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Biomedical subjects

U Hobohm

Publications and source records attributed to U Hobohm.

14 recordsLinked to original sources
PubMed2005

Fever therapy revisited.

The phenomenon of spontaneous regression and remission from cancer has been observed by many physicians and was described in hundreds of publications. However, suggestive clues on cause or trigger are sparse and not substantiated by much experimental evidence. In this review, literature is surveyed and summarised and possible causes are discussed. At least in a larger fraction of cases a hefty feverish infection is linked with spontaneous regression in time and is investigated as putative trigger. Epidemiological and immunological evidence is put into perspective. An online forum to discuss the possible application of fever therapy in the future can be accessed at http://bioinfo.tg.fh-giessen.de/fever-and-cancer.

Fever↗
PubMed2003

Normalization of DNA-microarray data by nonlinear correlation maximization.

Signal data from DNA-microarray ("chip") technology can be noisy; i.e., the signal variation of one gene on a series of repetitive chips can be substantial. It is becoming more and more recognized that a sufficient number of chip replicates has to be made in order to separate correct from incorrect signals. To reduce the systematic fraction of the noise deriving from pipetting errors, from different treatment of chips during hybridization, and from chip-to-chip manufacturing variability, normalization schemes are employed. We present here an iterative nonparametric nonlinear normalization scheme called simultaneous alternating conditional expectation (sACE), which is designed to maximize correlation between chip repeats in all-chip-against-all space. We tested sACE on 28 experiments with 158 Affymetrix one-color chips. The procedure should be equally applicable to other DNA-microarray technologies, e.g., two-color chips. We show that the reduction of noise compared to a simple normalization scheme like the widely used linear global normalization leads to fewer false-positive calls, i.e., to fewer genes which have to be laboriously confirmed by independent methods such as TaqMan or quantitative PCR.

Algorithms↗
PubMed2001

Fever and cancer in perspective.

CONTEXT: A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the phenomenon has not yet been made. OBJECTIVE: To bring together the isolated observations about the coincidence of spontaneous remissions with feverish infections and William Coley's seminal work, as a basis for devising an immunological hypothesis about the putative anti-cancer effect of fever. CONCLUSION: Fever induction under medical guidance may be considered as part of a therapy regimen for cancers of mesodermal origin.

Adult↗
PubMed2000

Heat shock and oxidative stress-induced exposure of hydrophobic protein domains as common signal in the induction of hsp68.

The hypothesis of a common signal for heat shock (HS) and oxidative stress (OS) was analyzed in C6 cells with regard to the induction of heat shock proteins (Hsps). The synthesis rate and level of the strictly inducible Hsp68 was significantly higher after HS (44 degrees C) compared with OS (2 mm H2O2). This difference corresponded to higher and lower activation of the heat shock factor (HSF) by HS and OS, respectively. OS, on the other hand, showed stronger cytotoxicity compared with HS as indicated by drastic lipid peroxidation and inhibition of protein synthesis as well as of mitochondrial and endocytotic activity. Lactic dehydrogenase also revealed stronger inhibition of enzyme activity by OS than by HS as shown in cells and in vitro experiments. Conformational analysis of lactic dehydrogenase by the fluorophore 1-anilinonaphtalene-8-sulfonic acid, however, showed stronger exposure of hydrophobic domains after HS than after OS which correlates positively with the Hsp68 response. Treatment of cells with deoxyspergualin, which exhibits high affinity to Hsps, the putative inhibitors of HSF, strongly increased only OS-induced hsp68 expression. In conclusion, the results suggest that exposure of hydrophobic domains of cytosolic proteins represents the common first signal in the multistep activation pathway of HSF.

