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Tsuyoshi Kayo

Publications and source records attributed to Tsuyoshi Kayo.

5 recordsLinked to original sources
PubMed2004

Empirical Bayes estimation of gene-specific effects in micro-array research.

Micro-array technology allows investigators the opportunity to measure expression levels of thousands of genes simultaneously. However, investigators are also faced with the challenge of simultaneous estimation of gene expression differences for thousands of genes with very small sample sizes. Traditional estimators of differences between treatment means (ordinary least squares estimators or OLS) are not the best estimators if interest is in estimation of gene expression differences for an ensemble of genes. In the case that gene expression differences are regarded as exchangeable samples from a common population, estimators are available that result in much smaller average mean-square error across the population of gene expression difference estimates. We have simulated the application of such an estimator, namely an empirical Bayes (EB) estimator of random effects in a hierarchical linear model (normal-normal). Simulation results revealed mean-square error as low as 0.05 times the mean-square error of OLS estimators (i.e., the difference between treatment means). We applied the analysis to an example dataset as a demonstration of the shrinkage of EB estimators and of the reduction in mean-square error, i.e., increase in precision, associated with EB estimators in this analysis. The method described here is available in software that is available at http://www.soph.uab.edu/ssg.asp?id=1087.

Bayes Theorem↗
PubMed2004

Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis.

Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS) that develops in genetically susceptible individuals who are exposed to undefined environmental risk factors. Epidemiological, genetic, and biological evidence suggests that insufficient vitamin D may be an MS risk factor. However, little is known about how vitamin D might be protective in MS. We hypothesized that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] might regulate gene expression patterns in a manner that would resolve inflammation. To test this hypothesis, experimental autoimmune encephalomyelitis (EAE) was induced in mice, 1,25-(OH)2D3 or a placebo was administered, and 6 h later, DNA microarray hybridization was performed with spinal cord RNA to analyze the gene expression patterns. At this time, clinical, histopathological, and biological studies showed that the two groups did not differ in EAE disease, but changes in several 1,25-(OH)2D3-responsive genes indicated that the 1,25-(OH)2D3 had reached the CNS. Compared with normal mice, placebo-treated mice with EAE showed increased expression of many immune system genes, confirming the acute inflammation. When 1,25-(OH)2D3 was administered, several genes like glial fibrillary acidic protein and eukaryotic initiation factor 2alpha kinase 4, whose expression increased or decreased with EAE, returned to homeostatic levels. Also, two genes with pro-apoptotic functions, calpain-2 and caspase-8-associated protein, increased significantly. A terminal deoxynucleotidyl transferase-mediated dUTP nicked end labeling study detected increased nuclear fragmentation in the 1,25-(OH)2D3-treated samples, confirming increased apoptosis. Together, these results suggest that sensitization of inflammatory cells to apoptotic signals may be one mechanism by which the 1,25-(OH)2D3 resolved EAE.

Animals↗
PubMed2002

Characterization of gene expression profile associated with energy restriction-induced cold tolerance of heart.

Hypothermia is known to be a common feature of energy restriction (ER) and essential for a life-prolonging effect of ER. The heart is sensitive to hypothermia, but the heart in ER mice acquires some adaptation to hypothermia. The aim of the present study was to characterize the gene expression profile associated with ER-induced cold resistance of heart. We analyzed the expression of heart mRNA from ER (200 kJ/week) or control (400 kJ/week) B6 11-month-old male mice using cDNA array membranes including 588 genes. Eighty-eight out of 588 genes were expressed in the heart. mRNAs increased by ER were glutathion S-transferase Mu1, transcriptional factor 1 for heat shock gene (HSF1), and fetal myosin alkali light chain genes. mRNA decreased by ER were seven genes in four categories: (1). cell cycle or apoptosis-related proteins (cyclin G and nucleoside diphosphate kinase B); (2). stress response proteins (oxidative stress-induced protein); (3). DNA repair proteins (protein involved in DNA double-strand break repair, Rad23 UV excision repair protein homologue and ubiquitin-conjugating enzyme); and (4). cell-surface antigens (lamimin receptor 1). These data suggest that the heart of ER mice adapts to hypothermia involving heat shock proteins and their transcriptional factors and by changing structure and property of myofibrils. It is also suggested that ER induces protection against oxidative stress and inhibits cell proliferation of "nonmuscle cells" in the heart. Gene expression analysis using cDNA array was useful for screening genes associated with ER-induced cold adaptation.

Animals↗
PubMed2002

Gene expression profiling of aging using DNA microarrays.

We have previously employed high density oligonucleotide arrays representing thousands of genes to determine the gene expression profile of the aging process in skeletal muscle (gastrocnemius) and brain (cerebellum and neocortex) of male C57BL/6 mice. Specific gene expression profiles are associated with the aging process of individual organs, and caloric restriction can prevent or retard the establishment of these gene expression alterations. The use of DNA microarrays may provide a new tool to measure biological age on a tissue-specific basis and to evaluate at the molecular level the efficacy of interventions designed to retard the aging process.

Aging↗