Epidemiological and clinical features of hMPV, RSV and RVs infections in young children.

BACKGROUND: Human metapneumovirus (hMPV) has recently been isolated from children with acute respiratory tract infections (RTIs). The epidemiological and clinical characteristics of hMPV infection need further investigation. OBJECTIVES: The purpose of this study was to compare the clinical features of hMPV, respiratory syncytial virus (RSV) and rhinoviruses (RV) infections in children less than 3 years of age presenting to an emergency department with acute respiratory illness. STUDY DESIGN: From December 2002 to April 2004, all children under age three (n=931) admitted for acute respiratory illness to Dijon Hospital, France, were investigated for respiratory viruses in nasal washes. RESULTS: hMPV was detected in 6% of children (in 10.1% (n=38) the first winter and in 3.3% (n=17) the second winter); RSV was detected in 28.5% of the children, while rhinoviruses were found in 18.3%. Five hMPV-infected children had evidence of dual infection, two with RSV and three others with RV. The median age of the patients with hMPV infection was 6 months, and the main clinical symptoms were rhinorrhea (74.5%) and cough (67%). A lower tract disease occurred in 66% of hMPV-positive patients. Gene sequencing of hMPV isolates revealed co-circulation of the two major groups of hMPV during the study period; no difference in pathogenicity was found. There was no difference in the prevalence of bronchiolitis where hMPV, RSV or rhinoviruses were present. Asthma was found more often in hospitalized children with hMPV and rhinoviruses than among those with RSV (p<0.001). CONCLUSIONS: These results provide further evidence of the importance of hMPV as a pathogen associated with respiratory tract infection in children.

Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes.

To understand better the defects in the proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells in primary culture. When compared with cells from control subjects, myotubes established from patients with type 2 diabetes presented the same defects as those previously evidenced in vivo in muscle biopsies, including defective stimulation of phosphatidylinositol (PI) 3-kinase activity, decreased association of PI 3-kinase with insulin receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation during insulin stimulation. In contrast to IRS-1, the signaling through IRS-2 was not altered. Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes. Concomitantly, there was a higher basal mitogen-activated protein kinase (MAPK) activity in these cells, and inhibition of the MAPKs with PD98059 strongly reduced the level of serine 636 phosphorylation. These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells.