Induction of cytolytic activity and interferon-gamma production in murine natural killer cells by polymyxins B and E

Natural killer (NK) cells are the primary effector cells of the innate immune system and have well-established roles in tumor rejection and resistance to viruses, bacteria and certain parasites. There is a need for more specific immune modulators of NK cell activity that tack the wide-ranging side effects of NK cell-stimulatory interleukins. The polycationic antibiotic polymyxin B (PMB) has been shown to have a unique ability to enhance activities of some immune cells, independent of its antibiotic properties. Here we report that both PMB and its analog potymyxin E (PME) markedly enhanced the activity of NK cells enriched from the murine spleen. Maximal activation of NK cell activity was obtained after 24 h of incubation with PMB at a dose of 300 mu g/ml. PMB nonapeptide, one of the two PMB domains, and PME methanesulfonate, the negatively charged derivative of PME, had little effect on NK cell activity. PMB induced interferon (IFN)-gamma and tumor necrosis factor-a production in NK cells. Proliferation of NK cells in vitro was significantly stimulated by being incubated with PMB. Administration of PMB to mice for 7 consecutive days stimulated splenic NK cell activity and increased NK cell populations in the spleen. These results suggest that the polycationic antibiotics PMB and PME may up-regulate innate and adaptive immune responses by induction of NK cell activity and IFN-gamma production.</p

ROKU: a novel method for identification of tissue-specific genes

BACKGROUND: One of the important goals of microarray research is the identification of genes whose expression is considerably higher or lower in some tissues than in others. We would like to have ways of identifying such tissue-specific genes. RESULTS: We describe a method, ROKU, which selects tissue-specific patterns from gene expression data for many tissues and thousands of genes. ROKU ranks genes according to their overall tissue specificity using Shannon entropy and detects tissues specific to each gene if any exist using an outlier detection method. We evaluated the capacity for the detection of various specific expression patterns using synthetic and real data. We observed that ROKU was superior to a conventional entropy-based method in its ability to rank genes according to overall tissue specificity and to detect genes whose expression pattern are specific only to objective tissues. CONCLUSION: ROKU is useful for the detection of various tissue-specific expression patterns. The framework is also directly applicable to the selection of diagnostic markers for molecular classification of multiple classes

潜水センサスを用いた瀬戸内海倉橋島における浅海魚類相 : 出現魚種の季節的消長 <原著論文>

瀬戸内海の倉橋島において，潜水センサスによる魚類相の周年調査を行った。本調査により，8目29科53種の魚類を確認した。これらは周年定住種16種，季節的定住種37種に分けられた。近年，瀬戸内海で報告されている暖海性魚類と思われる種は確認されなかった。月毎の出現魚種数は，9・10月の41種が最多であり，1・2月の18種が最少であった。冬期には，9・10月に認められた多くの季節的定住種はその姿を消し，周年定住種を中心とした魚類群集が形成された。本調査海域の冬期の最低水温は10℃であり，低水温が種数の変動に影響し，暖海性魚類の出現を制限する要因になっていると考えられた。We conducted a year-long underwater census to survey fish fauna on a reef off Kurahashi Island in the Seto Inland Sea. A total of 53 species (8 orders, 29 families) were recorded; 16 species were residents, 37 were seasonal residents. No tropical/warm-temperate fish were confirmed. The total number of fish species (41) peaked in September and October, but drastically decreased to just 18 species in January and February because of the disappearance of most seasonal residents. These seasonal residents appeared to be prevented from continuing residence in the central part of the Seto Inland Sea because of the low water temperature in winter.※誤植訂正のためPDF差し替え(2018年3月20日

Evaluating methods for ranking differentially expressed genes applied to microArray quality control data

