Functionally Distinct Subsets of CD1d-restricted Natural Killer T Cells Revealed by CD1d Tetramer Staining

CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines and to mediate cytolysis, but it is unclear how these contrasting functional activities are regulated. Using lipid antigen–loaded CD1d tetramers, we have distinguished two subsets of CD1d-restricted T cells in fresh peripheral blood that differ in cytokine production and cytotoxic activation. One subset, which was CD4−, selectively produced the Th1 cytokines interferon γ and tumor necrosis factor α, and expressed NKG2d, a marker associated with cytolysis of microbially infected and neoplastic cells. This subset up-regulated perforin after exposure to interleukin (IL)-2 or IL-12. In contrast, CD4+ CD1d-restricted NKT cells potently produced both Th1 and Th2 cytokines, up-regulated perforin in response to stimulation by phorbol myristate acetate and ionomycin but not IL-2 or IL-12, and could be induced to express CD95L. Further, for both CD1d-restricted NKT cell subsets, we found that antigenic stimulation induced cytokine production but not perforin expression, whereas exposure to inflammatory factors enhanced perforin expression but did not stimulate cytokine production. These results show that the various activities of CD1d-restricted T cells in tumor rejection, autoimmune disease, and microbial infections could result from activation of functionally distinct subsets, and that inflammatory and antigenic stimuli may influence different effector functions

In vitro differentiation of lineage-negative bone marrow cells into microglia-like cells

金沢大学医薬保健研究域医学系Microglia are believed to be the only resident immune cells in the CNS, originating from hematopoietic-derived myeloid cells and invading the CNS during development. However, the detailed mechanisms of differentiation and transformation of microglial cells are not fully understood. Here, we demonstrate that murine microglial cells show two morphological forms in vitro, namely, small round cells expressing CD11b, Iba1, triggering receptor expressing on myeloid cells-2 (TREM2), and weakly expressing major histocompatibility complex class II and large flat cells expressing only CD11b and Iba1. Moreover, lineage-negative bone marrow (LN) cells cultured with primary mixed glial culture cells could differentiate into only the small round microglia-like cells, despite the absence of CCR2 and Gr-1 expression. Addition of macrophage colony stimulating factor (M-CSF) to LN cell culture allowed the proliferation and expression of TREM2 in LN cells, and the addition of neutralizing anti-M-CSF antibodies suppressed the proliferation of LN cells despite the expression of TREM2. When LN cells were cultured with M-CSF, the number of small round cells in the culture was considerably low, indicating that the small round morphology of the immature cells is not maintained in the presence of only M-CSF. On the other hand, when LN cells were grown in the presence of astrocytes, the small round cells were maintained at a concentration of approximately 30% of the total population. Therefore, cell-cell contact with glial cells, especially astrocytes, may be necessary to maintain the small round shape of the immature cells expressing TREM2. © Federation of European Neuroscience Societies and Blackwell Publishing Ltd

Community midwifery initiatives in fragile and conflict-affected countries: a scoping review of approaches from recruitment to retention

Background: Birth assisted by skilled health workers is one of the most effective interventions for reducing maternal and neonatal mortality. Fragile and conflict-affected states and situations (FCAS), with one-third of global maternal deaths, face significant challenges in achieving skilled care at birth, particularly in health workforce development. The importance of community-level midwifery services to improve skilled care is internationally recognized, but the literature on FCAS is limited. This review aimed to examine community midwifery (CMW) approaches, from recruitment to retention, in FCAS.Methods: This scoping review design adapted Arksey and O'Malley's six-stage framework. Data collection included systematic searching of seven databases, purposive hand-searching of reference lists and web sites, and stakeholder engagement for additional information. Potential sources were screened against inclusion and exclusion criteria. Included sources were appraised for methodological quality using the McGill University Mixed Methods Appraisal Tool. Data were analysed thematically, using deductive (i.e. cadre definition, recruitment, education, deployment and retention) and inductive coding (i.e. capacity, gender and insecurity).Results: Twenty-three sources were included, of 2729 identified, discussing community midwifery programmes in six FCAS (i.e. eight for Sudan, six for Afghanistan, three each for Mali and Yemen, two for South Sudan and one for Somalia). Source quality was relatively poor, and cadre definitions were context dependent. Major enablers for effective CMW programmes were community linkages and acceptance, while barriers included inappropriate recruitment, non-standardized education, weak supportive environment, political insecurity and violence.Conclusions: While community engagement and acceptance were crucial, CMW programmes were weakened by inappropriate recruitment and training, lack of support and general insecurity. Further research and implementation evidence is needed to aid policy-makers, donors and implementing agencies in developing and implementing effective CMW programmes in FCAS

The Toll-like Receptor Protein Rp105 Regulates Lipopolysaccharide Signaling in B Cells

The susceptibility to infections induced by Gram-negative bacteria is largely determined by innate immune responses to bacteria cell wall lipopolysaccharide (LPS). The stimulation of B cells by LPS enhances their antigen-presenting capacity and is accompanied by B cell proliferation and secretion of large quantities of LPS-neutralizing antibodies. Similar to macrophages and neutrophils, the LPS-induced activation of B cells is dependent on Toll-like receptor (TLR)4. Here, we demonstrate that the responses of B cells to LPS are also regulated by another TLR protein, RP105, which is predominantly expressed on mature B cells in mice and humans. The analysis of mice homozygous for the null mutation in the RP105 gene revealed impaired proliferative and humoral immune responses of RP105-deficient B cells to LPS. Using originally LPS-unresponsive Ba/F3 cells expressing exogenous TLR4 and RP105, we demonstrate the functional cooperation between TLR4 and RP105 in LPS-induced nuclear factor κB activation. These data suggest the existence of the TLR4–RP105 signaling module in the LPS-induced B cell activation

