ABSTRACT
BACKGROUND: Aspirin-intolerant asthma (AIA) is a subtype of asthma induced by non-steroidal anti-inflammatory drugs and characterized by an aggressive mucosal inflammation of the lower airway (asthma) and the upper airways (rhinitis and nasal polyp). The lower airway lesion and the nasal polyp in AIA are postulated to have common pathogenic features involving aspirin sensitivity that would be reflected in the gene expression profile of AIA polyps. OBJECTIVE: This study was conducted to clarify the pathogenesis of AIA using gene expression analysis in nasal polyps, and identify genetic susceptibilities underlying AIA in a case-control association study. METHODS: Global gene expression of nasal polyps from nine AIA patients was examined using microarray technology in comparison with nasal polyps from five eosinophilic sinusitis (ES) patients, a related disease lacking aspirin sensitivity. Based on the AIA-specific gene expression profile of nasal polyp, candidate genes for AIA susceptibility were selected and screened by a case-control design of 219 AIA patients, 374 non-asthmatic control (CTR), and 282 aspirin-tolerant asthmatic (ATA) subjects. RESULTS: One hundred and forty-three elevated and three decreased genes were identified as AIA-specific genes that were enriched in immune response according to Gene Ontology analysis. In addition, a k-means-based algorithm was applied to cluster the genes, and a subclass characteristic of AIA comprising 18 genes that were also enriched in immune response was identified. By examining the allelic associations of single nucleotide polymorphisms (SNPs) of AIA candidate genes relevant to an immune response with AIA, two SNPs, one each of INDO and IL1R2, showed significant associations with AIA (P=0.011 and 0.026 after Bonferroni's correction, respectively, in AIA vs. CTR). In AIA-ATA association analysis, modest associations of the two SNPs with AIA were observed. CONCLUSION: These results indicate that INDO and IL1R2, which were identified from gene expression analyses of nasal polyps in AIA, represent susceptibility genes for AIA.
Subject(s)
Aspirin/adverse effects , Asthma/chemically induced , Asthma/genetics , Gene Expression Profiling , Genetic Predisposition to Disease , Nasal Polyps/genetics , Adult , Aged , Algorithms , Artificial Intelligence , Aspirin/immunology , Case-Control Studies , Cluster Analysis , Female , Genotype , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Male , Middle Aged , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Nasal Polyps/immunology , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide/genetics , Receptors, Interleukin-1 Type II/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
NAD+-dependent formate dehydrogenase was screened in various bacterial strains. Facultative methanol-utilizing bacteria isolated from soil samples, acclimated to a medium containing methanol and formate at pH 9.5, were classified as members of the genus Moraxella. From a crude extract of Moraxella sp. strain C-1, formate dehydrogenase was purified to homogeneity, as judged by disc gel electrophoresis. The enzyme has an isoelectric point of 3.9 and a molecular weight of approximately 98,000. The enzyme is composed of two identical subunits with molecular weights of about 48,000. The apparent Km values for sodium formate and NAD+ were calculated to be 13 mM and 0.068 mM, respectively.
Subject(s)
Aldehyde Oxidoreductases/isolation & purification , Formate Dehydrogenases/isolation & purification , Moraxella/enzymology , Soil Microbiology , Chromatography, High Pressure Liquid , Culture Media , Electrophoresis, Polyacrylamide Gel , Formate Dehydrogenases/analysis , Formates/metabolism , Hydrogen-Ion Concentration , Isoelectric Point , Kinetics , Methanol/metabolism , Molecular Weight , Moraxella/growth & development , Substrate Specificity , TemperatureSubject(s)
Endotoxins/toxicity , Glutathione/pharmacology , Lipid Peroxides/biosynthesis , Prednisolone/pharmacology , Superoxide Dismutase/pharmacology , Vitamin E/pharmacology , Animals , Escherichia coli , Liver/drug effects , Liver/metabolism , Lung/drug effects , Lung/metabolism , Male , Rats , Rats, Inbred Strains , Shock, Septic/drug therapyABSTRACT
The authors report on a 59-year-old man with opportunistic esophagitis caused by Aspergillus fumigatus. Although the patient had no underlying disease, esophagitis occurred after a short course of antibiotic therapy. A double contrast esophagogram showed multiple nodular or vertical plaque-like projections. Endoscopy provided pathological conformation of Aspergillus infection.
