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Background: The modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) are indicators of nutritional status in cancer patients; however, the effects of baseline mGPS and PNI on the duration of administration of the ghrelin receptor agonist anamorelin, which is used to treat cachexia in patients with cancer, are unclear. This study aimed to clarify the association of mGPS and PNI with the duration of oral anamorelin administration for patients who did not have beneficial effects from anamorelin., Methods: The attending physician determined the duration of oral anamorelin administration based on discontinuation due to cancer progression, poor efficacy, adverse events, or death., Results: The 12-week continuation rate of oral anamorelin was 30.4%. Univariate analysis revealed that an Eastern Cooperative Oncology Group performance status (ECOG-PS) of ≥2 (P < .001), concurrent chemotherapy (P = .002), albumin level (P = .005), C-reactive protein level (P = .013), and a mGPS of 2 (P = .014) were statistically significant predictors of the 12-week continuation rate of oral anamorelin. In the multivariate analysis, a mGPS of 2 remained a significant risk factor, and the ECOG-PS and concurrent chemotherapy had no effect on the association between the mGPS and 12-week continuation rate of oral anamorelin., Conclusion: Patients with a mGPS of 2, compared with mGPS of 0 or 1, are less likely to maintain oral anamorelin therapy, regardless of the ECOG-PS or concurrent chemotherapy. Therefore, it is necessary to consider initiating anamorelin administration at mGPS 0 or 1., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We conducted a descriptive study of the physicians' evidence-practice gap for adults covered by the 2017 clinical practice guidelines for the management of antineutrophil cytoplasmic antibody-associated vasculitis in Japan., Methods: This web-based survey, conducted between January and February 2021, involved physicians who had treated at least five patients in the preceding year at a regional core hospital. The outcome was the physicians' experience in treating patients with microscopic polyangiitis or granulomatosis with polyangiitis [prevalence with 95% confidence intervals (CIs)], defined as treating at least 60% of their patients with the recommended therapy during the year. A modified Poisson regression analysis was performed to explore the factors associated with concordance., Results: The 202 participants included 49 pulmonologists, 65 nephrologists, 61 rheumatologists, and other physicians. The concordance was 31.5% (95% CI, 25.1-38.5) of physicians who used cyclophosphamide or rituximab for the induction of remission. Rheumatology showed the highest concordance with published evidence (risk ratio = 2.4; 95% CI, 1.10-5.22, p = .03)., Conclusions: These results suggest an evidence-practice gap, which varies substantially among subspecialties. Further studies and a new promotional initiative are necessary to close this gap in clinical practice., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Verbal interaction and imitation are essential for language learning and development in young children. However, it is unclear how mother-child dyads synchronize oscillatory neural activity at the cortical level in turn-based speech interactions. Our study investigated interbrain synchrony in mother-child pairs during a turn-taking paradigm of verbal imitation. A dual-MEG (magnetoencephalography) setup was used to measure brain activity from interactive mother-child pairs simultaneously. Interpersonal neural synchronization was compared between socially interactive and noninteractive tasks (passive listening to pure tones). Interbrain networks showed increased synchronization during the socially interactive compared to noninteractive conditions in the theta and alpha bands. Enhanced interpersonal brain synchrony was observed in the right angular gyrus, right triangular, and left opercular parts of the inferior frontal gyrus. Moreover, these parietal and frontal regions appear to be the cortical hubs exhibiting a high number of interbrain connections. These cortical areas could serve as a neural marker for the interactive component in verbal social communication. The present study is the first to investigate mother-child interbrain neural synchronization during verbal social interactions using a dual-MEG setup. Our results advance our understanding of turn-taking during verbal interaction between mother-child dyads and suggest a role for social "gating" in language learning., (© The Author(s) 2022. Published by Oxford University Press.)

As soybean cultivars are adapted to a relatively narrow range of latitude, the effects of climate changes are estimated to be severe. To address this issue, it is important to improve our understanding of the effects of climate change by applying the simulation model including both genetic and environmental factors with their interactions (G×E). To achieve this goal, we conducted the field experiments for soybean core collections using multiple sowing times in multi-latitudinal fields. Sowing time shifts altered the flowering time (FT) and growth phenotypes, and resulted in increasing the combinations of genotypes and environments. Genome-wide association studies for the obtained phenotypes revealed the effects of field and sowing time to the significance of detected alleles, indicating the presence of G×E. By using accumulated phenotypic and environmental data in 2018 and 2019, we constructed multiple regression models for FT and growth pattern. Applicability of the constructed models was evaluated by the field experiments in 2020 including a novel field, and high correlation between the predicted and measured values was observed, suggesting the robustness of the models. The models presented here would allow us to predict the phenotype of the core collections in a given environment., (© The Author(s) 2022. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

In natural indigo dyeing, the water-insoluble indigo included in the composted indigo leaves called sukumo is converted to water-soluble leuco-indigo through the reduction activities of microorganisms under alkaline conditions. To understand the relationship between indigo reduction and microorganisms in indigo-fermentation suspensions, we isolated and identified the microorganisms that reduce indigo and analyzed the microbiota in indigo-fermentation suspensions. Indigo-reducing microorganisms, which were not isolated by means of a conventional indigo carmine-reduction assay method, were isolated by using indigo as a direct substrate and further identified and characterized. We succeeded in isolating bacteria closely related to Corynebacterium glutamicum, Chryseomicrobium aureum, and Enterococcus sp. for the first time. Anthraquinone was found to be an effective mediator that facilitated the indigo-reduction activity of the isolated strains. On analysis of the microbiota in indigo-fermentation suspensions, the ratio of indigo-reducing bacteria and others was found to be important for maintaining the indigo-reduction activity., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Many individuals with autism spectrum disorders have comorbid epilepsy. Even in the absence of observable seizures, interictal epileptiform discharges are common in individuals with autism spectrum disorders. However, how these interictal epileptiform discharges are related to autistic symptomatology remains unclear. This study used magnetoencephalography to investigate the relation between interictal epileptiform discharges and altered functional brain networks in children with autism spectrum disorders. Instead of particularly addressing individual brain regions, we specifically examine network properties. For this case-control study, we analysed 70 children with autism spectrum disorders (52 boys, 18 girls, 38-92 months old) and 19 typically developing children (16 boys, 3 girls, 48-88 months old). After assessing the participants' social reciprocity using the Social Responsiveness Scale, we constructed graphs of functional brain networks from frequency band separated task-free magnetoencephalography recordings. Nodes corresponded to Desikan-Killiany atlas-based 68 brain regions. Edges corresponded to phase lag index values between pairs of brain regions. To elucidate the effects of the existence of interictal epileptiform discharges on graph metrics, we matched each of three pairs from three groups (typically developing children, children with autism spectrum disorders who had interictal epileptiform discharges and those who did not) in terms of age and sex. We used a coarsened exact matching algorithm and applied adjusted regression analysis. We also investigated the relation between social reciprocity and the graph metric. Results show that, in children with autism spectrum disorders, the average clustering coefficient in the theta band was significantly higher in children who had interictal epileptiform discharges. Moreover, children with autism spectrum disorders who had no interictal epileptiform discharges had a significantly lower average clustering coefficient in the theta band than typically developing children had. However, the difference between typically developing children and children with autism spectrum disorder who had interictal epileptiform discharges was not significant. Furthermore, the higher average clustering coefficient in the theta band corresponded to severe autistic symptoms in children with autism spectrum disorder who had interictal epileptiform discharges. However, the association was not significant in children with autism spectrum disorders who had no interictal epileptiform discharge. In conclusion, results demonstrate that alteration of functional brain networks in children with autism spectrum disorders depends on the existence of interictal epileptiform discharges. Interictal epileptiform discharges might 'normalize' the deviation of altered brain networks in autism spectrum disorders, increasing the clustering coefficient. However, when the effect exceeds tolerance, it actually exacerbates autistic symptoms., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

