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The gut-skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl sulfate was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated-dextran. The role of interleukin-13 (IL-13) in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, or innate lymph cell-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The uterus is known as one of the moving organs. We evaluated the movement of the uterus during irradiation and the effects of changes in the surrounding organs using a magnetic resonance (MR)-guided radiotherapy system. Seven patients with cervical cancer underwent pre- and posttreatment MR imaging to assess changes in the positioning of the uterus and cervix as well as the alterations in bladder and rectal volume. The study revealed that the movements of the uterus were greater than that of the cervix and showed a tendency to correlate with the bladder rather than the rectum. We also examined whether intrafractional motion could lead to insufficient dose coverage of the clinical target volume (CTV), specifically focusing on the D98% of the CTV in the uterine body and cervix. The impact of intrafractional motion on the D98% varied among patients, with one out of the seven patients experiencing an average dosimetric change of -2.6 Gy in the uterus, although larger planning target volume margins of 1.5 cm were applied, therefore, indicating the need for individualized optimal margins in each case. Online adaptive radiotherapy offers the advantage of modifying the treatment plan when irradiating moving organs, such as the uterus. However, it should be noted that this approach may result in longer overall treatment times compared with the traditional methods. Therefore, we must carefully consider the influence of intrafractional organ motions when opting for such a treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar., Methods: The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence)., Results: A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001)., Conclusion: It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated., (© Crown copyright 2023.)

This study aimed to clarify the differences in radiotherapy dose characteristics and delivery efficiency between the supine and prone positions in patients with prostate cancer using the CyberKnife. The planning computed tomography (CT) and delineations of the prone position were obtained by rotating the supine CT images with delineations of 180° using image processing software. The optimization parameters for planning target volume (PTV) and organs at risk (OARs) were based on the prone position. The optimization parameters determined for the prone position were applied to the supine position for optimization and dose calculation. The dosimetric characteristics of the PTV and OARs, and delivery efficiency were compared between the two different patient positions. The plans in the prone position resulted in better PTV conformity index (nCI), rectum V90%, V80%, V75%, V50% and bladder V50%. A significant difference was observed in treatment time and depth along the central axis (dCAX) between the two plans. The mean treatment time per fraction and dCAX for the supine and prone positions were 20.9 ± 1.7 min versus 19.8 ± 1.3 min (P = 0.019) and 151.1 ± 33.6 mm versus 233.2 ± 8.8 mm (P < 0.001), respectively. In this study the prone position was found to improve dosimetric characteristics and delivery efficiency compared with the supine position during prostate cancer treatment with the CyberKnife., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer., Methods: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%., Results: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036)., Conclusion: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Surgery is the standard modality for early-stage I-II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80-94). The median follow-up period and OS was 39.8 months (range, 10-101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0-1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Our previous study by Murakami N, Mori T, Nakamura S, Yoshimoto S, Honma Y, Ueno T, Kobayashi K, Kashihara T, Takahashi K, Inaba K, Okuma K, Igaki H, Nakayama Y, Itami J. (J Radiat Res. 2019 Jul 30. pii: rrz053. doi: 10.1093/jrr/rrz053. [Epub ahead of print]) showed that strong expression of epithelial cell adhesion molecule (EpCAM) was associated with radiation resistance in head and neck squamous cell cancer patients (SCC). In this study, the prognostic impact of histopathologic features including EpCAM for nasopharyngeal cancer (NPC) patients was investigated. Since 2009, our institution has performed chemoradiation for locally advanced NPC patients with intensity modulated radiation therapy (IMRT). Tri-weekly adjuvant cisplatin (CDDP, 80 mg/m2) was administered concurrently with definitive radiation therapy 70 Gy in 35 fractions. One month after radiation therapy, adjuvant chemotherapy of three cycles of CDDP/5 fluorouracil (5-FU) was administered. Using a pretreatment biopsy specimen, EBV-encoded small RNA in situ hybridization (EBER-ISH), EpCAM, p16 and p53 were assessed by immunohistochemical analysis. Between May 2009 and September 2017, 51 NPC patients received definitive radiation therapy. Five, 13, 17 and 16 patients were staged as I, II, III and IV, respectively. The median follow-up period for alive patients was 31.1 months (12.4-109.7 months). Three-year overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were 87.1, 57.1 and 85.7%, respectively. EpCAM, p16 and p53 were not associated with PFS, OS nor LRC. Three-year PFS for patients with keratinizing and non-keratinizing SCC were 25 and 60.5%, respectively (P = 0.033, hazard ratio 4.851 (95% confidence interval 1.321-17.814)).Prognosis of NPC patients with keratinizing SCC was worse than non-keratinizing SCC patients, suggesting a biological difference between the two types of tumor., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

