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Biomedical subjects

B Morgenstern

Publications and source records attributed to B Morgenstern.

At least 19 recordsLinked to original sources
PubMed2006

TICO: a tool for postprocessing the predictions of prokaryotic translation initiation sites.

Exact localization of the translation initiation sites (TIS) in prokaryotic genomes is difficult to achieve using conventional gene finders. We recently introduced the program TICO for postprocessing TIS predictions based on a completely unsupervised learning algorithm. The program can be utilized through our web interface at http://tico.gobics.de/ and it is also freely available as a commandline version for Linux and Windows. The latest version of our program provides a tool for visualization of the resulting TIS model. Although the underlying method is not based on any specific assumptions about characteristic sequence features of prokaryotic TIS the prediction rates of our tool are competitive on experimentally verified test data.

Algorithms↗
PubMed2005

Stability and inactivation of SARS coronavirus.

The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56 degrees C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60 degrees C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agents tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.

Animals↗
PubMed2004

Infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus.

To identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (SARS) we tested the sensitivity of six human intestinal epithelial cell lines to infection with SARS coronavirus (SARS-CoV). In permissive cell lines, effects of SARS-CoV on cellular gene expression were analysed using high-density oligonucleotide arrays. Caco-2 and CL-14 cell lines were found to be highly permissive to SARS-CoV, due to the presence of angiotensin-converting enzyme 2 as a functional receptor. In both cell lines, SARS-CoV infection deregulated expression of cellular genes which may be important for the intestinal pathogenesis of SARS.

Caco-2 Cells↗
PubMed2004

[Analysis of Foetal Heart Rate Data using Complex Software: Comparison of Recurrence Plot of Foetal Heart Rate with the Course of Pregnancy -].

BACKGROUND: Is it useful to further analyse foetal heart rate to improve the prediction of pregnancy complications? The analysis of the foetal heart rate is usually based on the variability of the heart rate, i. e. the more variable the heart rate presents - except a decrease - the better the condition of the foetus is. The same concept is applied in our own analysis which differs only in the presentation of the data. MATERIAL AND METHODS: We analysed 25 non-stress-tests from unselected third trimester pregnancies using sophisticated software. The recurrence plot (RP) is able to rearrange data from foetal heart rate monitoring in order to make the heart rate variability visible. We developed criteria for a normal and an abnormal test result describing the structure of the diagram to predict an uneventful and a high-risk pregnancy, respectively. RESULTS: 11 out of 11 patients with uneventful course and outcome of pregnancy showed a coarse and blurred RP pattern. 12 out of 14 (86 %) patients developing either intrauterine growth retardation or preeclampsia and requiring caesarean section because of foetal heart rate abnormalities showed a fine and clear RP pattern. CONCLUSIONS: Our preliminary results show that it makes sense to further evaluate foetal heart rate variability in order to predict pregnancy complications. Computer programs including the algorithms needed (calculation of the recurrence plot) are not expensive and easy to handle. A widespread use of these programs represents the basis requirement for large controlled clinical trials.

Analysis of Variance↗
PubMed2004

[Primary diagnosis of hormone-secreting pituitary adenoma during pregnancy and after birth -- a rare occurrence].

About seven to ten percent of all brain tumours are neoplasias of the pituitary gland. Pituitary gland tumours can cause different clinical symptoms often making it difficult to come to the correct diagnosis. They can lead to severe complications such as hypopituitarism with secondary hypogonadism, hypothyroidism, and adrenocortical insufficiency, compression of the optic tract or obstructive hydrocephalus. We report on two patients with hormone-secreting pituitary tumours that were unknown prior to pregnancy. The first woman suffered from a growth hormone-producing pituitary adenoma, causing persistent headaches after birth. The second woman showed a significant loss of vision and visual field defects in the 32nd week of gestation, caused by a prolactin-producing pituitary tumour.

Adult↗
PubMed2003

Treatment of SARS with human interferons.