We analyzed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26 000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r ~ 0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes (~51%) captured ~1.5 times more genetic variance than the rest, and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAF <5% captured

Objectives: Subcutaneous involvement, including calcinosis and panniculitis, is a more common complication in juvenile dermatomyositis (JDM) than in adult dermatomyositis. Magnetic resonance imaging (MRI) is useful for evaluating disease distribution. We investigated the clinical significance of subcutaneous involvement in JDM. Methods: Thighs and hips in 18 newly diagnosed JDM patients were evaluated with fat-suppression MRI. Bilateral muscle, fascial and subcutaneous fat involvement were scored from 0 to 8 points according to the severity of distribution on MRI. Associations between clinical manifestations, serum muscle enzymes, and MRI scores were also evaluated. Results: Abnormal MRI findings in muscle, fascia and subcutaneous fat were observed in 18, 18, and 10 patients, respectively. Subcutaneous fat scores were significantly higher in early-diagnosed JDM patients (diagnosed less than 2 months from onset) than in late-diagnosed JDM patients (diagnosed later) ( p  = .025). Serum aldolase was elevated in all patients, although only eight demonstrated elevated serum creatine phosphokinase. Serum aldolase was significantly correlated with MRI scores for subcutaneous fat ( p  < .0001, ρ = .787) and fascia ( p  = .013 ρ = 0.574), but not muscle. Additionally, serum aldolase was significantly correlated with serum triglycerides ( p  = .009, ρ = 0.629). Conclusion: Subcutaneous fat involvement is a characteristic finding in early-diagnosed JDM and correlates with elevated serum aldolase.

Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS] and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (Pbest = 4.1 × 10-10), SLC38A3 (Pbest = 5.7 × 10-10), and CABP1-ACADS (Pbest = 9.8 × 10-9). Subsequent meta-analysis between our samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and another study detected 12 additional susceptibility loci. Polygenic risk score (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest = 4.0 × 10-11) and between SCZ and BD in the JPN population (P ~ 10-40); however, a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD within/across populations. Genetic correlation analysis supported the PRS results; the genetic correlation between JPN-SCZ and PGC-SCZ was ρ = 0.58, whereas a similar/lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, ρ = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible susceptibility genes for SCZ and (b) SCZ "risk" effect is shared with other psychiatric disorders even across populations., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: In performing an open biopsy of a neck mass, an incisional biopsy may increase the risk of cancer cell seeding and dissemination that, ultimately, worsens a patient's survival. The aim of this study was to compare the impact of incisional and excisional biopsies of cervical lymph node metastases of solid tumors on patients' survival., Methods: A retrospective review was made of patients with cervical metastases of solid tumors who underwent an open biopsy for a diagnosis between 2005 and 2015. Sixty-four patients met the criteria out of 524 open biopsy cases undertaken during the period. Survival analyses were estimated from 33 cases whose initial symptoms were the presence of a neck mass, using two modes of biopsy: excisional and incisional., Results: The 2-year overall survival rates in incisional and excisional biopsy groups were 65% and 43%, respectively, and 2-year disease-specific survival rates were 74% and 43%, respectively. The differences were not significant. For lung cancer or head and neck cancer subgroups, survival differences between incisional and excisional biopsy groups were also not significant., Conclusions: A carefully targeted physical examination and performing a fine needle aspiration are essential to establish a diagnosis for the etiology of an unknown neck mass. In performing an open biopsy, the effect of an incisional biopsy on patients' survival was no worse than that of an excisional biopsy, despite the latter being theoretically preferable.

Background: In Japan, there has been a lot of reports showing an association between facial flushing after light alcohol consumption and heterozygosity for inactive aldehyde dehydrogenase-2 (ALDH2). Persons with inactive ALDH2 may have a higher risk of alcohol-related oral, pharyngeal and esophageal cancers, compared with those with wild-type ALDH2. The purpose of this study was to examine whether flushers with oral or pharyngeal squamous cell carcinoma have an increased risk of synchronous or metachronous cancer of the upper gastrointestinal (UGI) tract., Methods: A retrospective study was performed by medical chart review and through a questionnaire sent to 285 patients treated for oral and pharyngeal cancer. Responses were obtained from 150 patients (52.6%), who were classified as flushers or non-flushers, smokers (≥20 pack-year; 1 pack-years = number of cigarettes/20 per day) or non-smokers, and drinkers (≥14 units of alcohol consumption per week; 1 unit = 22 g) or non-drinkers. Relationships of these factors with occurrence of second primary cancers (SPCs) in the UGI tract were investigated., Results: In Kaplan-Meier analysis, there was a significantly higher rate of SPC at 5 years in flushers and drinkers, but no relationship with smoking. In multivariate analyses, a history of flushing was significantly associated with SPC in the UGI tract (HR 2.64, 95% CI 1.25-5.52, P = 0.0109), but not with smoking or alcohol consumption., Conclusions: A simple interview on history of facial flushing after alcohol intake can be useful for identifying patients at high risk for synchronous or metachronous cancers of the UGI tract., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Podocyte depletion causes glomerulosclerosis, with persistent podocyte loss being a major factor driving disease progression. Urinary podocyte mRNA is potentially useful for monitoring disease progression in both animal models and in humans. To determine whether the same principles apply to crescentic glomerular injury, a rat model of anti-glomerular basement membrane (anti-GBM) nephritis was studied in parallel with a patient with anti-GBM nephritis., Methods: Podocyte loss was measured by Wilms' Tumor 1-positive podocyte nuclear counting and density, glomerular epithelial protein 1 or synaptopodin-positive podocyte tuft area and urinary podocyte mRNA excretion rate. Glomerulosclerosis was evaluated by Azan staining and urinary transforming growth factor (TGF)-β1 mRNA excretion rate., Results: In the rat model, sequential kidney biopsies revealed that after a threshold of 30% podocyte loss, the degree of glomerulosclerosis was linearly associated with the degree of podocyte depletion, compatible with podocyte depletion driving the sclerotic process. Urinary podocyte mRNA correlated with the rate of glomerular podocyte loss. In treatment studies, steroids prevented glomerulosclerosis in the anti-GBM model in contrast to angiotensin II inhibition, which lacked a protective effect, and urinary podocyte and TGF-β1 mRNA markers more accurately reflected both the amount of podocyte depletion and the degree of glomerulosclerosis compared with proteinuria under both scenarios. In a patient successfully treated for anti-GBM nephritis, urinary podocyte and TGB-β1 mRNA reflected treatment efficacy., Conclusion: These results emphasize the role of podocyte depletion in anti-GBM nephritis and suggest that urinary podocyte and TGF-β1 mRNA could serve as markers of disease progression and treatment efficacy., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The proband was a 67-year-old man with transverse and sigmoid colon cancer. Microsatellite instability analysis revealed a high frequency of microsatellite instability, and immunohistochemical staining showed the absence of both MLH1 and PMS2 proteins in the sigmoid colon cancer tissue specimens from the patient. DNA sequencing revealed a nucleotide substitution c.543C>T in MLH1, but this variant did not substitute an amino acid. The MLH1 c.543C>T variant was located 3 bases upstream from the end of exon 6 and created a new splice donor site 4 bases upstream from the end of exon 6. Consequently, the last 4 bases of exon 6 were deleted and frameshift occurred. Thus, the MLH1 c.543C>T silent mutation is considered 'pathogenic'., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A large number of morphological studies of intergranular carbides in steels have always been carried out in two dimensions without considering their dispersion manners. In this article, focused ion beam serial-sectioning tomography was carried out to study the correlation among the grain boundary characteristics, the morphologies and the dispersions of intergranular carbides in 347 austenitic stainless steel. More than hundred intergranular carbides were characterized in three dimensions and finally classified into three different types, two types of carbides probably semi-coherent to one of the neighboring grains with plate-type morphology, and one type of carbides incoherent to both grains with rod-type morphology. In addition, the rod-type carbide was found as the largest number of carbides among three types. Since large numbers of defects, such as misfit dislocations, may be present at the grain boundaries, which can be ideal nucleation sites for intergranular rod-type carbide precipitation., (© The Author 2016. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed. (i) The median TaqMeth value of CDO1 methylation was 9.4, ranging from 0 to 279.5. CDO1 methylation was significantly different between cStage I and cStage II/III (P = 0.02). (ii) On the log-rank plot, the optimal cut-off value was determined to be 8.9; ESCC patients with high CDO1 methylation showed a significantly worse prognosis than those with low CDO1 methylation (P = 0.02). (iii) A multivariate Cox proportional hazards model identified only CDO1 hypermethylation as an independent prognostic factor (HR 2.00, CI 1.09-3.78, P = 0.03). (iv) CDO1 hypermethylation stratified ESCC patients' prognosis in cStage II/III for both neoadjuvant chemo(radio)therapy (NAC)-positive and NAC-negative cases. Moreover, the CDO1 methylation level was significantly lower in cases with Grade 2/3 than in those with Grade 0/1 (P = 0.02) among cStage II/III ESCC patients with NAC. Promoter DNA hypermethylation of CDO1 could be an independent prognostic factor in ESCC; it may also reflect NAC eradication of tumor cells in the primary tumors., (© 2016 International Society for Diseases of the Esophagus.)

The cytotoxic evaluation of natural and synthetic callipeltins is described. Cyclic depsipeptide callipeltin B and linear peptides callipeltins E and M synthesized by us showed no cytotoxic activity. In contrast, natural callipeltin B purified from Callipelta sp. showed CC50 = 130 μM against Hela cells. We found that purified callipeltin B included the contamination of callipeltins C and H at a ratio of approximately 15%. These results suggested that the cytotoxicity of natural callipeltin B was derived from callipeltins C and H.

Objective: To examine and delineate inflammatory focus in patients with juvenile idiopathic arthritis (JIA), (18)F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) ((18)F-FDG-PET) was applied to patients with JIA, and the images of these patients were compared., Methods: Sixty-eight children (59 with systemic JIA (s-JIA) and 9 with polyarticular JIA) were included. The diagnosis of JIA was done to meet the International League of Associations for Rheumatology (ILAR) criteria. After 6-h fasting, whole-body positron emission tomography (PET) scans were acquired 60 min after intravenous injection of 3-5 MBq/kg (18)F-FDG. The interpretation of (18)F-FDG uptake was based on visual characteristics., Results: Two types of PET images were outstanding in s-JIA; one was (18)F-FDG uptake in red bone marrow, such as the spine, pelvis, and long bones as well as spleen (12 cases), and other type was the uptake in the major joints, such as hips, elbows, wrists, knees, and ankles (8 cases). The former findings were correlated with elevated levels of inflammatory markers, while the latter were with significantly increased levels of MMP-3 (p < 0.05)., Conclusion: There was a noticeable accumulation of (18)F-FDG uptake in bone marrow of s-JIA patients which may indicate the inflammatory focus of this disease and play an important role in the pathogenic basis of arthritis and systemic inflammation of s-JIA.