Animals↗
PubMed1999

Reliable automatic protein identification from matrix-assisted laser desorption/ionization mass spectrometric peptide fingerprints.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of protein samples from two-dimensional (2-D) gels in conjunction with protein sequence database searches is frequently used to identify proteins. Moreover, the automatic analysis of complete 2-D gels with hundreds and even thousands of protein spots ("proteome analysis") is possible, without human intervention, with the availability of highly accurate mass spectrometry instruments, and high-throughput facilities for preparation and handling of protein samples from 2-D gels. However, the lack of software for precise automatic analysis and annotation of mass spectra, as well as software for in-batch sequence database queries, is increasingly becoming a significant bottleneck for the proteomics work flow. In the present paper we outline an algorithm for reliable, accurate, and automatic evaluation of mass spectrometric data and database searches. We show here that simply selecting from the sequence database the protein that has the most matching fragment masses often leads to false-positive results. Reliable protein identification is dependent on several parameters: the accuracy of fragment mass determination, the number of masses submitted for query, the mass distribution of query masses, the number of masses matching between sample and database protein, the size of the sequence database, and the kind and number of modifications considered. Using these parameters, we derive a simple statistical estimation that can be used to calculate the probability of true-positive protein identification.

Automation↗
PubMed1995

A sequence property approach to searching protein databases.

Currently available sequence alignment programs are generally not capable of detecting functional and structural homologs in the twilight zone of sequence similarity, i.e. when the sequence identity falls below about 25%. Here we attempt to detect such weak similarities using an approach based on a notion of protein sequence similarity radically different from that used in sequential alignment. The approach defines protein sequence dissimilarity (or distance) as a weighted sum of differences of compositional properties such as singlet and doublet amino acid composition, molecular weight, isoelectric point (protein property search or PropSearch). With PropSearch, either single sequences can be used for a database query, or multiple sequences can be merged into an "average" sequence reflecting the average composition of a protein family. First, we show that members of structural protein families have a low mutual PropSearch distance when the weights are optimized to discriminate maximally between structural families. Second, we demonstrate the results of database searches using the PropSearch method. Such searches are very rapid when scanning a preprocessed database and do not require alignments. In cases in which conventional alignment tools fail to detect similarities, PropSearch can be used to generate hypotheses about possible structural or functional relationships between a new sequence and sequences in the database.

Algorithms↗
PubMed1994

Enlarged representative set of protein structures.

To reduce redundancy in the Protein Data Bank of 3D protein structures, which is caused by many homologous proteins in the data bank, we have selected a representative set of structures. The selection algorithm was designed to (1) select as many nonhomologous structures as possible, and (2) to select structures of good quality. The representative set may reduce time and effort in statistical analyses.

Amino Acid Sequence↗
PubMed1994

Amino acid analysis and protein database compositional search as a rapid and inexpensive method to identify proteins.

The identification of protein samples in minute quantities of protein samples, e.g., from two-dimensional polyacrylamide gel electrophoresis analysis, is an everyday problem in biology laboratories. Here we show that computer-assisted amino acid analysis can fulfill this task. Amino acid analysis data can be used to compare the amino acid composition of an unknown protein with protein compositions in a database (compositional search). Routine amino acid analysis data can, despite a certain margin of error, be used to identify a protein. Compared to protein sequencing, amino analysis is much cheaper, faster, and allows higher sample throughput. Thus, the method may replace protein sequencing as a first attempt in identification, provided a homolog can be found in the database.

Amino Acid Sequence↗
PubMed1994

A human cDNA coding for the Leydig insulin-like peptide (Ley I-L).

cDNA clones for the human Leydig insulin-like peptide (Ley I-L) have been isolated and characterized. The nucleotide sequence of the 743-bp cDNA includes an incomplete 7-bp 5'-noncoding region, an open reading frame of 393 bp, and a 343-bp 3'-noncoding region. By primer extension analysis, the transcription start site was determined as being 14-bp upstream of the translation start site. The underlying gene is expressed in the testis but not in other organs. From the cDNA sequence, it can be deduced that the Ley I-L protein is synthesized as a 131-amino-acid (aa) preproprotein and that it contains a 24-aa signal peptide. Comparison of the pro Ley I-L protein with members of the insulin-like hormone superfamily predicts that the biologically active hormone, after proteolytic processing of the C peptide, consists of a 31-aa long B chain and a 26-aa long A chain, and that it has a molecular weight of 6.25 kDa.

Amino Acid Sequence↗
PubMed1993

Does the HIV Nef protein mimic the MHC?