A reliable biomarker can contribute to appropriate treatment selection in the management of head and neck squamous cell carcinoma (HNSCC). Recently, epithelial cell adhesion molecule (EpCAM) was shown to have prognostic features in several malignancies. However, it remains to be elucidated whether EpCAM predicts prognosis of HNSCC after radiotherapy. Therefore, the prognostic potential of EpCAM in HNSCC patients treated by radiotherapy was investigated in this study. All HNSCCs patients examined between January 2013 and December 2015 were analyzed for the expression of EpCAM. One hundred HNSCC patients were identified who were treated by primary radiotherapy. Intense expression of EpCAM was found in 29 HNSCC patients. Two-year overall survival (OS) for patients with intense EpCAM expression was 62.2%, whereas it was 87.9% for those without (P = 0.011). In multivariate analysis, intense EpCAM expression was found to be an independent prognostic factors for OS (P = 0.036). Overall, EpCAM was found to be an independent prognostic factor for HNSCC., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The current study retrospectively analyzed the results of radiotherapy for clinically localized sebaceous carcinoma of the eyelid.We reviewed records of 83 patients with histologically confirmed sebaceous carcinoma who were treated radiotherapeutically between 1983 and 2015. Sixty-five patients (78%) were initially treated with radiotherapy of curative intent, while the remaining 18 patients underwent postoperative radiotherapy due to tumor recurrence or positive surgical margins. Thirty-seven patients belonged to T1-2, while 46 belonged to T3-4. All 83 patients were treated with radiotherapy with a median radiation dose of 60 Gy. The median follow-up period was 92.1 months (range, 2.8-310.3 months). At the time of analysis, 13 patients (15.1%) died, and 36 patients (43.3%) had local recurrence. The 7-year overall survival, freedom from neck lymph node recurrence, and local control (LC) rates for all patients were 83.5%, 75.5%, and 52.3%, respectively. Patients with a tumor size ≤10 mm had a higher 7-year LC rate than those with a tumor size >10 mm (58.8% vs 46.6%, P = 0.054). Neck lymph node recurrence was observed in 17 patients (20%) and significantly related to the tumor size. Late toxicity of an eyelid dysfunction of grade 3 was observed in 1 patient with T3 tumor. Radiotherapy for sebaceous carcinoma of the eyelid is a reasonable alternative to surgical resection for tumors <10 mm in size with few severe complications, while larger tumors should be treated with surgery if feasible., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The aim of the study was to compare incidences of late gastrointestinal adverse events and clinical outcomes between 3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) after radical hysterectomy for cervical cancer patients. Between March 2007 and May 2014, 73 cervical cancer patients with high-risk prognostic factors (pelvic lymph node metastasis and/or parametrial invasion) underwent postoperative pelvic radiation therapy (RT) after radical hysterectomy. Of these patients, 33 (45%) and 40 (55%) received 3DCRT and IMRT, respectively. Because the gastrointestinal obstruction rate after postoperative pelvic 3DCRT was high, no concurrent chemotherapy was applied until 2015. The median follow-up period for patients with 3DCRT and IMRT was 82 months (6-113) and 50 months (5-74), respectively. There was no significant difference in overall survival (OS) (4-year OS: 85% vs 78%, P = 0.744) or disease-free survival (DFS) (4-year DFS: 73% vs 64%, P = 0.696) between the two groups. Eleven (33%) and 13 (33%) patients experienced recurrence after 3DCRT and IMRT, respectively. The patients who had vaginal invasion from the postoperative pathological finding more frequently had loco-regional recurrence than the patients who did not have vaginal invasion (2.3% vs 17%, P = 0.033). Gastrointestinal obstruction was observed in 9 (27%) and 3 (7.5%) patients for 3DCRT and for IMRT, respectively (P = 0.026). Severe gastrointestinal obstruction that required surgery was observed in 6 (19%) patients, all of whom received adjuvant RT by 3DCRT. IMRT could reduce the incidence of late severe gastrointestinal obstruction after postoperative pelvic RT with a non-inferior clinical efficacy compared with 3DCRT., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Small cell carcinoma of the bladder is extremely rare, accounting for <1% of all malignant tumours in the urinary tract. Thus, no standard therapy modality for this malignancy has been established. This study aimed to retrospectively analyse the clinical outcomes associated with definitive radiotherapy for small cell carcinoma of the bladder. A questionnaire-based survey of patients with pathologically proven small cell carcinoma of the bladder treated with definitive radiation therapy between 1990 and 2010 was conducted by the Japanese Radiation Oncology Study Group. The clinical records of 12 eligible patients were collected from nine institutions. The median age of the patients was 70.5 years (range: 44-87 years), and the median follow-up period was 27.3 months (range: 3.3-117.8 months). The median prescribed dose was 60 Gy (range: 50.0-61.0 Gy), and a median of 2.0 Gy (range: 1.2-2.0 Gy) was administered per fraction. Systemic chemotherapy combined with radiotherapy was performed in eight cases (66.7%). The 3- and 5-year overall survival rates were 50.0% and 33.3%, respectively. And the 3- and 5-year local control rates were 66.7% and 55.6%, respectively. Chemotherapy significantly improved overall survival and relapse-free survival (P = 0.006 and 0.001, respectively). No serious adverse events occurred in the observation period. All patients who achieved local control maintained functional bladders. In conclusion, radiotherapy is a potential local treatment option and has an important role in maintaining quality of life. Systemic chemotherapy combined with local radiotherapy seems to be effective in improving survival., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Perirectal hyaluronate gel injection (HGI) appears to be a promising technique for healthy tissue dose sparing in pelvic radiotherapy. In this analysis, we report our initial experience of HGI in gynecologic brachytherapy, focusing on its safety and effectiveness for dose reduction to the rectum. Between July 2013 and May 2014, 36 patients received HGI for primary/salvage gynecologic brachytherapy. Dosimetric effect analysis was based on pre- and post-HGI computed tomography dataset registration with corresponding dose-volume histogram evaluation. The maximum dose to the most exposed 0.1 cm3 (D0.1cm3) and 2.0 cm3 (D2.0cm3) were used as index values for rectum and bladder dose evaluation. The dose indexes for target volume (TV) coverage were TV D90/V100. In all cases, HGI was well tolerated, with no acute or late adverse events documented at a median follow-up of 220 days (range, 18-1046 days). Rectum D2.0cm3 and D0.1cm3 were significantly decreased by HGI (P < 0.001 and P = 0.003, respectively), with no significant impact on dosimetric parameters of bladder and TV coverage. Factors correlating negatively with the dosimetric effect of HGI were an increasing number of interstitial catheters (P = 0.003) as well as Lcranial100% (P = 0.014) and Lcranial80% (P = 0.001) [i.e. the length from the anal verge to the most cranial point at which the 100% and 80% isodose lines, respectively, crossed the rectum]. The concept of HGI for gynecologic brachytherapy is plausible, and our initial experience indicates it to be an effective technique for rectal dose reduction in radiotherapy of intrapelvic tumours., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Palliative care specialists (PCS) and burn surgeons (BS) were surveyed regarding: 1) importance of goals of care (GoC) conversations for burned seniors; 2) confidence in their own specialty's ability to conduct these conversations; and 3) confidence in the ability of the other specialty to do so. A 13-item survey was developed by the steering committee of a multicenter consortium dedicated to palliative care in the injured geriatric patient and beta-tested by BS and PCS unaffiliated with the consortium. The finalized instrument was electronically circulated to active physician members of the American Burn Association and American Academy for Hospice and Palliative Medicine. Forty-five BS (7.3%) and 244 PCS (5.7%) responded. Palliative physicians rated being more familiar with GoC, were more comfortable having a discussion with laypeople, were more likely to have reported high-quality training in performing conversations, believed more palliative specialists were needed in intensive care units, and had more interest in conducting conversations relative to BS. Both groups believed themselves to perform GoC discussions better than the other specialty perceived them to do so. BS favored leading team discussions, whereas palliative specialists preferred jointly led discussions. Both groups agreed that discussions should occur within 72 hours of admission. Both groups believe themselves to conduct GoC discussions for burned seniors better than the other specialty perceived them to do so, which led to disparate views on perceptions for the optimal leadership of these discussions.