Effective antiviral agents are needed to treat severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. We assessed the antiviral potential of recombinant interferons against two clinical isolates of SARS-CoV--FFM-1, from Frankfurt patients, and Hong Kong--replicated in Vero and Caco2 cells. Interferon beta was five to ten times more effective in Caco2 cells. Interferon alpha effectively inhibited SARS-CoV replication, but with a selectivity index 50-90 times lower than that for interferon beta. Interferon gamma was slightly better than interferon alpha in Vero cell cultures, but was completely ineffective in Caco2 cell cultures. Interferon beta could be useful alone or in combination with other antiviral drugs for the treatment of SARS.

Antiviral Agents↗
PubMed2003

Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus.

The outbreak of SARS warrants the search for antiviral compounds to treat the disease. At present, no specific treatment has been identified for SARS-associated coronavirus infection. We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. Of all the compounds, glycyrrhizin was the most active in inhibiting replication of the SARS-associated virus. Our findings suggest that glycyrrhizin should be assessed for treatment of SARS.

Animals↗
PubMed2002

MIPS: a database for genomes and protein sequences.

The Munich Information Center for Protein Sequences (MIPS-GSF, Neuherberg, Germany) continues to provide genome-related information in a systematic way. MIPS supports both national and European sequencing and functional analysis projects, develops and maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences, and provides tools for the comprehensive analysis of protein sequences. This report updates the information on the yeast genome (CYGD), the Neurospora crassa genome (MNCDB), the databases for the comprehensive set of genomes (PEDANT genomes), the database of annotated human EST clusters (HIB), the database of complete cDNAs from the DHGP (German Human Genome Project), as well as the project specific databases for the GABI (Genome Analysis in Plants) and HNB (Helmholtz-Netzwerk Bioinformatik) networks. The Arabidospsis thaliana database (MATDB), the database of mitochondrial proteins (MITOP) and our contribution to the PIR International Protein Sequence Database have been described elsewhere [Schoof et al. (2002) Nucleic Acids Res., 30, 91-93; Scharfe et al. (2000) Nucleic Acids Res., 28, 155-158; Barker et al. (2001) Nucleic Acids Res., 29, 29-32]. All databases described, the protein analysis tools provided and the detailed descriptions of our projects can be accessed through the MIPS World Wide Web server (http://mips.gsf.de).

Amino Acid Sequence↗
PubMed2001

The HIB database of annotated UniGene clusters.

SUMMARY: The HumanInfoBase (HIB) is a database of putative human gene transcripts. UniGene clusters are assembled, and the resulting consensus sequences are submitted to the PEDANT software system (Frishman,D., Albermann,K., Hani,J., Heumann,K., Metanomski,A., Zollner,A. and Mewes,H.-W., 2001, Bioinformatics, 17, 44--57) for fully automatic sequence analysis and annotation. Predicted transcripts are classified using a variety of functional and structural categories, and hyperlinks to various databases are provided for additional information. A WWW-based graphical user interface represents the assembly process as well as functionally important sites in the putative transcripts.

Data Collection↗
PubMed2001

Impact of total body water errors on Kt/V estimates in children on peritoneal dialysis.

Determining Kt/V in peritoneal dialysis (PD) requires estimation of total body water (TBW). The Dialysis Outcomes Quality Initiative (DOQI) guidelines recommend use of the Mellits and Cheek (MC) formulas for the estimation of TBW in children. However, the MC formulas were developed from healthy children and may not apply to children on PD. Re-evaluating the MC data with additional, recent data from healthy infants has led to the development of new formulas. In addition, and as part of a prospective study of children initiating PD, the Pediatric Peritoneal Dialysis Study Consortium (PPDSC) has directly measured TBW using H2[18O]. To assess the impact of various TBW estimates, KPDt/V values prospectively collected in 24 children were calculated using H2[18O]-measured TBW (O18), MC-derived TBW (MCD), and new-formula TBW (NEW). The mean weekly KPDt/V by O18 was 2.2; by MCD, it was 2.0; and by NEW, it was 2.0. The results derived using the O18 method varied from both the MCD and the NEW results (p < 0.001). The mean deviation from the measured KPDt/V using O18 was 9.5% (maximum: 16%) using the MCD estimate and 7.8% (maximum: 18%) using the NEW formulas. Determinations of KPDt/V are significantly affected by the method of estimating TBW. The PPDSC formulas for children on PD based on the use of H2[18O] offer the most accurate means of calculating TBW and should replace formulas derived from healthy children. The use of Kt/V itself as a marker of adequacy in children will be validated only in prospective studies.

