The MHV68 M2 Protein Drives IL-10 Dependent B Cell Proliferation and Differentiation

Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1α. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10−/− B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells—perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis—identifying a strategy that appears to be conserved between at least EBV and MHV68

Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams

Enhanced recognition of words previously presented in a task with nonfocal prospective memory requirements

Remembering to perform deferred actions when events are encountered in the future is referred to as event-based prospective memory. Individuals can be slower to respond to ongoing tasks when they have prospective memory task requirements. These costs are interpreted as evidence for cognitive control processes allocated to the prospective memory task, but we know little about these processes. In the present article, the recognition of nontargets previously presented in an ongoing task with prospective memory task requirements provided evidence for the differential processing of individual ongoing task items. Participants performed a lexical decision task, where some participants were required to make an alternative prospective memory response either to a specific word (focal) or to exemplars of a category (nonfocal). Participants were slower to respond to the ongoing task in the nonfocal conditions than in the control condition (costs), regardless of whether or not prospective memory task importance was emphasized. Participants were also slower to respond to the ongoing task in the focal conditions than in the control condition, but only when prospective memory task importance was emphasized. This task was followed by a surprise recognition memory test in which nontarget words from the lexical decision task were intermixed with new words. Focal conditions, but not nonfocal conditions, showed better discrimination on the recognition task, as compared with the control condition. Participants in nonfocal conditions mapped the semantic features of the ongoing task letter strings onto the semantic features of their prospective memory category, and this elaboration in the processing of individual nontargets increased incidental learning and produced the recognition benefit

Laparoscopic transhiatal esophagectomy for esophageal adenocarcinoma identified at laparoscopic Roux-en-Y gastric bypass

Introduction: More than one third of Americans are obese. Obesity is a risk factor for gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma (EA). The only durable treatment for morbid obesity and its comorbid conditions is bariatric surgery. There is no consensus among bariatric surgeons, however, regarding the role of preoperative screening upper endoscopy in bariatric surgery. Presentation of case: Two cases of incidental EA were identified by completion EGD following laparoscopic Roux-en-Y gastric bypass (LRYGB). EGD was done for anastomotic surveillance and provocative leak testing. Esophageal masses were identified and biopsies demonstrated adenocarcinoma. In both cases a laparoscopic transhiatal esophagectomy (LTHE) was completed using the gastric remnant as conduit; the biliopancreatic limb was divided proximal to the jejunojejunostomy and anastomosed to the proximal roux limb to complete the reconstruction. Discussion: Obesity is a risk factor for GERD and EA. The role of EGD prior to bariatric surgery is unclear. Studies have demonstrated routine EGD prior to bariatric surgery may diagnose foregut pathology; however, few of the findings alter the planned treatment. The cost effectiveness of this strategy is questionable. There are reports of EA developing after bariatric surgery; however, we found no previous case reports of EA identified at LRYGB. Conclusion: Our institution has opted for selective preoperative endoscopy in patients with preoperative gastrointestinal symptoms. In post gastric bypass patients LTHE can be performed with good results