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Lawrence Gelbert

Publications and source records attributed to Lawrence Gelbert.

2 recordsLinked to original sources

Assessing the variability in GeneChip data.

INTRODUCTION: Oligonucleotide and cDNA microarray experiments are now common practice in biological science research. The goal of these experiments is generally to gain clues about the functions of genes by measuring how their expression levels rise and fall in response to changing experimental conditions. Measures of gene expression are affected, however, by a variety of factors. This paper introduces statistical methods to assess the variability of Affymetrix GeneChip data due to randomness. METHODS: The variation of Affymetrix's GeneChip signal data are quantified at both chip level and individual gene level, respectively, by the agreement study method and variance components method. Three agreement measurement methods are introduced to assess the variability among chips. Variation sources for gene expression data are decomposed into four categories: systematic experiment variation, treatment effect, biological variation, and chip variation. The focus of this paper is on evaluating and comparing the last two kinds of variations. RESULTS: Measurement of agreement and variance components methods were applied to an experimental data, and the calculation and interpretation were exemplified. The variability between biological samples were shown to exist and were assessed at both the chip level and individual gene level. Using the variance components method, it was found that the biological and chip variation are roughly comparable. The Statistical Analysis System (SAS) program for doing the agreement studies can be obtained from the correspondence author.

Algorithms↗

Aldosterone stimulates angiotensin-converting enzyme expression and activity in rat neonatal cardiac myocytes.

BACKGROUND: Members of the nuclear receptor family proteins function as transcription factors upon ligand binding and thereby regulate gene expression in host cells. Aldosterone, the high-affinity endogenous ligand for the mineralocorticoid receptor, induces cardiac hypertrophy and fibrosis in a variety of animal models, but the transcriptional targets for aldosterone in the myocardium are not well-described. METHODS AND RESULTS: Using quantitative reverse transcription-polymerase chain reaction method, we show that in cultured rat neonatal cardiomyocytes, aldosterone stimulates expression of angiotensin converting enzyme (ACE) in a concentration and time-dependent manner. Aldosterone (50 and 100 nM) increased levels of ACE mRNA by 1.8- and 2.2-fold, respectively. Aldosterone-induced ACE gene expression was blocked by spironolactone (1 microM), a mineralocorticoid receptor antagonist. In contrast, the expressions of the type I angiotensin receptor was not induced by aldosterone in either cardiac myocytes or fibroblasts. Consistent with the increased ACE mRNA level, 100 nM aldosterone also induced a 2-fold increase in ACE activity in cardiac myocytes. CONCLUSION: ACE gene expression may be a target for mineralocorticoid receptors in the myocardium, supporting the notion that at least some of the known adverse effects of aldosterone on the myocardium are mediated by increased angiotensin II.

Aldosterone↗