Cilia and flagella are cell machines that power hydrodynamic forces by fast beating. They are composed of bundles of 9 + 2 microtubules that associate with several protein structures including axonemal dyneins and their regulators. Spermatozoa are single cells with in most cases a single flagellum and are good cell models to study how flagellar movements are regulated and linked to cell behavior. In addition, the assessment of sperm motility is an important diagnostic tool for evaluating male fertility in human reproductive medicine, and in livestock and fisheries sciences. Microscopic analyses of the movements of spermatozoa and their flagellar waveforms and propagation have been carried out using high-speed cameras and stroboscopic illumination. Computer-assisted sperm analysis (CASA) now comprises an automated set of methods to evaluate sperm quality for fertility. Here, we summarize the microscopy systems used for evaluating sperm motility, including CASA, and introduce updates on the molecular mechanism of flagellar movement and regulation that are linked to motility parameters. Furthermore, we introduce recent techniques employed to measure key factors controlling sperm motility.

Background: Detailed information regarding the clinical efficacy of radiotherapy (RT) for primary tumor in patients with unresectable pancreatic neuroendocrine tumors (pNETs) is unknown. We therefore performed a retrospective study to evaluate the efficacy and safety of RT for primary pancreatic tumors in patients with pNETs., Methods: We investigated 11 patients with pNETs who received RT to the primary site between January 1997 and June 2015. Seven patients had Grade 2 neuroendocrine tumors (NET-G2) and four had neuroendocrine carcinoma (NEC) according to the 2010 WHO histopathological classification., Results: The tumor response and control rates were 27.2% and 100%, respectively (3: partial response, 8: stable disease). Among patients with NET-G2 tumors, the response rate was 28.5% (2/7 patients) and symptomatic improvement was noted in 33.3% of the patients (1/3 patients). The response rate for patients with NEC were 25% (1/4), one NEC patients with symptoms exhibited symptomatic improvement. The median overall survival and median progression-free survival were 35.9 months and 5.5 months, respectively. Grade 3 diarrhea as an acute toxicity and Grade 3 gastrointestinal hemorrhage as a late toxicity were observed., Conclusions: RT to the primary cancer site in patients with pNETs was an effective modality for local disease control and the treated patients had good outcomes. If metastatic tumors are under control, RT to the primary site may be beneficial for patients with pNETs., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

