Influenza B-cells Protective Epitope Characterization: A Passkey for the Rational Design of New Broad-Range Anti-Influenza Vaccines

The emergence of new influenza strains causing pandemics represents a serious threat to human health. From 1918, four influenza pandemics occurred, caused by H1N1, H2N2 and H3N2 subtypes. Moreover, in 1997 a novel influenza avian strain belonging to the H5N1 subtype infected humans. Nowadays, even if its transmission is still circumscribed to avian species, the capability of the virus to infect humans directly from avian reservoirs can result in fatalities. Moreover, the risk that this or novel avian strains could adapt to inter-human transmission, the development of resistance to anti-viral drugs and the lack of an effective prevention are all incumbent problems for the world population. In this scenario, the identification of broadly neutralizing monoclonal antibodies (mAbs) directed against conserved regions shared among influenza isolates has raised hopes for the development of monoclonal antibody-based immunotherapy and “universal” anti-influenza vaccines.     

Thoracoabdominal approach in liver surgery: how,when, and why

Liver resection can be performed with different surgical approaches whether abdominal or combined thoracoabdominal. This work focuses on the surgical technique for the thoracoabdominal approach in liver surgery, describing the technique, the rationale, and making a review of the current literature on such subject.     

Endoluminal Nd:YAG laser application in ex vivo biliary porcine tissue

Adequate biliary drainage with endoscopic or percutaneous placement of self-expandable metal stents represents the goal of palliation in patients with inoperable malignant obstruction of the biliary tree. As an adjunct to stenting, various tissue ablation treatments have been proposed with conflicting results. The aim of this study was to test the effect on biliary tissue of a new ablation technique based on Nd:YAG laser light delivery. The study was conducted on ex vivo specimens of 18 healthy farm pigs, using cystic ducts that are the simplest biliary structures to isolate and cannulate ex vivo. A 22G cannula was positioned into the cystic duct and a quartz optical fibre, with a prototypal cooling system, was inserted into the cannula. Nd:YAG laser output powers of 10, 12, and 15 W were tested, with a total delivered energy of 1000 J in continuous mode in each case. After laser treatment, histological analysis was performed. At macroscopical examination, no lesions of the external wall of the cystic ducts were detected. At histopathological examination, a coagulative necrosis involving the entire mucosa up to the muscolaris propria without significant changes of periductal tissues was observed in all specimens. This study shows the possibility of using Nd:YAG laser on ex vivo porcine biliary ducts with the effect of obtaining a coagulative necrosis involving the whole mucosa.     

Orthodeoxia without platypnea from interatrial defect associated with persistent left superior vena cava in the absence of pulmonary hypertension

Orthodeoxia-platypnea is a rare but increasingly recognized syndrome of upright hypoxemia usually associated to breathlessness relieved by recumbency. We report the case of isolated orthodeoxia discovered in a military recruit who referred only fatigability as the clinical symptom after a forced march. Transesophageal echocardiography demonstrated the presence of interatrial defect ostium secundum type with the persistence of left superior vena cava draining into coronary sinus. Right-to-left shunt was visualized by peripheral saline contrast infusion, despite normal right hemodynamics at heart catheterization. Hypoxemia recovered after the percutaneous closure of the interatrial defect. Orthodeoxia and platypnea could occur as separate disease manifestations, the latter probably being a rarer acute event, whereas orthodeoxia was underestimated and potentially earlier screenable.     

Multiple fragments of human TG are capable of inducing oral tolerance to whole human TG

Oral tolerance is the mechanism by which the immune system remains unresponsive to orally administered soluble antigens. Mice immunized with human TG (hTG), resulting in the induction of experimental autoimmune thyroiditis (EAT), provide an ideal in vivo system in which to examine oral tolerance to hTG. In the present study, we characterize epitopes of hTG that are capable of inducing oral tolerance. hTG is a large homodimeric protein, 660 Kd. The limited proteolysis of hTG using trypsin (TR) generates several smaller fragments of hTG ranging in size from 29 Kd to 145 Kd. Using hTG fragments h1TR (residues 1-521), h4bisTR (residues 2513-2713), h6TR (residues 522-1626), and h7TR (residues 1627-2512), prepared from both iodine rich and iodine poor hTG, we investigated the ability of these fragments to induce oral tolerance. The oral administration of iodine rich h6TR or h7TR suppresses hTG specific immune responses in a manner similar to whole hTG. In contrast, the oral administration of iodine rich h1TR or h4bisTR exacerbates hTG specific immune responses. Unlike iodine rich h1TR or h4bisTR, the oral administration of iodine poor h1TR or h4bisTR fails to augment hTG specific immune responses. In fact, h4bisTR suppresses hTG specific immune responses. These results indicate that hTG contains multiple epitopes that differentially affect oral tolerization. Tolerogenic epitopes reside within fragments h6TR and h7TR. The removal of iodine, and presumably hormone, from h4bisTR converts an immunogenic epitope to a tolerogenic epitope.     

The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.