Adolescent↗
PubMed2000

A space-efficient algorithm for aligning large genomic sequences.

SUMMARY: In the segment-by-segment approach to sequence alignment, pairwise and multiple alignments are generated by comparing gap-free segments of the sequences under study. This method is particularly efficient in detecting local homologies, and it has been used to identify functional regions in large genomic sequences. Herein, an algorithm is outlined that calculates optimal pairwise segment-by-segment alignments in essentially linear space. AVAILABILTIY: The program is available at the Bielefeld Bioinformatics Server (BiBiServ) at http://bibiserv.techfak. uni-bielefeld.de/dialign/

Algorithms↗
PubMed1999

Renal function following combination chemotherapy with ifosfamide and cisplatin in patients with osteogenic sarcoma.

BACKGROUND: Ifosfamide and cisplatin are active agents that are currently used in the treatment of osteosarcoma. Nephrotoxicity has been reported following their use in combination and alone. This study evaluates renal function in children and adolescents (median age 16 years) at least 3 months following completion of a chemotherapy regimen which included 54 g/m2 ifosfamide, 360 mg/m2 cisplatin, doxorubicin, and high-dose methotrexate. PROCEDURE: Mean glomerular filtration rate (GFR) was determined by inulin or iothalamate clearance; proximal tubular function was evaluated by measuring fractional excretion of glucose (FEglu), tubular maximum phosphate reabsorption per GFR (TMP/GFR), FE of urate, and 24-hour amino acid excretion. Distal tubular function was evaluated by 24-hour urinary calcium, FE of magnesium, and urinary osmolality after water deprivation. Twenty-four-hour urinary protein excretion was measured. RESULTS: The mean GFR was 97 ml/min/1.73 m2. Although 10 of 24 patients had GFRs lower than normal, the lowest value was only 22% below the lower limit of normal and would not account for any clinical compromise. Proximal tubular function evaluation revealed normal FEglu, normal mean TMP/GFR values, and high FE of urate (1 5.7%). Two of twenty-four patients were shown to have mild generalized aminoaciduria. Distal tubular function evaluation showed normal 24-hour urinary calcium levels (mean 3.4 mg/kg) and FE of magnesium as well as normal urinary osmolality. Twenty-four-hour urinary protein excretion was normal in all patients. CONCLUSIONS: The lack of clinically significant renal abnormalities observed in patients who received combination chemotherapy with ifosfamide and cisplatin for osteosarcoma is encouraging for future osteosarcoma protocol development.

Adolescent↗
PubMed1999

An exact solution for the segment-to-segment multiple sequence alignment problem.

MOTIVATION: In molecular biology, sequence alignment is a crucial tool in studying the structure and function of molecules, as well as the evolution of species. In the segment-to-segment variation of the multiple alignment problem, the input can be seen as a set of non-gapped segment pairs (diagonals). Given a weight function that assigns a weight score to every possible diagonal, the goal is to choose a consistent set of diagonals of maximum weight. We show that the segment-to-segment multiple alignment problem is equivalent to a novel formulation of the Maximum Trace problem: the Generalized Maximum Trace (GMT) problem. Solving this problem to optimality, therefore, may improve upon the previous greedy strategies that are used for solving the segment-to-segment multiple sequence alignment problem. We show that the GMT can be stated in terms of an integer linear program and then solve the integer linear program using methods from polyhedral combinatorics. This leads to a branch-and-cut algorithm for segment-to-segment multiple sequence alignment. RESULTS: We report on our first computational experiences with this novel method and show that the program is able to find optimal solutions for real-world test examples.

