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Biomedical subjects

T Werner

Publications and source records attributed to T Werner.

At least 19 recordsLinked to original sources
PubMed2003

[Teleteaching in otorhinolaryngology (part 1). Real-time transmission of a congress in picture and tone into the Internet].

The transmission of scientific seminars into the Internet represents a new application of modern technologies for teleteaching. We digitally recorded 74 seminars and discussions during the 8th annual meeting of the German Society of Skull Base Surgery with five cameras and eight microphones, and transformed the data live with the real-Producer using a video card.This transferred data stream was sent via ISDN (128 kbit/s) to a real-server at the university, which was used for distribution in the net. The seminars could be called up in the display format of 320x240 pixels with a delay of 3 min (minimum: 30 s, as a function of the connection of the user) at each computer with Internet entrance. Altogether,we registered 3,284 accesses to the presentations following the congress until June 2002. The quality of picture transmission (24-36 kbit/s) and the quality of tone (audio stream: 5 kbit/s) were sufficient to understand the contents of the slide, video or computer presentation. The transmission of scientific meetings into the Internet can increase, with a justifiable technical expenditure, their efficiency by the ubiquitous availability of the information and the extension of the audience.

Computer Systems↗
PubMed2003

[Teleteaching in otorhinolaryngology. Part 2: the European database "medicstream"].

Searching the medical literature is mainly characterized by the use of databases. The time for reviewing and printing a paper causes a delay between the first presentation of scientific results in a lecture and the appearance of the appropriate journal publication. Moreover, the possibilities for the integration of multimedia data are limited. Because of the development of new compression algorithms for audiovisual digitization software, the near simultaneous transmission of scientific presentations, both visually and aurally, has been possible since 1999. The section telemedicine of the interdisciplinary study group on image guided surgical navigation from the University of Leipzig has developed "medicstream" as a unique, audiovisual, scientific internetdatabase. It allows the documentation of presentations at congresses and courses, including the discussion,over a freely accessible, widely available homepage, using a home developed streaming technology. All presentations are examined by an authorized editorial committee consisting of representatives with different medical specializations for content before the admission to the data base. A total of 392 presentations from seven scientific meetings can be selected by an integrated search machine and viewed with Windows Media Player or Real Player using a conventional or faster internet connection to the homepage www.medicstream.de. The quality of the audiovisual transmission depends on the receiver-lateral data transmission rate,whereby the minimum variant of 56 kB/s is characterized by good detectability of the contents. In an analysis period of 242 days,we registered 44,199 accesses and 4,488 attendances. The telemedicine data base "medicstream" can optimize quality and extend medical education by live-streaming as well as by archiving scientific presentations as audiovisual data.

Congresses as Topic↗
PubMed2002

Regulatory modules shared within gene classes as well as across gene classes can be detected by the same in silico approach.

Transcriptional regulation depends on the binding of transcription factors to their corresponding binding sites. The response to cellular signals is often mediated by the cooperative binding of transcription factors to well defined regulatory modules consisting of at least two transcription factor binding sites. Such regulatory modules can be responsible for the common regulation of genes within a gene class or confer a common function to promoters belonging to different gene classes. We developed in silico models representing a common framework of potential regulatory sites specific for one promoter class (actins). We also generated models for two different functional promoter modules both of which confer responsiveness to tumor necrosis factor (TNF) and interferon (IFN) to a variety of promoters. All models exhibited high selectivity, e.g. the mammalian muscle actin promoter model produced no false negatives in a database search.

Actins↗
PubMed2001

Regulation of plant growth by cytokinin.

Cytokinins are a class of plant-specific hormones that play a central role during the cell cycle and influence numerous developmental programs. Because of the lack of biosynthetic and signaling mutants, the regulatory roles of cytokinins are not well understood. We genetically engineered cytokinin oxidase expression in transgenic tobacco plants to reduce their endogenous cytokinin content. Cytokinin-deficient plants developed stunted shoots with smaller apical meristems. The plastochrone was prolonged, and leaf cell production was only 3-4% that of wild type, indicating an absolute requirement of cytokinins for leaf growth. In contrast, root meristems of transgenic plants were enlarged and gave rise to faster growing and more branched roots. These results suggest that cytokinins are an important regulatory factor of plant meristem activity and morphogenesis, with opposing roles in shoots and roots.

