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Systemic evaluation of gene expression changes in major target organs induced by atorvastatin

EUROPEAN JOURNAL OF PHARMACOLOGY 2008年第2-3期584卷 376-389页

作者： Kato, Norihiro Liang, Yi-Qiang Ochiai, Yoshinori Jesmin, Subrina Int Med Ctr Japan Res Inst Dept Gene Diagnost & Therapeut Shinjuku Ku Tokyo 1628655 Japan

Statins have been reported to protect against end-organ damage in essential hypertension;however, detailed mechanisms underlying organ-protective actions of statins remain unclear. Statins can exert pleiotropic effects aside from lowering cholesterol and blood pressure levels through several different pathways, which may lead to distinct patterns of changes in gene expression in vital end-organs. The aim of the present study was to systemically evaluate gene expression changes in three major end-organs (the brain, heart and kidney) induced by atorvastatin at a dose that altered neither blood pressure nor plasma total cholesterol levels. The stroke-prone spontaneously hypertensive (SHRSP) rats, an established model of hypertension and end-organ damage, was treated with atorvastatin (15 rng/kg/day) for 4 weeks from 12 to 16 weeks of age. DNA microarray technology was used to identify gene expression changes in three end-organs. In the current experimental setting, 4 weeks of atorvastatin treatment lowered plasma levels of non-esterified fatty acid significantly (P=0.0012) and triglyceride modestly (P=0.07) without altering blood pressure and plasma total cholesterol levels in male SHRSP rats. The level of expression of a number of genes was changed in an organ-specific manner after 4 weeks of drug administration to SHRSP rats. Among the end-organs studied, the most prominent alteration in gene expression was observed in the heart. The identical treatment protocol was applied to age-matched normotensive control rats, Wistar Kyoto rats, and this also caused a number of genes to be differentially expressed in an organ-specific manner. These results provide new insights into the mechanisms underlying the potential efficacy of statins in protecting against end-organ damage in essential hypertension and thus lay the foundation for future studies. (c) 2008 Elsevier B.V. All rights reserved.

关键词： SHRSP (stroke-prone spontaneously hypertensive) end-organ protection atorvastatin gene expression microarray technology

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Candesartan-Induced Gene Expression in Five Organs of Stroke-Prone Spontaneously Hypertensive Rats

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HYPERTENSION RESEARCH 2008年第10期31卷 1963-1975页

作者： Kato, Norihiro Liang, Yi-Qiang Ochiai, Yoshinori Birukawa, Naoko Serizawa, Masakuni Jesmin, Subrina Int Med Ctr Japan Res Inst Dept Gene Diagnost & Therapeut Shinjuku Ku Tokyo 1628655 Japan

To test the functional consequences of blocking the local renin-angiotensin system (RAS), we investigated the effects of an angiotensin II type 1 receptor blocker (ARB), candesartan, on the systemic gene expression profile of five important organs (brain, heart, kidney, liver and adipose tissues) in the stroke-prone spontaneously hypertensive rat (SHRSP), an established model of essential hypertension and cardiovascular disorders, and its normotensive control, the Wistar Kyoto (WKY) rat. Rats were treated with candesartan (5 mg/kg/d) for 4 weeks from 12 to 16 weeks of age. DNA microarray technology was used to identify changes in gene expression. Four weeks of treatment with candesartan significantly lowered systolic blood pressure in male rats of both the SHRSP and the WKY strains (p < 0.0005). Candesartan differentially modulated the gene expression profile in an organ-specific manner in male SHRSP;of the five organs tested, gene expression was most prominently altered in the hearts of SHRSP. In contrast, candesartan treatment exerted minimal or no significant effects on the gene expression profile of the corresponding organs of male WKY rats. The inter-strain differences in gene expression changes induced by candesartan were considered to be associated with both blood pressure-dependent and independent mechanisms. These results help to delineate the mechanisms that underlie the organ or tissue protection conferred by ARB at the levels of cellular biology and genomics in the context of the local RAS. Further studies are warranted to investigate not only individual genes of interest but also genetic "networks" that involve differential orclan- or tissue-specific gene expression induced by the blockade of RAS in essential hypertension. (Hypertens Res 2008;31: 1963-1975)

