Showing papers in "Physiological Genomics in 2001"
TL;DR: A compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology is created and subsets of tissue-selective genes are identified that define key biological processes characterizing each organ.
Abstract: This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.
479 citations
TL;DR: Artificial selection for intrinsic aerobic endurance running capacity was started using genetically heterogeneous N:NIH stock of rats as a founder population using a velocity-ramped running protocol and produced changes in body weight as a correlated trait.
Abstract: Artificial selection for intrinsic aerobic endurance running capacity was started using genetically heterogeneous N:NIH stock of rats as a founder population (n = 168). Selection for low and high c...
368 citations
TL;DR: Investigation of gene expression profiles in cultured human aortic endothelial cells in response to 24 h of laminar shear stress suggests that 24-h shearing may keep ECs in a relatively noninflammatory and nonproliferative state compared with static cells.
Abstract: The recently developed DNA microarray technology provides a powerful and efficient tool to rapidly compare the differential expression of a large number of genes. Using the DNA microarray approach,...
297 citations
TL;DR: It is shown that CV parameters can be monitored continuously before, during, and after pregnancy in mice using this alternative implantation approach and demonstrate the feasibility of stress-free, long-term monitoring of CV parameters in pregnant or nonpregnant mice of typical size.
Abstract: The recent miniaturization of implantable radiotelemetric devices offers the possibility of an accurate, reliable, and simple phenotyping tool for long-term, hands-off measurement of blood pressure...
284 citations
TL;DR: Modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.
Abstract: Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-d-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABA(A) receptor subunits alpha3, beta1, beta2, and beta3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel K(V)2.1, hK(V)beta3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.
231 citations
TL;DR: The newest member of the capsaicin (vanilloid) receptor-like genes exist, the newest member, VRL-2 is found in airway and kidney epithelia and in the autonomic nervous system.
Abstract: Remarkable progress has been made recently in identifying a new gene family related to the capsaicin (vanilloid) receptor, VR1. Using a combination of in silico analysis of expressed sequence tag (...
231 citations
TL;DR: Housekeeping genes are constitutively expressed to maintain cellular function and are presumed to produce the minimally essential transcripts necessary for normal cellular physiology.
Abstract: housekeeping genes are constitutively expressed to maintain cellular function. As such, they are presumed to produce the minimally essential transcripts necessary for normal cellular physiology. With the advent of microarray technology, it has recently become possible to identify at least the “
206 citations
TL;DR: Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord, and phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly.
Abstract: We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.
154 citations
TL;DR: Microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology, as well as evaluate hybridization specificity, and confirm data for six genes using quantitative RT-PCR.
Abstract: Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using micr...
150 citations
TL;DR: The results suggest that reprogramming of gene expression within focused functional categories represents a fundamental aspect of cellular differentiation.
Abstract: Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization. Physiol Genomics 7: 135–148, 2001. First published September 21, 2001; 10.1152/physiolgeno...
146 citations
TL;DR: Findings show that heterozygous loss of AQP0 is sufficient to trigger cataractogenesis in mice and suggest that this MIP is required for optimal focusing of the crystalline lens.
Abstract: Aquaporin-0 (AQP0), a water transport channel protein, is the major intrinsic protein (MIP) of lens fiber cell plasma membranes. Mice deficient in the gene for AQP0 (Aqp0, Mip) were generated from ...
TL;DR: A statistical procedure to flag spots with weak signal intensity based on the standard deviation of background differences between a spot and the neighboring spots is developed, suggesting that decreasing the background noise is critical to improve the quality of microarray experiments.
Abstract: Over the last few years, there has been a dramatic increase in the use of cDNA microarrays to monitor gene expression changes in biological systems. Data from these experiments are usually transfor...
TL;DR: Rather than identifying a single common hypertrophic cardiomyopathy gene program, data suggest that extensive groups of genes may be useful for the prediction of specific underlying genetic determinants and condition-specific therapeutic approaches.
Abstract: To define molecular mechanisms of cardiac hypertrophy, genes whose expression was perturbed by any of four different transgenic mouse hypertrophy models [protein kinase C-e activation peptide (ΨeRA...
TL;DR: Self-organizing map (SOM) gene cluster techniques are applied to the analysis of cDNA microarray analysis of gene expression changes occurring in the early stages of genitourinary inflammation, providing a powerful technical basis for future analysis of mechanisms of bladder inflammation.
