversely, no such association with the rs671 variant was observed in participants with a history of habitual alcohol use. Instead, hippocampal atrophy and silent infarcts were associated with MCI., Conclusions: This is the first study to demonstrate an association between the rs671 variant and MCI morbidity. The findings highlight the need for race-specific preventive strategies and suggest potential unrecognized mechanisms in dementia development.

Background: In Japan, the fourth round of coronavirus disease (COVID-19) vaccination is ongoing and is targeted at medical staff and nursing home workers, individuals aged ≥60 years, and those with comorbidities or other high-risk factors, including body mass index (BMI) ≥30 kg/m 2 . The incidence of severe COVID-19 decreased markedly after widespread COVID-19 vaccination drives, and our hospital experienced a similar trend. We, therefore, examined the characteristics of our patients to clarify who benefited the most from vaccination., Methods: We retrospectively investigated all patients hospitalized for COVID-19 in Osaka City Juso Hospital between March 1, 2021, and June 30, 2022. Using multivariable logistic analysis, we calculated the adjusted odds ratios (aORs) for severe disease after vaccination in the whole dataset and in subsets stratified by age, sex, BMI, smoking history, pre-hospitalization location, and comorbidities., Results: The analysis included 1041 patients. Multivariable logistic analysis showed that vaccination was associated with a low risk of severe disease, with an aOR of 0.21 (95% confidence interval: 0.12-0.36, p < 0.001). On stratifying the analysis according to background characteristics, lower aORs for severe COVID-19 were found for patients aged ≥60 years and for those with diabetes or hypertension. Notably, patients with BMI >30 kg/m 2 and those with BMI ≥18 kg/m 2 and ≤30 kg/m 2 benefited from vaccination., Conclusions: Individuals with diabetes or hypertension and those of age ≥60 years benefited more from vaccination than did their counterparts. We recommend extending the fourth round of vaccinations to individuals with a BMI of 18-30 kg/m 2 ., Competing Interests: Conflict of Interest Tomoya Kawaguchi received a research grant from Chugai Pharmaceutical Co., Ltd.,TAIHO Pharmaceutical Co., Ltd., and ONO Pharmaceutical Co., Ltd.; Tetsuya Watanabe received lecture fees from GlaxoSmithKline and AstraZeneca. Other authors declare no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Long term monitoring of atmospheric wet and dry depositions and associated nutrients fluxes was conducted on the coast of Japan facing the East China Sea continuously for 1 year and 2 months, with the origin of air mass investigated based on isotope analyses (Sr, Nd, and NO 3 ). During the same period, intensive observations of ocean conditions and the chemical composition of sinking particles collected using sediment traps were conducted to investigate the effects of atmospheric deposition-derived nutrients on phytoplankton blooms. Dry-deposition-derived nutrient inputs to the surface ocean were larger during autumn to spring than in summer due to the effect of continental air mass occasionally carrying Asian dust (yellow sand). However, these nutrients fluxes were limited (1.1-1.5 mg-N m -2 day -1 on average) and didn't appear to cause phytoplankton blooms through the year. Although average dissolved inorganic nitrogen (DIN) concentrations in rainwater were lower in oceanic air masses compared to continental air masses, wet-deposition-derived nutrient inputs to the surface ocean on rainy days during the summer (26.0 mg-N m -2 day -1 on average) were large due to higher precipitation from oceanic air masses. Wet-deposition-derived nutrients significantly increased nutrient concentrations in the surface ocean and seemed to cause phytoplankton blooms in the warm rainy season when nutrients in the surface were depleted due to increased stratification. The increase in phytoplankton biomass was reflected in increased particle sinking into the bottom layer, as well as changing chemical characteristics. The supply of flesh phytoplankton-derived labile organic matter into the bottom layer could be expected to promote rapid bacterial decomposition and contribute to the formation of hypoxic water masses in early summer when the ocean was strongly stratified. Atmospheric deposition-derived nutrients in East Asia will have important impacts on not only the oligotrophic outer ocean but also surrounding coastal areas in the warm rainy season., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The impact of using an older donor pancreas on the clinical outcomes of pancreas transplantation (PTx) is unknown. We investigated this by comparing the outcomes of PTx using older and younger donors in a single Japanese center, to expand the donor criteria., Methods: The subjects were 54 patients who received PTx from deceased donors in our institution. Posttransplant outcomes were analyzed based on donor age, with older donors defined as those aged ≥ 60 years., Results: The donors included six older (11.1%; aged 64 ± 4 years) and 48 younger donors (88.9%; aged 43 ± 12 years). There was no significant difference in the donor age between the recipients with vs. those without postoperative complications or between those with vs. those without early pancreas graft loss. Long-term outcomes, including overall, pancreas graft, and kidney graft survival after PTx, did not differ significantly between the older and younger donor groups. Graft age, defined as the age of the donor at the time of procurement plus the graft survival period, was not associated with graft loss., Conclusion: Our results suggest that post-transplant outcomes of PTx using pancreas from older donors aged ≥ 60 years are comparable to those using pancreas from younger donors, and support expansion of the donor pool for transplantation therapy for type 1 diabetes mellitus.

