In vitro immuno-prevention of nitration/dysfunction of myogenic stem cell activator HGF, towards developing a strategy for age-related muscle atrophy.

In response to peroxynitrite (ONOO-) generation, myogenic stem satellite cell activator HGF (hepatocyte growth factor) undergoes nitration of tyrosine residues (Y198 and Y250) predominantly on fast IIa and IIx myofibers to lose its binding to the signaling receptor c-met, thereby disturbing muscle homeostasis during aging. Here we show that rat anti-HGF monoclonal antibody (mAb) 1H41C10, which was raised in-house against a synthetic peptide FTSNPEVRnitroY198EV, a site well-conserved in mammals, functions to confer resistance to nitration dysfunction on HGF. 1H41C10 was characterized by recognizing both nitrated and non-nitrated HGF with different affinities as revealed by Western blotting, indicating that the paratope of 1H41C10 may bind to the immediate vicinity of Y198. Subsequent experiments showed that 1H41C10-bound HGF resists peroxynitrite-induced nitration of Y198. A companion mAb-1H42F4 presented similar immuno-reactivity, but did not protect Y198 nitration, and thus served as the control. Importantly, 1H41C10-HGF also withstood Y250 nitration to retain c-met binding and satellite cell activation functions in culture. The Fab region of 1H41C10 exerts resistivity to Y250 nitration possibly due to its localization in the immediate vicinity to Y250, as supported by an additional set of experiments showing that the 1H41C10-Fab confers Y250-nitration resistance which the Fc segment does not. Findings highlight the in vitro preventive impact of 1H41C10 on HGF nitration-dysfunction that strongly impairs myogenic stem cell dynamics, potentially pioneering cogent strategies for counteracting or treating age-related muscle atrophy with fibrosis (including sarcopenia and frailty) and the therapeutic application of investigational HGF drugs.

Risk of Seasonal Influenza by Occupation in a Railway Company in a Metropolitan Area of Japan during Three Influenza Seasons.

Station staff may be at high risk for influenza due to high frequency contact with other people. We examined the risk of influenza by occupational group in a railway company. A retrospective observational study was conducted among employees at a branch office of a railway company in eastern Japan, located in a metropolitan area, for 2012/13, 2013/14, and 2014/15 influenza seasons. The study population included employees who had received influenza vaccination for the season in question and the previous season. Outcome was defined as self-reported influenza illness during the respective season, identified through the vaccine screening questionnaire in the following season. Study participants included employees whose outcome information could be obtained. Standardized morbidity ratios (SMRs) by occupational group (station staff, engineers, train crew) for each season were calculated. For 2012/13, 2013/14, and 2014/15 seasons, attack rates were 4.7% (19/403), 5.2% (21/407), and 7.8% (31/397), respectively. Among the participants, SMRs of station staff were lower in the 2012/13 (SMR = 57; 95% confidence intervals [CI] = 18-133) and 2014/15 (SMR = 75; 95%CI = 36-138) seasons and similar to other groups in the 2013/14 season. Enhanced countermeasures, regardless of occupational group, may be effective in preventing the spread of influenza infection.