Eosinophils cluster around airway nerves in patients with fatal asthma and in antigen-challenged animals. Activated eosinophils release major basic protein, which blocks inhibitory M2 muscarinic receptors (M2Rs) on nerves, increasing acetylcholine release and potentiating vagally mediated bronchoconstriction. We tested whether GW701897B, an antagonist of CCR3 (the receptor for eotaxin as well as a group of eosinophil active chemokines), affected vagal reactivity and M2R function in ovalbumin-challenged guinea pigs. Sensitized animals were treated with the CCR3 antagonist before inhaling ovalbumin. Antigen-challenged animals were hyperresponsive to vagal stimulation, but those that received the CCR3 antagonist were not. M2R function was lost in antigen-challenged animals, but not in those that received the CCR3 antagonist. Although the CCR3 antagonist did not decrease the number of eosinophils in lung tissues as assessed histologically, CCR3 antagonist prevented antigen-induced clustering of eosinophils along the nerves. Immunostaining revealed eotaxin in airway nerves and in cultured airway parasympathetic neurons from both guinea pigs and humans. Both IL-4 and IL-13 increased expression of eotaxin in cultured airway parasympathetic neurons as well as in human neuroblastoma cells. Thus, signaling via CCR3 mediates eosinophil recruitment to airway nerves and may be a prerequisite to blockade of inhibitory M2Rs by eosinophil major basic protein.

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The five diffusion coefficients characterizing a binary mixture and the relationships between them are discussed. Measurements are reported of the self-diffusion coefficients for each component of ethyl iodide + n-butyl iodide mixtures over the whole composition range, using radioactive iodine as tracer. For one composition, the effect of temperature was studied.Recently, a study has been made by one of us (L. H. S.) on self-diffusion in the lower alkyl bromides and iodides, as will be reported elsewhere. At the conclusion of the foregoing work, it was decided to extend it by self-diffusion measurements in a mixture, n-butyl iodide and ethyl iodide, labelled with 1131, as the components. In a 1 : 1 M mixture, the self-diffusion coefficient of labelled ethyl iodide was appreciably different from that of labelled butyl iodide. This has been explained in the papers of Darken 1 and of Hartley and Crank,2 who, between them, have shown that a binary mixture is characterized by, not one, but five diffusion coefficients. Of these, the two self-diffusion coefficients must be regarded as the most fundamental, and, from these, the interdiffusion coefficient normally measured, as well as the " intrinsic diffusion coefficient " of Hartley and Crank can be derived.Acceptance of this viewpoint implies a re-orientation in present views on measurement and recording of diffusion data. Future presentation of diflwion data in n-component systems should be in terms of the n self-diflusion coefficients.At first sight, it seems undesirable to replace the single inter-diffusion coefficient used for binary systems by two self-diffusion coefficients; but this apparent simplicity disappears when the number of components exceeds two. Thus, for a ternary system, it is customary to refer to the three binary inter-diffusion coefficients, but it is simpler and more logical to refer to the three self-diffusion coefficients .At present, data on self-diffusion in mixtures are meagre. The systems chosen were non-ideal, and no system has been followed over the whole range of compositions. The system EtI + n-BuI should be nearly ideal for all compositions, and the measurements reported in the present paper covered the whole range of compositions at 19-35°C. In addition, for the 1 :1 M mixture, three temperatures were employed.

Background Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized pancreatic neoplasm characterized by excessive mucin secretion by ductal epithelial cells resulting in a cystic dilation of the pancreatic duct. Aim The objective of this study was to review Thomas Jefferson University’s experience and the literature to determine the significance of extra-pancreatic mucin when associated with an IPMN. Results A retrospective analysis at our institution revealed only two cases of IPMN associated with extra-pancreatic mucin, which were classic IPMNs with rupture of the pancreatic duct and peritoneal mucin spillage. This specific finding is not previously described, although is assumed as five cases were reported in the literature with IPMN and mucin extension demonstrated by pseudomyxoma peritonei (PMP). We propose IPMN of the pancreas may be grossly compared to a mucocele of the appendix, as both are characterized by excessive secretion of mucin by ductal epithelial cells. A morbid complication of a mucocele is PMP. The presence of extra-pancreatic mucin with an IPMN could present a rare but important marker of the eventual seeding of tumor outside the primary IPMN. This has been documented with cases of iatrogenic spilling of pancreatic mucin, as well as multiple cases of IPMN associated with pseudomyxoma peritonei. Conclusions At this time, there is scant reporting and consensus for the treatment of IPMN with extra-pancreatic mucin.

Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S. stercoralis would trigger eosinophil chemotaxis, and to then compare the chemotactic migration response, including second messenger signals and receptors, to those mechanisms triggered by host chemoattractants. Eosinophils undergo both chemotaxis and chemokinesis to soluble parasite extract in transwell plates. Pretreatment of eosinophils with pertussis toxin, a G protein-coupled receptor inhibitor, inhibited migration of the eosinophils to the parasite extract. Likewise, blocking PI3K, tyrosine kinase, p38 and p44/42 inhibited eosinophil chemotaxis to parasite extract. Furthermore, CCR3, CXCR4 or CXCR2 antagonists significantly inhibited eosinophil chemotaxis to the parasite extract. Molecular weight fractionation of parasite extract revealed that molecules attracting eosinophils were present in several fractions, with molecules greater than 30 kDa being the most potent. Treating the extract with proteinase K or chitinase significantly inhibited its ability to induce chemotaxis, thereby demonstrating that the chemoattractants were both protein and chitin. Therefore, chemoattractants derived from parasites and host species stimulate similar receptors and second messenger signals to induce eosinophil chemotaxis. Parasite extract stimulates multiple receptors on the eosinophil surface, which ensures a robust innate immune response to the parasite.

Introduction Dorsal agenesis of the pancreas (DAP) is a rare congenital anomaly, with only 44 cases having been reported in the English literature since 1966. Materials and Methods A retrospective review of our IRB-approved pancreatic surgery database was performed from November 2005 to November 2010 searching for cases of DAP. Discussion Disorders in the retinoic acid (Raldh) and hedgehog (Hh) signaling pathways, which appear to play a role in the development of DAP, have been implicated in other diseases of the pancreas such as pancreatic ductal adenocarcinoma (PDA) and nonalcoholic chronic calcific pancreatitis (NCCP). Conclusion In this report, we describe three cases of DAP in the setting of PDA, two of which include the third component of NCCP. We provide a discussion of the clinical features of this novel triad and address the molecular pathways that relate to these respective diseases.