Background/purpose: Grade C postoperative pancreatic fistula (POPF), as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication after pancreatoduodenectomy (PD). This study aims to evaluate risk factors for Grade C POPF after PD., Methods: This is a prospective, multicenter study based in Japan and Taiwan. Between December 2014 and May 2017, 3022 patients were enrolled in this study and 2762 patients were analyzed. We analyzed risk factors of Grade C POPF based on the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death)., Results: Among 2762 patients, 46 patients (1.7%) developed Grade C POPF after PD. The mortality rate of the 46 patients with Grade C POPF was 37.0%. On the multivariate analysis, six independent risk factors for Grade C POPF were found; BMI ≥ 25.0 kg/m 2 , chronic steroid use, preoperative serum albumin <3.0 mg/dL, soft pancreas, operative time ≥480 minutes, and intraoperative transfusion. The c-statistic of our risk scoring model for Grade C POPF using these risk factors was 0.77. The score was significantly higher in Grade C POPF than in Grade B POPF (P < .001) or none/biochemical leak (P < .001)., Conclusions: This prospective study showed risk factors for Grade C POPF after PD., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: In heart failure (HF) patients implanted with high-energy devices, worsening of HF can be diagnosed from intrathoracic impedance (ITI) before symptoms appear. Early therapeutic intervention can prevent HF worsening, but the optimal intervention remains unknown. This study aimed to examine which lifestyle modifications or medications can improve HF indicators in asymptomatic HF patients diagnosed from ITI., Methods and results: This multicenter, prospective, randomized study included patients with high-energy devices, left ventricular ejection fraction <40%, or with a history of HF hospitalization. After the OptiVol alert was evoked by decreased ITI, patients underwent examinations. If they were diagnosed with HF, they were randomly assigned to 3 groups: lifestyle modification, diuretic, or nitrate. After 1 week, they underwent the same examinations. The primary endpoint was change in ITI and serum B-type natriuretic peptide (BNP). Totally, 57 patients were randomized. In all 3 groups, ITI was significantly increased post-intervention compared with pre-intervention. In the diuretic and nitrate groups, logBNP post-intervention was significantly lower than pre-intervention, but not in the lifestyle modification group., Conclusions: Compared with lifestyle modifications, diuretic and nitrate therapy for 1 week may be more effective management of HF detected by decreased ITI. However, lifestyle modification may have the additional benefits of reducing the workload or cost.

Objective: The causality and pathogenic mechanism of microbiome composition remain elusive in many diseases, including autoimmune diseases such as rheumatoid arthritis (RA). This study aimed to elucidate gut microbiome's role in RA pathology by a comprehensive metagenome-wide association study (MWAS)., Methods: We conducted MWAS of the RA gut microbiome in the Japanese population ( n case =82, n control =42) by using whole-genome shotgun sequencing of high depth (average 13 Gb per sample). Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis and pathway analysis)., Results: Phylogenetic case-control association tests showed high abundance of multiple species belonging to the genus Prevotella (e.g., Prevotella denticola ) in the RA case metagenome. The non-linear machine learning method efficiently deconvoluted the case-control phylogenetic discrepancy. Gene functional assessments showed that the abundance of one redox reaction-related gene (R6FCZ7) was significantly decreased in the RA metagenome compared with controls. A variety of biological pathways including those related to metabolism (e.g., fatty acid biosynthesis and glycosaminoglycan degradation) were enriched in the case-control comparison. A population-specific link between the metagenome and host genome was identified by comparing biological pathway enrichment between the RA metagenome and the RA genome-wide association study results. No apparent discrepancy in alpha or beta diversities of metagenome was found between RA cases and controls., Conclusion: Our shotgun sequencing-based MWAS highlights a novel link among the gut microbiome, host genome and pathology of RA, which contributes to our understanding of the microbiome's role in RA aetiology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study provides an overview of the epidemiology and secular trends of malignant lymphoma in Japan. Using data from clinics and hospitals throughout Japan, we analyzed 9426 cases of malignant lymphoma diagnosed in 2007-2014. We show that the proportion of follicular lymphoma and methotrexate-associated lymphoproliferative disorder increased during this time, as did the onset age for follicular lymphoma and diffuse large B-cell lymphoma. Significant increases in onset age for follicular lymphoma and diffuse large B-cell lymphoma were observed in both men and women (all P values <0.0001 except for P = 0.0448 for the latter disease in women). Further studies are required to determine the reasons for the higher proportion of and onset age for these lymphomas. Additionally, we believe that continued observation of these trends is necessary., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Landfill sites are significant sources of methane gas globally. Understanding the temporal variabilities of methane emissions from landfill sites is necessary for estimating such emissions. In this study, an automated monitoring system was used to monitor methane emission flux and concentration on daily and hourly time scales at a landfill site. Measured methane emission fluxes were almost negligible in the studied area. However, methane concentration at landfill surface at nighttime was significantly higher than those in the daytime, which demonstrates the importance of investigating methane emissions at an hourly time scale, including during nighttime. The daily and hourly variations in methane concentration were well correlated with either soil temperature or volumetric water content near the surface. The obtained relations indicate that the automated monitoring system measurements can facilitate a more comprehensive understanding of the methane emission mechanisms at different time scales.

Background: Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors' practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon., Materials and Methods: From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor., Results: A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction., Conclusion: Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.

Objectives: This study sought to investigate the 3-year follow-up results of OLIVE registry patients., Background: Although favorable 12-month clinical outcomes after endovascular therapy (EVT) in OLIVE registry patients with critical limb ischemia (CLI) from infrainguinal disease have been reported, long-term results after EVT remain unknown., Methods: This was a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal EVT for CLI. The primary outcome was 3-year amputation-free survival (AFS), whereas secondary outcome measures were 3-year freedom from major adverse limb events (MALE), wound-free survival, and wound recurrence rate. Prognostic predictors for each outcome were also elucidated by Cox proportional hazard regression analysis or the log-rank test., Results: The completion rate of 3-year follow-up was 95%. Three-year AFS, freedom from MALE, and wound-free survival rates were 55.2%, 84.0%, and 49.6%, respectively. Wound recurrence out to 3 years was 43.9%. After multivariable analysis, age (hazard ratio [HR]: 1.43, p = 0.001), body mass index ≤18.5 (HR: 2.17, p = 0.001), dialysis (HR: 2.91, p < 0.001), and Rutherford 6 (HR: 1.64, p = 0.047) were identified as predictors of 3-year major amputation or death. Statin use (HR: 0.28, p = 0.02), Rutherford 6 (HR: 2.40, p = 0.02), straight-line flow to the foot (HR: 0.27, p = 0.001), and heart failure (HR: 1.96, p = 0.04) were identified as 3-year MALE predictors. Finally, CLI due to isolated below-the-knee lesion was a wound recurrence predictor (HR: 4.28, p ≤ 0.001). Three-year survival, freedom from major amputation, and reintervention rates were 63.0%, 87.9%, and 43.2%., Conclusions: In CLI patients with infrainguinal lesions, 3-year clinical results of EVT were reasonable despite high reintervention and moderate ulcer recurrence rate. (A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia [OLIVE 3-Year Follow-Up Study]; UMIN000014759)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The prevalence of Campylobacter jejuni in wild birds is a potential hazard for human and animal health. The aim of this study was to establish the prevalence of C. jejuni in wild birds in Tokachi area, Hokkaido, Japan and investigate their virulence in vitro. In total, 173 cloacal swabs from individual wild birds were collected for the detection of Campylobacter spp. Thirty four samples (19.7%) were positive for Campylobacter of which 94.1% (32/34 samples) were C. jejuni. Additionally, one C. coli and one C. fetus were isolated. Seven C. jejuni isolates (one from crows and the other from pigeons) had important virulence genes including all three CDT genes (cdtA, cdtB and cdtC) and flaA, flaB, ciaB and cadF, and the other isolates were lacking cdtA gene. Further studies on in vitro virulence-associated phenotypes, such as motility assay on soft agar and invasion assay in Caco-2 cells, were performed. The wild bird C. jejuni isolates adhered and invaded human cells. Although the numbers of viable intracellular bacteria of wild bird isolates were lower than a type strain NCTC11168, they persisted at 48-hr and underwent replication in host cells.

Background/aims: To clarify whether or not use of an endoscopic biliary stenting (EBS) is superior to endoscopic nasobiliary drainage (ENBD) in cases of acute cholangitis due to choledocholithiasis., Methodology: Of 447 patients with choledocholithiasis who were treated in the Department of Gastroenterology, Fukuoka University Chikushi Hospital between January 1994 and September 2006, the subjects were 99 moderate acute cholangitis patients who underwent endoscopic drainage as initial treatment. Clinical efficacy, complications and patient satisfaction (meal intake rete) were investigated in the EBS group (67 patients) and the ENBD group (32 patients)., Results: There were no significant differences in the improvement in inflammation, total bilirubin, or biliary enzymes between the EBS and ENBD groups. Catheter occlusion was seen in three patients (4%) in the EBS group, and the catheter was self-extracted by three patients (10%) in the ENBD group., Conclusion: In moderate acute cholangitis due to choledocholithisis, the treatment efficacy and safety of EBS are equal to those of ENBD, and EBS appears to be a better choice in elderly patients in particular.

