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Background: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection., Methods: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted., Results: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic., Conclusion: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Multiple water swallows (MWS) stimulates neural inhibition, resulting in abolition of contractions in the esophageal body and complete lower esophageal sphincter relaxation, which is followed by peristalsis and the lower esophageal sphincter contraction. We assessed the relationship between MWS and gastroesophageal reflux in patients with esophageal symptoms and with normal findings by high-resolution manometry (HRM). We retrospectively reviewed the clinical records of patients who underwent HRM and a 24-hour ambulatory impedance-pH study. Correlation between the findings of the impedance-pH study and abnormal MWS responses without motility disorders was evaluated. Independent t-tests were used for statistical analysis. Of 28 patients, 20 (71%) had abnormal MWS responses: four (20%) had abnormal responses during MWS, six (30%) had abnormal responses after MWS, and 10 (50%) had abnormal responses both during and after MWS. Total acid exposure times were significantly longer in patients with abnormal MWS responses than in patients with normal MWS responses. In particular, upright acid exposure time and all reflux percent times were significantly longer in patients with abnormal MWS responses. However, bolus clearance time and longest reflux episode were not different between the two groups. Abnormal MWS responses predicted increased acid exposure times in patients with normal findings of HRM by the Chicago classification., (© 2014 International Society for Diseases of the Esophagus.)

Background: Concerns have emerged about the adverse effect of phthalates on human health., Objectives: The aim of this study was to investigate the association between di(2-ethylhexyl) phthalate (DEHP) exposure and atopic dermatitis (AD) in Korean children, focusing on the potential dose-response relationship., Methods: A matched case-control study was conducted from May to October 2012. Subjects from 3 to 6 years of age were recruited from kindergartens and daycare centres in Seoul, Korea. The clinical diagnosis of AD was made by dermatologists. A total of 224 cases and 224 age- and sex-matched controls were included. The levels of two phthalate metabolites [mono(2-ethyl-5-hydrohexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] of DEHP in urine samples were measured., Results: The effects of DEHP varied by age, and an increased risk for AD was associated with DEHP at age 3 years (odds radio 2.51, 95% confidence interval 1.02-6.20). The association was in the opposite direction in the other age groups although there was no statistical significance. The effects of DEHP on AD was observed differently by the level of the body burden. The predicted risk for AD based on the results of multiple logistic regression analysis showed a nonmonotonous association (U-shaped) between the level of DEHP and the risk of AD., Conclusions: This finding might suggest that the effects of DEHP on AD may be different according to the exposure level or age of the subject. Further longitudinal investigations with a suitable design to investigate the nonmonotonous association should be encouraged., (© 2014 British Association of Dermatologists.)

A panel screening using cdc mutants of Schizosaccharomyces pombe identified radicicol as a potent growth inhibitor of certain mutants at the permissive temperature. The strains sensitive to radicicol were cdc7, cdc11, and cdc14, all of which are defective in early septum formation. Cytokinesis but not nuclear division of these mutants was inhibited by radicicol, but that of cells with the wild-type background was not. A biologically active derivative of radicicol with a biotin moiety at the C-11 position bound Swo1, an Hsp90 homologue in S. pombe. Increased Swo1 expression partially suppressed radicicol sensitivity of cdc14 and almost completely rescued morphological abnormalities in cdc14 and cdc7 cells induced by radicicol at the permissive temperature. On the other hand, the increased Swo1 expression did not restore septum formation at the nonpermissive temperature. These results suggest that Swo1, as a molecular chaperone, plays a role in stabilizing these temperature-sensitive proteins at the permissive temperature or in activating the cytokinesis signaling cascade.

