Neutrophils modulated antigen presentation following immunization with antigens in complete or incomplete Freund's adjuvant or alum. The neutrophils had an important negative role in the CD4 T cell and B cell responses to three protein antigens, hen-egg white lysozyme (HEL), ovalbumin (OVA) and listeriolysin O (LLO). In their absence (by depleting with antibodies for only the first twenty-four hours, or using genetically neutropenic mice), the cellular responses increased several fold. The CD8 response was not affected or slightly decreased. Competition for antigen between the presenting cells and the neutrophils, as well as an effect on the response to antigen-bearing dendritic cells (DC) was documented. Neutrophils entered the draining lymph nodes, rapidly and for a brief period of several hours, localizing mainly to the marginal sinus and superficial cortex. There they established brief contacts with DC and macrophages. Moreover, neutrophils imprinted on the quality of the subsequent DC-T cell interactions, despite no physical contacts with them: by intravital microscopy, the clustering of antigen-specific T cells and DC was improved in neutropenic mice. Thus, neutrophils are obligate cells that briefly enter sites of immunization and set the level of antigen presentation: a brief depletion may have a considerably positive impact on vaccination.

Neutrophil-produced thromboxane A2 controls the magnitude and spread of T cell responses to distal lymph nodes.

The contribution of CD8 T cells in host defense against histoplasmosis is minor in the CD4 T cell-intact mouse, as it has been shown that depleting CD8 T cells only marginally affects fungal clearance. However, it remains to be determined whether the CD8 T cells are protective in a host lacking functional CD4 T cells. In this study, MHC class II-deficient mice infected with Histoplasma capsulatum (Histoplasma) kept the fungus in check for up to 16 wk, indicating that CD8 T cells are able to limit fungal replication. Ex vivo studies showed that CD8 T cells from Histoplasma-infected mice expressed both intracytoplasmic IFN-γ and granzyme B. Furthermore, CD8 T cells exhibited cytotoxic activity against macrophage targets containing Histoplasma. We demonstrated that the macrophage, being the primary host cell as well as the effector cell, can also serve as Ag donor to dendritic cells. Histoplasma-specific CD8 T cells are stimulated by dendritic cells that present exogenous Histoplasma Ags, either through direct ingestion of yeasts or through uptake of apoptotic macrophage-associated fungal Ags, a process known as “cross-presentation.” Based on these results, we present a model detailing the possible sequence of events leading to a cell-mediated immune response and fungal clearance in Histoplasma-infected hosts.

VATS lobectomy in patients treated with induction therapy for locally advanced NSCLC is feasible and effective and does not appear to compromise oncologic outcomes.

The DENN domain is an evolutionary conserved protein module found in all eukaryotes and serves as an exchange factor for Rab-GTPases to regulate diverse cellular functions. Variants in DENND1B are associated with development of childhood asthma and other immune disorders. To understand how DENND1B may contribute to human disease, Dennd1b(-/-) mice were generated and exhibit hyper-allergic responses following antigen challenge. Dennd1b(-/-) TH2, but not other TH cells, exhibit delayed receptor-induced T cell receptor (TCR) downmodulation, enhanced TCR signaling, and increased production of effector cytokines. As DENND1B interacts with AP-2 and Rab35, TH2 cells deficient in AP-2 or Rab35 also exhibit enhanced TCR-mediated effector functions. Moreover, human TH2 cells carrying asthma-associated DENND1B variants express less DENND1B and phenocopy Dennd1b(-/-) TH2 cells. These results provide a molecular basis for how DENND1B, a previously unrecognized regulator of TCR downmodulation in TH2 cells, contributes to asthma pathogenesis and how DENN-domain-containing proteins may contribute to other human disorders.

Background Salvage surgical resection for non-small cell lung cancer (NSCLC) patients initially treated with definitive chemotherapy and radiation can be performed safely, but the long-term benefits are not well characterized. Methods Perioperative complications and long-term survival of all patients with NSCLC who received curative-intent definitive radiation with or without chemotherapy followed by lobectomy from 1995-2012 were evaluated. Results During the study period, 31 patients met inclusion criteria. Clinical stage distribution was: stage I (n=2,6%); stage II (n=5,16%); stage IIIA (n=15,48%);stage IIIB (n=5,16%); stage IV (n=3,10%); and unknown (n=1,3%). The reasons surgery was initially not considered were: patients deemed medically inoperable (5 [16%]); extent of disease considered unresectable (21 [68%]); small cell lung cancer misdiagnosis (1 [3%]); and unknown (4 [13%]). Definitive therapy was radiation alone (n=2, 6%), concurrent chemoradiation (n=28, 90%), and sequential chemoradiotherapy (n=1, 3%). The median radiation dose was 60 Gy. Patients were subsequently referred for resection because of obvious local relapse, medical tolerance of surgery or post-therapy imaging suggested residual disease.Median time from radiation to lobectomy was 17.7 weeks.There were no perioperative deaths, and morbidity occurred in 15 (48%) patients. None of 3 patients with residual pathologic nodal disease survived longer than 37 months, but the 5-year survival of pN0 patients was 36%. Patients who underwent lobectomy for obvious relapse (n=3) also did poorly with median overall survival of 9 months. Conclusion Lobectomy after definitive radiation therapy can be done safely and is associated with reasonable long-term survival, particularly when patients do not have residual nodal disease.

Lowbush blueberries have been processed by freeze dry, forced air, vacuum oven, and micro-convection methods to a moisture content of 16-25%. The drying effect on the product quality was evaluated. There were no significant differences in vitamin A and niacin retention except freeze dried berries had higher vitamin C retention. No significant differences occurred in retention of mineral content except higher sodium and lower magnesium were found in the micro-convection and freeze dry methods, respectively. Freeze dried and vacuum dried blueberries had higher soluble solids retention and were darker and redder than forced air or micro-convection dried berries. Freeze dried berries were found to have highest rehydration ratio and lowest bulk density.

This paper considers the analysis of Weibull distributed lifetime data observed under Type II progressive censoring with random removals, where the number of units removed at each failure time follows a binomial distribution. Maximum likelihood estimators of the parameters and their asymptotic variances are derived. The expected time required to complete the life test under this censoring scheme is investigated.