Human lipoproteins comprise at least 12 different classes that are lognormally distributed.

This study presents the results of HPLC, a gentler and rapid separation method in comparison with the conventional ultracentrifugation, for 55 human serum samples. The elution patterns were analysed parametrically, and the attribute of each class was confirmed biochemically. Human samples contained 12 classes of lipoproteins, each of which may consist primarily of proteins. There are three classes of VLDLs. The level of each class was distributed lognormally, and the standard amount and the 95% range were estimated. Some lipoprotein classes with a narrow range could become ideal indicators of specific diseases. This lognormal character suggests that the levels are controlled by the synergy of multiple factors; multiple undesirable lifestyle habits may drastically increase the levels of specific lipoprotein classes. Lipoproteins in medical samples have been measured by enzymatic methods that coincide with conventional ultracentrifugation; however, the high gravity and time required for ultracentrifugation can cause sample degradation. Actually, the enzymatic methods measured the levels of several mixed classes. The targets of enzymatic methods have to be revised.

Principal Component Analysis applied directly to Sequence Matrix.

Sequence data is now widely used to observe relationships among organisms. However, understanding structure of the qualitative data is challenging. Conventionally, the relationships are analysed using a dendrogram that estimates a tree shape. This approach has difficulty in verifying the appropriateness of the tree shape; rather, horizontal gene transfers and mating can make the shape of the relationship as networks. As a connection-free approach, principal component analysis (PCA) is used to summarize the distance matrix, which records distances between each combination of samples. However, this approach is limited regarding the treatment of information of sequence motifs; distances caused by different motifs are mixed up. This hides clues to figure out how the samples are different. As any bases may change independently, a sequence is multivariate data essentially. Hence, differences among samples and bases that contribute to the difference should be observed coincidentally. To archive this, the sequence matrix is transferred to boolean vector and directly analysed by using PCA. The effects are confirmed in diversity of Asiatic lion and human as well as environmental DNA. Resolution of samples and robustness of calculation is improved. Relationship of a direction of difference and causative nucleotides has become obvious at a glance.

Identification of a cell line producing high levels of TSLP: advantages for screening of anti-allergic drugs.

Thymic stromal lymphopoietin (TSLP) plays critical roles in the induction and exacerbation of allergic diseases. These findings suggest that an inhibitor of TSLP production may be a novel drug for allergic diseases. However, conducting high-throughput screening of such compounds is difficult because there is currently no appropriate in vitro system. In the present study, we demonstrated that the mouse keratinocyte cell line KCMH-1 produced higher amounts of TSLP than the mouse keratinocyte cell line PAM-212, human keratinocyte cell line HaCaT, or bronchial cell line BEAS-2B. A reporter gene assay revealed that transcriptional activity of the TSLP gene was also markedly higher in KCMH-1 than in PAM212 cells. Both dexamethasone and the retinoid X receptor agonist HX600 inhibited the production of TSLP in KCMH-1 cells, which indicated that its production could be pharmacologically regulated. Moreover, the biological activity of TSLP released from KCMH-1 cells in the medium was endorsed by the induction of OX40L expression in bone marrow-derived dendritic cells. These results indicate that KCMH-1 can be utilized in high-throughput screening of inhibitors of TSLP production and also as a source of native TSLP.

Induction of thymic stromal lymphopoietin production by nonanoic acid and exacerbation of allergic inflammation in mice.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) plays critical roles in the induction and exacerbation of allergic diseases. We tested various chemicals in the environment and found that xylene and 1,2,4-trimethylbenzene induced the production of TSLP in vivo. These findings prompted us to search for additional chemicals that induce TSLP production. In this study, we examined whether fatty acids could induce the production of TSLP in vivo and exacerbate allergic inflammation. METHODS: Various fatty acids and related compounds were painted on the ear lobes of mice and the amount of TSLP in the homogenate of ear lobe tissue was determined. The effects of nonanoic acid on allergic inflammation were also examined. RESULTS: Octanoic acid, nonanoic acid, and decanoic acid markedly induced TSLP production, while a medium-chain aldehyde and alcohol showed only weak activity. Nonanoic acid induced the production of TSLP with a maximum at 24 h. TSLP production was even observed in nonanoic acid-treated C3H/HeJ mice that lacked functional toll-like receptor 4. The aryl hydrocarbon receptor agonist ß-naphthoflavone did not induce TSLP production. Nonanoic acid promoted sensitization to ovalbumin, resulting in an enhancement in the cutaneous anaphylactic response. In addition, painting of nonanoic acid after the sensitization augmented picryl chloride-induced thickening of the ear, which was reversed in TSLP receptor-deficient mice. CONCLUSIONS: Nonanoic acid and certain fatty acids induced TSLP production, resulting in the exacerbation of allergic inflammation. We propose that TSLP-inducing chemical compounds such as nonanoic acid be recognized as chemical allergo-accelerators.

Induction of thymic stromal lymphopoietin production by xylene and exacerbation of picryl chloride-induced allergic inflammation in mice.

BACKGROUND: Some chemical compounds in the environment worsen allergic inflammation. In this study, we examined whether organic solvents induce the production of thymic stromal lymphopoietin (TSLP) which elicits Th2-type immune responses. METHODS: Organic solvents were painted on the earlobes of BALB/c mice. The expression of TSLP in the ear was determined by ELISA. RESULTS: Xylene and toluene, but not chloroform or ethyl acetate, induced the expression of mRNA for TSLP in the earlobe tissue. Among the aromatic compounds, xylene, especially m-xylene, and trimethylbenzene caused apparent TSLP production. The level of TSLP in the xylene-treated earlobes reached a maximum at 24 h, and TSLP was expressed in epithelial tissues. Production of TSLP was unaffected in mast cell-deficient W/W(v) mice but apparently diminished in TNF-α knockout mice and IL-4 receptor knockout mice. Repeated painting of xylene for 7 days induced an increase in the weight of cervical lymph nodes and expression of OX40 ligand, both of which were inhibited in TSLP receptor knockout mice. Xylene promoted the picryl chloride-induced thickening of the ear and IL-4 production, which were reversed in TSLP receptor knockout mice. CONCLUSION: Xylene induced TSLP production, resulting in an exacerbation of allergic inflammation. Thus, xylene might be a good tool for examining the roles of TSLP in eliciting allergy in experimental animals.