关键词： candesartan stroke-prone spontaneously hypertensive rat microarray technology gene expression end organ damage

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Genetic Evaluation of Intellectual Disabilities

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SEMINARS IN PEDIATRIC NEUROLOGY 2008年第1期15卷 2-9页

作者： Moeschler, John B. Dartmouth Hitchcock Med Ctr Lebanon NH 03756 USA

All children with an intellectual disability (mental retardation) or global developmental delay should have a comprehensive evaluation to establish the etiology of the disability. A specific etiologic diagnosis offers the opportunity to discuss treatment, prognosis, and genetic recurrence risk. A diagnosis also avoids unnecessary testing and can lead to opportunities for improved health and functional outcomes. The key elements of the diagnostic evaluation are the medical and developmental history, 3-generation family history, dysmorphologic examination, neurologic examination, and judicious use of the laboratory and neuroimaging. All published guidelines for the evaluation of children with intellectual disability acknowledge that there is a substantial percentage of patients who are undiagnosed after a comprehensive evaluation and who deserve ongoing follow-up for the purpose of establishing a diagnosis. Recently, studies of the clinical application of array comparative genomic hybridization (aCGH) to individuals with intellectual disability indicate that this approach provides a diagnosis in as much as 10% of patients and that this technique is replacing the use of fluorescent in situ hybridization for subtelomere imbalances now used for such patients when the standard karyotype is normal. The literature suggests that history and examination by an expert clinician will lead to a diagnosis in 2 of 3 patients in whom a diagnosis is made. Laboratory studies alone, including neuroimaging, provide a diagnosis in the remaining one third. The approach to the evaluation of the patient in whom an etiologic diagnosis is not suspected after the history and physical examinations includes a standard karyotype, Fragile X molecular genetic testing, aCGH, and neuroimaging, based on the evidence to date. One can expect rapid changes in the microarray technology in the near future. Semin Pediatr Neurol 15:2-9 (C) 2008 Elsevier Inc. All rights reserved.

关键词： Child Cytogenetic Analysis Diagnostic Imaging Fragile X Syndrome Humans 儿童诊断显像脆性X染色体综合征原位杂交精神发育迟滞 diagnostic imaging Diagnosis Fragile X Syndrome Neuroimaging comprehensive assessment microarray technology developmental delay Cytogenetic Analysis Intellectual Disability Child Patients Array-Based Comparative Genomic Hybridization

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Global characterization of cell-specific gene expression through fluorescence-activated sorting of nuclei

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PLANT PHYSIOLOGY 2008年第1期147卷 30-40页

作者： Zhang, Changqing Barthelson, Roger A. Lambert, Georgina M. Galbraith, David W. Univ Arizona Dept Plant Sci Tucson AZ 85721 USA Univ Arizona BIO5 Inst Collaborat Biores Tucson AZ 85721 USA

We describe a simple and highly effective means for global identification of genes that are expressed within specific cell types within complex tissues. It involves transgenic expression of nuclear-targeted green fluorescent protein in a cell-type-specific manner. The fluorescent nuclei are then purified from homogenates by fluorescence-activated sorting, and the RNAs employed as targets for microarray hybridization. We demonstrate the validity of the approach through the identification of 12 genes that are selectively expressed in phloem.

