Biomedical subjects

Anne Glass

Publications and source records attributed to Anne Glass.

12 recordsLinked to original sources

PubMed2006

Inhibitory effects of interferon-gamma on activation of rat pancreatic stellate cells are mediated by STAT1 and involve down-regulation of CTGF expression.

Pancreatic stellate cells (PSCs) are the main source of extracellular matrix proteins in pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Interferon-gamma (IFN-gamma) is an antifibrotic cytokine, but how precisely it exerts its effects on PSCs is largely unknown. Here, we have focussed on the role of STAT1 as well as target genes of IFN-gamma signalling. Our data indicate that IFN-gamma regulates the expression of two autocrine mediators of PSC activation, connective tissue growth factor and endothelin-1, in a transforming growth factor-beta1-antagonistic manner. STAT1 overexpression under the control of a tetracycline-dependent promoter revealed a close correlation between STAT1 expression and activation, the biological effects of IFN-gamma (growth inhibition, induction of apoptosis), and target gene expression. Our data further support the hypothesis that IFN-gamma interferes with stellate cell activation in the pancreas and suggest activated STAT1 as an inductor of a quiescent PSC phenotype.

Animals↗

PubMed2006

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Atorvastatin mediated effects depend on the activation status of target cells in PLP-EAE.

The effect of Atorvastatin on transcriptional activity in murine experimental autoimmune encephalomyelitis (EAE) induced by PLP peptide 139-151 was analyzed by DNA microarray technique in lymph nodes and spinal cord at onset (10 days), height (20 days) and first remission (30 days) of disease. Fourteen genes were selectively influenced by Atorvastatin in EAE mice. They are mainly related to immune cell functions and regulation of cell-to-cell interaction. Interestingly, seven genes were also differentially regulated in CFA-injected control mice. But qualitative and quantitative differences to EAE mice argue for a dependency of statin effects on the activation status of target cells. Differential regulation of the newly detected candidate genes of statin effects COX-1 and HSP-105 and the previously known statin-responsive genes ICAM-1 and CD86 was confirmed by Western blot and immunohistochemistry. Flow cytometric analysis of lymph node cells revealed that the effect of Atorvastatin treatment in non-immunized healthy animals resembled the effect of immunization with PLP peptide regarding changes of T helper cells, activated B cells and macrophages. In EAE mice, these effects were partially reversed by Atorvastatin treatment. Monitoring of expression of the newly identified candidate genes and patterns of lymphocyte subpopulations might predict the responsiveness of multiple sclerosis patients to statin treatment.

Animals↗

PubMed2006

The Autoimmune Disease Database: a dynamically compiled literature-derived database.

BACKGROUND: Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes or the involvement of common genes. To gain an overview of these related diseases it is not feasible to do a literary review but it requires methods of automated analyses of the more than 500,000 Medline documents related to autoimmune disorders. RESULTS: In this paper we present the first version of the Autoimmune Disease Database which to our knowledge is the first comprehensive literature-based database covering all known or suspected autoimmune diseases. This dynamically compiled database allows researchers to link autoimmune diseases to the candidate genes or proteins through the use of named entity recognition which identifies genes/proteins in the corresponding Medline abstracts. The Autoimmune Disease Database covers 103 autoimmune disease concepts. This list was expanded to include synonyms and spelling variants yielding a list of over 1,200 disease names. The current version of the database provides links to 541,690 abstracts and over 5,000 unique genes/proteins. CONCLUSION: The Autoimmune Disease Database provides the researcher with a tool to navigate potential gene-disease relationships in Medline abstracts in the context of autoimmune diseases.

Autoimmune Diseases↗

PubMed2006

Delayed response toward activation stimuli in pancreatic stellate cells.

OBJECTIVES: Pancreatic stellate cells (PSCs) are known to be crucially involved in the development of pancreatic fibrosis, a characteristic feature of chronic pancreatitis and pancreatic cancer. The key event in the pathogenesis of fibrosis represents a transition process of quiescent PSCs into a myofibroblastlike phenotype associated with cell activation in terms of proliferation and synthesis of profibrogenic substances. There is little information available regarding the dynamics of the complex processes initiated by an activating stimulus in quiescent stellate cells. METHODS: Using microarray analysis, we characterized the expression profiles during PSC activation caused by in vitro cultivation on days 2, 4, 7, and 14 after cell isolation. Activation status has been identified by the expression of the activation marker alpha-smooth muscle actin. Genes of interest were subjected to reverse transcription-polymerase chain reaction. To test biologic functions, the responsiveness of stellate cells toward the activators activin A and transforming growth factor-beta1 was investigated in dependence on the cell transition status. RESULTS: Our results revealed that freshly isolated (=quiescent) PSCs were refractory to stimuli for several days, a phenomenon that we referred to as delay phase. CONCLUSION: The retarded response could be considered a protection mechanism to prevent inappropriate stellate cell activation.

Animals↗

PubMed2005

Inhibition of lymphocyte apoptosis by pancreatic stellate cells: impact of interleukin-15.

There is growing evidence that pancreatic stellate cells (PSCs) produce cytokines and take part in the regulation of inflammatory processes in the pancreas. IL-15 inhibits apoptosis of various cell populations. This study was performed to investigate whether PSCs produce IL-15 and thereby can affect lymphocytes. Primary PSCs were isolated from the rat pancreas using density gradient centrifugation. mRNA expression of IL-15 was demonstrated by RT-PCR, and IL-15 protein was analyzed by immunoblotting. Lymphocytes obtained from rat mesenterial lymph nodes were cocultured with in vitro activated PSCs. Apoptosis has been quantified by the binding of annexin V-FITC with a flow cytometer. Proliferation was monitored using [3H]thymidine incorporation. PSCs express two splice variants of IL-15. The protein was detectable only in cell lysates but not in the cell culture supernatant. Cocultivation of lymphocytes with PSCs and IL-15 inhibited spontaneous lymphocyte apoptosis, and this effect was reduced by an anti-IL-15 antibody. Lymphocytes induced vice versa the proliferation and collagen production of PSCs. The inhibition of spontaneous lymphocyte apoptosis in cocultures with PSCs was at least partially mediated by cell-bound IL-15. This effect and the stimulation of PSCs by lymphocytes may lead to a circulus vitiosus, resulting in the persistence of inflammatory processes and the development of fibrosis during chronic pancreatitis.

Animals↗

PubMed2005

Representation of individual gene expression in completely pooled mRNA samples.

Designing microarray experiments, scientists are often confronted with the question of pooling due to financial constraints, but discussion of the validity of pooling tends toward a sub-pooling recommendation. Since complete pooling protocols can be considered part of sub-pooling designs, gene expression data from three complete pooling experiments were analyzed. Data from complete pooled versus individual mRNA samples of rat brain tissue were compared to answer the question whether the pooled sample represents individual samples in small-sized experiments. Our analytic approach provided clear results concerning the Affymetrix MAS 5.0 signal and detection call parameters. Despite a strong similarity of arrays within experimental groups, the individual signals were evidently not appropriately represented in the pooled sample, with slightly more than half of all the genes considered. Our analysis reveals problems in cases of small complete pooling designs with less than six subjects pooled.

Animals↗

PubMed2004

Generation and characterization of immortalized rat pancreatic stellate cells.

Pancreatic stellate cells (PSCs) are involved in, among other things, the pathogenesis of pancreatic fibrosis. Here, we present the generation of immortalized PSCs 7 and 14 days after isolation by retroviral gene transfer of the SV40 large T antigen encoding region. Propagated cell lines [large T immortalized cells (LTC)-7, LTC-14] retained characteristics of primary cells in terms of morphology, responsiveness to mediators regulating cellular functions such as proliferation, and expression profile of a number of investigated genes. Whereas LTC-14 kept the morphological features of the differentiation status of the primary cells they were made of, LTC-7 appeared similar to an earlier stage. Thus the established cell lines represent a versatile tool to investigate various aspects of PSC biology.

Animals↗

PubMed2004

Automatic construction of gene relation networks using text mining and gene expression data.

Microarray gene expression analysis is a powerful high-throughput technique that enables researchers to monitor the expression of thousands of genes simultaneously. Using this methodology huge amounts of data are produced which have to be analysed. Clustering algorithms are used to group genes together based on a predefined distance measure. However, clustering algorithms do not necessarily group the genes in a biological meaningful way. Additional information is needed to improve the identification of disease relevant genes. The primary objective of our project is to support the analysis of microarray gene expression data by construction of gene relation networks (GRNs). Required information can not be found in a structured representation like a database. In contrast, a large number of relations are described in biomedical literature. The main outcome of this project is the implementation of a software system that provides clinicians and researchers with a tool that supports the analysis of microarray gene expression data by mapping known relationships from the biomedical literature to local gene expression experiments.

Abbreviations as Topic↗

PubMed2003

[No influence of urinary nitrate excretion on the goitre prevalence in Germany].

