Acute viral gastroenteritis in children hospitalized in Iksan, Korea during December 2010-June 2011

PurposeViral etiology is common in cases of children with acute diarrhea, and antibiotic therapy is usually not required. Therefore, it is important to determine the distribution of common viruses among children hospitalized with acute diarrhea.MethodsWe included 186 children who suffered from acute diarrhea and were hospitalized at the Wonkwang University Hospital Pediatric ward from December 1, 2010 to June 30, 2011 in this study. Stool samples were collected and multiplex reverse transcriptase polymerase chain reaction (multiplex RT-PCR) was used to simultaneously determine the viral etiology such as rotavirus, norovirus, astrovirus, or adenovirus.ResultsCausative viruses were detected in 72 of the 186 cases (38.7%). The mean age of the virus-positive cases was 1 year and 9 months (range, 1 month to 11 years). Rotavirus was detected in 50/186 (26.9%); norovirus, in 18/186 (9.7%); and astrovirus, in 3/186 cases (1.6%). Adenovirus was not detected in any of the cases. Proportions of norovirus genogroups I and II were 21.1% and 78.9%, respectively. Four of the 51 rotavirus-positive cases (7.8%) had received rotavirus vaccination at least once. The mean duration of diarrhea was 2.8 days (range, 1 to 10 days) and vomiting occurred in 39 of the 72 cases (54.2%).ConclusionViral etiology was confirmed in about one-third of the children with acute diarrhea, and the most common viral agent was rotavirus, followed by norovirus

KIR3DL2 is a coinhibitory receptor on Sézary syndrome malignant T cells that promotes resistance to activation-induced cell death

© 2014 by The American Society of Hematology. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published version of a Published Work that appeared in final form in Blood. To access the final edited and published work see https://doi.org/10.1182/blood-2014-09-59899

SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation

T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2

Cost-effectiveness of introducing a rotavirus vaccine in developing countries: The case of Mexico

<p>Abstract</p> <p>Background</p> <p>In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program.</p> <p>Methods</p> <p>A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months.</p> <p>Results</p> <p>Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved.</p> <p>Conclusion</p> <p>At prices below US$15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be significantly more cost-effective among poorer populations and among those with less access to prompt medical care – such that poverty reduction programs would be expected to reduce the future cost-effectiveness of the vaccine.</p

Adaptor SKAP-55 Binds p21ras Activating Exchange Factor RasGRP1 and Negatively Regulates the p21ras-ERK Pathway in T-Cells

While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21ras activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21ras activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55−/− primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21ras becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21ras-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion

Evaluation of immunophenotypic and molecular biomarkers for Sézary syndrome using standard operating procedures: multicenter study of 59 cases

Abstract Differentiation between Sézary syndrome (SS) and erythrodermic inflammatory dermatoses (EID) can be challenging and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criterion. In this European multicenter study the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in SS was investigated. Peripheral blood CD4+ T-cells from 59 SS and 19 EID patients were analyzed for cell surface proteins by flow cytometry, and for copy number alterations and differential gene expression using custom made qPCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%), upregulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%) and PLS3 (66%) and downregulation of STAT4 (91%). Loss of CD26 (≥ 80% CD4+ T-cells) and/ or CD7 (≥ 40% CD4+ T-cells) and combination of altered expression of STAT4, TWIST1 and DNM3 or PLS3, could distinguish respectively 83% and 98% of SS patients from EID cases with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of SS versus EID