Objectives: The purpose of this study was to clarify the clinicopathological characteristics of autoimmune pancreatitis (AIP) in Japanese patients with inflammatory bowel disease (IBD)., Methods: The clinicopathological findings of 7 patients with IBD whose definite AIP was diagnosed in our hospital according to the International Consensus Diagnostic Criteria were reviewed., Results: Five (0.5%) of 961 patients with ulcerative colitis (UC) and 2 (0.3%) of 790 patients with Crohn disease had AIP. All of 7 patients whose AIP was diagnosed were type 2. The rate of elevated values of serum immunoglobulin G4 was 0%. Most patients with the diagnosis of IBD preceded that of AIP, and disease activity of IBD were active. Granulocyte epithelial lesion is similar to the cryptitis seen in colonic tissue of UC. All of 7 patients were given corticosteroids, immunomodulators, and/or biological agents for IBD. One patient had a recurrence., Conclusions: The frequency of AIP in Japanese patients with IBD was low. All cases were type 2 and responded well to corticosteroids, immunomodulators, and biological agents. Autoimmune pancreatitis in UC patients may be an extraintestinal manifestation of UC.

The production and consumption of domestic natural cheese in Japan is increasing year by year. More than ninety percent of domestic natural cheese is produced in Hokkaido region of Japan, while information on its quality and safety related to foodborne pathogens is limited. To assess the microbiological safety of domestic natural cheese, a total of 126 natural cheese samples produced in Hokkaido were collected from December, 2012, to July, 2013. In addition to standard plate count (SPC) and coliform counts, the prevalence study of three pathogens (Listeria monocytogenes, pathogenic Escherichia coli, and Salmonella spp.) was performed on each sample. Real-time PCR and matrix-assisted laser desorption-ionization time-of-flight mass spectrometer methods were employed for identification of presumptive pathogens. Coliform was detected in 25 samples (19.8%) with a minimum of 25 cfu/g and a maximum of more than 3.0 × 10(6) cfu/g. Salmonella spp. and L. monocytogenes were not isolated from any of the samples. Only one sample (0.80%) showed positive PCR amplification for ipaH gene suggesting possible contamination of enteroinvasive E. coli or Shigella in this product. Overall results indicate that natural cheeses produced in Hokkaido region were satisfactory microbiological quality according to existing international standards.

Listeria monocytogenes is a foodborne pathogen that causes gastroenteritis, maternofetal infections and meningoencephalitis in humans. Here we report that an intrahost genome mutation alters bacterial acid resistance and the abilities for replication/invasion in tissue cell culture. Among the L. monocytogenes isolates from the recent outbreak in Japan, we found that one food strain, 668, exhibited the greatest acid resistance, whereas one human clinical strain, 690, sharing identical pulsed-field gel electrophoresis (PFGE) and ribotyping patterns, exhibited an acid-sensitive phenotype. Passage of the 668 food strain through the mouse intestine increased its acid sensitivity without altering the macrogenotypes, indicating intrahost alteration of the bacterial acid-resistant phenotype. Genetic and proteomic analyses revealed a link between acid resistance and SigB (RNA polymerase SigmaB subunit) activity. Compared with the strain 668, the clinical and 4 of 5 mice-passaged strains showed a mutation in the rsbW locus, whose product controls the regulation of SigB activity. Corresponding to the SigB activity, the host-passaged strains had reduced abilities to survive inside macrophages and to invade Caco-2 cells, compared with the food strain 668. Overall, we have demonstrated the first example of a host environment promoting the alteration of SigB-dependent acid resistance and host cell-associated actions of L. monocytogenes. Our study provides new insight into the potential role of intrahost environment in the process of bacterial evolution., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Recently about 90% of radiographs have been taken by the digital radiographic system in Japan, but the exposure dose of the patients are about ten-times different among the systems. We understood it by a surveytaken in 2007. We studied the visual evaluation with varying exposure doses using the image phantom of the lumber AP, lumber lateral and hip AP. Additionally we measured quantum efficiency (DQE) of the digital systems. We also studied the exposure index (EI) of IEC standard to see whether it is able to be the sensitivity index among the digital systems. DQE in 1.0 cycle/mm of CR, FPD (GOS), FPD (CsI, a-Se) became 0.2-0.25, 0.3, 0.5, respectively. Our results display that the dose reduction is relative to DQE. The visual evaluation results also show that dose reduction is possible among the systems. From these results, we are able to reduce the exposure dose of the patients at the clinical site. We also suggest that we manage the exposure dose using the E.I of the IEC standard.

