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Peter Ernst

Publications and source records attributed to Peter Ernst.

12 recordsLinked to original sources
PubMed2006

CAFTAN: a tool for fast mapping, and quality assessment of cDNAs.

BACKGROUND: The German cDNA Consortium has been cloning full length cDNAs and continued with their exploitation in protein localization experiments and cellular assays. However, the efficient use of large cDNA resources requires the development of strategies that are capable of a speedy selection of truly useful cDNAs from biological and experimental noise. To this end we have developed a new high-throughput analysis tool, CAFTAN, which simplifies these efforts and thus fills the gap between large-scale cDNA collections and their systematic annotation and application in functional genomics. RESULTS: CAFTAN is built around the mapping of cDNAs to the genome assembly, and the subsequent analysis of their genomic context. It uses sequence features like the presence and type of PolyA signals, inner and flanking repeats, the GC-content, splice site types, etc. All these features are evaluated in individual tests and classify cDNAs according to their sequence quality and likelihood to have been generated from fully processed mRNAs. Additionally, CAFTAN compares the coordinates of mapped cDNAs with the genomic coordinates of reference sets from public available resources (e.g., VEGA, ENSEMBL). This provides detailed information about overlapping exons and the structural classification of cDNAs with respect to the reference set of splice variants. The evaluation of CAFTAN showed that is able to correctly classify more than 85% of 5950 selected "known protein-coding" VEGA cDNAs as high quality multi- or single-exon. It identified as good 80.6 % of the single exon cDNAs and 85 % of the multiple exon cDNAs. The program is written in Perl and in a modular way, allowing the adoption of this strategy to other tasks like EST-annotation, or to extend it by adding new classification rules and new organism databases as they become available. We think that it is a very useful program for the annotation and research of unfinished genomes. CONCLUSION: CAFTAN is a high-throughput sequence analysis tool, which performs a fast and reliable quality prediction of cDNAs. Several thousands of cDNAs can be analyzed in a short time, giving the curator/scientist a first quick overview about the quality and the already existing annotation of a set of cDNAs. It supports the rejection of low quality cDNAs and helps in the selection of likely novel splice variants, and/or completely novel transcripts for new experiments.

Chromosome Mapping↗
PubMed2004

Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia.

T-cell-targeting immunotherapy is now considered in acute myelogenous leukemia (AML). Immunotherapy seems most effective for patients with a low AML cell burden, and a possible strategy is therefore to administer immunotherapy early after intensive chemotherapy when patients have a low leukemia cell burden and severe treatment-induced cytopenia. To further investigate this possible therapeutic approach we used a whole blood assay to characterize the proliferative responsiveness (3H-thymidine incorporation) of circulating T cells from AML patients with severe treatment-induced leukopenia, i.e., peripheral blood leukocyte counts < 0.5x10(9)/l. This assay will reflect both quantitative and qualitative differences. Responses were compared for 17 AML patients, 6 patients with acute lymphoblastic leukemia (ALL), and a group of 21 healthy controls. Most circulating leukocytes in the AML patients were T lymphocytes, whereas B lymphocytes and monocytes usually constituted < 10%. Anti-CD3-stimulated proliferation was significantly lower for AML patients compared with healthy controls. However, proliferation in response to anti-CD3 + anti-CD28 did not differ for AML patients and healthy controls, an observation suggesting that T cells from AML patients have an increased responsiveness in the presence of optimal costimulation that compensates for the quantitative T-cell defect. In contrast, the responses were significantly lower for ALL than for AML patients. We conclude that the remaining T-cell population in AML patients with severe chemotherapy-induced cytopenia show an increased proliferative responsiveness and may represent a therapeutic target when antileukemic immunotherapy is tried in combination with intensive chemotherapy.

