To determine the prevalence of Hepatitis E virus (HEV) in industrialized nations, we analyzed the excretion of HEV strains by the populations of Spain, France, Greece, Sweden, and the United States. Twenty of 46 (43.5%) urban sewage samples collected in Barcelona from 1994 to 2002 tested positive for HEV. We identified 15 HEV strains, which were similar to two HEV isolates previously described in Barcelona in clinical samples and to strains from diverse geographic HEV-nonendemic areas. We also identified two HEV strains in sewage samples from Washington, D.C., and Nancy, France; these samples were also positive for Hepatitis A virus. In addition, we studied the role of pigs as a reservoir for HEV and identified one new swine HEV strain. Our results suggest that HEV may be more prevalent than previously considered in industrialized countries and that variants of the virus circulate simultaneously in one region.

We evaluated the effects of a plant extracts mixture (XT) standardized in 5% (wt/wt) carvacrol, 3% cinnamaldehyde, and 2% capsicum oleoresin (oregano, cinnamon and Mexican pepper), alone or in combination with formic acid (FA), on the productive performance and the intestinal ecosystem of the early-weaned pig. Pigs weaned at 20 ± 1 d of age (n = 216) were allocated in 24 pens and fed a standard medicated prestarter diet for 12 d. Twelve days after weaning, a stress management system based on social and dietary stress factors was applied to the animals, after which, each group was allocated to one of six dietary treatments, which followed a factorial arrangement, with three levels (as-fed basis) of the XT (0, 150, and 300 mg/kg) and two levels of FA (0 and 0.5%). On d 24 and 25 after the stress episode, eight pigs per treatment were killed to examine variables describing some aspects of the gastrointestinal ecology. Two days after the stress episode, an Escherichia coli K88 diarrhea episode occurred, and five casualties were registered. Four of the five deaths occurred in pens of pigs not fed the XT. The FA resulted in better G:F (P = 0.040) in coincidence with shorter villous height (P = 0.073) and lower rectal total microbial mass (P = 0.078). Both XT and FA addition increased stomach content (P = 0.006 and 0.003, respectively) and percentage of DM (P = 0.089 and 0.010, respectively), suggesting an increased gastric retention time; consequently, pH was also increased (P = 0.005 and 0.060, respectively). The XT decreased ileum total microbial mass (P = 0.025) and increased the lactobacilli:enterobacteria ratio (P = 0.002). The VFA profile in the cecum and colon was modified by XT inclusion, increasing the proportion of acetate (P = 0.018 and 0.025, respectively) and diminishing the proportion of butyrate (P = 0.096 and 0.040, respectively) and valerate (P = 0.001 and 0.039, respectively). Both XT and FA were shown to be effective in modifying the gastrointestinal ecosystem, stomach contents, and stomach emptying rate, which are proposed as important aspects in the mechanisms of action for these additives.

The study of anaphylactoid reactions during perioperative procedures and anaesthesia represents a diagnostic challenge for allergists, as many drugs are administered simultaneously, and approximately half of them trigger allergic reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this study, we analyse the ability of certain drugs used during perioperative procedures and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and sera from patients who experienced an anaphylactoid reaction during the perioperative procedure. Using a β-hexosaminidase release assay, several drugs were seen to cause mast cell degranulation in vitro in comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium specifically triggered this receptor, as assessed by the release of β-hexosaminidase in the control versus the MRGPRX2-silenced cells. The same outcome was seen when measuring degranulation based on the percentage of CD63 expression at identical doses. Unlike that of the healthy controls, the sera of patients who had experienced an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a candidate for consideration in non-IgE-mediated allergic reactions to some perioperative drugs, reinforcing its role in mast cell responses and their pathophysiology.

CD84 is a member of the CD2 subset of the Ig superfamily of cell surface molecules. Its cytoplasmic tail binds to Src homology 2 domain-containing protein 1A (signaling lymphocytic activation molecule-associated protein), a protein encoded by the X-linked lymphoproliferative disease gene. It is preferentially expressed on B lymphocytes, monocytes, and platelets. We show that it is also expressed on thymocytes and T cells. CD84 was positive on CD4−CD8− thymocytes, and its expression decreased with cell maturation. It is expressed on mature T cells preferentially on CD45RO+. To identify the CD84 ligand, we generated a soluble Ig fusion protein containing the human CD84 extracellular domains (CD84-Ig). Because receptor-ligand interactions occur between several members of this subfamily, we assayed CD84-Ig binding with all members of the CD2 family. CD84-Ig bound to CD84-transfected cells, whereas no binding was detected with cells expressing other CD2 subfamily receptors, showing that CD84 binds to itself. Anti-CD84 mAbs recognizing epitopes wholly within domain 1 of CD84 blocked the binding of the CD84-Ig fusion protein to CD84-transfected cells and platelets. Data from CD84 domain human/mouse chimeras further revealed that only the first extracellular domain of the molecule is involved in the ligand receptor recognition. The CD84-CD84 interaction was independent of its cytoplasmic tail. Finally, concurrent ligation of human CD84 with mAbs or CD84-Ig and CD3 enhanced IFN-γ secretion in human lymphocytes. Thus, CD84 is its own ligand and acts as a costimulatory molecule.

The T and natural killer (NK) cell‐specific gene SAP (SH2D1A) encodes a ‘free SH2 domain’ that binds a specific tyrosine motif in the cytoplasmic tail of SLAM (CD150) and related cell surface proteins. Mutations in SH2D1A cause the X‐linked lymphoproliferative disease, a primary immunodeficiency. Here we report that a second gene encoding a free SH2 domain, EAT‐2, is expressed in macrophages and B lympho cytes. The EAT‐2 structure in complex with a phosphotyrosine peptide containing a sequence motif with Tyr281 of the cytoplasmic tail of CD150 is very similar to the structure of SH2D1A complexed with the same peptide. This explains the high affinity of EAT‐2 for the pTyr motif in the cytoplasmic tail of CD150 but, unlike SH2D1A, EAT‐2 does not bind to non‐phosphorylated CD150. EAT‐2 binds to the phosphorylated receptors CD84, CD150, CD229 and CD244, and acts as a natural inhibitor, which interferes with the recruitment of the tyrosine phosphatase SHP‐2. We conclude that EAT‐2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen‐presenting cells.