92 research outputs found
The Meaning of the Amendment form \u27Crimes of Cournterrevolution\u27 to \u27Crimes of Endangering National Security\u27 in the Chinese Criminal Code : with the Deletion of \u27the Aims of Counterrevolution\u27 as the Key
チュウカ ジンミン キョウワコク ジンミン ケイサツホウ ノ リュウチ セイド ト ソノ ウンヨウ 1995 カラ 2004ネン シュウヨウ シンサ セイド ハイシゴ ノ ウンヨウ カラ ミル セイド ヘンドウ ト ジツム ノ カンケイ ヲ チュウシン ニ
論
Positive allosteric modulation of the calcium-sensing receptor by physiological concentrations of glucose
The calcium-sensing receptor (CaSR) is activated by various cations, cationic compounds, and amino acids. In the present study we investigated the effect of glucose on CaSR in HEK293 cells stably expressing human CaSR (HEK-CaSR cells). When glucose concentration in the buffer was raised from 3 to 25 mM, a rapid elevation of cytoplasmic Ca2+ concentration ([Ca2+](c)) was observed. This elevation was immediate and transient and was followed by a sustained decrease in [Ca2+](c). The effect of glucose was detected at a concentration of 4 mM and reached its maximum at 5 mM. 3-O-Methylglucose, a non-metabolizable analogue of glucose, reproduced the effect of glucose. Sucrose also induced an elevation of [Ca2+](c) in HEK-CaSR cells. Similarly, sucralose was nearly as effective as glucose in inducing elevation of [Ca2+](c). Glucose was not able to increase [Ca2+](c) in the absence of extracellular Ca2+. The effect of glucose on [Ca2+](c) was inhibited by NPS-2143, an allosteric inhibitor of CaSR. In addition, NPS-2143 also inhibited the [Ca2+](c) responses to sucralose and sucrose. Glucose as well as sucralose decreased cytoplasmic cAMP concentration in HEK-CaSR cells. The reduction of cAMP induced by glucose was blocked by pertussis toxin. Likewise, sucralose reduced [cAMP](c). Finally, glucose increased [Ca2+](c) in PT-r parathyroid cells and in Madin-Darby canine kidney cells, both of which express endogenous CaSR. These results indicate that glucose acts as a positive allosteric modulator of CaSR
Regulatory T Cells in Type 1 Autoimmune Pancreatitis
Autoimmune pancreatitis (AIP) is a newly recognized pancreatic disorder. Recently, International Consensus Diagnostic Criteria for AIP (ICDC) was published. In this ICDC, AIP was classified into Type 1 and Type 2. Patients with Type 1 AIP have several immunologic and histologic abnormalities specific to the disease, including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. Among the involved organs showing extrapancreatic lesions, the bile duct is the most common, exhibiting sclerosing cholangitis (IgG4-SC). However, the role of IgG4 is unclear. Recently, it has been reported that regulatory T cells (Tregs) are involved in both the development of various autoimmune diseases and the shift of B cells toward IgG4, producing plasmacytes. Our study showed that Tregs were increased in the pancreas with Type 1 AIP and IgG4-SC compared with control. In the patients with Type 1 AIP and IgG4-SC, the numbers of infiltrated Tregs were significantly positively correlated with IgG4-positive plasma cells. In Type 1 AIP, inducible costimulatory molecule (ICOS)+ and IL-10+ Tregs significantly increased compared with control groups. Our data suggest that increased quantities of ICOS+ Tregs may influence IgG4 production via IL-10 in Type 1 AIP
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