Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells.

Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRα1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRα1 expression by the transfection of siRNA for TRα1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRα1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration.

Tuberculosis screening using a T-cell interferon-γ release assay in Japanese medical students and non-Japanese international students.

Screening of medical students and international students for tuberculosis (TB) at the time of admission is a key strategy to control and prevent the spread of infection on university campus and teaching hospitals because of the high risk of exposure to TB patients. The Mycobacterium tuberculosis antigen-specific T-cell interferon-γ release assays (IGRAs) are specific latent tuberculosis detection methods used in such groups. Currently, in Japan, there are no guidelines and no baseline data on IGRAs to evaluate the risk of TB in these high-risk groups. In order to evaluate TB risk at the time of admission in university campus and medical schools in Japan, a retrospective study was conducted. A total of 969 students (585 Japanese students and 384 international students) were screened for TB using the IGRAs at the time of admission. Eight Japanese students (0.9%) were positive for IGRAs, but none were diagnosed with active TB at the follow-up. In contrast, 30 international students (7.8%) were positive for IGRAs, including two students diagnosed with active TB during follow up. Positive ratio of IGRAs in international students was significantly higher than that of medical students at the time of admission. Here we propose a standard approach for TB screening with IGRAs at the time of admission for medical students and international students in Japan.

Coculture with a human granulosa cell line enhanced the development of murine preimplantation embryos via SCF/c-kit system.

PURPOSE: To evaluate the effect on the coculture of murine embryos with a human ovarian granulosa tumor derived cell line (KGN cells). METHODS: We observed microscopically the growth of murine preimplantation embryos in the coculture system with KGN cells or in the presence with exogenous stem cell factor (SCF). The reverse transcriptase-polymerase chain reaction (RT-PCR) method was used to analyze the gene expression of SCF in KGN cells cocultured with murine embryos. RESULTS: The coculture system with KGN cells significantly increased the rate of embryo development to late blastocyst and to hatching stage. We also found that coculture with murine embryos enhanced the gene expression of SCF in KGN cells. Adding human recombinant SCF to the medium significantly enhanced embryo development to late blastocyst and hatching stage. CONCLUSIONS: KGN cells may facilitate preimplantion embryo development through SCF/c-kit paracrine system.