Abstract: In this study, self-organizing map (SOM) gene cluster techniques are applied to the analysis of cDNA microarray analysis of gene expression changes occurring in the early stages of genitourinary in...
TL;DR: It is concluded that the expression of hypoglossal LTF differs between SD rat substrains, indicating a difference in their genetic predisposition to neural plasticity.
Abstract: Long-term facilitation (LTF) is a prolonged, serotonin-dependent augmentation of respiratory motor output following episodic hypoxia. Previous observations lead us to hypothesize that LTF is subjec...
TL;DR: Results from analysis of transcription profiling data from tumor/nontumor colon adenocarcinoma samples support the general utility of the proposed feature relevance experts as a method for identifying marker genes.
Abstract: Transcription profiling experiments permit the expression levels of many genes to be measured simultaneously. Given profiling data from two types of samples, genes that most distinguish the samples (marker genes) are good candidates for subsequent in-depth experimental studies and developing decision support systems for diagnosis, prognosis, and monitoring. This work proposes a mixture of feature relevance experts as a method for identifying marker genes and illustrates the idea using published data from samples labeled as acute lymphoblastic and myeloid leukemia (ALL, AML). A feature relevance expert implements an algorithm that calculates how well a gene distinguishes samples, reorders genes according to this relevance measure, and uses a supervised learning method [here, support vector machines (SVMs)] to determine the generalization performances of different nested gene subsets. The mixture of three feature relevance experts examined implement two existing and one novel feature relevance measures. For each expert, a gene subset consisting of the top 50 genes distinguished ALL from AML samples as completely as all 7,070 genes. The 125 genes at the union of the top 50s are plausible markers for a prototype decision support system. Chromosomal aberration and other data support the prediction that the three genes at the intersection of the top 50s, cystatin C, azurocidin, and adipsin, are good targets for investigating the basic biology of ALL/AML. The same data were employed to identify markers that distinguish samples based on their labels of T cell/B cell, peripheral blood/bone marrow, and male/female. Selenoprotein W may discriminate T cells from B cells. Results from analysis of transcription profiling data from tumor/nontumor colon adenocarcinoma samples support the general utility of the aforementioned approach. Theoretical issues such as choosing SVM kernels and their parameters, training and evaluating feature relevance experts, and the impact of potentially mislabeled samples on marker identification (feature selection) are discussed.
TL;DR: Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanoc Cortin receptors.
Abstract: Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either α-melanocyte-stimulating hormone (α-MSH) or desacetyl-α-MSH, mediate increase...
TL;DR: It is suggested that differentiation is augmented by "categorical reprogramming" in which the function of induced genes is enhanced by preventing the further synthesis of categorically related gene products.
Abstract: Placental development results from a highly dynamic differentiation program. We used DNA microarray analysis to characterize the process by which human cytotrophoblast cells differentiate into sync...
TL;DR: The results suggest that in addition to NO-independent mechanisms, NO derived from both nNOS and eNOS plays a role in the integrative vascular response of contracting skeletal muscle.
Abstract: During skeletal muscle contraction, NO derived from neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers or from endothelial cells (eNOS) may relax vascular smooth muscle contributing to...
TL;DR: The cDNA of an uncoupling protein (UCP) homolog has been cloned from the swallow-tailed hummingbird, Eupetomena macroura, and this is the first report of an UCP homolog in birds.
Abstract: The cDNA of an uncoupling protein (UCP) homolog has been cloned from the swallow-tailed hummingbird, Eupetomena macroura. The hummingbird uncoupling protein (HmUCP) cDNA was amplified from pectoral...
TL;DR: Using the cDNA microarray approach, a number of nicotine-modulated genes encoding a protein involving in signal transduction or transcriptional regulation are identified and are relevant to understanding the mechanisms underlying the pathophysiological effect of nicotine and smoking, particularly on endothelial function and pathogenesis of atherosclerosis.
Abstract: Cigarette smoking causes vascular endothelial dysfunction and is a major risk factor for cardiovascular diseases. Nicotine, a major constituent of cigarette smoke, has been shown to alter gene expr...
TL;DR: Seven genes with higher expression levels in brown and white preadipocytes are identified and three are structural genes implicated in cell adhesion and cytoskeleton organization and four that might function in gene transcription and protein synthesis are identified.
Abstract: White (WAT) and brown (BAT) adipose tissue are tissues of energy storage and energy dissipation, respectively. Experimental evidence suggests that brown and white preadipocytes are differentially d...
