SEARCH · PubMed Health

Results for “Tissue Array Analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources

PubMed2001

DNA array analysis of changes in preovulatory gene expression in the rat ovary.

During the periovulatory period, the mammalian ovary is the site of dramatic functional and structural changes, leading to oocyte maturation, follicle rupture, and corpus luteum formation. To a large extent, these processes result from changes in the transcriptome of various ovarian cell types. To develop a broader view of periovulatory changes in gene expression in the ovary and to identify further genes involved in periovulatory events, we used the recently developed DNA array technology. Immature female eCG-primed rats were killed either immediately before or 6 h after ovulation induction with hCG. Total ovarian RNA was isolated and used to prepare radiolabeled cDNA probes, which were hybridized to DNA arrays representing approximately 600 rat genes. Quantitative analysis identified a multitude of regulated gene messages, including several genes involved in extracellular matrix degradation and lipid/steroid metabolism previously reported to be induced by hCG. This screening also identified a group of candidate genes whose ovarian expression and gonadotropin regulation was hitherto unknown. The induction of three of these genes, encoding cutaneous fatty acid-binding protein, the interleukin-4 receptor alpha chain, and prepronociceptin, was confirmed and further characterized by Northern blot analysis. In addition, in situ hybridization analysis showed that hCG administration resulted in exclusive or predominant expression of all three genes in theca cells. These results demonstrate that DNA arrays can be used to identify genes regulated during the periovulatory period, thus contributing to a more detailed understanding of the molecular mechanisms of ovulation.

Animals↗

PubMed2006

Cell-type-specific signatures of microRNAs on target mRNA expression.

Although it is known that the human genome contains hundreds of microRNA (miRNA) genes and that each miRNA can regulate a large number of mRNA targets, the overall effect of miRNAs on mRNA tissue profiles has not been systematically elucidated. Here, we show that predicted human mRNA targets of several highly tissue-specific miRNAs are typically expressed in the same tissue as the miRNA but at significantly lower levels than in tissues where the miRNA is not present. Conversely, highly expressed genes are often enriched in mRNAs that do not have the recognition motifs for the miRNAs expressed in these tissues. Together, our data support the hypothesis that miRNA expression broadly contributes to tissue specificity of mRNA expression in many human tissues. Based on these insights, we apply a computational tool to directly correlate 3' UTR motifs with changes in mRNA levels upon miRNA overexpression or knockdown. We show that this tool can identify functionally important 3' UTR motifs without cross-species comparison.

3' Untranslated Regions↗

PubMed2005

Allelic imbalance analysis of oral tongue squamous cell carcinoma by high-density single nucleotide polymorphism arrays using whole-genome amplified DNA.

Multiple displacement-based whole-genome DNA amplification is a promising tool to obtain sufficient DNA from small tissue specimens for various genetic analyses, such as SNP array-based analysis. Using Affymetrix 10 K and 100 K SNP mapping array, we evaluated the performance of the Phi29 DNA polymerase-based genome amplification. Greater than 99% concordance in genotyping calls were achieved between amplified and non-amplified DNAs for both arrays. By utilizing the Affymetrix GeneChip Chromosome Copy Number Tool, the allelic imbalance profiles for the advanced stage oral tongue squamous cell carcinoma (OTSCC) were generated based on 10 K and 100 K SNP mapping array results. The results from these two array platforms agree closely, but more precise allelic imbalance patterns can be revealed from the 100 K SNP mapping array data. Furthermore, our data suggested a frequent loss at 3p11-p12 for advanced stage OTSCC.

Allelic Imbalance↗

PubMed2001

N-methyl-D-aspartate receptors regulate a group of transiently expressed genes in the developing brain.

Mammalian brain development requires the transmission of electrical signals between neurons via the N-methyl-d-aspartate (NMDA) class of glutamate receptors. However, little is known about how NMDA receptors carry out this role. Here we report the first genes shown to be regulated by physiological levels of NMDA receptor function in developing neurons in vivo: NMDA receptor-regulated gene 1 (NARG1), NARG2, and NARG3. These genes share several striking regulatory features. All three are expressed at high levels in the neonatal brain in regions of neuronal proliferation and migration, are dramatically down-regulated during early postnatal development, and are down-regulated by NMDA receptor function. NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a yeast N-terminal acetyltransferase that regulates entry into the G(o) phase of the cell cycle. The results suggest that highly specific NMDA receptor-dependent regulation of gene expression plays an important role in the transition from proliferation of neuronal precursors to differentiation of neurons.

Acetyltransferases↗

PubMed2003

Protein expression changes in spinal muscular atrophy revealed with a novel antibody array technology.

