Biomedical subjects

Karen Schlauch

Publications and source records attributed to Karen Schlauch.

9 recordsLinked to original sources

PubMed2006

Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

BACKGROUND: Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. METHODS: Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). RESULTS: Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). CONCLUSIONS: Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

Adult↗

PubMed2005

The zinc-finger protein Zat12 plays a central role in reactive oxygen and abiotic stress signaling in Arabidopsis.

Plant acclimation to environmental stress is controlled by a complex network of regulatory genes that compose distinct stress-response regulons. In contrast to many signaling and regulatory genes that are stress specific, the zinc-finger protein Zat12 responds to a large number of biotic and abiotic stresses. Zat12 is thought to be involved in cold and oxidative stress signaling in Arabidopsis (Arabidopsis thaliana); however, its mode of action and regulation are largely unknown. Using a fusion between the Zat12 promoter and the reporter gene luciferase, we demonstrate that Zat12 expression is activated at the transcriptional level during different abiotic stresses and in response to a wound-induced systemic signal. Using Zat12 gain- and loss-of-function lines, we assign a function for Zat12 during oxidative, osmotic, salinity, high light, and heat stresses. Transcriptional profiling of Zat12-overexpressing plants and wild-type plants subjected to H(2)O(2) stress revealed that constitutive expression of Zat12 in Arabidopsis results in the enhanced expression of oxidative- and light stress-response transcripts. Under specific growth conditions, Zat12 may therefore regulate a collection of transcripts involved in the response of Arabidopsis to high light and oxidative stress. Our results suggest that Zat12 plays a central role in reactive oxygen and abiotic stress signaling in Arabidopsis.

Arabidopsis↗

PubMed2005

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse-transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention.

Adult↗

PubMed2005

Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non-alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized. AIM: This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics. DESIGN: Consecutive patients undergoing bariatric surgery were prospectively recruited. Extensive clinical data and two liver biopsy specimens were obtained at the time of enrollment. A single hepatopathologist reviewed and classified the liver biopsies. Patients with excessive alcohol use and other causes of liver disease were excluded. A group of 29 NASH patients, 12 with steatosis alone, seven obese controls and six non-obese controls were selected for further investigation. Customized cDNA microarrays containing 5220 relevant genes were designed specifically for this study. Microarray experiments were run in triplicate for each sample and a selected group of genes were confirmed using real-time PCR. OUTCOME MEASURE: Differential hepatic gene expressions in patients with NASH as compared with controls. RESULTS: Thirty-four genes with significant differential expression were identified in patients with NASH when compared with non-obese controls. Moreover, 19 of these genes showed no significant expression differences in obese vs. non-obese controls, suggesting a stronger association of these genes to NASH. CONCLUSIONS: Several differentially expressed genes in patients with NASH are related to lipid metabolism and extracellular matrix remodeling. Additionally, genes related to liver regeneration, apoptosis, and the detoxification process were differentially expressed. These findings may help clarify the molecular pathogenesis of NASH and identify potential targets for therapeutic intervention.

Adult↗

PubMed2005

Microarray technology in the study of obesity and non-alcoholic fatty liver disease.

The recent development of high-throughput gene expression technology permits simultaneous investigation of thousands of genes, providing a snapshot of the transcription state of diseased tissue. Microarray-based expression profiling is well suited to investigate the molecular basis of complex diseases such as obesity and chronic liver disease. With the help of microarray technology, functional genomics will surely advance our understanding of these diseases, and lead to more effective, targeted interventions that lack the toxicity of many conventional treatments. Despite their tremendous potential, microarray studies are subject to potential flaws in experimental design, experimental techniques, data analysis, and data interpretation. Besides the technical issues, the most important challenge is to develop integrative databases that combine gene expression data with the clinical data. Over the next few years, advances in technology and refinements in study design and data analysis will make clinically relevant translational research even more engaging and productive.

Fatty Liver↗

PubMed2004

Cytosolic ascorbate peroxidase 1 is a central component of the reactive oxygen gene network of Arabidopsis.

