Interleukin 2 induces rapid phosphorylation of cellular proteins in murine T-lymphocytes

AbstractWhen quiescent murine T-lymphocyte cells were stimulated by the addition of interleukin 2 (IL-2), they reinitiated DNA synthesis after a lag period of 5 h. Under these conditions, rapid but transient phosphorylation of two cellular proteins with Mr, values of 27000 and 26000 was detected; maximal phosphorylation occurred within 10–15 min after the addition of IL-2. The protein of Mr, 27 000 contained phosphoserine, while the protein of Mr 26000 contained phosphothreonine

IL-1β Suppresses the Formation of Osteoclasts by Increasing OPG Production via an Autocrine Mechanism Involving Celecoxib-Related Prostaglandins in Chondrocytes

Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1β stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE2 production. However, the effect of IL-1β on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1β and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1β on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1β; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1β. Conditioned medium from IL-1β-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1β suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs

Risk assessment for hepatitis E virus infection from domestic pigs introduced into an experimental animal facility in a medical school

Hepatitis E virus (HEV) is known to cause zoonotic infections from pigs, wild boars and deer. Domestic pigs have been used as an experimental animal model in medical research and training; however, the risks of HEV infection from pigs during animal experiments are largely unknown. Here, we retrospectively investigated the seroprevalence and detection rates of viral RNA in 73 domestic pigs (average 34.5 kg) introduced into an animal experimental facility in a medical school during 2012-2016. We detected anti-HEV immunoglobulin G antibodies in 24 of 73 plasma samples (32.9%), though none of the samples were positive for viral RNA. Plasma samples of 18 pigs were sequentially monitored and were classified into four patterns: sustained positive (5 pigs), sustained negative (5 pigs), conversion to positive (6 pigs) and conversion to negative (2 pigs). HEV genomes were detected in 2 of 4 liver samples from pigs that were transported from the same farm during 2016-2017. Two viral sequences of the overlapping open reading frame (ORF) 2/3 region (97 bp) were identical and phylogenetically fell into genotype 3. A 459-bp length of the ORF2 region of an amplified fragment from a pig transported in 2017 was clustered with the wbJYG1 isolate (subgenotype 3b) with 91.5% (420/459 bp) nucleotide identity. Based on our results, we suggest that domestic pigs introduced into animal facilities carry a potential risk of HEV infection to researchers, trainees and facility staff. Continuous surveillance and precautions are important to prevent HEV infection in animal facilities

Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition)

The version of record of this article, first published in Annals of Nuclear Medicine, is available online at Publisher’s website: https://doi.org/10.1007/s12149-024-01916-6.Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients’ caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer