Altered Homeostasis of CD4+ Memory T Cells in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Chronic Graft-versus-Host Disease Enhances T Cell Differentiation and Exhausts Central Memory T Cell Pool

AbstractAn increased risk of late infection is a serious complication after allogeneic hematopoietic stem cell transplantation (AHSCT), especially for recipients with defective CD4+ T cell recovery. Although chronic graft-versus-host disease (cGVHD) negatively influences CD4+ T cell reconstitution, the mechanisms leading to this defect are not well understood. We found that the proportion of CD27− CD4+ T cells was remarkably increased in ASHCT recipients with cGVHD or with repetitive infectious episodes. Isolated CD27− CD4+ T cells from ASHCT recipients had significantly shortened telomere length, displayed enhanced vulnerability to activation-induced cell death, and showed extremely reduced clonal diversity, when compared with CD27− CD4+ T cells from healthy donors. Also, CD27+ CD4+ T cells from AHSCT recipients easily lost their expression of CD27 in response to antigen stimulation regardless of cGVHD status. Taken together, these data indicate that homeostasis of memory CD4+ T cells from AHSCT recipients is altered, and that they easily transit into CD27− effector memory T cells. Increased in vivo T cell stimulation observed in recipients with cGVHD further promotes the transition to effector memory cells, a change that decreases the central memory CD4+ T cell pool and consequently weakens the recipient’s defense against persistently infecting pathogens

Oil-in-water emulsion lotion providing controlled release using 2-methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer as emulsifier

AbstractLotion is a useful vehicle for active ingredients used to treat skin disease because it can be applied to the scalp, can cover large areas of skin, and it is easy to spread due to low viscosity. An emulsion lotion (EL) containing 2-methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer (PMB) as an emulsifier that provides controlled-release was developed. Diphenhydramine (DPH) was used as a model drug. Formulation with 5% DPH, 5% soybean oil, and 4% PMB in water was emulsified using a high-pressure homogenizer. Polysorbate 80 (TO) was used instead of PMB for comparison. They were applied in vitro to Yucatan micropig intact or stripped skin at a practical dose (2μL/cm2). For stripped skin, penetration of DPH from 4% PMB EL was slower than that from 1% TO EL; results for intact skin were similar. The same phenomenon was observed with application to rabbit skin in vivo. When 4% PMB EL dried on the skin, it made a thin film matrix incorporating the oil phase, which controlled the release of DPH. The release rate could be controlled by the ratio of oil phase to PMB. The EL with PMB shows promise as a vehicle for long-acting treatment of skin diseases

Novel Therapeutic Strategies for Malignant Salivary Gland Tumors: Lessons Learned from Breast Cancer

Malignant salivary gland tumors (MSGTs) account for 2–6% of all head and neck cancers. Despite the rarity, MSGTs have been of great interest due to a wide variety of pathological features and high metastasis rates resulting in poor prognosis. Surgical resection followed by radiation therapy represents the main treatment of this malignancy. Adjuvant therapy is reserved for the management of local recurrence, no longer amenable to additional local therapy, and for metastasis. Based on the studies from other types of tumors, particularly breast cancer, the expression and function of sex steroid hormone receptors in cancer have been extensively studied and applied to diagnosis and treatment. Although a number of studies in MSGTs have been published, the rationale for hormone therapy is still controversial due to the disparate results and insufficient number of cases. However, some recent reports have demonstrated that certain salivary gland neoplasms are similar to breast cancer, not only in terms of the pathological features, but also at the molecular level. Here, we shed light on the biological similarity between MSGTs and certain types of breast cancer, and describe the potential use of hormone and additional therapies for MSGTs

Perceptions of Aging and Disability among College Students in Japan

Japan launched the Long-term Care Insurance program in 2000, and ratified the United Nations` Convention on the Rights of Persons with Disabilities in 2014. Japan has been taking significant steps to support their elderly population and individuals with disabilities. However, information is lacking on the understanding and opinions of either of these groups among Japanese college students, many of whom will have significant impact on the development of relevant programs in the future. The purpose of this study is to explore perceptions of the elderly, individuals with a physical disability, and individuals with a mental disability. Three focus groups were held with a total of 20 college students throughout June and July 2015 in Japan. Lack of formal and human resources are issues for the elderly and people with physical disabilities. It is important to increase awareness of struggles related to physical and mental disabilities. Images of physical and mental disabilities in society and media need to be improved. Future studies need to expand in the following areas: 1) to examine the issues of lack of formal and human resources and its impact on the elderly, families and society; 2) to develop programs to increase awareness of the issues of disabilities and evaluate the effectiveness of the programs; and 3) to examine the impact of media on perceptions of people with a disability. Keywords: aging, disability, perceptions, college students, Japa

Human T-cell leukemia virus type I infects human lung epithelial cells and induces gene expression of cytokines, chemokines and cell adhesion molecules

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type I (HTLV-I) is associated with pulmonary diseases, characterized by bronchoalveolar lymphocytosis, which correlates with HTLV-I proviral DNA in carriers. HTLV-I Tax seems to be involved in the development of such pulmonary diseases through the local production of inflammatory cytokines and chemokines in T cells. However, little is known about induction of these genes by HTLV-I infection in lung epithelial cells.</p> <p>Results</p> <p>We tested infection of lung epithelial cells by HTLV-I by coculture studies in which A549 alveolar and NCI-H292 tracheal epithelial cell lines were cocultured with MT-2, an HTLV-I-infected T-cell line. Changes in the expression of several cellular genes were assessed by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. Coculture with MT-2 cells resulted in infection of lung epithelial cells as confirmed by detection of proviral DNA, HTLV-I Tax expression and HTLV-I p19 in the latter cells. Infection was associated with induction of mRNA expression of various cytokines, chemokines and cell adhesion molecule. NF-κB and AP-1 were also activated in HTLV-I-infected lung epithelial cells. <it>In vivo </it>studies showed Tax protein in lung epithelial cells of mice bearing Tax and patients with HTLV-I-related pulmonary diseases.</p> <p>Conclusion</p> <p>Our results suggest that HTLV-I infects lung epithelial cells, with subsequent production of cytokines, chemokines and cell adhesion molecules through induction of NF-κB and AP-1. These changes can contribute to the clinical features of HTLV-I-related pulmonary diseases.</p

Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs

Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-α, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-α further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs

Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer

Table S2. Change in NK population in PBL

An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney

金沢大学大学院医学系研究科We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-125I-iodo-L-meta-tyrosine (4- 125I-mTyr). Results obtained for L-14C-Tyr and 3- 125I-iodo-α-methyl-L-tyrosine (125I-IMT) were used for comparison. Methods: In vivo biodistribution studies of 4- 125I-mTyr were performed in male ddY mice. Urinary excretion of 4-125I-mTyr and 125I-IMT with administration of probenecid was studied. Local distribution of 4-125I-mTyr and 125I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-125I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-125I-mTyr were compared with those of 125I-IMT and the parent L-14C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK1 in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na +-free medium, and at 4°C. Results: 4-125I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of 125I-IMT. Blood clearance of 4-125I-mTyr was faster than that of 125I-IMT. Three hours after administration, >70% of 4-125I-mTyr was excreted via the urine, whereas 98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-125I-mTyr into LLC-PK1 cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4°C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-14C-Tyr and 125I-IMT showed similar results; however, uptake of 125I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. Conclusion: The artificial amino acid 4-125I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radioiabeled L-Tyr analogs. 4-125I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-125I-mTyr demonstrates different pharmacologic features than those of 125I-IMT, particularly in renal handling. 4-125I-mTyr may potentially be applied as a new amino acid transport marker