Background: Chronic oral aphthae, recurrent genital ulcers and uveitis are the three main manifestations of Behçet's disease (BD). The aetiopathogenesis of BD is still obscure, but herpes simplex virus (HSV) is one of the possible causal factors. Various kinds of drugs, including immunosuppressants and aciclovir have been used in treatment, but effectiveness is variable., Objectives: To demonstrate the efficacy of famciclovir, an antiviral compound that acts against HSV, varicella-zoster virus and hepatitis B virus, in a murine model of BD., Methods: Using the HSV-induced BD mouse model, famciclovir was administered variously before and after inoculation or from the day of lesion occurrence, with appropriate controls. Ulceration of the mouth and genital skin and eye involvement were monitored. In addition, spleen cytokine expression was measured by polymerase chain reaction., Results: Pretreatment and concurrent treatment did not affect the occurrence of BD, but treatment from the appearance of lesions was effective in improving BD and preventing recurrence. After famciclovir, interleukin 2 expression correlated with the recurrence of BD symptoms., Conclusions: This model suggests the possible role of immune response to viral infection in the development and activation of BD. The study provides a rationale for clinical trials of famciclovir in the human form of BD.

In the etiology of Behçet's disease (BD), viral infection has long been postulated as a contributing factor, and viral involvement has been demonstrated. However, viral infection alone is not sufficient to explain the pathogenesis of BD, and some evidence suggests that immunologic abnormalities are also important. To study the possible role of immune regulation in the development of BD-like symptoms induced by herpes simplex virus inoculation in ICR mice, macrophages were deleted by use of liposome-encapsulated clodronate (lip-Cl(2)MDP). Treatment with lip-Cl(2)MDP suppressed the development of BD-like symptoms, and this suppression was correlated with the induction of interleukin-4 expression in mouse spleens. When the Th2 adjuvant ovalbumin (OVA)-alum was injected into mice with BD-like symptoms, their cutaneous symptoms improved. Adoptive transfer with splenocytes from OVA-alum-injected mice also resulted in improvement. These findings suggest that up-regulated Th2 cytokine expression can attenuate the development of and improve some BD-like symptoms.

Alignments of 105 site-specific recombinases belonging to the Int family of proteins identified extended areas of similarity and three types of structural differences. In addition to the previously recognized conservation of the tetrad R-H-R-Y, located in boxes I and II, several newly identified sequence patches include charged amino acids that are highly conserved and a specific pattern of buried residues contributing to the overall protein fold. With some notable exceptions, unconserved regions correspond to loops in the crystal structures of the catalytic domains of lambda Int (Int c170) and HP1 Int (HPC) and of the recombinases XerD and Cre. Two structured regions also harbor some pronounced differences. The first comprises beta-sheets 4 and 5, alpha-helix D and the adjacent loop connecting it to alpha-helix E: two Ints of phages infecting thermophilic bacteria are missing this region altogether; the crystal structures of HPC, XerD and Cre reveal a lack of beta-sheets 4 and 5; Cre displays two additional beta-sheets following alpha-helix D; five recombinases carry large insertions. The second involves the catalytic tyrosine and is seen in a comparison of the four crystal structures. The yeast recombinases can theoretically be fitted to the Int fold, but the overall differences, involving changes in spacing as well as in motif structure, are more substantial than seen in most other proteins. The phenotypes of mutations compiled from several proteins are correlated with the available structural information and structure-function relationships are discussed. In addition, a few prokaryotic and eukaryotic enzymes with partial homology with the Int family of recombinases may be distantly related, either through divergent or convergent evolution. These include a restriction enzyme and a subgroup of eukaryotic RNA helicases (D-E-A-D proteins).

Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause morphological reversion of v-Ha-ras-transformed NIH3T3 fibroblasts and T24 human urinary bladder carcinoma cells that contain an activated ras mutation. The network of actin stress fibers was restored during the treatment with radicicol. A similar morphological change was observed with another protein-tyrosine kinase inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of the active GTP binding form of p21ras or its subcellular localization. These results rule out the possibility that the morphological reversion by radicicol is due to direct or indirect inhibition of the p21ras function. Cycloheximide and actinomycin D inhibited the morphological change by radicicol, suggesting that the induced transcription of a gene(s) followed by de novo protein synthesis is required for suppression of the transformed phenotype in ras-transformed cells by tyrosine kinase inhibitors.