BACKGROUND: It has long been known that nitrate combined with iodiduria < 100 micro gI(-)/l has a goitrogenic effect. The cause is a partial blockage of the sodium- iodide symporter together with a hindrance to iodide absorption in the intestine. 90% of the intake of nitrate is excreted in urine. Therefore nitraturia provides information about the population. The rare epidemiological studies of the influence of NO(3)(-) on goitre are limited to a small selection of older, regional samples. Our aim was to investigate the role of nitrate in the occurrence of goitre in Germany. METHODS: Using random samples from 3,059 clinically healthy persons of both sexes between 18 and 70 years old from all over Germany, we examined nitraturia and the prevalence of goitre or nodules, including the corresponding iodiduria. (Sonography: 7.5 MHz linear transducer; nitrate determination: isocratic ion chromatography; iodide determination: cerium-arsenite method.) Both the NO(3)(-) and the iodide excretion in spontaneous urine were measured in relation to 1 g creatinine. Statistical processing: Mann-Whitney U-Test, correlation analysis, multivariate linear regression analysis. RESULTS: Median for nitraturia: 55.2 mg NO(3)(-)/g creatinine (men 61.5, women 51.5; p < 0.03). Significant increase in regional nitrate excretion from North to South and from East to West. No statistical connection between nitraturia, thyroid size and nodules. In the multivariate linear regression analysis relating to thyroid size/focal lesions, NO(3)(-) played the smallest part among the variables age, gender, body mass index, iodiduria, nitraturia. In the case of iodiduria with < 50 micro g I(-)/g creatinine (n = 71), there was a correlation between nitraturia and thyroid size (r = 0.18; p < 0.05). All persons with a nitraturia of > 60 mg NO(3)(-)/g creatinine (n = 1,166) evidenced a correlation with the thyroid size (r = 0.18; p < 0.01). CONCLUSION: Since alimentary iodine shortage in Germany has been overcome to a large extent (iodiduria 100-200 micro gI(-)/l) and the nitrate content lies clearly below the WHO limit, the goitrogenic effect of nitrate is only of individual and not of epidemiological importance. The slight regional differences in NO(3)(-) excretion are the consequence of the nitrate content in drinking water and have no effect on the thyroid gland.

Adolescent↗

PubMed2003

Influence of two Wolbachia strains on population structure of East African Drosophila simulans.

Drosophila simulans is hypothesized to have originated in continental East Africa or Madagascar. In this study, we investigated evolutionary forces operating on mitochondrial DNA (mtDNA) in populations of D. simulans from Zimbabwe, Malawi, Tanzania, and Kenya. Variation in mtDNA may be affected by positive selection, background selection, demographic history, and/or any maternally inherited factor such as the bacterial symbiont Wolbachia. In East Africa, the wRi and wMa Wolbachia strains associate with the siII or siIII mitochondrial haplogroups, respectively. To ask how polymorphism relates to Wolbachia infection status, we sequenced 1776 bp of mitochondrial DNA and 1029 bp of the X-linked per locus from 79 lines. The two southern populations were infected with wRi and exhibited significantly reduced mtDNA variation, while Wolbachia-uninfected siII flies from Tanzania and Kenya showed high levels of mtDNA polymorphism. These are the first known populations of D. simulans that do not exhibit reduced mtDNA variation. We observed no mitochondrial variation in the siIII haplogroup regardless of Wolbachia infection status, suggesting positive or background selection. These populations offer a unique opportunity to monitor evolutionary dynamics in ancestral populations that harbor multiple strains of Wolbachia.

Africa, Eastern↗

PubMed2002

A system architecture for genomic data analysis.

MOTIVATION: Most of diseases are caused by a set of gene defects, which occur in a complex association. The association scheme of expressed genes can be modelled by genetic networks. Genetic networks are efficiently facilities to understand the dynamic of pathogenic processes by modelling molecular reality of cell conditions. In this sense a genetic network consists of first, a set of genes of specified cells, tissues or species and second, causal relations between these genes determining the functional condition of the biological system, i. e. under disease. A relation between two genes will exist if they both are directly or indirectly associated with disease [8]. Our goal is to characterize diseases (especially autoimmune diseases like chronic pancreatitis CP, multiple sclerosis MS, rheumatoid arthritis RA) by genetic networks generated by a computer system. We want to introduce this practice as a bioinformatic approach for finding targets.

Genetic Predisposition to Disease↗

PubMedDate not supplied

Peroxisome proliferator-activated receptor gamma overexpression inhibits pro-fibrogenic activities of immortalised rat pancreatic stellate cells.

Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis, a constant feature of chronic pancreatitis and pancreatic cancer. In response to pro-fibrogenic mediators, PSCs undergo an activation process that involves proliferation, enhanced production of extracellular matrix proteins and a phenotypic transition towards myofibroblasts. Ligands of the peroxisome proliferator-activated receptor gamma (PPARgamma), such as thiazolidinediones, are potent inhibitors of stellate cell activation and fibrogenesis in pancreas and liver. The effects of PPARgamma ligands, however, are at least in part mediated through PPARgamma-independent pathways. Here, we have chosen a different approach to study regulatory functions of PPARgamma in PSCs. Using immortalised rat PSCs, we have established a model of tetracycline (tet)-regulated PPARgamma overexpression. Induction of PPARgamma expression strongly inhibited proliferation and enhanced the rate of apoptotic cell death. Furthermore, PPARgamma-overexpressing cells synthesised less collagen than controls. To monitor effects of PPARgamma on PSC gene expression, we employed Affymetrix microarray technology. Using stringent selection criteria, we identified 21 up- and 19 down-regulated genes in PPARgamma-overexpressing cells. Most of the corresponding gene products are either involved in lipid metabolism, play a role in signal transduction, or are secreted molecules that regulate cell growth and differentiation. In conclusion, our data suggest an active role of PPARgamma in the induction of a quiescent PSC phenotype. PPARgamma-regulated genes in PSCs may serve as novel targets for the development of antifibrotic therapies.

Animals↗