The operations of carbonization facilities for municipal solid waste treatment in Japan were examined. Input waste, system processes, material flows, quality of char and its utilization, fuel and chemical consumption, control of facility emissions, and trouble areas in facility operation were investigated and analyzed. Although carbonization is a technically available thermochemical conversion method for municipal solid waste treatment, problems of energy efficiency and char utilization must be solved for carbonization to be competitive. Possible solutions include (1) optimizing the composition of input waste, treatment scale, organization of unit processes, operational methods, and quality and yield of char on the basis of analysis and feedback of long-term operating data of present operating facilities and (2) securing stable char demands by linking with local industries such as thermal electric power companies, iron manufacturing plants, and cement production plants., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Asazuke is a ready-to-eat Japanese light pickle, mainly made of vegetables which are known to be one of the sources of Listeria monocytogenes contamination. Although asazuke is a popular side-dish in Japan, the hazard of bacterial contamination has not been evaluated yet. In this study, we investigated the prevalence of L. monocytogenes, Salmonella spp., verotoxigenic E. coli (VTEC) and coliforms in 108 asazuke samples that randomly collected from supermarkets in Obihiro (Hokkaido prefecture, Japan) during the period of June to November 2007. Twelve (11.11%) L. monocytogenes were isolated with predominant serotype 4b (seven isolates) followed by 1/2a (two isolates), 1/2b, 3b and 4c (one isolate each) while Salmonella spp., VTEC and coliforms were not detected. All L. monocytogenes isolates demonstrated hemolytic activity by CAMP test and possessed all the virulence-associated genes (prfA, actA, mpl, inlA, inlC, plcA, plcB, hly, iap, clpC and opuCA) as resulted in PCR, thus revealed their potential pathogenicity. Moreover, 7 out of 12 isolates were from asazuke samples produced by the same factory and their pulsed-field gel electrophoresis (PFGE) profiles suggested that 6 of them were indistinguishable and one was different. L. monocytogenes contamination in the asazuke factory environment was further investigated and 23 out of 60 environmental swabs (38.33%) contained the bacterium. Comparison of PFGE profiles showed relatedness between food and environmental isolates indicating that contamination probably occurred in the asazuke factory during manufacturing. Interestingly, after HACCP training course conducted to the factory workers, 20 samples collected during the period of November to December 2008 were negative to L. monocytogenes revealing that the hygienic status has improved., (2010 Elsevier B.V. All rights reserved.)

The estrogen metabolite, 4-hydroxy-estrogen, has been shown to play a role in malignant transformation of male kidneys. To counteract the effects of this catechol-estrogen, the catechol-O-methyltransferase (COMT) enzyme is capable of neutralizing the genotoxic effects of this compound. A polymorphic variant of COMT has been shown to have a reduced enzyme activity, and thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for renal cell cancer (RCC). To determine this hypothesis, a study of a Japanese male population was used and the genetic distributions of COMT polymorphisms at codons 62 (C-->T), 72 (G-->T), and 158 (G-->A) were analyzed in 157 normal healthy subjects and 123 sporadic RCC (clear cell type) samples by using a sequence-specific PCR technique. These experiments show that the variant genotype (P = 0.025) and allele (P = 0.011) at codon 62 is a risk factor for RCC. The odds ratio and 95% confidence interval for cancer were 3.16 and 1.29 to 7.73, respectively, for the T/T genotype as compared with wild-type. No associations for renal cancer were found at either codons 72 or 158 in this Japanese male population. However, codons 62 and 158 were observed to be in linkage disequilibrium, and haplotype analysis shows the combined forms of T-A, T-G, and C-A to be associated with RCC as compared with C-G (P < 0.001). When evaluating the risk of COMT polymorphisms with grade of cancer, no associations were observed for any of the genotypes. This study is the first to report COMT polymorphism to be associated with RCC. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of RCC.

The environmental fate of 40 existing chemicals is discussed using the EUSES multimedia distribution and risk assessment model with site-specific parameter setting in an urban area of Japan including a highly industrial region. There has been a strong need to assess the environmental fate of a huge number of existing chemicals. Data on the emission amounts of chemicals are essential for such prediction, and PRTR surveys may yield this data. The study delivered the following results: (1) Volatile compounds with large amounts of emission showed higher predicted concentrations in air, and the concentrations of several compounds agreed well with averaged monitoring data within an order of magnitude. (2) A close relationship was found between the concentration of water and that of sediment, suggesting that the fate of chemicals in sediment essentially depended on the water environment. (3) A group of volatile solvents had high mass distribution ratio to air. Some compounds having high solubility in water were also included in that group due to the high ratio of air emission. Highly hydrophobic compounds with logK(OW) larger than 6.0 showed a high distribution ratio to soil and sediment. (4) Volatile compounds were mostly taken through air. The exposure through fish is a dominant pathway for highly hydrophobic compounds. (5) Exposure ratio could be gathered from physicochemical properties. The exposure from fish intake was roughly estimated by logK(OW), whereas exposure from air and water intake was difficult to estimate simply by vapor pressure and solubility in water, respectively.

