The association of Toll-like receptor 4 gene polymorphisms with the development of emphysema in Japanese subjects: a case control study

<p>Abstract</p> <p>Background</p> <p>The principal role of Toll-like receptor 4 (TLR4) is the induction of immune responses to lipopolysaccharides. Previously, mice deficient in the <it>TLR4 </it>gene exhibited up-regulation of the NADPH oxidase system in the lungs. This resulted in increased oxidant generation and elastolytic activity, which led to pulmonary emphysema. It was suggested that TLR4 might maintain constitutive lung integrity by modulating oxidant generation. We investigated whether single nucleotide polymorphisms (SNPs) in the <it>TLR4 </it>gene were associated with the emphysema phenotype in Japanese subjects with chronic obstructive pulmonary disease (COPD).</p> <p>Results</p> <p>Seven SNPs in the <it>TLR4 </it>gene (<it>rs10759930</it>, <it>rs1927914</it>, <it>rs12377632</it>, <it>rs2149356, rs11536889</it>, <it>rs7037117</it>, and <it>rs7045953</it>) were genotyped with allelic discrimination assays. The frequencies of SNPs were compared between 106 patients with the emphysema phenotype of COPD and 137 healthy smokers. We found that the positivity of the individuals with the major G allele of <it>rs11536889 </it>was significantly less in the emphysema group than the control group (<it>p </it>= 0.019). The frequencies of the minor C allele and the distribution of the CC genotype as well as the frequency of the major haplotype that carried the minor C allele of <it>rs11536889 </it>were all significantly higher in the emphysema group than the control group (<it>p </it>= 0.0083, 0.019, and 0.004, respectively). Furthermore, the strength of the association of the CC genotype with the emphysema phenotype was in an odds ratio of 2.60 with 95% confidence intervals from 1.17 to 5.78. However, these significances were not apparent after adjust for age and smoking history by logistic regression. No associations were observed between the <it>rs11536889 </it>and the low attenuation area score, the forced expiratory volume, and the carbon monoxide diffusion capacity in the emphysema group.</p> <p>Conclusions</p> <p>The minor C allele of the <it>rs11536889 </it>SNP in the <it>TLR4 </it>gene is likely associated with the risk of developing emphysema in the Japanese population.</p

Reeb components of leafwise complex foliations and their symmetries I

We review the standard Hopf construction of Reeb components with leafwise complex structure and almost determine the group of leafwise holomorphic smooth automorphisms for Reeb components of certain type in the case of complex leaf dimension one. In particular, it contains an infinite dimensional vector space.Comment: This paper has been withdrawn because together with arXiv:1511.08985, the contents are improved and unified into a new one arXiv:1605.0897

Detection of Antilymphocyte Antibody with Two-Color Method in Systemic Lupus Erythematosus and Its Heterogeneous Specificities against Human T-Cell Subsets

The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M. The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tγ) and lacking (Tγ[-]) cells, 64% of ALA showed preferential reactivity with Tγ cells and 14% with Tγ(-) cells. The remainder had no selective reactivity against Tγ or Tγ(-) cells. Tγ cells were shown to have suppressor activity, whereas Tγ(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tγ cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tγ(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis. These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets