Pseudomonas aeruginosa suppresses interferon response to rhinovirus infection in cystic fibrosis but not in normal bronchial epithelial cells

Despite increased morbidity associated with secondary respiratory viral infections in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, the underlying mechanisms are not well understood. Here, we investigated the effect of P. aeruginosa infection on the innate immune responses of bronchial epithelial cells to rhinovirus (RV) infection. CF cells sequentially infected with mucoid P. aeruginosa (MPA) and RV showed lower levels of interferons (IFNs) and higher viral loads than those of RV-infected cells. Unlike results for CF cells, normal bronchial epithelial cells coinfected with MPA/RV showed higher IFN expression than RV-infected cells. In both CF and normal cells, the RV-stimulated IFN response requires phosphorylation of Akt and interferon response factor 3 (IRF3). Preinfection with MPA inhibited RV-stimulated Akt phosphorylation and decreased IRF3 phosphorylation in CF cells but not in normal cells. Compared to normal, unstimulated CF cells or normal cells treated with CFTR inhibitor showed increased reactive oxygen species (ROS) production. Treatment of CF cells with antioxidants prior to MPA infection partially reversed the suppressive effect of MPA on the RV-stimulated IFN response. Together, these results suggest that MPA preinfection inhibits viral clearance by suppressing the antiviral response particularly in CF cells but not in normal cells. Further, increased oxidative stress in CF cells appears to modulate the innate immune responses to coinfection.     

Tandem Duplication in Bacteriophage P2: Electron Microscopic Mapping

The physical position of vir37, a new immunity-insensitive mutant of Escherichia coli bacteriophage P2, was mapped by the electron microscopic heteroduplex method. In P2 vir37, a segment equivalent to 2.8% of P2 DNA is added. The addition was characterized as a tandem duplication of the segment occurring between 77.2 and 80.0% from the left end of P2 DNA (the right half of P2 DNA is arbitrarily defined, from denaturation map studies, as the half richer in A + T). The point of addition of the duplicated segment (the "novel-joint") was, thus, 80.0% from the left end of P2 DNA. On the basis of previous studies on P2 vir22, it was tentatively concluded that the physical and genetic maps of P2 are colinear. This conclusion is now further supported by physical and genetic data on P2 vir37.     

Inhibition of hemagglutinins by N-substituted glycosylamines

The inhibition reaction has been used to explore further the chemical nature of the Rh antigens, D, C and E, using a number of N-substituted glycosylamines as inhibitors. A marked inhibition of the anti-Rh sera by the p-aminophenol compounds was noticed. Of the various compounds tested, p-hydroxy-N-phenyl-d -galactosylamine seem to be the best inhibitor of anti-D sera. The best inhibitor of the anti-C was p-hydroxy-N-phenyl-d -ma::nosylamine. Anti-E was inhibited by this compound as well as by p-hydroxy-N-phenyl-l -mannosylamine and p-hydroxy-N-phenyl-l -glucosylamine. Activity of the l -sugar derivatives was observed, especially in the inhibition of anti-E and anti-D. The three Rh antigens seem possibly to show a basic resemblance in structure.     

Electron microscope heteroduplex mapping of P2 Hy dis bacteriophage DNA

Barley plants infected with both barley stripe mosaic virus (BSMV) and brome mosaic virus (BMV) had more severe symptoms than plants infected with either virus alone, although the viruses were present in lower concentrations than in singly infected plants. To determine whether BMV protein encapsidated BSMV RNA in vivo, assay plants were inoculated with BMV virions purified from doubly infected plants. These assay plants later contained a small number of BSMV virions in addition to a high concentration of BMV virions. The BSMV virions presumably resulted from infection by BSMV RNA encapsidated by BMV protein.     

Correlation of neomycin, faecal neutral and acid sterols with colon carcinogenesis in rats.

High fat diets have been implicated in incidence of colon cancer both in epidemiological and animal studies. Present investigation deals with the incidence, location and numbers of large and small bowel tumours induced by 1,2-dimethyl hydrazine (DMH) in rats fed high fat diets and neomycin. Neomycin was used to modify the faecal sterol metabolism and the relationship of the high fat diet and faecal neutral and acid sterols to the large bowel tumorigenesis was evaluated. DMH administered rats were fed with (a) 20% safflower oil; (b) 20% safflower oil and neomycin; (c) 20% safflower oil, cholesterol and cholic acid; and (d) 20% safflower oil, cholesterol, cholic acid and neomycin. Neomycin was found to be associated with both increase and decrease of tumour numbers. The faecal sterols lithocholic and deoxycholic acids were found to have no participation, while cholesterol and cholic acid were found to decrease with increase in tumour numbers. However, faecal coprostanol has been found to have a significant positive correlation with tumorigenesis in all dietary groups. Therefore coprostanol might possibly be associated with colon carcinogenesis in DMH-fed rats and cholesterol metabolism in gut appears to be related to the development of tumours.