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Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets.We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls.HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling.This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.

TGF-β family members are multipotent cytokines that are involved in many cellular processes, including cell differentiation, organ development, wound healing and immune regulation. TGF-β has pleiotropic effects on adaptive immunity, especially in the regulation of CD4(+) T cell and B cell responses. Furthermore, identification of CD4(+) T cell subsets that produce TGF-β3 revealed unexpected roles of TGF-β3 in the control of adaptive immunity. In contrast to TGF-β1, which induces extensive fibrosis, TGF-β3 induces non-scarring wound healing and counteracts tissue fibrosis. Recent progress in the understanding of the activation mechanism of TGF-β may enable us to develop novel biologic therapies based on advanced protein engineering.

Summary Objectives To investigate the effect of weight perception and lifestyle on body mass index (BMI) over a 2-year period. Study design Longitudinal study to compare the change in BMI (kg/m 2 ) according to weight perception and lifestyle at baseline. Methods Study subjects were 6029 men and 18,567 women aged 20–69 years who worked at a large financial firm in Japan. Subjects' weight and height were measured in 2004 and 2006. The data in 2004 were used as baseline data. Weight perception and lifestyle factors, including eating, physical exercise, hours of sleep, smoking and alcohol consumption, were determined by a self-administered questionnaire in 2004. Results The age-adjusted mean change in BMI over the 2-year period was –0.0593 among men and 0.0890 among women. In men, subjects who perceived themselves to be overweight had a reduced BMI 2 years later compared with subjects who perceived themselves to be ‘just right' or underweight. Multiple regression analysis of lifestyle factors, adjusted for age and BMI at baseline, indicated that less time spent commuting, not having a hobby, not having a fixed lunch time, consumption of sweets, smoking and colleagues' smoking were associated with increased BMI among men. Fewer hours of sleep, no fixed lunch time and frequent soft drink consumption were associated with increased BMI among women. Conclusions A perception of being overweight was associated with a decrease in BMI for Japanese male workers. Positive lifestyle factors associated with a decrease in BMI in both men and women include having a fixed lunch time and being older. These factors should therefore be highlighted in future health promotion activities in workplaces.

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members of the steroid/thyroid hormone receptor superfamily. We have shown that two homologous COUP-TF genes, COUP-TFI and COUP-TFII, are expressed in developing mouse retina with a unique gradient along the dorsal-ventral axis. In this work, we aimed to characterize the detailed expression patterns of COUP-TFs in mature retina. Their functions in retinal progenitor cell differentiation into subtypes of mature retinal cells were also examined. Immunostaining of frozen mouse retinal sections with antibodies against COUP-TFs and markers for retinal subtypes revealed that COUP-TFI and -TFII are expressed in amacrine cells, especially in a glycinergic subtype in mature mouse retina. Forced expression of COUP-TFI and -TFII in mouse retinal explant culture by retrovirus-mediated gene transfer promoted amacrine and cone photoreceptor cell differentiation, whereas that of rod photoreceptors decreased. Cell proliferation and apoptosis were not affected by the perturbation of COUP-TFI and -TFII expression levels. Using the Y79 retinoblastoma cell line, we observed that COUP-TFI and -TFII suppressed the transcriptional activation of the Nrl gene. We then analyzed one another member of COUP-TF transcription factors, COUP-TFgamma, whose structure is relatively distant from those of COUP-TFI and -TFII. It is expressed mainly in horizontal cells and has weak activity in inducing amacrine cells when COUP-TFgamma was ectopically expressed in retinal explants. In summary, we found that COUP-TFI and -TFII play roles in amacrine cell differentiation, and COUP-TFgamma has distinct expression pattern and roles during retinal development.

Recently several strategies to treat ischemic diseases have been proposed but the ideal way has to be determined. We explored whether human placenta-derived mesenchymal cells (hPDMCs) can be used for this purpose because placenta is very rich in vessels. First, production of human vascular endothelial growth factor (hVEGF) from hPDMCs was examined. The amount of hVEGF secreted by hPDMCs was similar to the amount produced by HeLa cells. hVEGF was barely detected in human umbilical vein endothelial cells (hUVECs) or human peripheral blood mononuclear cells. hVEGF secreted from hPDMCs stimulated the proliferation of hUVECs, indicating its biological activity. Transplantation of hPDMCs to the ischemic limbs of NOD/Shi-scid mice significantly improved the blood flow of the affected limbs. Blood vessel formation was more prominently observed in the limbs of treated mice as compared to the control mice. Real-time RT-PCR revealed that hPDMCs produced hVEGF for at least 7 days after transplantation. Thus, transplantation of hPDMCs could potentially be a promising treatment for human ischemic diseases.

We report on high resolution studies of the nuclear region of NGC 3079 using H2O maser, continuum emission and HI absorption with both Japan VLBI Netowrk and global VLBI Network including the VLBA, the phased VLA and Effelsberg 100-m telescope. We identify the nucleus and rotation axis of the central 10 pc region, and suggest a rotating torus to explain the results.