Algorithms↗
PubMed1999

DIALIGN 2: improvement of the segment-to-segment approach to multiple sequence alignment.

MOTIVATION: The performance and time complexity of an improved version of the segment-to-segment approach to multiple sequence alignment is discussed. In this approach, alignments are composed from gap-free segment pairs, and the score of an alignment is defined as the sum of so-called weights of these segment pairs. RESULTS: A modification of the weight function used in the original version of the alignment program DIALIGN has two important advantages: it can be applied to both globally and locally related sequence sets, and the running time of the program is considerably improved. The time complexity of the algorithm is discussed theoretically, and the program running time is reported for various test examples. AVAILABILITY: The program is available on-line at the Bielefeld University Bioinformatics Server (BiBiServ) http://bibiserv.TechFak.Uni-Bielefeld.DE/dial ign/

Algorithms↗
PubMed1999

Evolution of bHLH transcription factors: modular evolution by domain shuffling?

Multidomain proteins usually contain several conserved and apparently independently evolved domains. As a result, classifications based on only a single small domain may obscure the true evolutionary relationships of the proteins. The current classification of basic helix-loop-helix (bHLH) domain-containing proteins is based on the conserved bHLH domain alone. Herein, we explore whether sequence homology and, therefore, evolutionary relationships can be detected among the flanking or non-bHLH components of the amino acid sequences of 122 bHLH proteins. These 122 proteins were the same proteins previously used to construct the existing classification of the bHLH-domain-containing proteins. Several possible scenarios are examined in order to explain the observed patterns of sequence divergence, including (1) monophyly, (2) convergent evolution, (3) addition of functional components to the bHLH domain, and (4) modular evolution with domain shuffling. Drawing on several lines of evidence, we suggest that modular evolution by domain shuffling may have played an important role in the evolution of this large group of transcriptional regulators.

DNA-Binding Proteins↗
PubMed1998

Report of the American Society of Nephrology meetings.

PURPOSE: We summarize presentations on topics of interest to the pediatric urologist from the annual meeting of the American Society of Nephrology, November 1996. MATERIALS AND METHODS: We reviewed all abstracts submitted for presentation and subsequently published in abstract form. Only those abstracts containing information pertinent to the field of pediatric urology were summarized for this report. RESULTS: A total of 24 abstracts addressing a variety of topics were summarized. Obstructive uropathy was represented by the greatest number of papers and reflects the multiple investigative efforts currently evaluating the cellular aspects of this disorder. The genetic basis of hypercalciuria and the impact of water metabolism on nephroliathisis were also discussed. CONCLUSIONS: Clinical and basic research activities that are of mutual interest to pediatric urologists and nephrologists are being conducted. The topic of obstructive uropathy has received the greatest attention during the last year. However, additional research, potentially collaborative in nature, on topics such as nephroliathisis and reflux nephropathy should be encouraged.

Child↗
PubMed1998

DIALIGN: finding local similarities by multiple sequence alignment.

MOTIVATION: DIALIGN is a new method for pairwise as well as multiple alignment of nucleic acid and protein sequences. While standard alignment programs rely on comparing single residues and imposing gap penalties, DIALIGN constructs alignments by comparing whole segments of the sequences. No gap penalty is employed. This point of view is especially adequate if sequences are not globally related, but share only local similarities, as is the case in genomic DNA sequences and in many protein families. RESULTS: Using four different data sets, we show that DIALIGN is able correctly to align conserved motifs in protein sequences. Alignments produced by DIALIGN are compared systematically to the results of five other alignment programs. AVAILABILITY: DIALIGN is available to the scientific community free of charge for non-commercial use. Executables for various UNIX platforms including LINUX can be downloaded at http://www.gsf.de/biodv/dialign.html CONTACT: werner, morgenstern@gsf.de

Algorithms↗