Adolescent↗
PubMed2004

Cellular immune responses in multiple myeloma patients with treatment-induced cytopenia early after high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

Proliferative T cell responses were compared for two patient groups with severe treatment-induced leukopenia (white blood cell counts < 0.5 x 10(9)/l): (i). multiple myeloma patients receiving high-dose melphalan and autologous peripheral blood stem cell transplantation; (ii). patients receiving conventional intensive chemotherapy for acute leukemia or myelodysplasia. Although the majority of circulating leukocytes were CD2(+)TCRalphabeta(+) in both groups, the myeloma patients showed significantly lower T cell proliferation in responses to several activation signals (anti-CD3, anti-CD3 + IL2, anti-CD3 + anti-CD28, anti-CD3 + anti-CD28+IL2. Our results suggest that myeloma patients with post-transplant cytopenia have a more severe cellular immune defect than patients with other hematological malignancies and severe cytopenia due to conventional intensive chemotherapy.

Adolescent↗
PubMed2004

Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States.

Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.

Adolescent↗
PubMed2003

ESTAnnotator: A tool for high throughput EST annotation.

In high throughput sequence analysis, it is often necessary to combine the results of contemporary bioinformatics tools, because no individual tool alone computes all the requested information. ESTAnnotator is a tool for the high throughput annotation of expressed sequence tags (ESTs) by automatically running a collection of bioinformatics applications. In the first step, a quality check is performed and repeats, vector parts and low quality sequences are masked. Then successive steps of database searching and EST clustering are performed. Already known transcripts present within mRNA and genomic DNA reference databases are identified. Subsequently, tools for the clustering of anonymous ESTs, and for further database searches at the protein level, are applied. Finally, the outputs of each individual tool are gathered and the relevant results presented in a descriptive summary. ESTAnnotator was already successfully applied for the systematic identification and characterisation of novel human genes involved in cartilage/bone formation, growth, differentiation and homeostasis. ESTAnnotator is available at http://genome.dkfz-heidelberg.de, contact: genome@dkfz.de.

Cartilage↗
PubMed2003

A task framework for the web interface W2H.

SUMMARY: The W3H task framework allows the execution of compound jobs utilizing the description of work and data flows in a heterogeneous bioinformatics environment using meta-data information. By means of these descriptions, the task system can schedule the necessary execution of applications available in the environment, depending on rules specified in the meta-data. By integrating this task framework into the publicly available web interface W2H, similarly based on meta-data, web access and data management are immediately available for each task description. Authors of task descriptions can base their work on the underlying classes and objects to be able to describe dependency rules between previously independent applications. The result of a compound task is given as XML data that is translated according to XSLT data into web pages or plain text to report the result of the task to the user. AVAILABILITY: Within the HUSAR environment at DKFZ http://genome.dkfz-heidelberg.de/

Database Management Systems↗
PubMed2003

The angioregulatory phenotype of native human acute myelogenous leukemia cells: influence of karyotype, Flt3 abnormalities and differentiation status.

INTRODUCTION: The cytogenetic abnormalities and the response to induction therapy have been regarded as the most important prognostic parameters in acute myelogenous leukemia (AML) patients. Recent studies have demonstrated that internal tandem duplications and specific D-835 point mutations of the Flt3 gene, as well as the angioregulatory phenotype represent additional adverse prognostic factors. The aim of the study was to investigate possible associations between genetic abnormalities, differentiation status and angioregulatory phenotype in native human AML blasts. METHOD: Native AML blasts derived from consecutive patients were cultured in vitro and concentrations of angioregulatory molecules determined in the supernatants. RESULTS: Most patients released at least two different angioregulatory mediators. Pro-angiogenic interleukin 8 (IL8) was released at relatively high levels for most patients, many of these patients showed additional release of pro-angiogenic vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). High release of anti-angiogenic IL12 was associated with high release of pro-angiogenic IL8 and VEGF. Furthermore, patients with D-835 mutations showed increased IL12 release, whereas patients with normal karyotype had decreased HGF release. Myelomonocytic differentiation was associated with IL18 release and CD34 expression with low IL12 release. CONCLUSION: Our results suggest that native human AML blasts have a pro-angiogenic phenotype. Although the investigated genetic abnormalities are associated with variation in the in vitro release of angioregulators, these differences are relatively small and do not quantitatively involve the most important IL8 release. It therefore seems unlikely that this phenotypic variation can explain the prognostic impact of the genetic abnormalities.

Adult↗
PubMed2003

Allogeneic bone marrow transplantation for severe post-splenectomy thrombophilic state in leaky red cell membrane haemolytic anaemia of the stomatocytosis class.