It has been suggested that dichloromethane (DCM) and 1,2-dichloropropane (DCP) are responsible for occupational cholangiocarcinoma. Dihaloalkanes are metabolically activated by GSH S-transferase theta1 (GSTT1) to yield products such as episulfonium ions. However, whether the GSTT1-mediated step of these dihaloalkanes is related to occupational cholangiocarcinoma is not known. In the present study, we investigated the influence of GSTT1 activation on the mutagenicity of DCM and 1,2-DCP using GSTT1-expressing Salmonella typhimurium TA100 (TA100-GST). Since the mutagenicity of DCM was significantly increased in TA100-GST compared with mock control (TA100-pCTC), GSTT1 is thought to be involved in the mutagenicity of DCM. Mutation spectrum analysis on the hisG gene revealed that C:G to A:T transversions were the predominant form observed in DCM-treated TA100-pCTC. However, C:G to T:A transitions were dramatically increased in TA100-GST. We also analysed the DCM-DNA adduct, N2-GSH-Me-dG, and formation of N2-GSH-Me-dG was increased in TA100-GST compared with TA100-pCTC. On the other hand, 1,2-DCP did not increase the numbers of revertants in TA100-GSTT1. In mutation spectrum analysis, C:G to T:A transitions was predominant in both TA100-pCTC and TA100-GSTT1. These findings suggest that GSTT1 has little involvement in DCP mutagenicity, and other mechanisms might be more important for bioactivation and consequent genotoxicity. Clarification of the mechanisms underlying the development of DCM- and/or 1,2-DCP-related human cholangiocarcinoma may help establish risk assessment and prevention strategies against occupational cancer., (© The Author 2017. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There are many reports concerning patient-specific quality assurance (QA) for intensity-modulated radiation therapy (IMRT). However, reports about the statistical results of QA are lacking. Management methods for the results of the QA are needed, even though we have the ESTRO group recommendation that a tolerance limit of 1.96 standard deviation (SD) be established in each institution. The purpose of this study was to establish a management method for determining the tolerance limit and to report the statistical results of patient-specific QA. From April 2006 to March 2015, five linacs in the National Cancer Center, Tokyo, Japan, were used to treat 1185 patients with IMRT. Patient-specific QA was performed using an ion chamber, films, and some detectors. To establish a management method for the results, differences between the measured and calculated doses in the ion chamber were analyzed for each linac, each phantom, and each treatment site. The overall mean dose difference was 0.5 ± 1.3%, and the mean dose difference in each linac was 0.6 ± 1.2%, 0.9 ± 1.3%, -0.4 ± 1.4%, -0.1 ± 1.2% and -0.1 ± 0.9%. The difference between linacs and between treatment sites was significant (P < 0.001 and 0.01, respectively). The proportion of the dose difference within ±3% was 97.7%, and that was improved from 2006 to 2014. The results of the patient-specific QA should be managed for each linac and each treatment site in order to decide the suitable tolerance limit. Reports of statistical results will be helped if a new tolerance limit and action level will be considered., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The brachytherapy dose calculations used in treatment planning systems (TPSs) have conventionally been performed assuming homogeneous water. Using measurements and a Monte Carlo simulation, we evaluated the dosimetric impact of an air passage on brachytherapy for bronchus cancer. To obtain the geometrical characteristics of an air passage, we analyzed the anatomical information from CT images of patients who underwent intraluminal brachytherapy using a high-dose-rate 192 Ir source (MicroSelectron V2r®, Nucletron). Using an ionization chamber, we developed a measurement system capable of measuring the peripheral dose with or without an air cavity surrounding the catheter. Air cavities of five different radii (0.3, 0.5, 0.75, 1.25 and 1.5 cm) were modeled by cylindrical tubes surrounding the catheter. A Monte Carlo code (GEANT4) was also used to evaluate the dosimetric impact of the air cavity. Compared with dose calculations in homogeneous water, the measurements and GEANT4 indicated a maximum overdose of 5-8% near the surface of the air cavity (with the maximum radius of 1.5 cm). Conversely, they indicated a minimum overdose of ~1% in the region 3-5 cm from the cavity surface for the smallest radius of 0.3 cm. The dosimetric impact depended on the size and the distance of the air passage, as well as the length of the treatment region. Based on dose calculations in water, the TPS for intraluminal brachytherapy for bronchus cancer had an unexpected overdose of 3-5% for a mean radius of 0.75 cm. This study indicates the need for improvement in dose calculation accuracy with respect to intraluminal brachytherapy for bronchus cancer., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy)., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Intensity-modulated radiation therapy (IMRT) was recently introduced to the field of gynecologic malignancies; however, its value is not yet validated. A clinical trial is in preparation to investigate the efficacy and feasibility of IMRT for postoperative cervical cancer. The object of this study was to perform a surveillance study of IMRT for post-operative cervical cancer. A questionnaire regarding the precise methods of conducting IMRT was sent to six institutions that had already introduced IMRT for post-operative cervical cancer, and the data were analyzed. Half of the institutions used static IMRT and the others used volumetric-modulated arc therapy (VMAT). Most institutions used body-immobilizing devices for patient fixation. Most institutions instructed patients to fill their bladder before undergoing planning CT or daily treatment. While one institution inserted metallic markers and another one used radio-contrast-soaked gauze to visualize the vaginal cuff, the other institutions used nothing for vaginal cuff visualization. Most institutions defined the clinical target volumes according to the Japan Clinical Oncology Group or the Radiation Therapy Oncology Group guidelines. Only one institution used a prescribed dose based on 95% of the PTV (D(95)), while the rest used the mean dose (D(mean)). This valuable information from six leading institutions will be utilized in a future prospective clinical trial., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Because self-incompatibility loci are maintained heterozygous and recombination within self-incompatibility loci would be disadvantageous, self-incompatibility loci are thought to contribute to structural and functional differentiation of chromosomes. Although the hermaphrodite chordate, Ciona intestinalis, has two self-incompatibility genes, this incompatibility system is incomplete and self-fertilization occurs under laboratory conditions. Here, we established an inbred strain of C. intestinalis by repeated self-fertilization. Decoding genome sequences of sibling animals of this strain identified a 2.4-Mbheterozygous region on chromosome 7. A self-incompatibility gene, Themis-B, was encoded within this region. This observation implied that this self-incompatibility locus and the linkage disequilibrium of its flanking region contribute to the formation of the 2.4-Mb heterozygous region, probably through recombination suppression. We showed that different individuals in natural populations had different numbers and different combinations of Themis-B variants, and that the rate of self-fertilization varied among these animals. Our result explains why self-fertilization occurs under laboratory conditions. It also supports the concept that the Themis-B locus is preferentially retained heterozygous in the inbred line and contributes to the formation of the 2.4-Mb heterozygous region. High structural variations might suppress recombination, and this long heterozygous region might represent a preliminary stage of structural differentiation of chromosomes., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During radiotherapy for gastric lymphoma, it is difficult to protect the liver and kidneys in cases where there is considerable overlap between these organs and the target volume. This study was conducted to compare the three radiotherapy planning techniques of four-fields 3D conformal radiotherapy (3DCRT), half-field radiotherapy (the half-beam method) and intensity-modulated radiotherapy (IMRT) used to treat primary gastric lymphoma in which the planning target volume (PTV) had a large overlap with the left kidney. A total of 17 patients with gastric diffuse large B-cell lymphoma (DLBCL) were included. In DLBCL, immunochemotherapy (Rituximab + CHOP) was followed by radiotherapy of 40 Gy to the whole stomach and peri-gastric lymph nodes. 3DCRT, the half-field method, and IMRT were compared with respect to the dose-volume histogram (DVH) parameters and generalized equivalent uniform dose (gEUD) to the kidneys, liver and PTV. The mean dose and gEUD for 3DCRT was higher than for IMRT and the half-beam method in the left kidney and both kidneys. The mean dose and gEUD of the left kidney was 2117 cGy and 2224 cGy for 3DCRT, 1520 cGy and 1637 cGy for IMRT, and 1100 cGy and 1357 cGy for the half-beam method, respectively. The mean dose and gEUD of both kidneys was 1335 cGy and 1559 cGy for 3DCRT, 1184 cGy and 1311 cGy for IMRT, and 700 cGy and 937 cGy for the half-beam method, respectively. Dose-volume histograms (DVHs) of the liver revealed a larger volume was irradiated in the dose range <25 Gy with 3DCRT, while the half-beam method irradiated a larger volume of liver with the higher dose range (>25 Gy). IMRT and the half-beam method had the advantages of dose reduction for the kidneys and liver., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Recent studies have suggested that same-admission delayed cholecystectomy is a safe option. Patients with diabetes have been shown to have less favourable outcomes after cholecystectomy, but the impact of timing of operation for acute cholecystitis during the same admission is unknown., Methods: This was a retrospective analysis of patients undergoing laparoscopic cholecystectomy for acute cholecystitis between 2004 and 2010, from the American College of Surgeons National Surgical Quality Improvement Program database. Patients with no significant co-morbidities (American Society of Anesthesiologists grade I or II) were included. Propensity score matching (PSM) was used to match patients with diabetes with those who did not have diabetes, in a ratio of 1:3, to ensure homogeneity of the two groups. Logistic regression models were applied to adjust for differences between early (within 24 h) and delayed (24 h or more) surgical treatment. The primary outcome was development of local and systemic infectious complications. Secondary outcomes were duration of operation and length of hospital stay., Results: From a total of 2892 patients, 144 patients with diabetes were matched with 432 without diabetes by PSM. Delaying cholecystectomy for at least 24 h after admission in patients with diabetes was associated with significantly higher odds of developing surgical-site infections (adjusted odds ratio 4.11, 95 per cent confidence interval 1.11 to 15.22; P = 0.034) and a longer hospital stay. For patients with no diabetes, however, delaying cholecystectomy had no impact on complications or length of hospital stay., Conclusion: Patients with diabetes who undergo laparoscopic cholecystectomy 24 h or more after admission may have an increased risk of postoperative surgical-site infection and a longer hospital stay than those undergoing surgery within 24 h of admission., (© 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V100 achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D100 was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D90 was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D2cm(3): 408 ± 71 cGy vs manual optimization D2cm(3): 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D2cm(3): 452 ± 60 cGy vs manual optimization D2cm(3): 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.