关键词： microarray technology sorting programs Genes Authentication phloem Staphylococcal Protein A cell type

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Trefoil factor 3: A novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas

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BRITISH JOURNAL OF CANCER 2008年第5期99卷 768-773页

作者： Bignotti, E. Ravaggi, A. Tassi, R. A. Calza, S. Rossi, E. Falchetti, M. Romani, C. Bandiera, E. Odicino, F. E. Pecorelli, S. Santin, A. D. Yale Univ Sch Med Dept Obstet Gynecol & Reprod Sci New Haven CT 06520 USA Univ Brescia Dept Obstet & Gynecol Div Gynecol Oncol I-25123 Brescia Italy Univ Brescia Sect Med Stat & Biometry Dept Biomed Sci & Biotechnol I-25123 Brescia Italy Univ Brescia Dept Pathol I-25123 Brescia Italy

This study identifies the genetic fingerprint of poorly differentiated endometrioid endometrial carcinomas (G3-EEC) and analyses the potential utility of trefoil factor 3 (TFF3) as novel serum marker in G3-EEC. Affymetrix microarrays were used to identify the gene expression patterns of 19 snap-frozen G3-EEC and 15 normal endometrium ( NE) biopsies. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to validate TFF3 expression. Finally, TFF3 serum levels were determined by ELISA in 25 G3-EEC patients, 42 healthy controls, and in 13 endometrial hyperplasia patients. Hierarchical cluster analysis showed TFF3 as the top differentially expressed gene between 363 upregulated genes in G3-EEC, when compared with NE. Trefoil factor 3 gene expression levels analysed by qRT-PCR significantly correlated with Affymetrix results ( P<0.001;rs = 0.85). By immunohistochemistry, TFF3 protein was significatively more expressed in EEC compared with NE ( P<0.01), with cytoplasmatic positivity in 79% G3-EEC and 18% NE. Patients harbouring G3-EECs had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients ( P<0.001) or patients harbouring endometrial hyperplasia ( P = 0.012). In conclusion, TFF3 is highly expressed at gene and protein level in G3-EEC. Further investigations on a wider set of samples are warranted to validate TFF3 as a novel serum marker for early detection and/or monitoring of G3-EEC patients.

关键词： G3 endometrioid endometrial carcinoma microarray technology trefoil factor serum marker sandwich ELISA

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Perylenediimide-metal ion dyads for photo-induced electron transfer

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CHEMICAL COMMUNICATIONS 2008年第17期000卷 1986-1988页

作者： Qvortrup, Katrine Bond, Andrew D. Nielsen, Anne McKenzie, Christine J. Kilsa, Kristine Nielsen, Mogens Brondsted Univ Copenhagen Dept Chem DK-2100 Copenhagen Denmark Univ So Denmark Dept Chem & Phys DK-5230 Odense Denmark

A novel perylene diimide incorporating a tetradentate ligand was synthesized and the photophysical properties of its Cu+, Cu2+, and Fe3+ complexes were investigated by fluorescence experiments.

关键词： Reaction centers Perylene Photosynthetic Reaction Centers Dyads Redox processes Photosynthesis microarray technology Solar Energy Diimide Ions electron transfer

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Molecular profiling in the diagnosis and treatment of high grade sarcomas

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ULTRASTRUCTURAL PATHOLOGY 2008年第2期32卷 37-42页

作者： Antonescu, Cristina R. Mem Sloan Kettering Canc Ctr Dept Pathol New York NY 10021 USA

High-density microarrays are used to measure in a comprehensive manner large-scale ("profile") gene expression patterns (when tumor RNA is tested) or gene copy number changes (when tumor genomic DNA is tested). microarray-based studies are increasingly useful in addressing a wide variety of questions in sarcoma biology. This review includes a brief description of the microarray methodology and data analysis, followed by few examples of the recent applications of gene expression in the diagnosis, classification, and treatment of sarcomas.