Autosomal recessive proximal spinal muscular atrophy (SMA) is a severe neurodegenerative disease of childhood causing weakness and wasting secondary to motor neuron dysfunction. Over 97% of cases are caused by deletions or mutations within the survival motor neuron (SMN) gene. The SMN protein is highly expressed within brain, spinal cord and muscle, and is decreased in SMA patients. It has been shown to have an important role in RNA metabolism, but the reason for the specific motor neuron loss is still unclear. We have used a novel antibody array technology to look for differences in the expression patterns of primary muscle cultures from a type II SMA patient and a normal control. A relatively small number of differences were found within a group of proteins that function as both RNA binding proteins and transcription factors. Interactions between a number of these proteins are well established, and three of them bind in turn to p53 which interacts with SMN. A number of the changes were confirmed with western blot analysis both in the primary muscle cultures and in skeletal muscle samples from SMA patients and controls. Changes at the mRNA level were also confirmed with oligonucleotide arrays. These results suggest that a common transcription pathway may be altered in the disease state, and suggests that down-regulation of transcription factors contributes to SMA pathogenesis.

Adolescent↗

PubMed2006

Connexin43 and the brain transcriptome of newborn mice.

Our previously reported cDNA array datasets from neonatal wild-type and Cx43-/- (approved gene symbol Gja1) mouse brains were further analyzed to identify underlying interlinkages in the brain transcriptome. The analysis revealed that no gene cohort sharing either primary function or chromosomal location was significantly altered (up-and down-regulation were roughly balanced) in Cx43-/- brains, but each cohort exhibited significant perturbation of transcript abundance proportions and reduced expression variability and coordination. By comparing pairwise expression correlations of all genes with one another in wild-type brains, we found genes exhibiting remarkable similarity or opposition to the coordination profile (set of synergistically, antagonistically, and independently expressed partners) of Cx43, one of the most similar being pannexin1, a vertebrate homolog of invertebrate gap junction proteins. This study indicates striking redundancy of expression controls over functional pathways and suggests that certain genes may play roles similar to or opposite that of Cx43 in organizing the brain transcriptome.

Animals↗

PubMed2002

Effect of immunosuppression on gene expression in the HSV-1 latently infected mouse trigeminal ganglion.

PURPOSE: To determine alterations in expression of genes in herpes simples virus (HSV)-1 latently infected mouse trigeminal ganglia (TGs), after treatment with cyclophosphamide and dexamethasone. METHODS: Scarified corneas of female BALB/c mice were inoculated with HSV-1 strain McKrae. Four weeks after inoculation, cyclophosphamide and dexamethasone were intravenously injected to induce HSV-1 reactivation. Uninfected mice were also treated with the immunosuppressants. Four groups of animals were studied: uninfected, not treated; uninfected, drug treated; latently infected, not treated; and latently infected, drug treated. PolyA+ mRNA from the TGs of each group was reverse transcribed, labeled with 32P, incubated on a 1185-gene array membrane, and analyzed by phosphorimaging. As a comparison and to confirm microarray results, semiquantitative RT-PCR was also performed for selected genes. RESULTS: The immunosuppressive drugs significantly increased expression of two genes (calpactin 1 light chain and guanine nucleotide-binding protein alpha-stimulating polypeptide [GNAS]) in the ganglia of uninfected mice compared with those in untreated uninfected mice. Ten genes were shown to be significantly increased in the latent TGs of mice treated with immunosuppressants compared with latently infected untreated mice. These genes were prostaglandin E2 receptor EP4 subtype (PTGER4), insulin promoter factor 1 (IPF1), glutathione S-transferase mu2, cyclin D2, peripherin, plasma glutathione peroxidase, methyl CpG-binding protein 2, retinal S-antigen, ErbB2 proto-oncogene, and GNAS. Eight genes were shown to be significantly decreased in the HSV-1 latent TGs treated with the drugs, compared with untreated latently infected mice. These genes were peripheral myelin protein 22, decorin, transcription factor AP-1, dystroglycan 1, myelin protein zero, mitogen-activated protein kinase 3, prothymosin beta 4, and brain lipid-binding protein. The results obtained by semiquantitative RT-PCR were similar to those obtained by microarray analysis. CONCLUSIONS: Those genes with expression altered by immunosuppressive drug treatment may play an important role in ocular HSV-1 recurrence. Changes in expression of genes in the prostaglandin pathway, a transcription factor, and an enzyme in the cell cycle are considered especially important in HSV-1 reactivation by immunosuppression and are reviewed.

Animals↗

PubMed1993

Evaluation of structural change in diffuse liver disease with frequency domain analysis of ultrasound.

To evaluate structural changes in diffuse liver disease, frequency domain analysis was applied to ultrasonic signals from the liver. We assumed that liver tissue is a collection of semiregularly arrayed small scatterers of ultrasound. We applied cepstral analysis to the ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum caused by an interference effect among liver scatterers of a given spacing. Patients with liver conditions involving nonspecific change (n = 6), chronic hepatitis (n = 11), cirrhosis (n = 7) or fatty liver (n = 6) were examined. One hundred ultrasonic signals were obtained noninvasively with a 3.5-MHz transducer, and the space among scatterers was calculated for each signal using cepstrum analysis. Two statistical parameters, mode and kurtosis, were determined from the distribution of the space among scatterers for each patient; these parameters were compared with the histological findings in the liver. Space among scatterers kurtosis decreased with progress of liver fibrosis, and space among scatterers mode increased in cirrhosis. Neither space among scatterers kurtosis nor space among scatterers mode was affected by pathological fat in the liver. These results suggest that we can evaluate fibrotic changes in diffuse liver disease and that we can also noninvasively discriminate diffuse fibrotic liver disease from fatty liver.

Chronic Disease↗

PubMed2002

Gene expression in colorectal cancer.

Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226 known genes and 157 ESTs were found to be highly relevant for CRC. The alteration of known genes was confirmed in >70% of the cases by array analysis of 25 single samples. Two-way hierarchical average linkage cluster analysis clustered normal tissue together with Dukes' A, clustered Dukes' B with Dukes' C, and clustered Dukes' D separately. Real-time PCR of 10 known genes and 5 ESTs demonstrated excellent reproducibility of the array-based findings. The most frequently altered genes belonged to functional categories of metabolism (22%), transcription and translation (11%), and cellular processes (9%). Fifteen nuclear encoded mitochondrial proteins were all down-regulated in CRC. We identified several chromosomal locations with clusters of either potential oncogenes or potential tumor suppressors. Some of these, such as aminopeptidase N/CD13 and sigma B3 protein on chromosome 15q25, coincided with a high frequency of loss of heterozygosity. The genes and ESTs presented in this study encode new potential tumor markers as well as potential novel therapeutic targets for prevention or therapy of CRC.

Biomarkers, Tumor↗

PubMed2003

Identification of gene products suppressed by human immunodeficiency virus type 1 infection or gp120 exposure of primary human astrocytes by rapid subtraction hybridization.

Neurodegeneration and human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are the major disease manifestations of HIV-1 colonization of the central nervous system (CNS). In the brain, HIV-1 replicates in microglial cells and infiltrating macrophages and it persists in a low-productive, noncytolytic state in astrocytes. Astrocytes play critical roles in the maintenance of the brain microenvironment, responses to injury, and in neuronal signal transmission, and disruption of these functions by HIV-1 could contribute to HAD. To better understand the potential effects of HIV-1 on astrocyte biology, the authors investigated changes in gene expression using an efficient and sensitive rapid subtraction hybridization approach, RaSH. Primary human astrocytes were isolated from abortus brain tissue, low-passage cells were infected with HIV-1 or mock infected, and total cellular RNAs were isolated at multiple time points over a period of 1 week. This approach is designed to identify gene products modulated early and late after HIV-1 infection and limits the cloning of genes displaying normal cell-cycle fluctuations in astrocytes. By subtracting temporal cDNAs derived from HIV-1-infected astrocytes from temporal cDNAs made from uninfected cells, 10 genes displaying reduced expression in infected cells, termed astrocyte suppressed genes (ASGs), were identified and their suppression was confirmed by Northern blot hybridization. Both known and novel ASGs, not reported in current DNA databases, that are down-regulated by HIV-1 infection are described. Northern blotting confirms suppression of the same panel of ASGs by treatment of astrocytes with recombinant HIV-1 envelope glycoprotein, gp120. These results extend our previous analysis of astrocyte genes induced or enhanced by HIV-1 infection and together they suggest that HIV-1 and viral proteins have profound effects on astrocyte physiology, which may influence their function in the CNS.

AIDS Dementia Complex↗

PubMed2006

Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer.

