Factors associated with kindergarten teachers' willingness to continue working.

The turnover rate among kindergarten teachers in advanced countries is extremely high. As such, there is an urgent need to determine the reasons for this turnover and to identify ways to prevent it. The current study investigates the individual and environmental factors that impact kindergarten teachers' willingness to continue working.

Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies.

Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours ('Color-flu' viruses) to facilitate the study of viral infection in in vivo models.

Regulation of intestinal IgA responses by dietary palmitic acid and its metabolism.

Enhancement of intestinal IgA responses is a primary strategy in the development of oral vaccine. Dietary fatty acids are known to regulate host immune responses. In this study, we show that dietary palmitic acid (PA) and its metabolites enhance intestinal IgA responses.

Characterization of H7N9 influenza A viruses isolated from humans.

Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission, and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively.

Critical role of dendritic cells in T cell retention in the interfollicular region of Peyer's patches.

Peyer's patches (PPs) simultaneously initiate active and quiescent immune responses in the gut. The immunological function is achieved by the rigid regulation of cell distribution and trafficking, but how the cell distribution is maintained remains to be elucidated. In this study, we show that binding of stromal cell-derived lymphoid chemokines to conventional dendritic cells (cDCs) is essential for the retention of naive CD4(+) T cells in the interfollicular region (IFR) of PPs.

Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice.

Intestinal plasma cells predominantly produce immunoglobulin (Ig) A, however, their functional diversity remains poorly characterized. Here we show that murine intestinal IgA plasma cells can be newly classified into two populations on the basis of CD11b expression, which cannot be discriminated by currently known criteria such as general plasma cell markers, B cell origin and T cell dependence. CD11b(+) IgA(+) plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b(-) IgA(+) plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance.

A pivotal role of vitamin B9 in the maintenance of regulatory T cells in vitro and in vivo.

Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from naïve T cells but failed to survive.

A retrospective analysis of bortezomib therapy for Japanese patients with relapsed or refractory multiple myeloma: beta2-microglobulin associated with time to progression.

Bortezomib is approved for the treatment of patients with relapsed or refractory multiple myeloma (MM), but only a few clinical studies for Japanese patients who were treated with bortezomib have been reported. We retrospectively analyzed 40 patients with relapsed or refractory MM who have received bortezomib at three collaborating centers in Miyagi prefecture in Japan. All the patients have been received bortezomib in combination with dexamethasone.

Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses.

It is well established that Peyer's patches (PPs) are sites for the differentiation of IgA plasma cell precursors, but molecular and cellular mechanisms in their trafficking remain to be elucidated. In this study, we show that alterations in type 1 sphingosine 1-phosphate (S1P) receptor expression during B cell differentiation in the PPs control the emigration of IgA plasma cell precursors. Type 1 S1P receptor expression decreased during the differentiation of IgM(+)B220(+) B cells to IgA(+)B220(+) B cells, but recovered on IgA(+)B220(-) plasmablasts for their emigration from the PPs.

Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkappaB-inducing kinase in stromal cells.

We previously reported that sphingosine 1-phosphate (S1P) regulates peritoneal B-cell trafficking and subsequent intestinal IgA production, but the underlying mechanisms remain obscure. We demonstrate here that nuclear factor kappaB-inducing kinase (NIK) is involved in the regulation of S1P-mediated trafficking of peritoneal B cells. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed type 1 S1P receptor (S1P(1)) at comparable levels and demonstrated normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P(1) modulator.

Interlaboratory comparison of quantitative RT-PCR based detection for minimal residual disease in leukemias: a standardization approach in Japan.

Real-time quantitative polymerase chain reaction (RQ-PCR) has been accepted as integral part of the management of patients with hematologic malignancies. Whereas standardization efforts of RQ-PCR, initiated by Europe Against Cancer (EAC) group, have been gradually widespread in the world, Japanese laboratories use their individual protocol for RQ-PCR analysis. Therefore, we assessed the variability of quantitative results obtained from 4 different laboratories in Japan, including 3 companies and Tohoku University Hospital, using identical peripheral blood or bone marrow samples of patients in chronic myeloid leukemia (CML; n = 11) and acute myeloid leukemia (AML; n = 2).

Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium.

It is well established that intraepithelial T lymphocytes (IELs) are derived from conventional single-positive (SP) thymocytes, as well as unconventional double-negative (DN) thymocytes and CD103+CD8alphabeta recent thymic emigrants (RTEs). We show that IELs can be divided into two groups according to their dependency on sphingosine 1-phosphate (S1P) for trafficking into the intestines. CD4 or CD8alphabeta naive lymphocytes originating from SP thymocytes express high levels of type 1 S1P receptor (S1P(1)), and their preferential migration into the large intestine is regulated by S1P.

Sphingosine 1-phosphate-mediated trafficking of pathogenic Th2 and mast cells for the control of food allergy.

Sphingosine 1-phosphate (S1P) has been proposed as a regulator of lymphocyte trafficking, but its role in mucosa-associated diseases, such as in food allergies, remains to be elucidated. To examine the role of S1P in allergic diseases in the intestine, we used a Th2 cell-mediated Ag-specific allergic diarrhea model and demonstrated that type 1 S1P receptor (S1P(1)) expression was preferentially associated with pathogenic CD4(+) T cells for the development of allergic reactions. Consistent with this demonstration, treatment with FTY720, a modulator of the S1P(1), prevented allergic diarrhea by inhibiting the migration of systemically primed pathogenic CD4(+) T cells induced by oral challenge with allergen into the large intestine.

Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production.

Sphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation of lymphocyte emigration from organized lymphoid tissues such as the peripheral lymph nodes and thymus, but its immunologic role in unorganized and diffused tissues remains to be elucidated. Here we show that the trafficking of peritoneal B cells is principally regulated by S1P. All peritoneal B cells including B1a, B1b, and B2 B cells express comparable levels of the type 1 S1P receptor.

Dose modification of imatinib by monitoring the level of BCR-ABL transcript in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a hematological malignancy that is characterized by the chromosome anomaly, t(9;22)(q34;q11). By this chromosomal translocation, a novel activated tyrosine kinase, BCR-ABL chimeric protein, is generated, and the protein is causative of the disease. Recently, Imatinib mesylate targeting to a BCR-ABL chimeric protein has been developed, and shown to achieve complete remission at a high rate.

Synergistic effect of arsenic trioxide and flt3 inhibition on cells with flt3 internal tandem duplication.

Flt3 internal tandem duplication (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). Flt3-ITD constitutively activates various signaling pathways, including a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and MEK inhibition were recently reported to interact synergistically to induce apoptosis in AML cells.

[Second transplant from the same donor without conditioning for bone marrow aplasia after non-myeloablative hematopoietic stem cell transplantation for chronic myeloid leukemia].

We describe a 56-year-old woman with chronic myeloid leukemia (CML) and a past history of stroke, who underwent nonmyeloablative hematopoietic stem cell transplantation (NST) with conditioning consisting of fludarabine and cyclophosphamide. The regimen related toxicity was minimal and patient did not require transfusions of any blood products nor did she have any infections after the NST Since mixed chimerism was observed in both lymphocytes (70% were donor type) and granulocytes (none were donor type) at 56 days after NST, donor lymphocyte infusion (DLI) was performed on day 68 and then immunosuppressant therapy was discontinued. DLI resulted in graft versus leukemia (GVL) effect, causing pancytopenia and bone marrow aplasia.

Primary marginal zone lymphoma of the thymus accompanied by chromosomal anomaly 46,X,dup(X)(p11p22).

We report a case of primary marginal zone lymphoma in the thymus of a 34-year-old woman. She was initially suspected of having a mediastinal plasmacytoma because of the presence of dominantly proliferating plasmacytic cells in a small fragment obtained by thoracoscopic biopsy, and an elevated level of serum monoclonal IgA. However, histology of the tissue obtained by a subsequent open surgical biopsy revealed diffuse proliferation of atypical monocytoid B-lymphocyte-like cells, which showed prominent plasmacytic differentiation and a close association with thymic epithelial cells consistent with the histology of a marginal zone lymphoma of the thymus.