<p>Abstract</p> <p>Background</p> <p>Statistical methods for ranking differentially expressed genes (DEGs) from gene expression data should be evaluated with regard to high sensitivity, specificity, and reproducibility. In our previous studies, we evaluated eight gene ranking methods applied to only Affymetrix GeneChip data. A more general evaluation that also includes other microarray platforms, such as the Agilent or Illumina systems, is desirable for determining which methods are suitable for each platform and which method has better inter-platform reproducibility.</p> <p>Results</p> <p>We compared the eight gene ranking methods using the MicroArray Quality Control (MAQC) datasets produced by five manufacturers: Affymetrix, Applied Biosystems, Agilent, GE Healthcare, and Illumina. The area under the curve (AUC) was used as a measure for both sensitivity and specificity. Although the highest AUC values can vary with the definition of "true" DEGs, the best methods were, in most cases, either the weighted average difference (WAD), rank products (RP), or intensity-based moderated <it>t </it>statistic (ibmT). The percentages of overlapping genes (POGs) across different test sites were mainly evaluated as a measure for both intra- and inter-platform reproducibility. The POG values for WAD were the highest overall, irrespective of the choice of microarray platform. The high intra- and inter-platform reproducibility of WAD was also observed at a higher biological function level.</p> <p>Conclusion</p> <p>These results for the five microarray platforms were consistent with our previous ones based on 36 real experimental datasets measured using the Affymetrix platform. Thus, recommendations made using the MAQC benchmark data might be universally applicable.</p

Association of serum gamma-glutamyltransferase (GGT) and diabetes with triglycerides-to-HDL cholesterol ratio in Japanese subjects: The Nagasaki Study

Background: Although we reported in a previous study that diabetes with a high serum triglycerides to high-density lipoproteincholesterol (TG-HDL) ratio constitutes a risk for atherosclerosis, associations in terms of TG-HDL ratio between diabetes and gamma-glutamyltransferase (GGT), which is also known as an independent risk factor for atherosclerosis, have not yet been clarified. The purpose of this study was to test the hypothesis that a positive association between GGT and diabetes may be confined to high TG-HDL. Methods: This was a cross-sectional study of 2,302 Japanese subjects who were undergoing a general health check in 2014. All subjects were divided into TG-HDL level tertiles and serum GGT and diabetes status were investigated. Results: Of 207 diabetes patients identified in this study, 94 had high TG-HDL, 63 intermediate TG-HDL, and 50 low TG-HDL. Independent of classical cardiovascular risk factors, serum GGT showed a positive association with diabetes in patients with high TG-HDL, but not in patients with intermediate and low TG-HDL diabetes. The multivariable adjusted odds ratios (OR) and 95% coincidence intervals (95%CI) of diabetes for 1 standard deviation (SD) increment of GGT were 1.64 (95%CI: 1.16-2.31) for high TG-HDL, 1.46 (95%CI: 0.95-2.26) for intermediate TG-HDL, and 1.04 (95%CI: 0.60-1.79) for low TG-HDL diabetes. Conclusion: Serum GGT is positively associated with diabetes in patients with high TG-HDL but not with intermediate or low TG-HDL diabetes. This finding may prove to be an efficient tool for estimating atherosclerotic risk in diabetes patients

Hemoglobin as a response marker of endothelial cell damage in elderly nonoverweight non-anemic subjects.

　An independent positive correlation between hemoglobin level and risk of hypertension has been reported for non-anemicnon-overweight men and women. Additionally, serum hepatocyte growth factor (HGF) concentration in hypertensive subjects was reported to be significantly higher than in normotensive subjects. However no studies have reported on the correlation betweenhemoglobin and HGF. A cross-sectional study of 695 elderly non-overweight non-anemic Japanese subjects (231 men and 464 women; range 60-92 years old; Body mass index (BMI)<25kg/m2; Hemoglobin (Hb)?13g/dL for men and Hb?12g/dL for women) who were undergoing general health checkups in 2014 was conducted. Multiple linear regression analysis adjustment for classical cardiovascular risk factors showed a significant positive correlation between hemoglobin and serum HGF concentration(parameter estimate (β) =31.8, P<0.001) for men and (β=21.7, P<0.001) for women. An independent positive correlation between hemoglobin and HGF was observed in elderly non-anemic non-overweight Japanese subjects. Since HGF level may become elevated in response to endothelial cell damage (vascular remodeling), these findings suggest that measuring hemoglobin level is clinically relevant for estimating the response to endothelial cell damage