Purpose: To analyze the results of radical radiotherapy by electron beams for squamous cell carcinoma (SCC) of the eyelid and to find the possible prognostic factors., Materials and Methods: Records of 38 patients with histologically confirmed SCC of the eyelid who underwent electron beam radiation therapy between 1964 and 2010 in our institution were retrospectively reviewed. Median tumor size was 15 mm (range, 3-40 mm). T stage was T1 in three, T2a in six, T2b in 14, and T3a in 15 patients. Four patients had nodal metastasis. Of the 38 patients, 14 had relapsed disease after prior treatment. Median radiation dose was 60.0 Gy (range, 45.0-70.4 Gy). Median follow-up was 72.5 months (range, 2.0-369 months)., Results: 5-year local relapse-free, nodal relapse-free, distant metastasis-free and relapse-free rates for all patients were 71.8%, 77.5%, 90.6% and 58.0%, respectively. In seven patients, lymph node metastases occurred in 11 faciocervical regions. The 5-year overall survival was 79.5%. T stage and radiation dose expressed in EQD2 Gy tended to have impacts on local control. Relapsed patients showed unfavorable local relapse-free rate, however this was without statistical significance. Of the 14 patients who died, 12 succumbed to concurrent diseases. Grade 3 or greater severe late morbidities (CTCAE ver4.0) were observed in nine patients. Due to the morbidities, two patients lost their vision., Conclusion: Radical radiotherapy for SCC of the eyelid yielded good results and could be a treatment option. Whether radiation-dose escalation could improve local control in advanced T stages and relapsed patients needs further study.

Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2-T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2-T3 disease resulted in good local control.

Background: The favorable response rate of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication has been demonstrated. However, there are limited data available on the long-term outcomes. The aim of this retrospective study was to evaluate the long-term outcomes of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication., Methods: Thirty-four consecutive patients with localized gastric mucosa-associated lymphoid tissue lymphoma that were refractory to eradication were treated with radiotherapy (a total dose of 30 Gy). The response and adverse events of radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence-free, overall and disease-specific survival rates were calculated as long-term outcomes., Results: Thirty-three (97.1%) patients achieved complete remission and radiotherapy was well tolerated. One patient underwent emergency gastrectomy due to severe hematemesis. Of the 34 patients during the median follow-up period of 7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one patient underwent surgery for bowel obstruction secondary to small bowel metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9 years. Pathologically, all three recurrences revealed mucosa-associated lymphoid tissue lymphoma without any transformation to high-grade lymphoma. None died of gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free survival rate was 97.0%. The 5-year overall survival rates and disease-specific survival rates were 97.0 and 100%, respectively., Conclusions: Radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication can achieve excellent overall survival. However, long-term surveillance is necessary to identify late recurrences.

The purpose of this retrospective study is to investigate the impact of concurrent chemotherapy on definitive radiotherapy for the International Federation of Gynecology and Obstetrics (FIGO) IIIb cervical cancer. Between 2000 and 2009, 131 women with FIGO IIIb cervical cancer were treated by definitive radiotherapy (i.e. whole pelvic external beam radiotherapy for 40-60 Gy in 20-30 fractions with or without center shielding and concomitant high-dose rate intracavitary brachytherapy with 192-iridium remote after loading system for 6 Gy to point A of the Manchester method). The concurrent chemotherapy regimen was cisplatin (40 mg/m(2)/week). After a median follow-up period of 44.0 months (range 4.2-114.9 months) and 62.1 months for live patients, the five-year overall survival (OS), loco-regional control (LRC) and distant metastasis-free survival (DMFS) rates were 52.4, 80.1 and 59.9%, respectively. Univariate and multivariate analyses revealed that lack of concurrent chemotherapy was the most significant factor leading to poor prognosis for OS (HR = 2.53; 95% CI 1.44-4.47; P = 0.001) and DMFS (HR = 2.53; 95% CI 1.39-4.61; P = 0.002), but not for LRC (HR = 1.57; 95% CI 0.64-3.88; P = 0.322). The cumulative incidence rates of late rectal complications after definitive radiotherapy were not significantly different with or without concurrent chemotherapy (any grade at five years 23.9 vs 21.7%; P = 0.669). In conclusion, concurrent chemotherapy is valuable in definitive radiotherapy for Japanese women with FIGO IIIb cervical cancer.

Background: The effects of anastomotic complications after laparoscopically assisted gastrectomy (LAG) have not been studied widely. The aims of this observational study were to identify potential factors that predict anastomotic complications and investigate the impact of anastomotic complications in patients undergoing gastrectomy for early gastric cancer., Methods: The study included consecutive patients with histologically proven T1 gastric adenocarcinoma treated by LAG with regional lymphadenectomy between August 1997 and March 2008, who had not received neoadjuvant chemotherapy. Anastomotic complications included anastomotic leakage, stricture and remnant gastric stasis of grade II or higher (modified Clavien classification) and were identified by clinical assessment and confirmatory investigation. Predictive factors for the development of anastomotic complications were identified by univariable and multivariable analyses. Long-term survival with or without anastomotic complications was examined., Results: Anastomotic complications occurred in 37 (9·3 per cent) of 400 patients. Multivariable analysis indicated surgeon experience as the only independent predictor of anastomotic complications (hazard ratio 4·40, 95 per cent confidence interval 2·04 to 9·53; P < 0·001). Patients with anastomotic complications had a significantly worse overall 5-year survival rate than those without (81 versus 94·2 per cent; P = 0·009)., Conclusion: Anastomotic complications after LAG lead to worse long-term survival., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol purified from black tea that activates mitochondrial respiration. It increased the mitochondrial membrane potential and motility of sea urchin sperm, by up to 8%, to the same extent as sperm-activating peptides (SAPs) secreted by the egg. Unlike SAPs, MAF had no effect on sperm swimming behavior, suggesting that the mechanism of sperm activation by MAF is different from that of SAPs.