Reactive oxygen species (ROS), such as O2- and H2O2, play a key role in plant metabolism, cellular signaling, and defense. In leaf cells, the chloroplast is considered to be a focal point of ROS metabolism. It is a major producer of O2- and H2O2 during photosynthesis, and it contains a large array of ROS-scavenging mechanisms that have been extensively studied. By contrast, the function of the cytosolic ROS-scavenging mechanisms of leaf cells is largely unknown. In this study, we demonstrate that in the absence of the cytosolic H2O2-scavenging enzyme ascorbate peroxidase 1 (APX1), the entire chloroplastic H2O2-scavenging system of Arabidopsis thaliana collapses, H2O2 levels increase, and protein oxidation occurs. We further identify specific proteins oxidized in APX1-deficient plants and characterize the signaling events that ensue in knockout-Apx1 plants in response to a moderate level of light stress. Using a dominant-negative approach, we demonstrate that heat shock transcription factors play a central role in the early sensing of H2O2 stress in plants. Using knockout plants for the NADPH oxidase D protein (knockout-RbohD), we demonstrate that RbohD might be required for ROS signal amplification during light stress. Our study points to a key role for the cytosol in protecting the chloroplast during light stress and provides evidence for cross-compartment protection of thylakoid and stromal/mitochondrial APXs by cytosolic APX1.

Arabidopsis↗

PubMed2004

GeneX Va: VBC open source microarray database and analysis software.

Developed by the Virginia Bioinformatics Consortium (VBC), GeneX Va is an open source, freeware database and bioinformatics analysis software for archiving and analyzing Affymetrix GeneChip data. It provides an integrated framework for management, documentation, and analysis of microarray experiments and data to support a range of users, from individual research laboratories to institutional microarray facilities. GeneX Va also provides web-based access to a PostgreSQL relational database system with a comprehensive security system. Data can be extracted from the database and delivered to interactive or scriptable statistical analysis protocols. The security system allows each investigator to manage their own array data and analysis output files and also provides custom access privileges for other users, groups, and internal/external collaborators. The analysis interface uses "Analysis Trees," an innovative user interface that allows researchers to interactively create a tree-structured flow chart of analysis routines. The latest GeneX Va software is available from and can be freely downloaded at the Sourceforge web site http://va-genex.sourceforge.net. To allow researchers to access the database and analysis capabilities of the GeneX Va system, microarray data from many VBC GeneChip experiments have been deposited into a public section of the GeneX Va system at the University of Virginia. The VBC GeneX Va sites, which include documentation, are at http://genes.med.virginia.edu/ of the University of Virginia and at http://genex.csbc.vcu.edu/ of the Virginia Commonwealth University.

Computer Security↗

PubMed2003

Distinct organization of the candidate tumor suppressor gene RFP2 in human and mouse: multiple mRNA isoforms in both species- and human-specific antisense transcript RFP2OS.

In the present study, we describe the human and mouse RFP2 gene structure, multiple RFP2 mRNA isoforms in the two species that have different 5' UTRs and a human-specific antisense transcript RFP2OS. Since the human RFP2 5' UTR is not conserved in mouse, these findings might indicate a different regulation of RFP2 in the two species. The predicted human and mouse RFP2 proteins are shown to contain a tripartite RING finger-B-box-coiled-coil domain (RBCC), also known as a TRIM domain, and therefore belong to a subgroup of RING finger proteins that are often involved in developmental and tumorigenic processes. Because homozygous deletions of chromosomal region 13q14.3 are found in a number of malignancies, including chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), we suggest that RFP2 might be involved in tumor development. This study provides necessary information for evaluation of the role of RFP2 in malignant transformation and other biological processes.

Alternative Splicing↗

PubMedDate not supplied

Obesity-related differential gene expression in the visceral adipose tissue.

BACKGROUND: This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis. METHODS: Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR. RESULTS: A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers. CONCLUSION: Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.

Adipose Tissue↗