TL;DR: It is shown that bone mass in older female mice with atherosclerosis has multiple genetic determinants and provides phenotypic and genetic evidence linking the regulation of bone density with adipose tissue and plasma lipids.
Abstract: This study investigates the phenotypic and genetic relationships among bone-density-related traits and those of adipose tissue and plasma lipids in mice with diet-induced atherosclerosis. Sixteen-month-old female F2 progeny of a C57BL/6J and DBA/2J intercross, which had received an atherogenic diet for 4 mo, were examined for multiple measures of femoral bone mass, density, and biomechanical properties using both computerized tomographic and radiographic methods. In addition, body weight and length, adipose tissue mass, plasma lipids and insulin, and aortic fatty lesions were assessed. Bone mass was inversely correlated with extent of atherosclerosis and with a prooxidant lipid profile and directly correlated with body weight, length, and, most strongly, adipose tissue mass. Quantitative trait locus (QTL) analysis, using composite interval mapping (CIM) and multi-trait analysis, identified six loci with multi-trait CIM LOD scores > 5. Three of these coincided with loci linked with adipose tissue and plasma high-density lipoprotein. Application of statistical tests for distinguishing close linkage vs. pleiotropy supported the presence of a potential pleiotropic effect of two of the loci on these traits. This study shows that bone mass in older female mice with atherosclerosis has multiple genetic determinants and provides phenotypic and genetic evidence linking the regulation of bone density with adipose tissue and plasma lipids.
TL;DR: It is concluded that accurate measurements of FRC in breathing mice can be made using a standard clinical CT scanner, and this method may be useful for repeated noninvasive assessment of both structural and functional changes in the lungs of experimental and genetically manipulated mice.
Abstract: We describe longitudinal measurements of functional residual capacity (FRC) in breathing mice using a clinical computed tomography (CT) scanner. Lungs of anesthetized mice from the A/J and C3H/HeJ ...
TL;DR: There was no evidence that older human muscle has increased expression of the stress response genes that are increased in old murine muscle, and there was evidence that the effect of age on the level of expression is not the same in mice and men.
Abstract: A microarray study of the effect of senescence in mice on gene expression in muscle has been published recently. The present analysis was done to evaluate the extent to which the age-related differ...
TL;DR: The current state of the art in cDNA library generation is reviewed, as well as an analysis of the different steps involved are presented.
Abstract: The development of functional genomic resources is essential to understand and utilize information generated from genome sequencing projects. Central to the development of this technology is the cr...
TL;DR: This study demonstrates the utility of genome-wide two-hybrid assays as an entry point for the further analysis of a large protein complex by identifying putative interactions between proteasome proteins and other proteins.
Abstract: A two-hybrid screen against an activation domain array of Saccharomyces cerevisiae proteins was carried out for 31 yeast proteasome proteins. Fifty-five putative interactions were identified: 21 between components of the proteasome complex and 34 between proteasome proteins and other proteins. Many of these latter interactions involved either proteins of the ubiquitin pathway, cell cycle proteins, protein kinases or a translation initiation factor subunit. The role of eleven proteins associated with proteasome function by these screens was analyzed by examining the corresponding deletion strains for temperature sensitivity and canavanine sensitivity and for the stability of a ubiquitin-β-galactosidase fusion protein. These assays additionally implicated three proteins, Bim1, Ump1, and YKL171W, in proteasome function. This study demonstrates the utility of genome-wide two-hybrid assays as an entry point for the further analysis of a large protein complex.
TL;DR: Data indicate that microarray analysis by itself is useful in describing the effect of well-known substances on the nervous system and provides sufficient information to propose a potentially novel pathway mediating its activity.
Abstract: The long-term response to neurotropic drugs depends on drug-induced neuroplasticity and underlying changes in gene expression. However, alterations in neuronal gene expression can be observed even ...
TL;DR: Improvements in reconstituted NT embryo culture and transfer are required for these methods to be an effective means of transgenic rat production.
Abstract: The present study examines the handling, activation, and micromanipulation of rat eggs in an attempt to produce live young using nuclear transfer (NT) of adult and genetically modified rat fetal ce...
TL;DR: The cellular response to mitochondrial damage and metabolic stress may reflect an adaptive process for mitochondrial repair in pancreatic acinar cells during chronic ethanol ingestion.
Abstract: Individuals with chronic excessive alcohol ingestion are put at the risk of acute and chronic pancreatitis. Underlying molecular mechanisms are unknown. Differential gene expression in the pancreas...