Phosphatidyl-inositol mannosides (PIM) are glycolipids unique to mycobacteria and other related bacteria that stimulate host immune responses and are implicated in mycobacteria pathogenicity. Here, we found that the FcRγ-coupled C-type lectin receptor DCAR (dendritic cell immunoactivating receptor; gene symbol Clec4b1) is a direct receptor for PIM. Mycobacteria activated reporter cells expressing DCAR, and delipidation of mycobacteria abolished this activity. Acylated PIMs purified from mycobacteria were identified as ligands for DCAR. DCAR was predominantly expressed in small peritoneal macrophages and monocyte-derived inflammatory cells in lungs and spleen. These cells produced monocyte chemoattractant protein-1 (MCP-1) upon PIM treatment, and absence of DCAR or FcRγ abrogated MCP-1 production. Upon mycobacterial infection, Clec4b1-deficient mice showed reduced numbers of monocyte-derived inflammatory cells at the infection site, impaired IFNγ production by T cells, and an increased bacterial load. Thus, DCAR is a critical receptor for PIM that functions to promote T cell responses against mycobacteria.
A self-control, randomized, and open-label clinical trial was performed to test the effects of the unicellular green algae Chlorella and hot water extract supplementation on quality of life (QOL) in patients with breast cancer. Forty-five female patients with breast cancer who were living at home and not hospitalized were randomly assigned to 3 groups receiving vitamin mix tablet (control), Chlorella granules (test food-1), or Chlorella extract drink (test food-2) daily for one month. The Functional Assessment of Cancer Therapy-Breast (FACT-B), the Izumo scale for abdominal symptom-specific QOL, and a narrative-form questionnaire were used to determine outcomes. Data of thirty-six subjects were included for final analysis. FACT-B scores at presupplementation found no significant group differences in all subscales. Scores on the breast cancer subscale in the Chlorella granule group significantly increased during the supplementation period (P = 0.042). Fifty percent of the Chlorella extract group reported positive effects by the test food such as reduction of fatigue and improvements of dry skin (P < 0.01 versus control group). The findings suggested the beneficial effects of Chlorella on breast cancer-related QOL and of Chlorella extract on vitality status in breast cancer patients. These findings need to be confirmed in a larger study.
There are seven Vγ gene segments in the TCR γ chain loci of mice. We developed monoclonal antibodies (mAbs) specific to the Vγ6 chain (Heilig & Tonegawa nomenclature). By immunizing Vγ4/6 KO mice with complementarity-determining region peptides in Vγ6 chains, we generated three hybridomas. These hybridomas produced mAbs capable of cell surface staining of Vγ6/Vδ1 gene–transfected T-cell line lacking TCR as well as of Vγ1− Vγ4− Vγ5− Vγ7− γδ T cells and the CD3high TCRδint γδ T cells in various organs. The location of Vγ6+ γδ T cells, which peaked in the newborn thymus, was associated with mTEC. In vivo administration of clone 1C10-1F7 mAb impaired protection against Klebsiella pneumoniae infection but ameliorated psoriasis-like dermatitis induced by imiquimod treatment. These new mAbs are useful to elucidate the development, location, and functions of Vγ6 γδ T cells in mice.
Aims Functional decline is associated with worse outcomes in patients with elderly heart failure (HF), but little is known about the prognostic impact of hospital-acquired disability (HAD) during hospital stay after acute HF. The present study examines the prognostic significance of HAD in the prediction of all-cause mortality in elderly patients who admitted for acute HF.Methods and results This retrospective study was performed in 1941 elderly patients aged ≥65 years or older from the cardiovascular physiotherapy for acute HF patients in the Tokyo metropolitan area registry and excluded those who died in hospital. HAD was defined as any decline in the Barthel index (BI) before discharge compared with the BI within 1 month before hospital admission. The primary outcome of this study was all-cause death and HF readmission. A total of 565 (29%) deaths and 789 (41%) HF readmission occurred over a median follow-up period of 1.7 years. A total of 476 patients (25%) had HAD during hospital stay after acute HF. In multivariable analysis, HAD predicted all-cause death [hazard ratio (HR): 1.772; 95% confidence interval (CI): 1.450-2.167; P < 60; 0.001] and with risk of HF readmission (HR: 1.193; 95% CI: 1.005-1.416; P = 0.043) after adjusting for the Meta-analysis Global Group in Chronic Heart Failure risk score. Conclusions Hospital-acquired disability is associated with an increased risk of all-cause death and readmission for HF in elderly patients with acute HF.
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