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B Morgenstern

Publications and source records attributed to B Morgenstern.

18 recordsLinked to original sources
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↗
PubMed1998

Segment-based scores for pairwise and multiple sequence alignments.

In this paper, we discuss a novel scoring scheme for sequence alignments. The score of an alignment is defined as the sum of so-called weights of aligned segment pairs. A simple modification of the weight function used by the original version of the DIALIGN alignment program turns out to have a crucial advantage: it can be applied to both, global and local alignment problems without the need to specify a threshold parameter.

Amino Acid Sequence↗
PubMed1997

Report of the American Society of Nephrology meeting.

PURPOSE: We summarize presentations on topics of interest to the pediatric urologist from the annual meeting of the American Society of Nephrology in November 1995. MATERIALS AND METHODS: We reviewed all abstracts submitted for presentation and subsequently published in abstract form in the Journal of the American Society of Nephrology, September 1995. Only abstracts containing information pertinent to the field of pediatric urology were summarized for this report. RESULTS: A total of 22 abstracts addressing the subjects of nephrolithiasis, obstructive uropathy, renal transplantation, vesicoureteral reflux and genetics/development was summarized. CONCLUSIONS: Research activities in various subject areas are applicable to the pediatric nephrology and urology communities. Sharing the results of these investigative efforts in forums such as this report is mutually beneficial and should be encouraged.

Child↗
PubMed1996

Multiple DNA and protein sequence alignment based on segment-to-segment comparison.

In this paper, a new way to think about, and to construct, pairwise as well as multiple alignments of DNA and protein sequences is proposed. Rather than forcing alignments to either align single residues or to introduce gaps by defining an alignment as a path running right from the source up to the sink in the associated dot-matrix diagram, we propose to consider alignments as consistent equivalence relations defined on the set of all positions occurring in all sequences under consideration. We also propose constructing alignments from whole segments exhibiting highly significant overall similarity rather than by aligning individual residues. Consequently, we present an alignment algorithm that (i) is based on segment-to-segment comparison instead of the commonly used residue-to-residue comparison and which (ii) avoids the well-known difficulties concerning the choice of appropriate gap penalties: gaps are not treated explicity, but remain as those parts of the sequences that do not belong to any of the aligned segments. Finally, we discuss the application of our algorithm to two test examples and compare it with commonly used alignment methods. As a first example, we aligned a set of 11 DNA sequences coding for functional helix-loop-helix proteins. Though the sequences show only low overall similarity, our program correctly aligned all of the 11 functional sites, which was a unique result among the methods tested. As a by-product, the reading frames of the sequences were identified. Next, we aligned a set of ribonuclease H proteins and compared our results with alignments produced by other programs as reported by McClure et al. [McClure, M. A., Vasi, T. K. & Fitch, W. M. (1994) Mol. Biol. Evol. 11, 571-592]. Our program was one of the best scoring programs. However, in contrast to other methods, our protein alignments are independent of user-defined parameters.

Algorithms↗
PubMed1996

First temporal and spatial quantification of single-shot electrohydraulic lithotripsy in vitro.

Single electrohydraulic lithotripsy (EHL) discharges from a human ureter were analyzed with a mechanical high-speed motion analysis camera. We found a cavitation bubble, at 650 mJ, 4-11 mm in size, with a lifetime of 400-500 microseconds. Varying sizes and lifetimes were found using single-shot analysis, as well as in different shot-sequences. This supports similar observations by recent investigations of cavitation bubble size with high-shutter-speed videofilm, which have depicted events at shutter speeds of 4000/s, i.e., an approximate exposure time of 250 microseconds. Due to the occurrence of high-voltage interference from the EHL high-voltage generator, no other technical electronic event timing equipment has so far been available capable of mechanical high-speed film motion analysis, while at the same time avoiding high-voltage interference.

Lithotripsy↗
PubMed1994

Renal function in children and adolescents following 72 g/m2 of ifosfamide.

A detailed analysis of the renal function of 18 children and adolescents aged 7-20 years (median, 16 years) was performed at least 3 months following the completion of a non-platinum-containing chemotherapy regimen with a total dose of 72 g/m2 of ifosfamide. Ifosfamide had been given as a 1-h infusion of 1.8 g/m2 daily for 5 days at 5- to 6-week intervals along with mesna uroprotection. The mean glomerular filtration rate (GFR) as determined by inulin clearance was 100 ml/min/1.73 m2. Although 6 of 18 patients had GFRs below normal, the lowest was only 18% less than the lower limit of normal and would not account for any clinical compromise. The renal plasma flow and filtration fraction were normal. Proximal tubular function evaluation revealed normal fractional excretion (FE) of glucose; normal mean tubular maximum phosphate reabsorption per GFR (TMP)/GFR values; high FE of urate (17%); and mild, generalized aminoaciduria in 6 of the 18 patients. Distal tubular function evaluation showed normal 24-h urinary calcium levels and FE of magnesium as well as normal urinary osmolality after water deprivation. Two patients had mild proteinuria. The findings in this study are encouraging in terms of the lack of clinically significant renal abnormalities observed in patients who had received a cumulative dose of 72 g/m2 of ifosfamide.

