[Diffuse panbronchiolitis].
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Bronchiolitis↗
Biomedical subjects
Naoto Keicho
Publications and source records attributed to Naoto Keicho.
Adenoviral E1A modulates inflammatory mediator expression by lung epithelial cells exposed to PM10.
We examined the hypothesis that ambient particulate matter with a diameter of <10 microm (PM(10))-induced lung inflammation is amplified by latent adenovirus infection. Inflammatory mediator expression in response to PM(10) exposure was compared between adenovirus E1A-transfected A549 alveolar epithelial cells and cells transfected with control plasmid. Messenger RNA was measured by the RNase protection assay and protein by ELISA or immunocytochemistry. Intercellular adhesion molecule-1 and IL-8 mRNA and protein were increased in E1A-positive cells exposed to 500 microg/ml PM(10). Monocyte chemoattractant protein-1 mRNA and protein were unchanged in E1A-positive cells but increased in E1A-negative cells after 100 and 500 microg/ml PM(10) exposure. Electrophoretic mobility shift assays showed increased NF-kappaB and decreased specificity protein 1 nuclear binding in E1A-positive cells exposed to PM(10). These results indicate that E1A modulates cytokine and adhesion molecule expression in epithelial cells in a manner that could amplify PM(10)-induced lung inflammation. We suggest that this amplified inflammatory response may contribute to the pathogenesis of exacerbations of chronic obstructive pulmonary disease associated with exposure to particulate matter air pollution.
Adenovirus E1A Proteins↗
Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC.
Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte antigens HLA-B54 in Japan and China and HLA-A11 in Korea suggest that the susceptible locus for DPB is located between the HLA-B and HLA-A genes. We have previously reported that the susceptibility gene for DPB could be localized within a 200-kb segment between the S and TFIIH loci in the HLA class I region, using refined microsatellite-based association mapping. However, no genes have been recognized in this candidate region to date. In order to identify a novel candidate gene for DPB from this segment, the expressed sequence tag databases were searched using the genomic sequence. As a result, a cDNA clone was isolated from a human lung cDNA library. This gene, designated C6orf37 (Chromosome 6 open reading frame 37), spans approximately 2.5 kb and consists of two exons encoding a 235-amino acid protein, sharing homology with the mucin-like domain of human zonadhesin, which is a sperm multiple-domain transmembrane protein with the sperm zona pellucida binding activity. Unexpectedly, RT-PCR analysis detected transcripts from the anti-sense DNA strand of this C6orf37 locus. The gene designated as C6orf37OS (C6orf37 Opposite Strand) and represented by these anti-sense transcripts contained no open reading frame. The transcripts from C6orf37 and C6orf37OS were observed in numerous tissues, with most-abundant expression in lung, kidney, and testis. Taken together, these results, especially the abundant expression in lung, indicate that C6orf37 and C6orf37OS are excellent candidate genes for DPB.
Amino Acid Sequence↗
Genetic variants of human beta-defensin-1 and chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is due to interactions between cigarette smoke exposure and other risk factors. Genetic variations of human beta-defensin-1 (hBD-1), an endogenous antimicrobial peptide in the airway, were investigated in 60 patients and 213 healthy volunteers by single-strand conformation and restriction fragment length polymorphism analysis and DNA sequencing. Four nucleotide variations in the 5' and 3' untranslated regions and two nonsynonymous substitutions in the coding region were identified. Of these, a newly found Ile38 variant was observed in 15.0% of patients but only in 2.8% of healthy individuals and was significantly associated with the disease (OR = 6.1, 95% confidence intervals 2.0-8.3, P = 0.0012). More than 80% of those with Ile38 experienced sputum production for more than 3 months during the follow-up period. Genetic variations in hBD-1 may define a high-risk subgroup of COPD where the component of chronic bronchitis is predominant.
Aged↗
Genotyping of hepatitis E virus from Vietnam.
To identify the genotype of Vietnamese isolates of human hepatitis E virus (HEV), phylogenetic analysis was performed for the open reading frame (ORF) 1 and ORF2 nucleotide sequences of the viral genome. HEV was detected by RT-PCR in 9 out of 141 sera collected from patients with a diagnosis of acute sporadic hepatitis in Hanoi, Vietnam. All of them had sequences related most closely to genotype 4. In addition, the Vietnamese isolate had a single nucleotide insertion in the ORF 3 region, a characteristic reported for genotype 4 with the possible change of initiation of ORF 3 and ORF 2.
Base Sequence↗
[The mechanism of HIV replication at the site of inflammation coinfected with HIV and M. tuberculosis].
HIV-1 replication is remarkably augmented in macrophages at the site of inflammation due to tuberculosis. Reduction of expression of an inhibitory C/EBP beta transcription factor and activation of NF-kappa B are observed at the site of inflammation. Of 18 paraffin embedded tissue sections of HIV-tuberculosis coinfected autopsy or biopsy samples, 9 samples were positive for HIV-p24 staining, which were all derived from patients with blood CD4 cell counts more than 50/mm3. Moreover, the P24 positive cells were morphologically macrophages or epithelioid cells. CD4 positive lymphocytes consistently located near the P24 positive macrophages. Therefore, we hypothesized that lymphocyte-macrophage contact is important for maximal HIV production from macrophages. In vitro experiments showed that contact between lymphocytes and macrophages reduced inhibitory C/EBP beta, activated NF-kappa B and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBP beta expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-kappa B was activated. Antibodies which cross-linked macrophage expressed B-7, VCAM and CD40 were used mimic lymphocyte contact. Cross-linking antibodies abolished inhibitory C/EBP beta expression; however, the HIV-1 LTR was not maximally stimulated and NF-kappa B was not activated. Maximal HIV-1 LTR stimulation required both lymphocyte derived soluble factors and cross-linking of macrophage expressed costimulatory molecules. These results demonstrate that neither contact nor soluble factor(s) are sufficient to maximally enhance HIV-1 LTR activity in macrophages. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBP beta, thereby derepressing the HIV-1 LTR. Lymphocyte derived soluble factor(s) activate NF-kappa B, further enhancing the HIV-LTR.
CCAAT-Enhancer-Binding Protein-beta↗