The sequence of the HIV Nef protein has no significant homology to other proteins in the SwissProt database, and experimental data concerning its function are sparse and contradictory. Using a novel protein sequence comparison method, we find similarities between different Nef sequences and the alpha chain of human MHC class I proteins. The possible biological implications of this finding are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A pattern search method for putative anchor residues in T cell epitopes.

The binding affinity between an antigenic peptide and its particular major histocompatibility complex (MHC) molecule seems to be largely determined by only a few residues. These residues have been called "anchors" because of their property of fitting into "pockets" inside the groove of the MHC molecule. To predict natural antigenic epitopes within a longer sequence, it therefore appears to be important to know the motif or pattern describing the anchors, i.e. the anchors amino acid residue preference and the distance between anchor residues. A large set of MHC class I-restricted peptides has been described. Peptide sequences vary in length and lack an obvious common sequence motif. For a list of peptides belonging to one type of MHC class I molecule, we describe a method to find the most prominent sequence motif with at least two anchor residues. Briefly, antigenic sequences are aligned, and two anchor positions are searched for, where all anchor residues share a high similarity. The alignments are scored according to the similarity of their anchor residues. We show that the motifs predicted for the MHC alleles A2.1, B27, Kb, Kd, Db are in substantial agreement with experimental data. We derive binding motifs for the MHC class I alleles HLA-A1, A11, B8, B14, H-2Ld and for the MHC class II alleles I-Ab and I-As. In some cases, higher scores were obtained by allowing a slight variation in the number of residues between anchors. Therefore, we support the view that the length of epitopes belonging to a particular class I MHC is not uniform. This method can be used to predict the natural short epitope inside longer antigenic peptides and to predict the epitopes anchor residues. Anchor motifs can be used to search for antigenic regions in sequences of infectious viruses, bacteria and parasites.

Amino Acid Sequence↗
PubMed1992

Selection of representative protein data sets.

The Protein Data Bank currently contains about 600 data sets of three-dimensional protein coordinates determined by X-ray crystallography or NMR. There is considerable redundancy in the data base, as many protein pairs are identical or very similar in sequence. However, statistical analyses of protein sequence-structure relations require nonredundant data. We have developed two algorithms to extract from the data base representative sets of protein chains with maximum coverage and minimum redundancy. The first algorithm focuses on optimizing a particular property of the selected proteins and works by successive selection of proteins from an ordered list and exclusion of all neighbors of each selected protein. The other algorithm aims at maximizing the size of the selected set and works by successive thinning out of clusters of similar proteins. Both algorithms are generally applicable to other data bases in which criteria of similarity can be defined and relate to problems in graph theory. The largest nonredundant set extracted from the current release of the Protein Data Bank has 155 protein chains. In this set, no two proteins have sequence similarity higher than a certain cutoff (30% identical residues for aligned subsequences longer than 80 residues), yet all structurally unique protein families are represented. Periodically updated lists of representative data sets are available by electronic mail from the file server "netserv@embl-heidelberg.de." The selection may be useful in statistical approaches to protein folding as well as in the analysis and documentation of the known spectrum of three-dimensional protein structures.

Algorithms↗
PubMed1990

A purified cellular extract accelerates the cell cycle in Physarum polycephalum.

Plasmodia of the myxomycete Physarum polycephalum (strain Cl) were collected at different times during the cell cycle and extracts were prepared from homogenates using a buffer optimized for microinjection into plasmodial veins. These extracts were injected into plasmodia during the first 3 h of the cell cycle. The time of the following mitosis was monitored and compared with that of the buffer-injected controls. Extracts of plasmodia homogenized 45 min before late telophase accelerated the onset of mitosis in the injected plasmodium up to 70 min, i.e., an advance of 10-14% compared to the 8- to 10-h cell cycle duration of the controls. The accelerating activity vanished completely after heating, freezing, or protease digestion, thus indicating the peptide nature of the active agent. Purification of the active compound by means of gel filtration revealed a molecular mass of about 2500 Da. The active portion of the extract was further fractionated by HPLC and the activity determined in a single peak.

Animals↗