Background: Podocyte depletion is a major mechanism driving glomerulosclerosis. We and others have previously projected from model systems that podocyte-specific mRNAs in the urine pellet might serve as glomerular disease markers. We evaluated IgA nephropathy (IgAN) to test this concept., Methods: From 2009 to 2013, early morning voided urine samples and kidney biopsies from IgAN patients (n = 67) were evaluated in comparison with urine samples from healthy age-matched volunteers (n = 28). Urine podocyte (podocin) mRNA expressed in relation to either urine creatinine concentration or a kidney tubular marker (aquaporin 2) was tested as markers., Results: Urine podocyte mRNAs were correlated with the severity of active glomerular lesions (segmental glomerulosclerosis and acute extracapillary proliferation), but not with non-glomerular lesions (tubular atrophy/interstitial fibrosis) or with clinical parameters of kidney injury (serum creatinine and estimated glomerular filtration rate), or with degree of accumulated podocyte loss at the time of biopsy. In contrast, proteinuria correlated with all histological and clinical markers. Glomerular tuft podocyte nuclear density (a measure of cumulative podocyte loss) correlated with tubular atrophy/interstitial fibrosis, estimated-glomerular filtration rate and proteinuria, but not with urine podocyte markers. In a subset of the IgA cohort (n = 19, median follow-up period = 37 months), urine podocyte mRNAs were significantly decreased after treatment, in contrast to proteinuria which was not significantly changed., Conclusions: Urine podocyte mRNAs reflect active glomerular injury at a given point in time, and therefore provide both different and additional clinical information that can complement proteinuria in the IgAN decision-making paradigm., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objective: The prognosis of differentiated thyroid carcinoma is generally favorable. However, some patients have negative radioiodine whole-body scans and detectable serum thyroglobulin with biochemical radioiodine-refractory carcinoma and are candidates for treatment with a multikinase inhibitor, such as sorafenib. The purpose of this study is to investigate the characteristics and prognosis of differentiated thyroid carcinoma patients who are thyroglobulin positive and scan negative., Methods: We retrospectively classified 153 patients treated for 15 years by serum thyroglobulin level and radioiodine scan results and examined the relationship between clinical characteristics and prognosis., Results: Overall, 27% of the patients were classified as thyroglobulin positive/scan negative (positive/negative) while 61% were thyroglobulin negative/scan negative (double negative). Compared with double-negative patients, positive/negative patients were significantly older, predominantly male, had a higher pT and pN, stage, and had higher pre-operative thyroglobulin values. Positive/negative patients showed worse prognosis in terms of overall survival, disease-specific survival and disease-free survival than double-negative patients (10-year overall survival, 85 vs. 93%, P = 0.001; 10-year disease-specific survival, 94 vs. 100%, P = 0.03, 10-year disease-free survival, 77 vs. 93%, P < 0.001). Multivariate analysis revealed that positive/negative status was the only factor associated with disease-free survival, including age and TNM stage (hazard ratio: 6.37, 95% confidence interval: 1.22-33.3). However, the median duration of disease-free period for positive/negative patients was 14.2 years., Conclusions: Few patients among thyroglobulin-positive/scan-negative patients are candidates for sorafenib, despite the significant survival differences from double-negative patients., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: We evaluated histological changes occurring in renal biopsy specimens, between the time before initial induction therapy and after 12 months' maintenance therapy, as well as changes in laboratory parameters, SLE disease activity (SLEDAI), and dosage of corticosteroid (CS) in childhood-onset systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF)., Methods: A retrospective analysis was performed on nine patients diagnosed with childhood-onset SLE and lupus nephritis. They were treated with pulsed mPSL and intravenous cyclophosphamide as induction therapy and MMF (500-1500 mg/day) plus CS as maintenance therapy. Renal biopsy was performed before the initial induction therapy and after 12 months' maintenance therapy., Results: Pathological findings at second biopsy were improved in eight of nine patients (89%). The findings of SLEDAI, urinalysis, and blood tests also showed improvement. CS doses could be tapered satisfactorily. Adverse events were observed in two patients. No patients treated with MMF experienced any disease flares during maintenance therapy., Conclusions: MMF as maintenance therapy might be useful in that not only the histological findings of lupus nephritis were improved, but also CS doses could be beneficially tapered. Nonetheless, this is a retrospective report of only nine cases and further prospective multicenter studies are necessary.

Inflammation has often been considered to be a nonspecific response and to play a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo. Due to the crucial role of inflammatory cytokines in the pathogenesis of autoimmune disorders, anti-cytokine treatment has been developed as a therapy for rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases. We recently completed several clinical trials of anti-cytokine treatment for children with systemic inflammatory diseases: anti-IL-6 receptor monoclonal antibody (tocilizumab) for children with two subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-α monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-β monoclonal antibody (canakinumab) for children with cryopyrin-associated periodic syndrome. This review summarizes the basis of inflammation in terms of innate immunity and adaptive immunity in these systemic inflammatory diseases, clinical efficacy, and tolerability of these biologic agents, and attempts to determine the roles of individual inflammatory cytokines in disease pathogenesis.

Purpose: To conduct a national survey of systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF). Based on current information on the use of MMF, we aimed to evaluate its efficacy and safety for childhood-onset (c-) SLE., Target: We evaluated 115 patients by questionnaire on MMF use for c-SLE in medical facilities specializing in pediatric rheumatic and renal diseases., Results: Average age at SLE onset was 10.6 (range, 2-15) years; average age at the time of starting MMF was 12.3 (range, 2-15) years. Average dose per body surface area was 1,059.3 mg/m(2)/day. Corticosteroid dosing was 20.9 mg/day before treatment but 7.7 mg/day after treatment. Laboratory values before and after MMF treatment were as follows: C3 increased from 67.0 to 84.9 mg/dl (p < 0.001), C4 increased from 10.2 to 15.1 mg/dl (p < 0.001), and anti-DNA antibody decreased from 154.2 to 18.4 IU/ml (p < 0.001). 24 adverse events in 21 cases were reported, but MMF was not discontinued in any., Conclusions: The amount of MMF for c-SLE in Japan is similar to the standard dose in other countries. Reduction of corticosteroid dose and improvement of laboratory values represent efficacy of MMF. The side effects recorded here indicated tolerability of the drug.

IntroductionCu is always present in the matrix when ferritic steels were prepared from ferrous scrap. When the ferritic steels are aged thermally, Cu precipitates start appear and disperse finely and homogeneously [1], which may make the steels strengthened by precipitation hardening. In this study, the interaction between Cu precipitates and dislocations was exmined via high-temperature in-situ TEM straining. ExperimentalCu-added ferritic stainless steel (Fe-18.4%Cr-1.5%Cu) was used in the present study. Specimen was aged at1073 K for 360 ks. Samples for TEM observation were prepared by focused ion beam (FIB; Quanta 3D 200i) method. Microstructure of specimen was analyzed by JEM-3200FSK and high-temperature in-situ TEM straining was conducted using JEM-1300NEF. Results and discussionInteraction between Cu precipitates and dislocation is seen from consecutive TEM images acquired by in-situ TEM straining at 1073 K, as shown in Fig.1. The size of Cu precipitates was about 70 nm and several dislocations were present within the field of view. In particular, progressing dislocations contacted with the Cu precipitate at right angle, as indicated by arrows in Fig.1 (b) to (d). This result implies that there is an attractive interaction between dislocations and the Cu precipitate. This is attributed to the fact that Stress field of dislocations was easily relaxed in interface between the Cu precipitate and matrix because of lattice and interface diffusion as well as slip in the interface [2,3]. Furthermore, dislocations pass through the particle after contacting it, so that the interaction with dislocations and particles should be explained by Srolovitz mechanism [4].jmicro;63/suppl&#95;1/i28/DFU083F1F1DFU083F1Fig. 1.TEM images foucused on interaction with dislocations and partticles., (© The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We determined the prevalence of macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium DNA specimens from men with non-gonococcal urethritis (NGU) and analysed their effects on antibiotic treatments of M. genitalium infections., Methods: In this retrospective study, we examined antibiotic resistance-associated mutations in the 23S rRNA, gyrA and parC genes of M. genitalium and the association of the mutations with microbiological outcomes of antibiotic treatments in men with M. genitalium-positive NGU., Results: No macrolide resistance-associated mutations in the 23S rRNA gene were observed in 27 M. genitalium DNA specimens in 2011 and in 24 in 2012. However, 5 of 17 in 2013 had 23S rRNA mutations. Three of 15 in 2011, 6 of 19 in 2012 and 8 of 17 in 2013 had fluoroquinolone resistance-associated alterations in ParC. Three in 2013 had both the antibiotic resistance-associated alterations coincidentally. In two men with M. genitalium harbouring 23S rRNA mutations, the mycoplasma persisted after treatment with a regimen of 2 g of extended-release azithromycin (AZM-SR) once daily for 1 day. All nine men with mycoplasma harbouring ParC alterations were microbiologically cured with a regimen of 100 mg of sitafloxacin twice daily for 7 days., Conclusions: Macrolide- or fluoroquinolone-resistant M. genitalium appears to be increasing, and the increase in fluoroquinolone-resistant mycoplasmas is especially remarkable in Japan. Mycoplasmas harbouring 23S rRNA mutations would be resistant to the AZM-SR regimen, but those harbouring ParC alterations would still be susceptible to the sitafloxacin regimen., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We describe the effectiveness of combinatorial therapy with plasma exchanges and methylprednisolone pulses followed by intravenous cyclophosphamide in a young girl with anti-signal recognition particle 54 (SRP54) antibody-associated myopathy. We also use a newly described quantitative assay to demonstrate the close association between the titers of anti-SRP54 antibodies and disease activity. This is the first report of a pediatric patient indicating that the serum levels of anti-SRP54 antibodies are also beneficial for monitoring the disease activity of progressive necrotizing myopathy.

Objectives: Aicardi-Goutières syndrome (AGS) is a rare, genetically determined, early onset progressive encephalopathy associated with autoimmune manifestations. AGS is usually inherited in an autosomal recessive manner. The disease is rare, therefore the clinical manifestations and genotype-phenotype correlations, particularly with regard to autoimmune diseases, are still unclear. Here we performed a nationwide survey of AGS patients in Japan and analysed the genetic and clinical data., Methods: Patients were recruited via questionnaires sent to paediatric or adult neurologists in Japanese hospitals and institutions. Genetic analysis was performed and clinical data were collected., Results: Fourteen AGS patients were identified from 13 families; 10 harboured genetic mutations. Three patients harboured dominant-type TREX1 mutations. These included two de novo cases: one caused by a novel heterozygous p.His195Tyr mutation and the other by a novel somatic mosaicism resulting in a p.Asp200Asn mutation. Chilblain lesions were observed in all patients harbouring dominant-type TREX1 mutations. All three patients harbouring SAMHD1 mutations were diagnosed with autoimmune diseases, two with SLE and one with SS. The latter is the first reported case., Conclusion: This study is the first to report a nationwide AGS survey, which identified more patients with sporadic AGS carrying de novo dominant-type TREX1 mutations than expected. There was a strong association between the dominant-type TREX1 mutations and chilblain lesions, and between SAMHD1 mutations and autoimmunity. These findings suggest that rheumatologists should pay attention to possible sporadic AGS cases presenting with neurological disorders and autoimmune manifestations.

Backgrounds: A p16 protein is known to be overexpressed in human papillomavirus-positive head and neck squamous cell carcinoma specimens. p53 is a tumor suppressor protein detectable by immunohistochemistry in carcinogen-associated head and neck squamous cell carcinoma as a result of gene mutations. The purpose of this study is to investigate the prognostic impact of p16 and p53 expression in oropharyngeal squamous cell carcinomas., Methods: We retrospectively examined the relationship between prognosis, and p16 and p53 expression levels of oropharyngeal squamous cell carcinoma specimens in 53 patients using immunohistochemistry., Results: Overall, 55% of patients were p16 positive and 45% p16 negative, while 28% were p53 positive and 72% p53 negative. The p16 status showed an inverse relationship with the p53 status. A survival analysis by p16 status, p53 status, Union for International Cancer Control stage and main treatment modality demonstrated that only p16 status was related to better prognosis in terms of overall survival and disease-specific survival (3-year overall survival, 87 vs. 62%, P = 0.02; 3-year disease-specific survival, 90 vs. 62%, P = 0.02). To evaluate the practical prognostic factors in oropharyngeal squamous cell carcinoma patients, we classified patients as either p16-positive or p53-negative oropharyngeal squamous cell carcinomas, representing human papillomavirus-related oropharyngeal squamous cell carcinoma with wild-type p53 or the remaining patients with p16-negative or p53-positive OPSCCs, respectively. The former group showed survival advantages in terms of overall survival and disease-specific survival by log-tank test compared with the latter group (3-year overall survival, 96 vs. 58%, P = 0.005; 3-year disease-specific survival, 96 vs. 63%, P = 0.02)., Conclusions: A group of patients who were p16 positive/p53 negative had better prognoses in terms of overall survival and disease-specific survival than that who were p16-positive alone.

Cryopyrin-associated periodic syndrome (CAPS) is an orphan disease with incidence of about one in 1,000,000 persons. This autoinflammatory disease develops in the neonatal period or early childhood, with various inflammatory symptoms occurring repeatedly throughout the patient's lifetime. It is caused by abnormality of the NLRP3 protein which mediates the intracellular signal transduction mechanism of inflammatory processes, resulting in continuous overproduction of interleukin (IL)-1β, which induces chronic inflammation and progressive tissue damage. Definitive diagnosis of CAPS is difficult, and treatment has also been difficult because of a lack of effective medications in Japan. Clinical studies of human anti-human IL-1β monoclonal antibody (canakinumab) treatment were conducted in Japan, and approval was granted for therapeutic use of canakinumab for CAPS in September 2011. Similar to other biological drugs, canakinumab is clinically highly effective. However, sufficient attention to the method of use and adverse drug reactions is necessary. This guidance describes the use of canakinumab in Japan for CAPS in relation to exclusion criteria, method of use, evaluation criteria, and adverse drug reactions.

