Recruitment of calcineurin to the TCR positively regulates T cell activation.

Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck (Lck that cannot be phosphorylated) or Lck (a phosphomimetic mutant).

A facile, regioselective synthesis of novel 3-(N-phenylcarboxamide)pyrazolo[1,5-a]pyrimidine analogs in the presence of KHSO4 in aqueous media assisted by ultrasound and their antibacterial activities.

An environmentally benign, simple, efficient, and convenient route is described for the synthesis of novel pyrazolo[1,5-a]pyrimidine derivatives under ultrasound irradiation. Condensation of aminopyrazole 5 with formylated active proton compounds (6, 8, E-G, 12, and 15) furnished pyrazolopyrimidine (7, 9, 10, 13, and 16) in high-to-excellent yields. In comparison with conventional methods, ultrasound irradiation offers several advantages, such as shorter reaction time, higher yields, milder conditions, and environmental friendliness.

Molecular characterization of tumor associated antigen in mice exposed to a hepatocarcinogen.

The present investigation is aimed to identify and characterize tumor-associated antigen (TAA) in animals exposed to hepatocarcinogen. Swiss albino mice showed an enhanced expression of an approximately 58 kDa glycoprotein in liver cells upon exposure to a potential hepatocarcinogen N-nitrosodibutylamine (DBN). Carcinogenesis induction in mice was monitored by assays of y-glutamyl transpeptidase (GGT), acetylcholine esterase (AChE), glutathione-S-transferase (GST) activities and the level of glutathione (GSH) in liver.

Radiomodulatory effect of liposome encapsulated AK-2123 on tumor in mice exposed to hepatocarcinogen.

An attempt was made to evaluate the whole body gamma-radiation effect on tumor in the presence of free and liposome encapsulated AK-2123, a hypoxic cell radiosensitizer that has widely been used in combination with a number of cancer therapies such as thermotherapy, chemotherapy and radiotherapy. Entrapment efficiency of AK-2123 into liposome was determined by LASER Raman spectroscopy. Cancer induction in mice was carried out by repeated exposure of N-nitrosodiethylamine (DEN) in combination with partial hepatectomy.