s / Placenta 35 (2014) A1eA23 A18 determined to identify what kind of cells produce IL-6 in placentae complicated with CAM and analyze the potential of targeting IKKb signaling to suppress IL-6 production, using a novel IKKb inhibitor, IMD0560 (IMMD Inc. Tokyo, Japan). Methods and Results: First, we examined the expressional pattern of IL6 in placentae complicated with severe CAM and found that IL-6 is mainly expressed in amniotic mesenchymal stromal cells (hAMSCs). Primary hAMSCs were collected and the strong expression of IL-6 as well as IL-6 receptor was confirmed by RT-PCR. In hAMSCs, treatment of inflammatory cytokines such as TNF-alpha and IL-1-beta drastically induced IL-6 production followed by the phosphorylation of IKK as confirmed by western blotting. The pretreatment of IMD-0560 to hAMSCs almost abolished IL-6 production enhanced by proinflammatory cytokines. Conclusion: IL-6 was strongly expressed mainly in amniotic mesenchymal stromal cells in placentae complicated with CAM. Targeting IKK-beta signaling could be a promising option for the prevention of preterm delivery and needs to be further explored for future clinical application. O-069. TWO CASES OF PLACENTAL MESENCHYMAL DYSPLASIA: CASE REPORTS Mariko Inoue , Usui Hirokazu , Akiko Omoto , Jun Okayama , Michio Sanada , Hirokazu Tanaka , Hisao Osada , Makio Shozu . Department of Obstetrics and Gynecology, Chiba University Hospital, Japan; Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Japan Introduction: Placentae with placental mesenchymal dysplasia (PMD) are typically larger than average, show cystic changes similar to those seen in moles on ultrasound. Fetal outcomes are variable and are often associated with growth restriction, sometimes intra uterine fetal death. We present two cases of PMD. Case 1: 29 years of age, secundipara. Ultrasonography at 18 weeks of gestation showed multiple small cysts in placenta, and was diagnosed as PMD. At 34 weeks, she was admitted with FGR and oligohydramnion, and had cesarean section due to NRFS. The neonate was male weighing 1620g with hypospadias. He was admitted in NICU, and was treated on RDS and PPHN. The placenta was 830g with multiple cysts and enlarged umbilical vessels, was diagnosed as PMD histologically. The karyotype of placenta was 47, XY, +13/47, XXY and that of the neonate was 47, XXY. Case 2: 22 years of age, primipara. At 9 weeks of gestation, she came to our hospital with doubt of partial mole, was diagnosed as PMD by ultrasonography. At 34 weeks, she was admitted with FGR and threatened premature labor, and had cesarean section due to fetal cardiac dilatation, fetal anemia, elevated maternal level of CPK. The neonate was female weighing 1610g. She was admitted in NICU, needed blood transfusion due to anemia (Hb8.6). The placenta was enlarged weighing 1650g, was diagnosed as PMD histologically. The karyotype of placenta was 46, XX, 1qh+1 supposed to be familial variation. Conclusion: Both of cases diagnosed as PMD by ultrasonography and confirmed the diagnosis by histologically. Both neonates showed FGR in their period of gestation, was treated on PPHN in case1 and fetal anemia in case2 after birth. It is necessary cases of PMD are followed carefully at the hospitals providing advanced neonatal care. O-070. PROFILING ANALYSIS FOR GENE EXPRESSION AND GLYCAN STRUCTURE IN EXTRAVILLOUS TROPHOBLAST CELLS WITH NEOPLASTIC TRANSFORMATION Yusuke Kobayashi , Kenta Masud , Eiichiro Tominaga , Kouji Banno , Kanako Nakamura , Masataka Adachi , Miho Iida , Kiyoko Umene , Yuya Nogami , Hiroyuki Nomura , Takatsune Shimizu , Hideyuki Saya , Daisuke Aoki . Department of Obstetrics and Gynecology, School of Medicine, Keio University, Japan; Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Japan Objectives: It has been cleared that the reregulation of extravillous trophoblast cells (EVT) invasion to the deciuda and its related disease. However, it is still remained that the alteration of gene expression and glycan structure in extravillous trophoblast cells with neoplastic transformation. We established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC3-1), from EVT. In this study, the alterations of gene expression and glycan structures in the development of choriocarcinoma were examined by conventional microarray and the recently introduced lectin microarray. Methods: iC3-1 cells were generated from HTR8/SVneo retrovirally transduced with activated HRASV12. We compared the gene expression and glycan structure of iC3-1 and control HTR8/SVneo cells by microarray analysis, quantitative RT-PCR and lectin microarray. Results: Gene expression study revealed that epithelial-mesenchymal transition related genes, matrix metalloproteinase family genes, HAS2 andCD44 were upregulated in iC3-1 cells. Lectin microarray analysis detected increased Helix pomatia agglutinin (HPA) and decreased Sambucus sieboldiana agglutinin (SSA), showing upregulation of Tn antigen and downregulation of alpha-2-6 sialic acids. Conclusions: With neoplastic transformation, some interested genes in proliferation, metastasis, angiogenesis and cancer stem cell marker were upregulated. In addition, glycan structure was partially altered with upregulation of Tn antigen and downregulation of alpha-2-6 sialic acids. O-072. A CASE OF CONGENITAL CUTANEOUS CANDIDIASIS FOLLOWING INTRAUTERINE INFECTION Akihisa Katayama, Fumitake Ito, Miyoko Waratani, Tadahiro Yasuo, Kazuhiro Iwasaku, Jo Kitawaki. Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Japan Introduction: Candida vaginalis has a high incidence of 10-35% during pregnancy; in contrast, congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature, because it is estimated that less than 1% of women develop chorioamnionitis that could be a cause of fetal infection. In this report, we present a case of threatened premature delivery due to Candida chorioamnionitis that caused congenital cutaneous candidiasis. Case report: A 34-year-old woman who was admitted for fetal membrane bulging at 20 weeks of gestati on underwent McDonald cervical cerclage. Since uterine contraction had occurred regularly at 22 weeks, the patient was transferred to our hospital. On admission, the uterine cervix shortened and showed funneling. Although blood examination did not reveal inflammatory reactions, the results for cervical neutrophil elastase reaction were positive. The vaginal suppository of ulinastatin was administered and the dose of ritodrine hydrochloride was increased up. At 23 weeks, the uterus recontracted regularly, and blood examination revealed severe inflammatory reaction. We diagnosed threatened premature delivery due to intrauterine infection, and then terminated the gestation by cesarean section. The patient delivered a living 604 g male infant in poor condition with an Apgar score of 2. The amniotic fluid was yellowish-stained and turbid. The infant had a prominent systemic desquamation on the skin. Intravenous administration of antifungal agent was given after the birth for the possibility of fungal infection. Candida albicans was detected in the infantile auricle, and neck. Histopathological examination of the placenta revealed infiltration of neutrophils and profound necrosis in the field and that Candida albicans mycelium invaded the placenta. Conclusion: In case intrauterine infection is suspicious, an appropriate antibacterial treatment is needed as soon as possible with the consideration of fungal infections as well as bacterial infection.