Adolescent↗
PubMed1992

[Effect of histological criteria (TpNM classification, degree of differentiation) on mortality of patients with retinoblastoma].

153 patients suffering from retinoblastoma and treated between 1960 and 1980 were analysed retrospectively. Median follow-up was 11.2 years. 13 patients (8.5%) died from retinoblastoma. 3 patients died from a secondary osteosarcoma. The survival rates from patients with differentiated retinoblastomas did not differ from those with undifferentiated tumor cells. Optic nerve invasion decreased significantly the survival rate and involvement of the sectional line led to a survival rate after 5 years of only 22.2%. Due to 3 cases of death from secondary osteosarcoma, the survival rate of 91.14% after 5 years deteriorated to 87.64% after 10 to 14 years.

Child↗
PubMed1982

Schedule-dependent synergy and antagonism between high-dose 1-beta-D-arabinofuranosylcytosine and asparaginase in the L5178Y murine leukemia.

The effect of schedule of drug administration on the biochemical and therapeutic effects of the combination of 1-beta-D-arabinofuranosylcytosine (ara-C) and asparaginase was investigated in vivo and in vitro using the murine leukemia L5178Y. Treatment of cells in vitro with either ara-C (10(-6) M) or asparaginase (0.5 IU/ml) for 8 hr resulted in 45 and 24% viability, respectively; simultaneous exposure to both drugs resulted in 25% viability, a subadditive effect. Sequential 8-hr in vitro treatments with asparaginase preceding ara-C or ara-C preceding asparaginase resulted in 43 and 8% viability, respectively, indicating strong schedule dependency. Recovery from drug-induced inhibition of cell growth in vivo suggested an optimal interval of 120 hr. Treatment of leukemic mice with asparaginase, ara-C, or both drugs simultaneously 3 days after inoculation of 10(6) cells resulted in mean survival times of 16, 21, and 18 days, respectively (control mean survival time, 10 days). With a 120-hr interval between the two drugs, treatment with ara-C followed by asparaginase resulted in 20 of 24 sixty-day survivors. In contrast, when asparaginase preceded ara-C, there was a mean survival time of only 23 days with no 60-day survivors. Maximal weight loss with either combination was only 10%. Mechanisms for the pharmacological antagonism include asparaginase-induced decreased cellular uptake and incorporation of ara-C into macromolecules. The apparent synergy is related to the timing of asparaginase treatment, the "optimal therapeutic effect" occurring when sequential asparaginase is administered before the cells recover from the ara-C effect. Since both drugs are probable components of antileukemic combinations, understanding of such drug-drug interactions would optimize clinical therapy.

Animals↗
PubMed1981

Yellow hyaline membrane disease. Identification of the pigment and bilirubin binding.

The distinguishing feature of yellow hyaline membrane disease (YHM) in the newborn is the presence of nonfading, bright yellow membrane lining the luminal aspects of conventional pink hyaline membranes (HM). Examination of yellow membranes, stained and unstained, under fluorescent microscopy reveals on orange-red fluorescent material heterogeneously dispersed within the membranes. Homogenates of lungs with YHM and HM were extracted with chloroform and tested spectrophotometrically, by thin layer chromatography, and for diazotized sulfanilic acid reactivity. Spectrophotometric profiles of YHM differed from those of HM by a unique absorption shoulder at 454 nm. in the former. This shoulder corresponded to the absorbance of unconjugated bilirubin. This profile could be reproduced by adding purified unconjugated bilirubin to non-YHM lung homogenate prior to extraction. Thin layer chromatography of the extracted YHM material produced two unique spots not found in extracts prepared from normal or HM-diseased lungs. These spots could be duplicated by thin layer chromatography using pure unconjugated bilirubin. The spots also fluoresced orange-red, the same color initially observed in the membranous preparations under fluorescent microscopy. Additional in vitro binding studies suggest that polymyxin, a decapeptide antibiotic used in endotracheal irrigation of newborn infants, binds bilirubin in pH-dependent, small molecular ratios. Although subsequent clinical studies disproved the etiologic significance of this particular drug, the unique properties of the bilirubin present in the YHMD lungs strongly suggest that the bilirubin there is bound by some yet unelucidated mechanism.

Bilirubin↗