The family of roundabout (Robo) proteins is related to the transmembrane receptors and plays a major role in the process of axonal guidance in neurogenesis. It has recently been shown that Robo proteins are also associated with tumor angiogenesis with Slit2 acting as the corresponding ligand. The aim of this study was to validate the differential expression by means of microarray analysis and real-time PCR and to analyze the in situ expression of Robo1 and Robo4 in colorectal cancer. Quantitative analyses of Robo1, Robo4 and Slit2 mRNA expression measured by large scale gene expression studies (Affymetrix U133A) showed a significant up-regulation of Robo1 in tumor vs. normal tissue, whereas Robo4 and Slit2 showed no significant deregulation. For subsequent real-time PCR experiments, paired colorectal tissue samples from cancerous and corresponding non-cancerous tissues were obtained from 50 colorectal cancer patients who underwent surgical resection. Robo1 mRNA overexpression in cancerous tissue compared with normal counterparts was observed in 80% of the patients with a 4-fold expression in 45% and a 12-fold expression in 15%. For Robo4, an up-regulation was detected in >70% (36/50). For Slit2, no differential expression was observed. The overexpression of Robo1 and Robo4 in tumor vs. normal tissue was verified using real-time PCR. The histological analysis revealed an expression of Robo1 mainly in tumor cells, whereas Robo4 is located primarily in endothelial cells of tumor vessels. Therefore, the Robo proteins provide potential target structures for the anti-tumorigenic and anti-angiogenic therapy of colorectal carcinoma.

Adult↗

PubMed2002

Molecular characterisation of soft tissue tumours: a gene expression study.

BACKGROUND: Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers. METHODS: We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition. FINDINGS: Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types. INTERPRETATION: These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.

Gene Expression Profiling↗

PubMed2004

Loss of apolipoprotein E receptor LR11 in Alzheimer disease.

BACKGROUND: Genetic, epidemiologic, and biochemical evidence suggests that apolipoprotein E, low-density lipoprotein receptors, and lipid metabolism play important roles in sporadic Alzheimer disease (AD). OBJECTIVE: To identify novel candidate genes associated with sporadic AD. DESIGN: We performed an unbiased microarray screen for genes differentially expressed in lymphoblasts of patients with sporadic AD and prioritized 1 gene product for further characterization in AD brain. SETTING: Emory University, Atlanta, Ga. SUBJECTS: Cell lines were used from 14 patients with AD and 9 normal human control subjects. RESULTS: Six genes were differentially expressed in lymphoblasts of 2 independent groups of patients with probable AD and autopsy-proven AD. We hypothesized that 1 of the genes, termed low-density lipoprotein receptor relative with 11 binding repeats (LR11) (reduced 1.8- and 2.5-fold in AD lymphoblasts vs controls), might be associated with sporadic AD on the basis of its function as neuronal apolipoprotein E receptor. We found dramatic and consistent loss of immunocytochemical staining for LR11 in histologically normal-appearing neurons in AD brains. This reduction of LR11 protein was confirmed by quantitative Western blotting (P =.01). CONCLUSIONS: There is loss of the microarray-derived candidate, LR11, in neurons of AD brains. This study shows that microarray analysis of widely available lymphoblasts derived from patients with AD holds promise as a primary screen for candidate genes associated with AD.

Adaptor Proteins, Vesicular Transport↗

PubMed2004

Proendocrine genes coordinate the pancreatic islet differentiation program in vitro.

In the developing pancreas, the basic helix-loop-helix (bHLH) protein Neurogenin3 (Ngn3) specifies which precursor cells ultimately will become endocrine cells and initiates the islet differentiation program. NeuroD1, a closely related bHLH protein and a downstream target of Ngn3, maintains the differentiation program initiated by Ngn3. We have developed an in vitro model of Ngn3-dependent differentiation by infecting pancreatic duct cell lines with an Ngn3-expressing adenovirus. We found that both Ngn3 and its downstream target NeuroD1 activated the islet differentiation program in these cells by inducing the expression of genes with early roles in the differentiation cascade, as well as genes characteristic of fully differentiated islet cells. Induction of these genes, as exemplified by the insulin1 gene, involved alteration of the local chromatin structure. Interestingly, the subsets of genes activated by Ngn3 and NeuroD1 were not completely overlapping, indicating that these two bHLH proteins serve specific functions in the development of the endocrine pancreas. In addition, microarray gene expression analysis identified a previously uncharacterized group of Ngn3-induced genes with potentially important roles in islet development and function. These studies demonstrate how Ngn3 initiates islet differentiation and provide us with a model for testing methods for producing islet cells for people with diabetes.

Animals↗

PubMed2006

Bayesian variable selection for gene expression modeling with regulatory motif binding sites in neuroinflammatory events.

Multiple transcription factors (TFs) coordinately control transcriptional regulation of genes in eukaryotes. Although numerous computational methods focus on the identification of individual TF-binding sites (TFBSs), very few consider the interdependence among these sites. In this article, we studied the relationship between TFBSs and microarray gene expression levels using both family-wise and memberspecific motifs, under various combination of regression models with Bayesian variable selection, as well as motif scoring and sharing conditions, in order to account for the coordination complexity of transcription regulation. We proposed a three-step approach to model the relationship. In the first step, we preprocessed microarray data and used p-values and expression ratios to preselect upregulated and downregulated genes. The second step aimed to identify and score individual TFBSs within DNA sequence of each gene. A method based on the degree of similarity and the number of TFBSs was employed to calculate the score of each TFBS in each gene sequence. In the last step, linear regression and probit regression were used to build a predictive model of gene expression outcomes using these TFBSs as predictors. Given a certain number of predictors to be used, a full search of all possible predictor sets is usually combinatorially prohibitive. Therefore, this article considered the Bayesian variable selection for prediction using either of the regression models. The Bayesian variable selection has been applied in the context of gene selection, missing value estimation, and regulatory motif identification. In our modeling, the regressor was approximated as a linear combination of the TFBSs and a Gibbs sampler was employed to find the strongest TFBSs. We applied these regression models with the Bayesian variable selection on spinal cord injury gene expression data set. These TFs demonstrated intricate regulatory roles either as a family or as individual members in neuroinflammatory events. Our analysis can be applied to create plausible hypotheses for combinatorial regulation by TFBSs and avoiding false-positive candidates in the modeling process at the same time. Such a systematic approach provides the possibility to dissect transcription regulation, from a more comprehensive perspective, through which phenotypical events at cellular and tissue levels are moved forward by molecular events at gene transcription and translation levels.

Amino Acid Motifs↗

PubMed2001

The role of eosinophils in asthma: Sarastro or the Queen of the Night?

Eosinophils used to be thought of as regulators of allergic inflammation, but there is now evidence to the contrary; eosinophils have been found to be the major effector cells responsible for the late asthmatic response (LAR), airway hyperresponsiveness (AHR) and, at least in part, airway remodeling by releasing leukotrienes and highly basic and cytotoxic proteins such as major basic protein (MBP). However, a recent clinical trial using humanized anti-interleukin-5 monoclonal antibody found a failure to reduce AHR and the LAR, whereas the antibody entirely abolished tissue eosinophilia. In addition, abundant MBP has recently been found in mast cells as well as in eosinophils by our transcriptome (the whole transcripts that a cell expresses) screening of all leukocyte types. Eosinophils are indeed unlikely to be involved in the LAR and may not be unique cytotoxic cells in asthma. It is now necessary to determine the real role of eosinophils and whether early intervention to block eosinophil recruitment into the asthmatic lung does prevent airway remodeling and AHR.

Asthma↗

PubMed2002

Memory-specific temporal profiles of gene expression in the hippocampus.

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, they did not uncover the collective behaviors or patterns of the genes. We have used genome-scale screening to analyze gene expression during spatial learning of rats in the Morris water maze. Our results show distinct temporal gene expression profiles associated with learning and memory. Exogenous administration of one peptide whose sustained increase during memory retention was implicated by microarray analysis, fibroblast growth factor (FGF)-18, improved spatial learning behavior, suggesting that pharmacological modulation of pathways and targets identified may allow new therapeutic approaches for improving learning and memory. Results of this study also suggest that while learning and physical activity involve common groups of genes, the behavior of learning and memory emerges from unique patterns of gene expression across time.

Animals↗

PubMed2004

Nxf and Fbxo33: novel seizure-responsive genes in mice.

Much is understood about the response of the brain to seizure but little is known in relation to the underlying molecular mechanisms involved. We used microarray technology to investigate the complex genetic response of the brain to generalized seizure. For this investigation a seizure-specific mouse brain cDNA library was generated and spotted onto microarray slides with the aim of increasing the likelihood of identifying novel genes responsive to seizure. Microarray analysis was performed on mouse hippocampus 1 h after generalized seizure pharmacologically induced by pentylenetetrazol (PTZ). Using the custom microarray slides, six genes were identified as being up-regulated in this seizure model and results were validated by real-time PCR. Four of the seizure-responsive genes had previously-reported roles in apoptosis, proliferation or differentiation of neural cells. Two of the genes were novel and in situ hybridization analysis demonstrated heightened mRNA expression in the hippocampus 1 h following generalized convulsive seizure, in a pattern which is typical for other activity-dependant genes expressed in this structure. In addition to being up-regulated postseizure, the genes described in this paper appear to be expressed normally in the adult hippocampus and during development.

Animals↗