DNA repair gene alterations have been shown to cause a reduction in DNA repair capacity and may influence an individual's susceptibility to carcinogenesis. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been shown to cause a reduction in repair activity. We hypothesized that SNPs of DNA repair genes may be a risk factor for renal cell carcinoma (RCC). To test this hypothesis, DNA samples from 112 cases of renal cell cancer and healthy controls (n=180) were analyzed by PCR-RFLP to determine the genotypic frequency of six different polymorphic loci on five DNA repair genes (XRCC1, XPC, ERCC1, XRCC3, and XRCC7). The chi(2) test was applied to compare the genotype frequency between patients and controls. We found that the frequency of 399Gln variant at XRCC1 Arg399Gln was significantly higher in RCC cases than in controls (OR=2.83, 95%CI=1.24-6.49, P=0.01). The frequency of T-A haplotype of XRCC1 194 Trp and XRCC1 399Gln was significantly higher in RCC than controls. No differences in genotypes were observed at the other sites. This is the first report on SNPs of DNA repair genes in renal cell carcinoma that suggests XRCC1 399Gln polymorphism may be a risk factor for RCC. Our present data suggest that the XRCC1 399Gln allele may be linked to susceptibility for RCC.

Food-borne outbreaks caused by Listeria monocytogenes have been recognized in US and European countries. Only sporadic cases, of neonatal listeriosis, have been reported in Japan. Since L. monocytogenes has been often isolated from foods in Japan, food-borne outbreaks potentially could have occurred. In February 2001, L. monocytogenes serotype 1/2b was isolated from a washed-type cheese during routine Listeria monitoring of 123 domestic cheeses. Further samples from products and the environments at the plant that produced the contaminated cheese were examined for L. monocytogenes. L. monocytogenes serotype 1/2b was detected in 15 cheese samples, at most probable number that ranged from <30 to 4.6 x 10(9)/100 g, and in environmental samples. Studies with people who had consumed cheese from the plant revealed 86 persons who had been infected with L. monocytogenes. Thirty-eight of those people had developed clinical symptoms of gastroenteritis or the common cold type after the consumption of cheese. Isolates from those patients exhibited the same serotype, pathogenicity for mice and HeLa cells, DNA fingerprinting patterns and PCR amplification patterns. From the epidemiological and genetic evidence, it appeared that the outbreak was caused by cheese. This is the first documented incidence of food-borne listeriosis in Japan.

The impact of atopic dermatitis on patients' quality of life was measured using the Japanese version of Skindex-16 in a cross-sectional and longitudinal questionnaire study. One hundred sixty-two adult patients completed Skindex-16 and were followed-up with a standard medical therapy. Three to six months after the initial testing, 135 (83.3%) of the patients again completed Skindex-16 and also answered a general question about whether their skin condition had improved, remained the same, or become worse. The scores of Skindex-16 of 162 patients with atopic dermatitis were significantly higher than those of patients with isolated lesions, particularly in the Symptoms and Emotions scales. Patients with severe atopic dermatitis showed significantly higher scores in the three scales (Symptoms, Emotions, and Functioning), and there was a significant positive correlation between the severity and the 3-scale scores. After the follow-up period, 78 of 135 patients (57.8%) reported that their skin condition had improved. Forty-six patients (34.1%) reported that their skin condition had remained the same, and 11 (8.1%) became worse. Among the patients who said their dermatitis had improved, the scores of Skindex-16 significantly decreased. On the other hand, patients who reported their dermatitis worse showed an increase in the scores. These findings suggest that Skindex-16 responsively measures the disease severity and clinical change in the estimation of the effects of atopic dermatitis on patients' quality of life. This practical and sensitive, skin-disease specific, quality-of-life instrument is valuable for assessing patients' outcomes, especially their response to therapy, and is useful to understanding and improving the quality of life of patients suffering with atopic dermatitis.

We measured the quality of life of Japanese patients with acne using the Japanese version of Skindex-16, a semantically equivalent and validated translation of the original version produced by Chren et al. A total of 210 acne patients were enrolled in this study. The results showed that patients with acne experienced more severe emotional effects from their skin disease than functional or symptomatic effects. The scores for emotional aspects were related to the severity of the patients' acne following a prescribed scale, but the scores were high even when the patients only had a few comedones. Akaike's information criterion showed that the scores for symptoms were related to the severity of the patients' acne, and the patients' emotions were related to the interval between clinic visits. To improve patients' quality of life, treatment of comedones should be fully respected. In addition, dermatologists should encourage patients to visit clinics regularly to help them improve the emotional aspects of their quality of life.