关键词： sarcoma gene expression microarray technology

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A nitty-gritty aspect of correlation and network inference from gene expression data

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BIOLOGY DIRECT 2008年第1期3卷 35-35页

作者： Klebanov, Lev B. Yakovlev, Andrei Yu Charles Univ Prague Dept Probabil & Stat CZ-18675 Prague 8 Czech Republic Univ Rochester Dept Biostat & Computat Biol Rochester NY 14642 USA

Background: All currently available methods of network/association inference from microarray gene expression measurements implicitly assume that such measurements represent the actual expression levels of different genes within each cell included in the biological sample under study. Contrary to this common belief, modern microarray technology produces signals aggregated over a random number of individual cells, a "nitty-gritty" aspect of such arrays, thereby causing a random effect that distorts the correlation structure of intra-cellular gene expression levels. Results: This paper provides a theoretical consideration of the random effect of signal aggregation and its implications for correlation analysis and network inference. An attempt is made to quantitatively assess the magnitude of this effect from real data. Some preliminary ideas are offered to mitigate the consequences of random signal aggregation in the analysis of gene expression data. Conclusion: Resulting from the summation of expression intensities over a random number of individual cells, the observed signals may not adequately reflect the true dependence structure of intra-cellular gene expression levels needed as a source of information for network reconstruction. Whether the reported effect is extrime or not, the important point, is to reconize and incorporate such signal source for proper inference. The usefulness of inference on genetic regulatory structures from microarray data depends critically on the ability of investigators to overcome this obstacle in a scientifically sound way. Reviewers: This article was reviewed by Byung Soo KIM, Jeanne Kowalski and Geoff McLachlan

关键词： microarray Data Gene Pair microarray technology Signal Aggregation Gene Expression Measurement

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Accurate prediction of BRCA1 and BRCA2 heterozygous genotypes using expression profiling of lymphocytes after irradiation-induced DNA damage

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BREAST CANCER RESEARCH 2008年第SUPPL 2期10卷 S11-S11页

作者： Kote-Jarai, Z. Jugurnauth, S. Matthews, L. Giddings, I. Bancroft, E. Williams, R. Girolami, M. Campbell, C. Eeles, R. A. Inst Canc Res Sutton Surrey England Royal Marsden NHS Fdn Trust London England Univ Glasgow Bioinformat Res Ctr Glasgow G12 8QQ Lanark Scotland Univ Bristol Computat Intelligence Grp Bristol BS8 1TH Avon England

P18

关键词： Support Vector Machine Mutation Carrier Support Vector Machine Classifier microarray technology BRCA2 Gene

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Transcriptome analysis of peripheral blood mononuclear cells from patients with chronic fatigue syndrome

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Journal of Chronic Fatigue Syndrome 2008年第3期14卷 7-25页

作者： Gräns, Hanna Evengård, Birgetta Nilsson, Peter Division of Clinical Bacteriology F82 Karolinska Institutet Stockholm Sweden Department of Proteomics Department of Gene Technology KTH-Royal Institute of Technology Stockholm Sweden Division of Clinical Bacteriology F82 Karolinska Institutet Karolinska University Hospital Huddinge Stockholm SE-141 86 Sweden

Objective: Chronic fatigue syndrome (CFS) is an illness defined by unexplained disabling fatigue lasting longer than six months, together with at least four out of eight specified symptoms. The etiology and pathophysiology of CFS are to a large degree unknown. Since much remains unclear about CFS we wanted to investigate transcript expression levels in peripheral blood mononuclear cells to identify genes that are involved in CFS. Method: Transcript expression profiles for 20 CFS patients were compared with 14 healthy controls using microarray technology. Results were verified with real-time PCR. Results: We have identified significantly differentially expressed genes comparing a female CFS patient subgroup with gradual illness onset and no previously documented infection with female healthy controls. We have also created a list of genes with indicated, but not verified, expression differences from comparisons between other subgroups and healthy controls. These genes are candidates for further study of potential involvement in CFS. Conclusion: Our results stress the necessity of subgrouping the heterogeneous CFS patient cohort. The mRNA expression differences identified here may be causal factors for the illness or symptoms observed in these patients, or a result of altered functions of other cellular components involved in the illness. The role of these genes in the CFS pathology needs further investigation. Copyright © by The Haworth Press, Inc. All rights reserved.

关键词： Chronic fatigue syndrome Gene expression microarray technology Transcriptome

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