Idiopathic pulmonary alveolar proteinosis (I-PAP) is a rare disease of unknown etiology in which the alveoli fill with lipoproteinaceous material. We report here that I-PAP is an autoimmune disease with neutralizing antibody of immunoglobulin G isotype against granulocyte/macrophage colony-stimulating factor (GM-CSF). The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases. It specifically bound GM-CSF and neutralized bioactivity of the cytokine in vitro. The antibody was also found in sera from all I-PAP patients examined but not in sera from a secondary PAP patient or normal subjects, indicating that it exists systemically in I-PAP patients. As lack of GM-CSF signaling causes PAP in congenital cases and PAP-like disease in murine models, our findings strongly suggest that neutralization of GM-CSF bioactivity by the antibody causes dysfunction of alveolar macrophages, which results in reduced surfactant clearance.

No abstract

M-177 is a protease-sensitive allergen. The breakdown products of M-177 provoked higher allergenic activity than the intact allergen.

One of the most promising objectives of clinical hematology is to derive engraftable autologous hematopoietic stem cells (HSCs) from human induced pluripotent stem cells (iPSCs). Progress in translating iPSC technologies to the clinic relies on the availability of scalable differentiation methodologies. In this study, human iPSCs were differentiated for 21 days using STEMdiff™, a monolayer-based approach for hematopoietic differentiation of human iPSCs that requires no replating, co-culture or embryoid body formation. Both monolayer and suspension cells were functionally characterized throughout differentiation. In the supernatant fraction, an early transient population of primitive CD235a+ erythroid cells first emerged, followed by hematopoietic progenitors with multilineage differentiation activity in vitro but no long-term engraftment potential in vivo. In later stages of differentiation, a nearly exclusive production of definitive erythroid progenitors was observed. In the adherent monolayer, we identified a prevalent population of mesenchymal stromal cells and limited arterial vascular endothelium (VE), suggesting that the cellular constitution of the monolayer may be inadequate to support the generation of HSCs with durable repopulating potential. Quantitative modulation of WNT/β-catenin and activin/nodal/TGFβ signaling pathways with CHIR/SB molecules during differentiation enhanced formation of arterial VE, definitive multilineage and erythroid progenitors, but was insufficient to orchestrate the generation of engrafting HSCs. Overall, STEMdiff™ provides a clinically-relevant and readily adaptable platform for the generation of erythroid and multilineage hematopoietic progenitors from human pluripotent stem cells.HighlightsRobust, scalable and clinically-relevant monolayer-based culture system for hematopoietic differentiation of human iPSCs.Successive emergence of primitive erythroid cells, definitive multilineage HSPCs and erythroid progenitors in the culture supernatant.Abundant mesenchymal cells and limited arterial vascular endothelium in the culture monolayer.CHIR/SB molecules increase arterial vascular endothelium formation, suppress primitive hematopoiesis and promote definitive multilineage and erythroid progenitors.

The Belle II detector is designed for a high luminosity upgrade of the Belle detector and the KEKB accelerator at High Energy Accelerator Research Organization (KEK), Japan, to study flavor physics. A design luminosity is about 40 times higher than the KEKB, 8xl0 35 cm-2 sl • The number of readout channels of the drift chamber is 14392 chs. In order to reduce the number of cables between the readout electronics and an electronics hut, the readout electronics is designed to locate at near an end plate of the chamber. The electronics consists of 300 modules having four interface cables: system interfaces, a trigger system interface, and a data acquisition system interface. We tested the electronics with a test detector and have confirmed that the test results meet the requirements from the Belle II experiment.