Background: The purpose of this study was to evaluate the prognostic value of lymph node metastasis along the superior mesenteric vein (station 14v) to determine the need for 14v dissection in gastric cancer surgery., Methods: A total of 1104 patients with gastric cancer who underwent gastrectomy including 14v dissection were enrolled. Patients were categorized into two groups: those with and those without 14v lymph node involvement by metastasis., Results: Of the total study population, 73 patients (6·6 per cent) had 14v-positive gastric cancer. These patients were more likely to have advanced tumour (T), node (N) and distant metastatic (M) status, and histologically undifferentiated gastric cancers. The 3- and 5-year survival rates of patients with 14v-positive disease were 24 and 9 per cent respectively. Survival in this group was similar to that of patients who had gastric cancer with distant metastasis (M1). Multivariable analysis demonstrated that 14v status was a significant prognostic factor for gastric cancer (hazard ratio 2·13; P < 0·001). After histologically complete (R0) resection, the overall survival of 14v-positive patients with any stage of cancer was significantly worse than that for 14v-negative patients with stage IV cancer (P = 0·006)., Conclusion: 14v status is an independent prognostic factor for gastric cancer, with 14v-positive gastric cancer having a poor prognosis, similar to that of M1 disease. The exclusion of 14v in regional lymph node dissection should be considered., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36,034 unique sequences, but for higher usability it covers 89,683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10,000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5.

The C-type lectin SIGNR3 is a mouse homologue of human DC-SIGN, which shares carbohydrate-binding specificity with human DC-SIGN. However, the expression profile of SIGNR3 is largely unknown. To examine the expression of SIGNR3 in immune cells, we generated SIGNR3-specific mAb and investigated SIGNR3 expression in vivo. SIGNR3 was expressed on a fraction of MHC II(+) DCs and Mϕs in the dermis and CD115(+)Ly6C(int-low) monocytes in the blood and BM. In the LNs, SIGNR3(+) cells localized adjacent to PNAd(+) HEV-like vessels. They were also found in interfollicular regions in sLNs but not mLNs. Those SIGNR3(+) cells expressed CD11b and variable levels of CD11c and MHC II. As in LNs, SIGNR3 was expressed on a large proportion of the CD11b(+)CD11c(int-high) cells in the spleen. In the lung, SIGNR3(+) cells belonged to the CD11b(+)CD11c(int) population, and Mϕs in the airway and lung faintly expressed SIGNR3. When PKH67-labeled CD115(+)Ly6C(high) BM monocytes were transferred into normal recipients, they up-regulated SIGNR3 expression along with the decrease in Ly6C expression during the circulation and upon arrival at the peripheral LNs through HEV. In addition, CD11b(high)Ly6C(high) monocytes that entered sLNs differentiated into CD11b(+) DCs in a couple of days, whereas those in the spleen, mLNs, and lung differentiated into CD11c(int) monocytic cells. These results suggest that SIGNR3 is a new differentiation marker for myeloid mononuclear cells and indicate that some DCs, especially in the sLNs, are possibly replenished by Ly6C(high) monocytes.

Background: This meta-analysis assessed the diagnostic and therapeutic role of water-soluble contrast agent (WSCA) in adhesive small bowel obstruction (SBO)., Methods: PubMed, Embase and Cochrane databases were searched systematically. The primary outcome in the diagnostic role of WSCA was its ability to predict the need for surgery. In the therapeutic role, the following were evaluated: resolution of SBO without surgery, time from admission to resolution, duration of hospital stay, complications and mortality. To assess the diagnostic role of WSCA, pooled estimates of sensitivity, specificity, positive and negative predictive values, and likelihood ratios were derived. For the therapeutic role of WSCA, weighted odds ratio (OR) and weighted mean difference (WMD) were obtained., Results: Fourteen prospective studies were included. The appearance of contrast in the colon within 4-24 h after administration had a sensitivity of 96 per cent and specificity of 98 per cent in predicting resolution of SBO. WSCA administration was effective in reducing the need for surgery (OR 0.62; P = 0.007) and shortening hospital stay (WMD -1.87 days; P < 0.001) compared with conventional treatment., Conclusion: Water-soluble contrast was effective in predicting the need for surgery in patients with adhesive SBO. In addition, it reduced the need for operation and shortened hospital stay., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

The National BioResource Project (NBRP) is a Japanese project that aims to establish a system for collecting, preserving and providing bioresources for use as experimental materials for life science research. It is promoted by 27 core resource facilities, each concerned with a particular group of organisms, and by one information center. The NBRP database is a product of this project. Thirty databases and an integrated database-retrieval system (BioResource World: BRW) have been created and made available through the NBRP home page (http://www.nbrp.jp). The 30 independent databases have individual features which directly reflect the data maintained by each resource facility. The BRW is designed for users who need to search across several resources without moving from one database to another. BRW provides access to a collection of 4.5-million records on bioresources including wild species, inbred lines, mutants, genetically engineered lines, DNA clones and so on. BRW supports summary browsing, keyword searching, and searching by DNA sequences or gene ontology. The results of searches provide links to online requests for distribution of research materials. A circulation system allows users to submit details of papers published on research conducted using NBRP resources.

For identification of genes responsible for varietal differences in flowering time and leaf morphological traits, we constructed a linkage map of Brassica rapa DNA markers including 170 EST-based markers, 12 SSR markers, and 59 BAC sequence-based markers, of which 151 are single nucleotide polymorphism (SNP) markers. By BLASTN, 223 markers were shown to have homologous regions in Arabidopsis thaliana, and these homologous loci covered nearly the whole genome of A. thaliana. Synteny analysis between B. rapa and A. thaliana revealed 33 large syntenic regions. Three quantitative trait loci (QTLs) for flowering time were detected. BrFLC1 and BrFLC2 were linked to the QTLs for bolting time, budding time, and flowering time. Three SNPs in the promoter, which may be the cause of low expression of BrFLC2 in the early-flowering parental line, were identified. For leaf lobe depth and leaf hairiness, one major QTL corresponding to a syntenic region containing GIBBERELLIN 20 OXIDASE 3 and one major QTL containing BrGL1, respectively, were detected. Analysis of nucleotide sequences and expression of these genes suggested possible involvement of these genes in leaf morphological traits.