現在の英語カリキュラムと新入生の学習者ビリーフに基づく発展的提案

In order to provide students with good teaching, the curriculum needs to be reviewed and revised periodically. Even minor changes can be of benefit. To prepare a better curriculum for students, teachers should know students’ needs and wants. In this report, the present English curriculum at Okayama Prefectural University is described. The present curriculum aims to improve students’ four skills: listening, reading, speaking, and writing in addition to increasing vocabulary and grammar knowledge. Then, the results of a survey on 2018 first-year students’ beliefs regarding learning English are reported. Students’ beliefs include attitude toward English learning, motivation, anxiety, and expectation. Last, based on the results of the survey, the strengths and weaknesses of the present curriculum are discussed.平成30年度に実施された英語カリキュラムを説明し、平成30年度入学生の入学直後の学習者ビリーフ（学習への期待、意欲、不安など）を調査した。調査の結果、3つの学部から構成される岡山県立大学は、学部ごとに、学習者ビリーフが大きく異なることが明らかになった。語学教育推進室は、全学を対象とした統一英語カリキュラムを実施しているが、学部ごとに、学生のニーズに合わせた英語カリキュラムを工夫していく必要がある

Lipopolysaccharide Interaction with Cell Surface Toll-like Receptor 4-MD-2: Higher Affinity than That with MD-2 or CD14

Toll-like receptors (TLRs) are innate recognition molecules for microbial products, but their direct interactions with corresponding ligands remain unclarified. LPS, a membrane constituent of gram-negative bacteria, is the best-studied TLR ligand and is recognized by TLR4 and MD-2, a molecule associated with the extracellular domain of TLR4. Although TLR4-MD-2 recognizes LPS, little is known about the physical interaction between LPS and TLR4-MD-2. Here, we demonstrate cell surface LPS–TLR4-MD-2 complexes. CD14 greatly enhances the formation of LPS–TLR4-MD-2 complexes, but is not coprecipitated with LPS–TLR4-MD-2 complexes, suggesting a role for CD14 in LPS loading onto TLR4-MD-2 but not in the interaction itself between LPS and TLR4-MD-2. A tentative dissociation constant (Kd) for LPS–TLR4-MD-2 complexes was ∼3 nM, which is ∼10–20 times lower than the reported Kd for LPS–MD-2 or LPS–CD14. The presence of detergent disrupts LPS interaction with CD14 but not with TLR4-MD-2. E5531, a lipid A antagonist developed for therapeutic intervention of endotoxin shock, blocks LPS interaction with TLR4-MD-2 at a concentration 100 times lower than that required for blocking LPS interaction with CD14. These results reveal direct LPS interaction with cell surface TLR4-MD-2 that is distinct from that with MD-2 or CD14

Retinol Supplements Antiviral Action of Interferon in Patients with Chronic Hepatitis C: A Prospective Pilot Study

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon α-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks. The retinol group, in addition to above treatment, received retinol 30,000 units per day orally for 3 weeks from one week before the start of interferon α-2b plus ribavirin combination therapy. The hepatitis C virus (HCV) RNA negativity rate at 1 week after the end of interferon α-2b and ribavirin combination therapy was 46.7% (28/60) for the retinol group and 31.7% (19/60) for the control group, which was significantly higher for the retinol group. The level of serum HCV RNA in the retinol group was significantly lower at 1 week after beginning treatment as compared to the control group (p<0.01). Furthermore, serum 2,5'AS protein at 1 week after beginning treatment was significantly higher in the retinol group (p = 0.0002). The results suggest that retinol supplement increases the antiviral effect of interferon α-2b plus ribavirin only during the administration of IFN α-2b, ribavirin and retinol in patients with chronic hepatitis C

Examination of density and mixing ratio of barium preparations, using an originally created phantom

胃Ⅹ線検査に造影剤として用いられる硫酸バリウム懸濁液の濃度を,簡便に,客観的に決定する目的で,歯科用アルギン酸塩印象材を用いて,コインの図柄を写しとったファントムを制作した｡これを使って二種類の硫酸バリウム製剤の適正濃度(PD)を調べた結果,BARITOP PとBARICON MEALを単体,若くは混合した場合には,おおよそ,PD(W/V%)=0.75C+165(ただし,CはBARICON MEALの混合比(%))となった｡また,BARICON MEALはコントラストが高く,精密検査に有利だと考えられ,BARITOP PとBARICON MEALを混合すると濃度の許容範囲が広がるため,通常の検査に都合がよいと考えられた｡更に,このファントムは簡便に作成することができ,しかも,硫酸バリウム懸濁 液との親和性も良いことから,硫酸バリウム製剤やⅩ線TV装置の評価,増感紙･フィルム系の評価等にも応用できると考えられた｡A phantom copied designs of coins was created with alginate dental impression material to establish a objective, simple and easy method for deciding density of barium sulfate suspensions which are used for stomach X-ray examination as contrast media. As a result of examining proper density (PD) of two kind of barium preparations with this phantom, in case of BARITOP P and BARICON MEAL, PD were almost shown by the next equation : PD(W/V%)=0.75C+165(C meant content of BARICON MEAL (%)). As BARICON MEAL resulted in hight contrast, it was thought to be suitable for a close examination. Mixture of BARITOP P and BARICON MEAL was thought to be suited to a routine examination becouse of wide permissible level of density. This phantom would be able to apply to the test of balium preparations, X-ray TV systems, screen/film systems and so on