The tendency for thrombosis to occur if haemolysis persists after splenectomy is especially marked in "hereditary stomatocytosis", in which the red cell membrane "leaks" Na and K. A 21-year-old woman, who was splenectomized in childhood for a congenital haemolytic state, presented with major pulmonary embolism that recurred despite anticoagulation. Tests showed a significant cation leak with a "shallow-slope" abnormality in temperature dependence. Allogeneic bone marrow transplantation caused the thrombophilic state to cease and subsequently anticoagulation was stopped without recurrence of thromboembolism. However, she died 9 months after transplantation: iron overload, intensified by the transfusion demands of the transplant, was a major factor.

Adult↗
PubMed2003

Paroxysmal nocturnal hemoglobinuria in pregnancy.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which a defect of glycophosphatidylinositol (GPI)-anchored proteins in the cell membrane of bone marrow stem cells leads to increased sensitivity of the red cells to complement, causing intravascular hemolysis and hemoglobinuria. Other clinical features of this disease are cytopenia and an increased frequency of thrombotic events. We report a case of a pregnant woman with PNH on high-dosage anticoagulation therapy, the follow-up during the pregnancy, the delivery and the postpartum period. The obstetric literature on women with PNH is reviewed, the maternal and fetal risks are evaluated and the management of pregnancies and deliveries in such patients are discussed. During the pregnancy our patient was hypertransfused and used anticoagulation treatment. A healthy child was delivered in week 37 by cesarean section because of premature rupture of the membranes, unsuccessful induction and intrauterine infection. Because of bleeding problems a hysterectomy also had to be performed. In the postpartum period the patient developed her second episode of a liver vein thrombosis. She recovered gradually and 18 months after the delivery her disease is now in a stable phase. The literature shows a high maternal morbidity and mortality among pregnant PNH patients. Fetal wastage and prematurity rate are also high. Pregnancy in patients with PNH represents a high-risk situation for both the mother and the child and should not be recommended. A pregnant PNH woman should be followed closely by both obstetricians and hematologists.

Adult↗
PubMed2003

Characterization of clonogenic progenitors in autologous peripheral blood stem cell grafts: evaluation of a simple in vitro assay suitable for routine clinical use.

Autologous peripheral blood stem cell (PBSC) transplantation has a low treatment-related morbidity and mortality when using appropriate criteria for patient selection and graft quality evaluation. It will be important to use simple and standardised procedures for evaluation of progenitor cell numbers when considering autografting in patients with malignant or non-malignant disorders and increased risk of prolonged posttransplant cytopenia. We determined the number of clonogenic cells in PBSC autografts after 7 days of in vitro culture, and these results were compared with both the total number of colonies and the numbers of colony subsets in conventional 14 days colony assays (colony-forming unit granulocyte-erythrocyte-macrophage-megakaryocyte, CFU-GEMM; CFU-E, CFU-GM; CFU-megakaryocyte). The total colony number after 7 days of culture correlated significantly with (i) the CD34+ cell number; (ii) the total colony number as well as the numbers of erythroid, nonerythroid and mixed colonies in a conventional assay using 14 days of culture; (iii) the number of megakaryocyte colonies. The total colony number after 7 days of in vitro culture is a simple in vitro parameter that seems to reflect the proliferative capacity of various progenitor subsets in PBSC autografts. This simple analysis may be used in combination with other in vitro techniques (e.g. estimation of stem cell viability and CD34+ cell subset analysis) for pretransplant evaluation of autografts. However, the possible clinical use of this parameter has to be examined in prospective clinical studies.

Antigens, CD34↗
PubMed2002

PATH: a task for the inference of phylogenies.

UNLABELLED: Phylogenetic Analysis Task in Husar (PATH) is a task for the inference of phylogenies. It executes three phylogenetic methods and automatically chooses the evolutionary model for each set of data. The output of the tasks shows the consensus trees together with full results obtained from all executed methods. AVAILABILITY: PATH is available at the German EMBnet node after registration via www at http://genome.dkfz-heidelberg.de

Databases, Nucleic Acid↗