Cytokinins↗
PubMed2001

Molecular and in silico characterization of a promoter module and C/EBP element that mediate LPS-induced RANTES/CCL5 expression in monocytic cells.

The chemokine RANTES/CCL5 is a proinflammatory agent produced by a variety of tissues in response to specific stimuli. In human monocytes, RANTES/CCL5 transcription is up-regulated rapidly and transiently in response to LPS. We describe here two regions that help control LPS-driven transcription from the human RANTES/CCL5 promoter in monocytic cells. These sites were analyzed by using DNase I footprinting, transient transfection assays, site-directed mutagenesis, and EMSA. RANTES site E (R(E), -125/-99) constitutively binds C/EBP proteins in monocytic Mono Mac 6 cells. Mutation of region R(E) led to a significant (40%-50%) reduction in LPS-induced promoter reporter activity. Region R(AB) is composed of tandem kB-like elements R(A) and R(B) (-73/-34). These sites working in concert act as an LPS-responsive promoter module. R(A) constitutively binds Sp1, and Rel p50/p65 following LPS stimulation. Either factor can mediate transcriptional effects at R(A). Induced Rel p50/p50 binding to site R(B) is required for LPS regulation of RANTES/CCL5 transcription. A series of computer models based on the RANTES/CCL5 promoter were generated to represent the organization of these functional elements. The models could identify LPS-regulated promoters in human, other vertebrate, and viral sequences in various databases.

CCAAT-Enhancer-Binding Proteins↗
PubMed2001

Fluorimetric determination of copper(II) in aqueous solution using lucifer yellow CH as selective metal reagent.

Lucifer yellow CH is shown to be a highly selective fluorescent reagent for the determination of Cu(III) in the microg L(-1) concentration range. The fluorophore is statically quenched by Cu(II); the carbohydrazide group was assigned as the complexing part of the dye molecule. A total range of Cu(II) determination from 0.06 mg L(-1) (1 micromol L(-1)) to 6.3 mg L(-2) (100 micromol L(-1)) with a limit of detection of 0.019 mg L(-1) (0.3 micromol L(-1)) was obtained, along with surprisingly high selectivity. There was no interference from alkaline and earth alkaline metal ions. The cross sensitivity to heavy metal ions was evaluated by the separate solution method and by competitive binding experiments. Calibration plots are shown for Cu(II) determination at different pH and the dissociation constant was determined. The application of the reagent was demonstrated by the determination of the Cu(II) content of tap water samples.

Journal Article↗
PubMed2001

Experimental data of a single promoter can be used for in silico detection of genes with related regulation in the absence of sequence similarity.

Gene expression is presently a major focus in genome analysis, and the experimental data on regulatory mechanisms and functional transcription factor binding sites are steadily growing. However, the annotation of transcriptional regulation of sequences cannot keep pace with the exponential growth of sequence databases. Employing detailed experimental data of a single promoter or enhancer to predict genes with similar regulation would provide a powerful method to link the literature about transcriptional regulation and sequence databases. To this end, we used information on individual functional transcription factor binding sites to compose in silico promoter and enhancer models of muscle-specific genes and to analyze the rodents section of EMBL with these models. Exhaustive evaluation of all hits revealed every second to third match to be a muscle-associated gene. Moreover, functionally related regulatory regions were detected by our model-based approach even in the absence of sequence similarity. We believe that this new approach is a substanial extension to database analysis by BLAST or FASTA, which are restricted to sequence similarity.

Animals↗
PubMed2001

Comparative analysis of the genomic organization of Pax9 and its conserved physical association with Nkx2-9 in the human, mouse, and pufferfish genomes.

