Carcinoid Tumour of the Appendix: An Analysis of 1,485 Consecutive Emergency Appendectomies

Aim: The aim of this study is to conduct a retrospective analysis of the incidence and long-term results of carcinoid tumours of the appendix in emergency appendectomies. Methods: A retrospective review of 1,485 appendectomies was performed in two centres from January 2000 until January 2006. Demographic data, clinical presentation, histopathology, operative reports and survival were scored and compared with the literature. Results: In three women and four men, carcinoid tumours were identified (0.47%). The mean age was 32.7 years (range, 20-59 years). The clinical presentation was resembling the symptoms of acute appendicitis in all cases. Laparoscopic appendectomy was the treatment of choice in five patients; in one of these patients, a conversion to laparotomy was necessary. The other two patients underwent primary open appendectomy. Five patients underwent additional surgery after the pathology report became available. Four patients underwent ileocecal resection; one other patient underwent right hemicolectomy. In none of the re-operation specimens was residual carcinoid tumour detected. After a mean follow-up of 65 months (range, 25-92), all patients were alive and disease- and symptom-free. Conclusion: Carcinoid tumours of the appendix most often present as acute appendicitis. It also emphasises the value of histopathological analysis of every removed appendix. The long-term prognosis of incidentally found carcinoids of the appendix is good

Malignant neuroendocrine tumour of the appendix in childhood with loco-regional lymph node invasion

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1006600359152743 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13000-015-0287-z) contains supplementary material, which is available to authorized users

Practical Verification of Decision-Making in Agent-Based Autonomous Systems

We present a verification methodology for analysing the decision-making component in agent-based hybrid systems. Traditionally hybrid automata have been used to both implement and verify such systems, but hybrid automata based modelling, programming and verification techniques scale poorly as the complexity of discrete decision-making increases making them unattractive in situations where complex log- ical reasoning is required. In the programming of complex systems it has, therefore, become common to separate out logical decision-making into a separate, discrete, component. However, verification techniques have failed to keep pace with this devel- opment. We are exploring agent-based logical components and have developed a model checking technique for such components which can then be composed with a sepa- rate analysis of the continuous part of the hybrid system. Among other things this allows program model checkers to be used to verify the actual implementation of the decision-making in hybrid autonomous systems

Molecular, Biochemical and Genetic Characteristics of BSE in Canada

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide

Pin1 Modulates the Type 1 Immune Response

BACKGROUND/ABSTRACT: Immune responses initiated by T cell receptor (TCR) and costimulatory molecule mediated signaling culminate in maximal cytokine mRNA production and stability. The transcriptional responses to co-stimulatory T cell signalling involve calcineurin and NF-AT, which can be antagonized by interference with the cis-trans peptidyl-prolyl isomerases (PPIase), cyclophilin A and FKBP. Signalling molecules downstream of CD28 which are essential for the stabilization of cytokine mRNAs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We now show that Pin1, a third member of the PPIase family mediates the post-transcriptional regulation of Th1 cytokines by activated T cells. Blockade of Pin1 by pharmacologic or genetic means greatly attenuated IFN-γ, IL-2 and CXCL-10 mRNA stability, accumulation and protein expression after cell activation. In vivo, Pin1 blockade prevented both the acute and chronic rejection of MHC mismatched, orthotopic rat lung transplants by reducing the expression of IFN-γ and CXCL-10. Combined transcriptional and post-transcriptional blockade with cyclosporine A and the Pin1 inhibitor, juglone, was synergistic. CONCLUSIONS/SIGNIFICANCE: These data suggest Pin1 inhibitors should be explored for use as immunosuppressants and employed with available calcineurin inhibitors to reduce toxicity and enhance effectiveness

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Dendritic Cells in Chronic Mycobacterial Granulomas Restrict Local Anti-Bacterial T Cell Response in a Murine Model

Background: Mycobacterium-induced granulomas are the interface between bacteria and host immune response. During acute infection dendritic cells (DCs) are critical for mycobacterial dissemination and activation of protective T cells. However, their role during chronic infection in the granuloma is poorly understood. Methodology/Principal Findings: We report that an inflammatory subset of murine DCs are present in granulomas induced by Mycobacteria bovis strain Bacillus Calmette-guerin (BCG), and both their location in granulomas and costimulatory molecule expression changes throughout infection. By flow cytometric analysis, we found that CD11c + cells in chronic granulomas had lower expression of MHCII and co-stimulatory molecules CD40, CD80 and CD86, and higher expression of inhibitory molecules PD-L1 and PD-L2 compared to CD11c + cells from acute granulomas. As a consequence of their phenotype, CD11c + cells from chronic lesions were unable to support the reactivation of newly-recruited, antigen 85Bspecific CD4 + IFNc + T cells or induce an IFNc response from naïve T cells in vivo and ex vivo. The mechanism of this inhibition involves the PD-1:PD-L signaling pathway, as ex vivo blockade of PD-L1 and PD-L2 restored the ability of isolated CD11c + cells from chronic lesions to stimulate a protective IFNc T cell response. Conclusions/Significance: Our data suggest that DCs in chronic lesions may facilitate latent infection by down-regulating protective T cell responses, ultimately acting as a shield that promotes mycobacterium survival. This DC shield may explai

Chemoproteomics reveals Toll-like receptor fatty acylation

Partial funding for Open Access provided by The Ohio State University Open Access Fund.Background: Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells. Results: A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands. Conclusions: This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. Spalmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity.This work was supported by funding from the NIH/NIAID (grant R00AI095348 to J.S.Y.), the NIH/NIGMS (R01GM087544 to HCH), and the Ohio State University Public Health Preparedness for Infectious Diseases (PHPID) program. NMC is supported by the Ohio State University Systems and Integrative Biology Training Program (NIH/NIGMS grant T32GM068412). BWZ is a fellow of the National Science Foundation Graduate Research Fellowship Program (DGE-0937362)

The striking geographical pattern of gastric cancer mortality in Spain: environmental hypotheses revisited

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is decreasing in most countries. While socioeconomic development is the main factor to which this decline has been attributed, enormous differences among countries and within regions are still observed, with the main contributing factors remaining elusive. This study describes the geographic distribution of gastric cancer mortality at a municipal level in Spain, from 1994-2003.</p> <p>Methods</p> <p>Smoothed relative risks of stomach cancer mortality were obtained, using the Besag-York-Molliè autoregressive spatial model. Maps depicting relative risk (RR) estimates and posterior probabilities of RR being greater than 1 were plotted.</p> <p>Results</p> <p>From 1994-2003, 62184 gastric cancer deaths were registered in Spain (7 percent of all deaths due to malignant tumors). The geographic pattern was similar for both sexes. RRs displayed a south-north and coast-inland gradient, with lower risks being observed in Andalusia, the Mediterranean coastline, the Balearic and Canary Islands and the Cantabrian seaboard. The highest risk was concentrated along the west coast of Galicia, broad areas of the Castile & Leon Autonomous community, the province of Cáceres in Extremadura, Lleida and other areas of Catalonia.</p> <p>Conclusion</p> <p>In Spain, risk of gastric cancer mortality displays a striking geographic distribution. With some differences, this persistent and unique pattern is similar across the sexes, suggesting the implication of environmental exposures from sources, such as diet or ground water, which could affect both sexes and delimited geographic areas. Also, the higher sex-ratios found in some areas with high risk of smoking-related cancer mortality in males support the role of tobacco in gastric cancer etiology.</p