Several loop-mediated isothermal amplification (LAMP) assays have been developed to detect common causative pathogens of bacterial meningitis (BM). However, no LAMP assay is reported to detect Streptococcus agalactiae and Streptococcus suis, which are also among common pathogens of BM. Moreover, it is laborious and expensive by performing multiple reactions for each sample to detect bacterial pathogen. Thus, we aimed to design and develop a single-tube LAMP assay capable of detecting multiple bacterial species, based on the nucleotide sequences of the 16S rRNA genes of the bacteria. The nucleotide sequences of the 16S rRNA genes of main pathogens involved in BM were aligned to identify conserved regions, which were further used to design broad range specific LAMP assay primers. We successfully designed a set of broad range specific LAMP assay primers for simultaneous detection of four species including Staphylococcus aureus, Streptococcus pneumoniae, S. suis and S. agalactiae. The broad range LAMP assay was highly specific without cross-reactivity with other bacteria including Haemophilus influenzae, Neisseria meningitidis and Escherichia coli. The sensitivity of our LAMP assay was 100-1000 times higher compared with the conventional PCR assay. The bacterial species could be identified after digestion of the LAMP products with restriction endonuclease DdeI and HaeIII., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Aims: Fibrosis and inflammation may play a significant role in the pathogenesis of atrial fibrillation (AF) recurrence. Type III procollagen-N-peptide (PIIINP) may be related to atrial fibrosis and play a role in predicting the recurrence of AF. We investigated whether PIIINP as a fibrosis marker predicts the recurrence of AF after cardioversion., Methods and Results: Serum PIIINP, interleukin-6, high-sensitivity C-reactive protein, brain natriuretic peptide, renin and aldosterone were measured at baseline and 24 months in 88 patients (62%) with sinus rhythm (SR) maintenance and 54 patients (38%) with AF recurrence. Furthermore, the root mean square voltage in the last 20 ms (RMS20) via P-wave signal-averaged electrocardiogram (P-SAECG) was measured and the relationship between fibrosis biomarkers and RMS20 was examined. Baseline PIIINP with AF recurrence was significantly higher than for those with SR maintenance (0.664 vs. 0.581 U/mL, P = 0.001). However, there were no significant differences in other biomarkers. A logistic regression identified PIIINP (odds ratio 2.61, P = 0.008) as an independent predictor of AF recurrence. The RMS20 as measured by P-SAECG with SR maintenance and PIIINP levels <0.72 U/mL (at baseline) was significantly higher after 24 months than at baseline. Furthermore, the RMS20 with AF recurrence and PIIINP levels >0.72 U/mL (at baseline) was significantly lower after 24 months than baseline., Conclusions: Elevated baseline PIIINP concentration is an independent predictor for AF recurrence after cardioversion. Furthermore, there is a relationship between PIIINP and RMS20 and the fibrosis of AF.

We performed this study to investigate the differences in radiological and laboratory findings between systemic juvenile idiopathic arthritis (s-JIA) and polyarthritis (p-JIA). Twenty-two patients with s-JIA and 18 with p-JIA were enrolled. Their laboratory findings and radiographs were examined retrospectively. Plain radiographs were obtained before the induction of biological agents. All radiographs were examined for the presence of soft tissue swelling, juxta-articular osteopenia, joint space narrowing, subchondral bone cyst, erosion, epiphyseal irregularity, and growth abnormalities. Carpal length and bone mineral density of the lumbar spine, an indicator of generalized osteoporosis, were also investigated in all the patients enrolled. Laboratory examinations involved white blood cell counts, platelets, C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and matrix metalloproteinase (MMP)-3. Comparisons of the laboratory findings between s-JIA and p-JIA indicated that the titers of anti-CCP antibody and RF were significantly increased in p-JIA sera (P < 0.05). There was no difference in BMD between the two groups of patients. Carpal length was significantly shorter in p-JIA patients than in s-JIA patients (P < 0.05). The most frequent radiological abnormality in s-JIA was juxta-articular osteopenia (93.8%), in comparison to a frequency of 50.0% in p-JIA. Joint space narrowing was shown in 9.8% of the s-JIA patients compared to 35.7% of the p-JIA patients. Subchondral bone cyst and erosion were more frequent in p-JIA than s-JIA. In conclusion, there were differences in radiographic characteristics and laboratory data between s-JIA and p-JIA in this study. In the radiological evaluation, bone-related abnormality was prominent in s-JIA and joint-related abnormality was striking in p-JIA, and these results indicated that the pathogenic bases of arthritis appear to differ between these two subtypes of JIA.

The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this study, we attempted to discover the factor that induces interconnection of FS cells and succeeded in identifying chemokine (CXC)-L12 and its receptor CXCR4 as potential candidate molecules. CXCL12 is a chemokine of the CXC subfamily. It exerts its effects via CXCR4, a G protein-coupled receptor. The CXCL12/CXCR4 axis is a potent chemoattractant for many types of neural cells. First, we revealed that CXCL12 and CXCR4 are expressed by FS cells in rat anterior pituitary gland. Next, to clarify the function of the CXCL12/CXCR4 axis in FS cells, we observed living anterior pituitary cells in primary culture with specific CXCL12 inhibitor or CXCR4 antagonist and noted that extension of cytoplasmic processes and interconnection of FS cells were inhibited. Finally, we examined FS cell migration and invasion by using Matrigel matrix assays. CXCL12 treatment resulted in markedly increased FS cell migration and invasion. These data suggest that FS cells express chemokine CXCL12 and its receptor CXCR4 and that the CXCL12/CXCR4 axis evokes interconnection of FS cells.

Specialized insect mouthparts, such as those of Drosophila, are derived from an ancestral mandibulate state, but little is known about the developmental genetics of mandibulate mouthparts. Here, we study the metamorphic patterning of mandibulate mouthparts of the beetle Tribolium castaneum, using RNA interference to deplete the expression of 13 genes involved in mouthpart patterning. These data were used to test three hypotheses related to mouthpart development and evolution. First, we tested the prediction that maxillary and labial palps are patterned using conserved components of the leg-patterning network. This hypothesis was strongly supported: depletion of Distal-less and dachshund led to distal and intermediate deletions of these structures while depletion of homothorax led to homeotic transformation of the proximal maxilla and labium, joint formation required the action of Notch signaling components and odd-skipped paralogs, and distal growth and patterning required epidermal growth factor (EGF) signaling. Additionally, depletion of abrupt or pdm/nubbin caused fusions of palp segments. Second, we tested hypotheses for how adult endites, the inner branches of the maxillary and labial appendages, are formed at metamorphosis. Our data reveal that Distal-less, Notch signaling components, and odd-skipped paralogs, but not dachshund, are required for metamorphosis of the maxillary endites. Endite development thus requires components of the limb proximal-distal axis patterning and joint segmentation networks. Finally, adult mandible development is considered in light of the gnathobasic hypothesis. Interestingly, while EGF activity is required for distal, but not proximal, patterning of other appendages, it is required for normal metamorphic growth of the mandibles.