The objectives of this work are to understand the details of the mechanism of dioxin formation in the part of a sintering bed termed the dry zone, and to obtain ideas on how to prevent their formation. Sinter mixtures of various composition types were heated in a packed bed reactor, and dioxins in the outlet gas and in the sinter mixture residue were measured. The dioxin formation potential of a simple sinter mixture composed of iron ore, coke and limestone was markedly lower than that of fly ash from a municipal solid waste incinerator (MSWI). In consideration of this result, a series of experiments were conducted using a sinter mixture impregnated with CuCl2. Experimental results showed that dioxin formation was temperature-dependent in the range of 300-550 degrees C, with the maximum observed at around 300 degrees C, which was quite similar to that of fly ash from the MSWI. The homologue distribution of PCDD/Fs in gas and solid reflected the possible difference in carbonaceous materials in coke and activated coke. Gaseous hydrogen chloride acted as a chlorinating reagent for dioxin formation.

A practical quality-of-life measure applicable to patients with skin diseases is necessary. Recently developed dermatological quality-of-life measures must be translated and adapted for use in cultures other than the ones in which they were created. In this study, we translated and adapted culturally into Japanese a skin-disease-specific, brief quality-of-life measure, Skindex-16, and studied its reliability and validity. Forward-and back-translations of Skindex-16 were carried out. Six doubtful items as well as the term "skin condition" required a second forward- and back-translation to reach satisfactory agreement with the original instrument. Cross-cultural adaptation and cross-sectional questionnaire studies were then performed to evaluate the reliability and validity of the instrument. One hundred patients and 30 healthy adults responded to the Japanese version. The internal-consistency reliability of the final Japanese version of Skindex-16 was high (range of Cronbach's alpha for each scale, symptoms, emotions, and functioning, was 0.83-0.92). The Japanese version showed construct and content validity. As hypothesized, scores for dermatological patients were higher than those for healthy persons (mean global scores 36 +/- 23 vs 1 +/- 2, p < 0.001) and scores for patients with inflammatory diseases were higher than those for patients with isolated skin lesions (mean global scores 48 +/- 21 vs 22 +/- 17, p < 0.001), indicating a poorer quality of life. Most patients' responses to an open-ended question about their skin disease were similar to those of the American responders and were addressed according to the items. In conclusion, we have developed a semantically equivalent translation of Skindex-16 into Japanese. It is a reliable and valid measure of the effects of skin disease on the quality of life in Japanese patients.

It is widely accepted that students in Japan sleep fewer hours than what they actually need. However, epidemiological data on sleep habits among students are scarce. The sleep habits and related problems among 1650 students in Akita prefecture were studied. The results revealed that schoolchildren attending elementary schools seemed to sleep for a sufficient number of hours, whereas students attending junior or senior high schools were not sleeping enough. In particular, approximately half of the students attending senior high schools answered that they slept 6 h or less on weekdays and nodded off during classes more than twice a week.

DZ-2640 is the ester-type oral carbapenem prodrug of an active parent compound, DU-6681. The pharmacokinetics and safety of DU-6681 were investigated in six studies after oral administration of a single dose of DZ-2640 to healthy male Japanese volunteers at doses of 25, 50, 100, 200, and 400 mg (as the equivalents of DU-6681) in the fasted state. The same volunteers received the drug at a dose of 100 mg in the fasted and fed states to examine the effect of food intake on the bioavailability of DZ-2640. The concentrations of DU-6681 in plasma and urine were determined by a validated high-performance liquid chromatography method and a bioassay. A good correlation between both methods was seen, indicating an absence of major active metabolites. The mean maximum concentrations of DU-6681 in plasma (C(max)) ranged from 0.263 microgram/ml (25-mg dose) to 2.489 microgram/ml (400-mg dose) and were reached within 1.5 h following drug administration. After reaching the C(max), plasma DU-6681 concentrations declined in a monophasic manner, with a half-life of 0.47 to 0.89 h. The area under the concentration-time curve (AUC) and C(max) increased almost linearly with the dose up to the 200-mg dose. The AUC and C(max) increased less than proportionally after administration of the 400-mg dose, suggesting a reduction in drug absorption. The plasma protein binding of DU-6681 was in the range of 23.3 to 25.6%. The cumulative urinary recoveries (0 to 24 h) were in the range of 31.9 to 44.9%. The AUC was slightly but statistically significantly reduced by food intake. However, the C(max), half-life, and recovery in urine were not affected by food intake. The renal clearance (402 to 510 ml/min) was much greater than the mean glomerular filtration rate (ca. 120 ml/min), which indicated active tubular secretion of the drug. A mild transient and moderate diarrhea was observed in two of six volunteers in the study with a single dose of 25 mg. Mild soft stools were observed in two of six volunteers who received a 400-mg dose of the drug.