As a first step towards the identification of cis-regulatory elements of Pax9 by means of comparative genomics, we have analyzed genome regions encompassing the Pax9 gene in three vertebrate species, humans, mice (Mus musculus), and the Japanese pufferfish (Fugu rubripes). We show the genomic organization of Pax9 and its physical association with Nkx2-9 conserved in the three species. We discuss about possible implications of the conserved synteny between Pax9 and Nkx2-9 in a context of vertebrate evolution. This report also includes the first description of the primary structures of Fugu Pax9 and Nkx2-9. Furthermore, we report the identification of a novel upstream exon and putative transcription start sites in mouse Pax9. Our results suggest that transcription of Pax9 may be initiated at two alternative start sites and driven by TATA-less promoters.

Amino Acid Sequence↗
PubMed2001

Target gene identification from expression array data by promoter analysis.

DNA microchips and expression arrays yield enormous amounts of data linking cDNA sequences to gene expression patterns. This now allows the characterization of gene expression in normal and diseased tissues as well as the response of tissues to the application of therapeutic reagents. Software currently exists to analyze DNA array/chip data with respect to corresponding mRNA sequences, which facilitates the precise determination of when and where certain groups of genes are expressed. The information concerning transcriptional regulatory networks responsible for the observed expression patterns is not contained within the cDNA sequences used to generate the arrays, but resides often within the promoter sequences of the individual genes (and/or enhancers). The complete sequence of the human genome will provide the molecular basis for the identification of such regulatory regions. Promoter sequences for specific cDNAs can be obtained reliably from genomic sequences simply by exon mapping. Promoter prediction tools can also be used to locate promoters directly in the genomic sequence in many cases in which cDNAs are 5'-incomplete. Once sufficient numbers of promoter sequences have been obtained, the comparative promoter analysis of the co-regulated genes and groups of genes can be applied in order to generate models describing the higher order levels of the transcription factor binding site organization within these promoter regions. As evident from several examples, this approach can identify promoter modules responsible for the common regulation of promoters solely by the application of bioinformatics methods. Such modules represent the molecular mechanisms through which regulatory networks influence gene expression. Another advantage of this approach is that it also provides a powerful alternative for elucidating functional features of genes with no detectable sequence similarity, by linking them to other genes on the basis of their common promoter structures.

Computational Biology↗
PubMed2001

The promoter connection.

The availability of the complete genomic sequence of yeast now enables elucidation of molecular mechanisms governing gene expression patterns. New results from the yeast genome and recent advances in predicting and finding human promoters support the use of similar combinatorial approaches to study genome-wide transcriptional regulation in humans.

Binding Sites↗
PubMed2001

First pass annotation of promoters on human chromosome 22.

The publication of the first almost complete sequence of a human chromosome (chromosome 22) is a major milestone in human genomics. Together with the sequence, an excellent annotation of genes was published which certainly will serve as an information resource for numerous future projects. We noted that the annotation did not cover regulatory regions; in particular, no promoter annotation has been provided. Here we present an analysis of the complete published chromosome 22 sequence for promoters. A recent breakthrough in specific in silico prediction of promoter regions enabled us to attempt large-scale prediction of promoter regions on chromosome 22. Scanning of sequence databases revealed only 20 experimentally verified promoters, of which 10 were correctly predicted by our approach. Nearly 40% of our 465 predicted promoter regions are supported by the currently available gene annotation. Promoter finding also provides a biologically meaningful method for "chromosomal scaffolding", by which long genomic sequences can be divided into segments starting with a gene. As one example, the combination of promoter region prediction with exon/intron structure predictions greatly enhances the specificity of de novo gene finding. The present study demonstrates that it is possible to identify promoters in silico on the chromosomal level with sufficient reliability for experimental planning and indicates that a wealth of information about regulatory regions can be extracted from current large-scale (megabase) sequencing projects. Results are available on-line at http://genomatix.gsf.de/chr22/.

Algorithms↗
PubMed2001

Cluster analysis and promoter modelling as bioinformatics tools for the identification of target genes from expression array data.