8-oxo-dGTP is generated in the nucleotide pool by direct oxidation of dGTP or phosphorylation of 8-oxo-dGDP. It can be incorporated into DNA during replication, which would result in mutagenic consequences. The frequency of spontaneous mutations remains low in cells owing to the action of enzymes degrading such mutagenic substrates. Escherichia coli MutT and human MTH1 hydrolyze 8-oxo-dGTP to 8-oxo-dGMP. Human NUDT5 as well as human MTH1 hydrolyze 8-oxo-dGDP to 8-oxo-dGMP. These enzymes prevent mutations caused by misincorporation of 8-oxo-dGTP into DNA. In this study, we identified a novel MutT homolog (NDX-1) of Caenorhabditis elegans that hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP. NDX-1 did not hydrolyze 8-oxo-dGTP, 2-hydroxy-dATP or 2-hydroxy-dADP. Expression of NDX-1 significantly reduced spontaneous A:T to C:G transversions and mitigated the sensitivity to a superoxide-generating agent, methyl viologen, in an E. coli mutT mutant. In C. elegans, RNAi of ndx-1 did not affect the lifespan of the worm. However, the sensitivity to methyl viologen and menadione bisulfite of the ndx-1-RNAi worms was enhanced compared with that of the control worms. These facts indicate that NDX-1 is involved in sanitization of 8-oxo-dGDP and plays a critical role in defense against oxidative stress in C. elegans.

Free haem is known to be toxic to organs, tissues and cells. It enhances permeability by binding to a cell membrane, which leads to cell death, and damages lipids, proteins and DNA through the generation of reactive oxygen species. Lysine- and arginine-specific gingipains (Kgp and RgpA/B) are major proteinases that play an important role in the pathogenicity of a black-pigmented periodontopathogen named Porphyromonas gingivalis. One of the adhesin domains of gingipain, HbR could bind haem as an iron nutrient source for P. gingivalis. Using erythrocyte and its membrane as a model, results from the present study demonstrate that recombinant HbR expressed in Escherichia coli could inhibit haem-induced haemolysis, probably through removing haem from the haem-membrane complex and lowering free haem toxicity by mediating dimerization of haem molecules. The ability to protect a cell membrane from haem toxicity is a new function for HbR.

C-Reactive protein (CRP) is an acute-phase protein that increases during systemic inflammation and is currently one of the most frequently studied inflammatory markers in epidemiology. We have determined CRP concentration using novel latex reagent with polyclonal antibody. In the present study, we determined the concentration of CRP using monoclonal antibodies, and evaluated the interaction of antigen-antibody reactive sites and latex agglutination to detect low CRP concentrations. We developed four novel monoclonal antibodies that we classified into two major groups, and that were used to prepare the latex reagents. The latex reagents prepared using a cocktail of monoclonal antibodies for different epitopes appeared highly sensitive. The lower limit of CRP detection, which was defined using the mean 3 SD method, was calculated to be 5 ng/ml for the latex reagents when oligoclonal antibodies were utilized. Furthermore, the latex reagents were found to react specifically with CRP in clinical samples.

The 5-formyluracil (5-foU), a major mutagenic oxidative damage of thymine, is removed from DNA by Nth, Nei and MutM in Escherichia coli. However, DNA polymerases can also replicate past the 5-foU by incorporating C and G opposite the lesion, although the mechanism of correction of the incorporated bases is still unknown. In this study, using a borohydride-trapping assay, we identified a protein trapped by a 5-foU/C-containing oligonucleotide in an extract from E. coli mutM nth nei mutant. The protein was subsequently purified from the E. coli mutM nth nei mutant and was identified as KsgA, a 16S rRNA adenine methyltransferase. Recombinant KsgA also formed the trapped complex with 5-foU/C- and thymine glycol (Tg)/C-containing oligonucleotides. Furthermore, KsgA excised C opposite 5-foU, Tg and 5-hydroxymethyluracil (5-hmU) from duplex oligonucleotides via a beta-elimination reaction, whereas it could not remove the damaged base. In contrast, KsgA did not remove C opposite normal bases, 7,8-dihydro-8-oxoguanine and 2-hydroxyadenine. Finally, the introduction of the ksgA mutation increased spontaneous mutations in E. coli mutM mutY and nth nei mutants. These results demonstrate that KsgA has a novel DNA glycosylase/AP lyase activity for C mispaired with oxidized T that prevents the formation of mutations, which is in addition to its known rRNA adenine methyltransferase activity essential for ribosome biogenesis.

Locomotory behavior (motility) and mechanosensation are of vital importance in animals. We examined the effects of ionizing radiation (IR) on locomotory behavior and mechanosensation using a model organism, the nematode Caenorhabditis elegans. Bacterial mechanosensation in C. elegans induces the dopamine-mediated slowing of locomotion in the presence of bacteria (food), known as the basal slowing response. We previously reported an IR-induced reduction of locomotory rate in the absence of food. In the present study, we observed a similar IR-induced reduction of locomotory rate in the cat-2 mutant, which is defective in bacterial mechanosensation. The dose response pattern of the locomotory rate in the presence of food was relatively flat in wild-type animals, but not in cat-2 mutants. This suggests that the dopamine system, which is related to bacterial mechanosensation in C. elegans, might have a dominant effect on locomotory rate in the presence of food, which masks the effects of other stimuli. Moreover, we found that the behavioral responses of hydrogen peroxide-exposed wild-type animals are similar to those of IR-exposed animals. Our findings suggest that the IR-induced reduction of locomotory rate in the absence of food is mediated by a different pathway from that for bacterial mechanosensation, at least partially through IR-produced hydrogen peroxide.