Ranking differentially expressed genes from Affymetrix gene expression data: methods with reproducibility, sensitivity, and specificity

<p>Abstract</p> <p>Background</p> <p>To identify differentially expressed genes (DEGs) from microarray data, users of the Affymetrix GeneChip system need to select both a preprocessing algorithm to obtain expression-level measurements and a way of ranking genes to obtain the most plausible candidates. We recently recommended suitable combinations of a preprocessing algorithm and gene ranking method that can be used to identify DEGs with a higher level of sensitivity and specificity. However, in addition to these recommendations, researchers also want to know which combinations enhance reproducibility.</p> <p>Results</p> <p>We compared eight conventional methods for ranking genes: weighted average difference (WAD), average difference (AD), fold change (FC), rank products (RP), moderated <it>t </it>statistic (modT), significance analysis of microarrays (samT), shrinkage <it>t </it>statistic (shrinkT), and intensity-based moderated <it>t </it>statistic (ibmT) with six preprocessing algorithms (PLIER, VSN, FARMS, multi-mgMOS (mmgMOS), MBEI, and GCRMA). A total of 36 real experimental datasets was evaluated on the basis of the area under the receiver operating characteristic curve (AUC) as a measure for both sensitivity and specificity. We found that the RP method performed well for VSN-, FARMS-, MBEI-, and GCRMA-preprocessed data, and the WAD method performed well for mmgMOS-preprocessed data. Our analysis of the MicroArray Quality Control (MAQC) project's datasets showed that the FC-based gene ranking methods (WAD, AD, FC, and RP) had a higher level of reproducibility: The percentages of overlapping genes (POGs) across different sites for the FC-based methods were higher overall than those for the <it>t</it>-statistic-based methods (modT, samT, shrinkT, and ibmT). In particular, POG values for WAD were the highest overall among the FC-based methods irrespective of the choice of preprocessing algorithm.</p> <p>Conclusion</p> <p>Our results demonstrate that to increase sensitivity, specificity, and reproducibility in microarray analyses, we need to select suitable combinations of preprocessing algorithms and gene ranking methods. We recommend the use of FC-based methods, in particular RP or WAD.</p

Association between white blood cell count and diabetes in relation to triglycerides-to-HDL cholesterol ratio in a Japanese population: The Nagasaki Islands study

Although our previous study found that diabetes combined with a high serum triglycerides to high-density lipoprotein cholesterol (TG-HDL) ratio constitutes a risk for atherosclerosis and chronic kidney disease (CKD), the association, in terms of TG-HDL ratio, between diabetes and white blood cell (WBC) count, which is an independent risk factor for atherosclerosis, has not been clarified. To investigate this association, we conducted a cross-sectional study of 3,998 Japanese subjects aged 30-89 years undergoing a general health check. We investigated the associations between WBC count and diabetes for all subjects, who were divided into tertiles according to TG-HDL level. Independent of classical cardiovascular risk factors, WBC count of both men and women was positively associated with diabetes combined with high but not with low TG-HDL. The multivariable odds ratios (ORs) and 95% confidence intervals (95%CIs) of 1SD (standard deviation) increment in WBC count (1,538/μL for men, 1,382/μL for women) for high TG-HDL diabetes and low TG-HDL diabetes were 1.39 (95%CI: 1.04-1.85) and 0.88 (95%CI: 0.66-1.19) for men, and 1.83 (95%CI: 1.45-2.33) and 0.91 (95%CI: 0.64-1.29) for women, respectively. In conclusion, for both men and women, WBC count is associated with high TG-HDL diabetes but not with low TG-HDL diabetes. These findings suggest that measuring WBC count is clinically relevant for estimating the risk of atherosclerosis and CKD in patients with diabetes categorized according to TG-HDL ratio