Expression arrays yield enormous amounts of data linking genes, via their cDNA sequences, to gene expression patterns. This now allows the characterisation of gene expression in normal and diseased tissues, as well as the response of tissues to the application of therapeutic reagents. Expression array data can be analysed with respect to the underlying protein sequences, which facilitates the precise determination of when and where certain groups of genes are expressed. More recent developments of clustering algorithms take additional parameters of the experimental set-up into account, focusing more directly on co-regulated set of genes. However, the information concerning transcriptional regulatory networks responsible for the observed expression patterns is not contained within the cDNA sequences used to generate the arrays. Regulation of expression is determined to a large extent by the promoter sequences of the individual genes (and/or enhancers). The complete sequence of the human genome now provides the molecular basis for the identification of many regulatory regions. Promoter sequences for specific cDNAs can be obtained reliably from genomic sequences by exon mapping. In the many cases in which cDNAs are 5'-incomplete, high quality promoter prediction tools can be used to locate promoters directly in the genomic sequence. Once sufficient numbers of promoter sequences have been obtained, a comparative promoter analysis of the co-regulated genes and groups of genes can be applied in order to generate models describing the higher order levels of transcription factor binding site organisation within these promoter regions. Such modules represent the molecular mechanisms through which regulatory networks influence gene expression, and candidates can be determined solely by bioinformatics. This approach also provides a powerful alternative for elucidating the functional features of genes with no detectable sequence similarity, by linking them to other genes on the basis of their common promoter structures.

Algorithms↗
PubMed2001

An adverse interaction between warfarin and capecitabine: a case report and review of the literature.

Warfarin is one of the most commonly used oral anticoagulants in the clinic. It is well established that a wide range of antineoplastic drugs interact with warfarin, resulting in altered coagulation parameters and/or bleeding sequelae. While altered coagulation parameters have been observed in patients taking the oral 5-fluorouracil prodrug, capecitabine, in combination with warfarin, no report to date has described clinically overt evidence of bleeding. Herein, we report 2 cancer patients who presented with bleeding episodes that most likely resulted from an adverse interaction between capecitabine and warfarin after 6 weeks of concomitant therapy. In each case, there was a marked elevation in both the prothrombin time and international normalized ratio (> 10), with subsequent gastrointestinal bleeding. The exact mechanism of this interaction is yet unknown, but it is possible that capecitabine might, in some manner, reduce the hepatic metabolism of warfarin. Close monitoring of coagulation parameters is recommended for all patients receiving concomitant warfarin and capecitabine, with appropriate adjustment of warfarin dosage. The nature and extent of this interaction requires further investigation.

Aged↗
PubMed2000

A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster.

Peptidoglycans from bacterial cell walls trigger immune responses in insects and mammals. A peptidoglycan recognition protein, PGRP, has been cloned from moths as well as vertebrates and has been shown to participate in peptidoglycan-mediated activation of prophenoloxidase in the silk moth. Here we report that Drosophila expresses 12 PGRP genes, distributed in 8 chromosomal loci on the 3 major chromosomes. By analyzing cDNA clones and genomic databases, we grouped them into two classes: PGRP-SA, SB1, SB2, SC1A, SC1B, SC2, and SD, with short transcripts and short 5'-untranslated regions; and PGRP-LA, LB, LC, LD, and LE, with long transcripts and long 5'-untranslated regions. The predicted structures indicate that the first group encodes extracellular proteins and the second group, intracellular and membrane-spanning proteins. Most PGRP genes are expressed in all postembryonic stages. Peptidoglycan injections strongly induce five of the genes. Transcripts from the different PGRP genes were found in immune competent organs such as fat body, gut, and hemocytes. We demonstrate that at least PGRP-SA and SC1B can bind peptidoglycan, and a function in immunity is likely for this family.

Amino Acid Sequence↗
PubMed2000

Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression.

IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppressive. IL-10 is regulated at the level of transcription, but the critical motifs and the relevant transcription factors controlling this gene have remained elusive to date. We now report that a sequence at -120 bp in the human IL-10 promoter binds Stat3 but no other Stat proteins. Mutation of this motif abrogates LPS-induced trans-activation. Overexpression of dominant negative Stat3 suppresses promoter activity, while wild-type Stat3 leads to an enhancement of this activity. Our results show that Stat3, by binding to a single motif in the IL-10 promoter, is controlling expression of the human IL-10 gene.

Cell Line↗