The biological kingdoms have evolved elaborate systems that ensure the catalysis of protein disulfide bond (dsb) formation in the cell. Coexisting in the periplasm of Escherichia coli are the DsbA-DsbB disulfide-introducing and DsbC-DsbD disulfide-isomerizing pathways, which promote the oxidative folding of secreted proteins. Recent structural studies of DsbB have illuminated conformational dynamics involved in the effective oxidation of the extremely reduction-prone oxidase, DsbA, as well as the structure of the reaction centre involved in protein Dsb formation de novo in conjunction with ubiquinone. Extensive genetic and biochemical analysis has recently provided insight into how DsbD transports electrons from cytosolic thioredoxin to periplasmic DsbC. To a great extent, the molecular mechanisms of the Dsb enzyme system in E. coli have been elucidated, and are applicable to the study of protein disulfide formation systems in other organisms.

Linear alkylbenzene sulfonates (LAS) constitute, quantitatively, the most important group of synthetic surfactants used today. We studied the gene expression of Nitrosomonas europaea in response to LAS using a DNA microarray because ammonia-oxidizers are thought to be more sensitive to LAS than other microorganisms. Our objective was to elucidate which genes are expressed for N. europaea in response to LAS exposure. Microarray analysis and real-time PCR assay revealed that c. 30 genes were significantly expressed after LAS exposure, in particular genes associated with energy production and conversion. Our findings demonstrate that physical disruption of membrane structures, which contain enzymes associated with energy production and conversion, might be an important explanation for the high sensitivity of N. europaea to LAS exposure.

Dendritic cells (DCs) are potent antigen-presenting cells and can induce tumour- or pathogen-specific T cell responses. For adoptive immunotherapy purposes, immature DCs can be generated from adherent monocytes using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4, and further maturation is usually achieved by incubation with tumour necrosis factor (TNF)-alpha. However, TNF-alpha-stimulated DCs produce low levels of IL-12. In this study, we compared the effects of TNF-alpha, interferon (IFN)-gamma, IL-1beta or IFN-gamma + IL-1beta on the phenotypic and functional maturation of DCs. Our results show that IFN-gamma, but not IL-1beta, augmented the surface expression of CD80, CD83 and CD86 molecules without inducing IL-12 production from DCs. However, IL-1beta, but not IFN-gamma, induced IL-12 p40 production by DCs without enhancing phenotypic maturation. When combined, IFN-gamma + IL-1beta treatment profoundly up-regulated the expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens. Furthermore, IFN-gamma + IL-1beta-treated DCs produced larger amounts of IL-12 and induced stronger T cell proliferation and IFN-gamma secretion in primary allogeneic mixed lymphocyte reaction (MLR) than did TNF-alpha-treated DCs. Our results show that IFN-gamma + IL-1beta induced human monocyte-derived DCs to differentiate into Th1-prone mature DCs.

The SAMP6 mouse (a substrain of senescence-accelerated mice) spontaneously develops osteoporosis early in life and is, therefore, a useful model for examining the mechanisms underlying osteoporosis. We have recently established a new bone marrow transplantation (BMT) method: the bone marrow cells (BMCs) of normal allogeneic mice are directly injected into the bone marrow (BM) cavity of irradiated (5.5 Gy x 2) recipients (IBM-BMT). Using IBM-BMT, we attempted to prevent osteoporosis in SAMP6 mice. The hematolymphoid system was completely reconstituted with donor-type cells after IBM-BMT. Thus-treated SAMP6 mice showed marked increases in trabecular bones even at 12 months of age, and the bone mineral density remained similar to that of normal B6 mice. In concordance with these findings, urinary deoxypyridinoline also remained continuously low until 10 months of age, indicating that IBM-BMT was effective in the prevention of bone absorption. In addition to the above, BM stromal cells in the treated SAMP6 mice were replaced with donor stromal cells, and the message level of interleukin-11 (IL-11), which is produced by the BM stromal cells and is known as an important factor in the regulation of bone remodeling, was restored to a level similar to that observed in normal B6 mice. Furthermore, the message level of IL-6, which is known to enhance osteoclastogenesis, was also restored to normal. These results indicate that the BM microenvironment was normalized after IBM-BMT and that the increased production of IL-11 and IL-6 ameliorated the imbalance between bone absorption and formation, resulting in the prevention of osteoporosis in SAMP6 mice.

Conformational changes of dynein during ATP hydrolysis are demonstrated by the difference in the tryptic fragments of the dynein heavy chain between in the absence and presence of ATP and vanadate. Here tryptic sites in the presence of ATP and vanadate (Tav sites) have been mapped on the betaheavy chain of outer arm dynein from sea urchin sperm flagella. Tav sites are located not only near the central catalytic domain which includes four P-loops, but also near the carboxyl-terminal coiled-coil region. The Tav2 site is located in the most carboxyl-terminal region, which is nearly 850 amino acid residues apart from the the fourth P-loop (P4 site). The region from the most amino-terminal Tav site (Tav1 site) to the Tav2 site covers approximately 2,100 amino acid residues, which is almost half the whole betaheavy chain. Comparison of the sequences around the tryptic sites of the sea urchin b chain and those of the dynein heavy chains from other organisms reveals that the sequence around the Tav1 site is highly conserved in both cytoplasmic and axonemal dyneins but that around Tav2 sites is only conserved in axonemal dyneins, suggesting functional differences in the Tav2 region between the two subfamilies of dynein.

There is considerable but as yet incomplete evidence for two developmental lineages of dendritic cells: a myeloid lineage shared with phagocytes and a lymphoid lineage shared with T cells. The two corresponding functional states, which may not require the existence of two formal lineages, are that myeloid dendritic cells capture antigens in the periphery and then migrate to the lymphoid organs to initiate immunity, whereas lymphoid dendritic cells are found in the thymic medulla and lymph node T cell areas and are responsible for tolerance. The latter may occur through immune regulation and/or deletion. Myeloid dendritic cells undergo many activities that contribute to the initiation of immunity. These are summarized here and include mobilization from progenitors and precursors in the blood and marrow, maturation from immature cells in the skin and interstitial spaces, formation of MHC-peptide complexes in MHC class II compartments or MIICs, migration to the T cell areas, and finally, mortality. The death of migratory dendritic cells seems to be accompanied by their phagocytosis and processing by other dendritic cells in the T area. We speculate that this transfer of antigens, including self-peptides captured by the uptake of apoptotic cells in peripheral tissues, is an important prelude to the regulatory function of resident or lymphoid dendritic cells in the T cell area. These features of dendritic cell biology provide targets to manipulate the immune response in vivo.

Dendritic cells (DC) are a distinct population of leukocytes and specialized antigen-presenting cells for T cell responses. Prior work has shown that GM-CSF can induce the development of large numbers of DC from proliferating progenitors in mouse bone marrow. We have monitored the effects of potentially enhancing and suppressive cytokines in these cultures. In this system, many immature DC develop from proliferating precursors during the first six days of culture, and between days 6-8 maturation of typical nonadherent and nonreplicating DC takes place. The maturation is accompanied by a large increase in the expression of major histocompatibilities complex class II (MHC II) and B7-2/CD86, and in mixed leukocyte reaction stimulating activity. Tumor necrosis factor-alpha (TNF-alpha), previously shown to be required for development of human DC, was found to enhance the maturation of mouse DC in the last two days of culture. Transforming growth factor-beta 1 (TGF-beta 1), on the other hand, almost totally blocked DC maturation, but it had to be given in the first six days of culture when the DC were actively proliferating. TGF-beta 1 did not block the production of immature, MHC II-positive but B7-2/CD86-negative DC. Maturation would take place between days 6-8 as long as the cultures were depleted of Fc-receptor-bearing cells, or if TNF-alpha were added. In both instances, maturation was not blocked even when TGF-beta 1 remained in the culture. We conclude that the development of DC, in response to GM-CSF, can be modified by other cytokines. TGF-beta 1 is suppressive but only indirectly via Fc-receptor-bearing suppressive cells, presumably suppressive macrophages, while TNF-alpha enhances the final maturation of DC.

Conformational changes of the dynein beta heavy chain/intermediate chain 1 (IC1) complex from outer arm dynein of sea urchin sperm flagella were examined by means of cross-linking experiments using a bifunctional cross-linker, dimethylsuberimidate. Cross-linking of the beta/IC1 complex in the absence of ATP and vanadate (Vi) produced five cross-linked products. Immunoblotting of the products with anti-beta chain and anti-IC1 antibodies revealed that all of them were cross-linked between beta chain and IC1. Cross-linking of the complex in the presence of ATP and Vi produced four cross-linked products, but their electrophoretic mobilities were different from those of the cross-linked products obtained in the absence of ATP and Vi. Immunoblotting showed that only one cross-linked product was formed by cross-linking between beta and IC1 and others were formed by intramolecular cross-linking of the beta chain. Quantitative analysis indicated that cross-linking between beta and IC1 decreased in the presence of ATP and Vi. These results suggest that conformational changes of the beta heavy chain occur and the interaction between beta chain and IC1 changes during ATP hydrolysis.

A gene encoding an Na+/H+ antiporter was cloned from chromosomal DNA of the slightly halophilic marine bacterium Vibrio parahaemolyticus. The host was an Escherichia coli mutant that lacked both of the two major Na+/H+ antiporters, NhaA and NhaB. Untransformed mutant cells were unable to grow in the presence of 0.6 M NaCl or 0.1 M LiCl, but Na+ and Li+ were non-toxic to cells transformed with a plasmid carrying the antiporter gene. Membrane vesicles prepared from the original E. coli mutant did not show any detectable Na+/H+ (and Li+/H+) antiport activity. However, we observed high Na+/H+ (and Li+/H+) antiport activity in membrane vesicles prepared from the transformed cells. The activity increased greatly when the pH of the assay medium was increased from 7.0 and 8.5. This property is very similar to that of the NhaA Na+/H+ antiporter of E. coli. Drastic decreases in Km values for Li+ and Na+ were observed with membrane vesicles prepared from the transformed cells compared with those observed with V. parahaemolyticus vesicles. The amino acid sequence deduced from the nucleotide sequence of the cloned gene showed high homology (59% identity and 87% similarity) with the NhaA Na+/H+ antiporter of E. coli. Thus, we conclude that the gene we cloned and sequenced is the nhaA of V. parahaemolyticus. We also found that several regions of the NhaA protein showed sequence similarity with transport proteins from some other organisms. Such regions seem to be important for Na+ recognition, transport or amiloride binding.

We isolated a mutant of Escherichia coli which was defective in an Na+/H+ antiporter and grew poorly under alkaline conditions [Ishikawa, T., Hama, H., Tsuda, T., and Tsuchiya, T. (1987) J. Biol. Chem. 262, 7443-7446]. Later, it was concluded that the defective Na+/H+ antiporter in the mutant was the NhaB system, and the nhaB gene was mapped to 25.6 min on the E. coli chromosome [Thelen, P., Tsuchiya, T., and Goldberg, E.B. (1991) J. Bacteriol. 173, 6553-6557]. We found that the NhaB-defective cells cannot grow in a high pH medium. Furthermore, intracellular pH in the mutant cells was almost the same as extracellular pH between 7.9 and 9.1, that is, intracellular pH was not regulated at this pH range. On the other hand, intracellular pH of the wild-type cells was maintained at about 7.6 when the extracellular pH was between 7.6 and 8.5. Thus, the NhaB Na+/H+ antiporter is essential for the regulation of intracellular pH under alkaline conditions in E. coli. Introduction of nhaA gene into the mutant cells increased Na+/H+ antiporter activity, but did not restore the defective growth and defective intracellular pH regulation under alkaline conditions.

The properties of the Na+/H+ antiporter in Vibrio parahaemolyticus, a slightly halophilic bacterium, were investigated using everted membrane vesicles. It appears that at least two Na+/H+ antiporters are present, one that is pH-dependent and one that is pH-independent. These two antiporters appear to correspond to the NhaA and NhaB antiporters of Escherichia coli, respectively. It seems that amiloride strongly inhibits the pH-dependent antiporter. Na+ is the best substrate for both of the two V. parahaemolyticus antiporters. Li+ is a poorer substrate and K+ is not a substrate. No K+/H+ antiport activity was detected in membrane vesicles of this organism. The Na+(Li+)/H+ antiport activity greatly increased with an increase in pH of the assay medium. pH did not affect the Km value of the Na+/H+ antiport, but it did increase the Vmax.