We examined refractions of 102 eyes in 51 Japanese children after the topical instillation of cycloplegics. Cyclopentolate 1% was instilled 3 times after 5-min intervals, and refractions were evaluated 45 min after the last instillation. Atropine, 0.5% or 1%, was instilled twice daily for 7 days. Refractions were measured by an autorefractometer. The mean refraction in 102 eyes measured after atropine instillation was +3.07 dpt, and the mean after cyclopentolate instillation was +2.35 dpt. The mean difference in the direction of meridians of maximal refractions measured after atropine and cyclopentolate was 22 degrees. Our finding showed that atropine instillation may be adequate to determine exact refractions in Japanese children.

The surveillance system of infectious disease in Japan started in 1981 and has been providing useful epidemiological information on 27 communicable diseases. The system consists of medical institutions (fixed monitoring stations), institutions of hygienic sciences, health centers, local governments and the ministry of health and welfare. There are two types of information about infectious diseases. One is clinical reports of incidence cases from medical institutions, and the other is laboratory information about etiologic agents. Between health centers, local governments and the department of statistics and information in the ministry of health and welfare, information is transmitted through the on-line network. Collected information is analyzed and submitted by both local and central committees of analysis. From the epidemiological point of view, quality control of the data and integration of other sources of data would be the next goal of the system.

Four patients with human T-lymphotropic virus type I associated myelopathy (HAM) were examined ophthalmologically, and serum titers to human T-lymphotropic virus type I (HTLV-I) in 11 patients with nonspecific retinal vasculitis or uveitis were determined. All of the patients lived in the Izumo area. All 4 patients with HAM (Cases 1 to 4) had vitreous opacities. Of the 11 patients with nonspecific retinal vasculitis or uveitis, 3 (Cases 5 to 7) had elevated titers to HTLV-I. We believe that HTLV-I infection may be involved in the causes of retinal vasculitis and uveitis in patients living not only in the endemic area but also outside the endemic area.

It has recently come to be thought that cases of juvenile polyposis have a natural tendency to develop adenoma and/or carcinoma. Here we present a case of juvenile polyposis coli with adenomatous change in a 21-year-old male, with a review of 34 cases of juvenile polyposis in the Japanese literature, and discuss the pathogenetic development of the polyps and their malignant potential. In this case, focal or entire adenomatous areas were found in large part of the polyps in the resected sigmoid colon and rectum, though these findings had not been recognized in 23 polypectomy specimens from the rectum 10 months prior to the operation. It was suggested that adenomatous change developed quickly in a very short time.

Air pollution by the principal chlorinated organic compounds chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and tetrachloroethylene was investigated over a period of approximately 1 year at 15 sites in an urban area. Each compound was detected in the range from approximately 0.1 to several ppb; the concentrations of these compounds, with the exception of carbon tetrachloride, were higher than their global pollution levels. The concentrations of 1,1,1-trichloroethane and trichloroethylene especially were very high in the industrial regions, and the concentration of tetrachloroethylene was very high in the industrial and commercial regions. Concentrations were low in spring and summer and high in fall, winter and the rainy season. The correlation between the reciprocal of wind speed and concentrations was found to be subject to seasonal variations. Intake of chlorinated organic compounds by man from the air was estimated from the data to be larger than the allowable intakes determined by WHO and EPA for drinking water.

One thousand-four hundred and twenty-four cases of gastric cancer registered at the Nagasaki Tumor Registry between 1973 and 1977 were studied. The incidence of gastric cancer tended to be higher in persons exposed to the atomic bomb within 2.0 km from the hypocenter, especially in young persons, than in non-exposed individuals, but the difference was not statistically significant. Compared with the nonexposed, the corrected relative risk of gastric cancer in persons exposed within 2.0 km from the hypocenter was 1.28 in males and 1.11 in females. In terms of histologic type or location, the incidence of gastric cancer showed no statistically significant difference between the exposed and nonexposed persons.

Otitis media is the most common pediatric disease as a complication of the upper respiratory infection and at least 10% of the otitis prone children will suffer from prolonged episodes of minor conductive hearing loss and communication disorder due to the presence of middle ear effusion (MEE). In spite of exhaustive studies presented in the past three international symposia on otitis media with effusion (OME), there still remain wide gaps in our knowledge regarding the etio-pathogenesis and appropriate treatments of the disease. A couple of years ago, a new project of clinical and laboratory researches on OME were initiated in the Department of Otolaryngology, Tohoku University School of Medicine and some results of the studies have been reported in recent Japanese academy meetings as well as in the 2nd and 3rd International Symposium of Recent Advances in OME. The purpose of this paper is to summarize the results of our recent studies performed by several investigators in our department and related hospitals.