Uracil arises in DNA from spontaneous deamination of cytosine and through incorporation of dUMP by DNA polymerase during DNA replication. Excision of uracil by the action of uracil-DNA glycosylase (Ung) initiates the base excision repair pathway to counter the promutagenic base modification. In this study, we cloned a cDNA-encoding Caenorhabditis elegans homologue (CeUng-1) of Escherichia coli Ung. There was 49% identity in amino acid sequence between E.coli Ung and CeUng-1. Purified CeUng-1 removed uracil from both U:G and U:A base pairs in DNA. It also removed uracil from single-stranded oligonucleotide substrate less efficiently than double-stranded oligonucleotide. The CeUng-1 activity was inhibited by Bacillus subtilis Ung inhibitor, indicating that CeUng-1 is a member of the family-1 Ung group. The mutation in the ung-1 gene did not affect development, fertility and lifespan in C.elegans, suggesting the existence of backup enzyme. However, we could not detect residual uracil excision activity in the extract derived from the ung-1 mutant. The present experiments also showed that the ung-1 mutant of C.elegans was more resistant to NaHSO(3)-inducing cytosine deamination than wild-type strain.

This report demonstrates for the first time that P5, a member of the protein disulphide isomerase (PDI) family, is present in the mitochondria. Various organelles were screened for proteins bearing the CGHC motif using an affinity column conjugated with the phage antibody 5E, which cross-reacts with PDI family proteins. P5 was found in bovine liver mitochondrial extract and identified by Western blot analysis using anti-P5 antibody and by mass spectrometric analysis. Results of cell fractionation, proteinase sensitivity experiments and immuno-electron microscopy supported the mitochondrial localization of P5 and also indicated the presence of ERp57, another PDI family protein, in mitochondria. Our findings will be useful for the elucidation of the translocation mechanism of PDI family proteins and their roles in mitochondria.

We investigated the mechanism of the antihypertensive effect of less-sodium soy sauce containing gamma-aminobutyric acid (GABA) in spontaneously hypertensive rats (SHRs). When SHRs were given a diet with less-sodium soy sauce containing GABA (GABA-rich soy sauce group) for 6 weeks, the systolic blood pressure decreased as compared with that in rats fed diets with less-sodium soy sauce or a solution of salt. Renal sympathetic nerve activity (RSNA) and positive Na balance were reduced, and the urinary Na excretion tended to increase in the GABA-rich soy sauce group. Vascular hypertrophy of the thoracic aorta and the coronary and renal interlobular arteries tended to reduce in the GABA-rich soy sauce group. These results suggest that inhibition of Na retention by natriuresis, as a result of inhibition of RSNA by the GABA in the soy sauce contributed to the antihypertensive effect of GABA in the SHRs. Intake of less-sodium soy sauce containing GABA might help to reduce overall cardiovascular risk.

For measuring the vital signs of casualties inside an isolation unit, we developed a noncontact vital sign monitoring system using a microwave radar. The system was tested on eight healthy volunteers ranging in age from 30 to 48 years. The heart and respiratory rates derived by the microwave radar correlated with the heart and respiratory rates determined by electrocardiogram and respiratory sensor (r = 0.98, p < 0.0001 for heart rate; r = 0.84, p < 0.01 for respiratory rate). The exhaled CO and CO2, as a measure of trauma injury, were measured using an exhaled gas analyzer. The CO and CO2 concentrations were found to average 3.8 +/- 4.3 ppm and 2.9 +/- 0.4%, respectively. The expired air temperature and body temperature, as indicators of hemorrhagic hypothermia, averaged 31.8 +/- 1.7 degrees C and 36.2 +/- 0.4 degrees C, respectively. The results show that our system is promising for future prehospital application in determining casualty conditions for fluid infusions by the Casualty Care System intravenous lines.

Background: Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites., Objectives: To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES., Methods: Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30., Results: CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder., Conclusions: We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.

Background: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin., Objectives: To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions., Methods: We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration., Results: The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells., Conclusions: Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.

The anti-allergic activity of a tomato extract was studied by using an in vitro histamine-release assay. The tomato skin extract exerted the strongest inhibition of histamine release. Chlorogenic acid, rutin and naringenin were identified in the 60% ethanol extract of tomato skin. However, the extract contained an unknown compound which strongly inhibited histamine release. This active compound in tomato skin was identified as naringenin chalcone (trans-2'4'6'4-tetrahydroxychalcone). Naringenin chalcone inhibited histamine release with an IC(50) value of 68 microg/ml. The anti-allergic activity of the tomato skin extract was next investigated by the in vivo mouse ear-swelling response. We found that naringenin chalcone showed the strongest inhibitory effect of the polyphenols of the tomato skin extract. These results indicate that a tomato skin extract could inhibit allergic reactions.

In 22 histologic cases of subcutaneous panniculitis-like lymphoma, we studied the clinicopathologic differences between CD56- and CD56+ cases (11 each). CD56- cases had skin ulcers (1 [9%]); tumor invasion in the superficial dermis (1 [9%]); erythrophagocytosis (10 [91%]); and medium-sized (11 [100%]), CD8+ (10 [91%]), T-cell receptor (TcR)betaF1+ (10 [91%]), and CD95 (Fas)- tumor cells. CD56+ cases had skin ulcers (9 [82%]); tumor invasion in the superficial dermis (8 [73%]); erythrophagocytosis (1 [9%]); and pleomorphic large (10 [91%]), CD8+ (2/10 [20%]), TcRbetaF1 + (3/10 [30%]), and CD95 (Fas)+ (7/10 [70%]) tumor cells. These 7 factors were significantly different between groups (P < .01). Median survival rates were 96 and 12 months for the CD56- and CD56+ groups, respectively. Age younger than 40 years, no skin ulcers, no tumor invasion in the superficial dermis, and CD8+, TcRbetaF1 +, CD95 (Fas)-, and CD56- tumor cells were significantly better prognostic factors (P < .01). The CD56- and CD56+ groups showed different tumor cell characteristics, clinicopathologic findings, and prognosis. In the CD56+ group, 1 was gamma/delta T-cell phenotype, 3 were alpha/beta T-cell, and 6 were TcRbetaF1- and gamma/delta- NK/T-cell, and 3 NK/T-cell cases had nuclear signals of Epstein-Barr virus-encoded RNA. Cases of CD56+ T- and NK/T-cell lymphoma had similar clinicopathologic findings and prognosis.

To confirm the absorption of proanthocyanidin (PA) into the human body, four healthy adults were administered 2.0 g of PA-rich grape seed extract (GSE). Blood were drawn before intake and 2 h after intake. Through the enzymatic treatment of sulfatase and beta-glucuronidase, blood samples were analyzed by HPLC coupled with mass-spectrometry (LC/MS). Procyanidin B1 [epicatechin-(4beta-->8)-catechin] was detected in human serum 2 h after intake. Its concentration was 10.6 +/- 2.5 nmol/l.