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  • 1
    ISSN: 1432-1432
    Schlagwort(e): Evolution ; κ-Casein ; Cytochrome b ; Artiodactyla ; Ruminantia ; Caprinae ; Capricornis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Nucleotide sequences for the κ-casein precursor proteins have been determined from the genomic DNAs or hair roots of the Ruminantia. The coding regions, exons 2, 3, and 4, were amplified separately via the three kinds of PCRs and then directly sequenced. The primers were designed from the sequence of bovine κ-casein gene; they were applicable for the amplification of the κ-casein genes from the 13 species in the Ruminantia except exon 2 of the lesser mouse deer. These results permitted an easy phylogenetic analysis based on the sequences of an autosomal gene. A phylogenetic tree was constructed from the mature K-casein sequences and compared with the tree of the cytochrome b genes which were sequenced from the same individuals. The Cervidae (sika deer, Cervus nippon) were separated from the branch of the Bovidae on the tree of κ-casein genes with a relatively high confidence level of the bootstrap analysis, but included in the branch of the Bovidae on the tree of cytochrome b genes. The κ-casein tree indicated a monophyly of the subfamily Caprinae, although the internal branches were uncertain in the Caprinae. The tree based on the nucleotide sequences of cytochrome b genes clearly showed the relationships of the closely related species in the genus Capricornis consisting of serow (C. smatorensis), Japanese serow (C. crispus), and Formosan serow (C. swinhoei). These results would be explained by the difference of resolving power between the κ-casein and the cytochrome b sequences.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 7 (1976), S. 133-149 
    ISSN: 1432-1432
    Schlagwort(e): 5S rRNA ; Nucleotide Sequence Homology ; Evolution ; Mutation Frequencies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The problem of choosing an alignment of two or more nucleotide sequences is particularly difficult for nucleic acids, such as 5S ribosomal RNA, which do not code for protein and for which secondary structure is unknown. Given a set of ‘costs’ for the various types of replacement mutations and for base insertion or deletion, we present a dynamic programming algorithm which finds the optimal (least costly) alignment for a set of N sequences simultaneously, where each sequence is associated with one of the N tips of a given evolutionary tree. Concurrently, protosequences are constructed corresponding to the ancestral nodes of the tree. A version of this algorithm, modified to be computationally feasible, is implemented to align the sequences of 5S RNA from nine organisms. Complete sets of alignments and proto-sequence reconstructions are done for a large number of different con-figurations of mutation costs. Examination of the family of curves of total replacements inferred versus the ratio of transitions/trans-versions inferred, each curve corresponding to a given number of in-sertions-deletions inferred, provides a method for estimating relative costs and relative frequencies for these different types of mutation.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 7 (1976), S. 111-131 
    ISSN: 1432-1432
    Schlagwort(e): Crustacea ; Evolution ; Repeated DNA ; Molecular Hybridization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Analysis of data obtained from molecular hybridization of3H-labeled repetitious DNA has been utilized to reconstruct the broad outlines of phylogenetic relationships among decapod Crustacea. This molecular reconstruction agrees reasonably well with the paleontological record, and with other schemes obtained by comparative morphological and serological approaches. Preliminary evidence is in line with the hypothesis that continuous addition of new repeated sequence families to the genome over long periods of time may in part account for the correlation observed between percent repetitious DNA hybridized and divergence time. It is tentatively concluded that a core of DNA base sequence homology has been highly conserved throughout the evolution of theCrustacea. Demonstration of inter-species sequence homology has important implications to models which relegate a genetic regulatory function to repeated DNAs.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 7 (1976), S. 185-195 
    ISSN: 1432-1432
    Schlagwort(e): Evolution ; Randomicity ; Counter-Example
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Specific counter-examples are derived theoretically to the hypothesis that a random amino acid composition signifies a random evolutionary process.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-1432
    Schlagwort(e): Bacilli, 16S rRNA ; Phylogeny ; Thermophile ; Evolution ; Oligonucleotide Fingerprint
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Two modifications in the Sanger two dimensional electrophoretic procedure for RNA analysis are reported. One increases resolution on the primary fingerprint to the point that digests of large RNAs, of the size 1500–3000 nucleotides yield well resolved fingerprint patterns. The other is a novel endonucleolytic procedure that proves useful in determining sequences of the large oligonucleotides produced by T1 ribonuclease. These modifications have been used in determining the catalogs of oligomers produced by T1 ribonuclease digestion of 16S rRNAs from three related organisms,Bacillus subtilis, B.pumilus andB.stearothermophilus. The possible effects of adaptation to a thermophilic niche on ribosomal RNA primary structure and the phylogenetic relatedness of the two mesophilic Bacilli are discussed.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 8 (1976), S. 79-94 
    ISSN: 1432-1432
    Schlagwort(e): Histones ; Evolution ; Prokaryotes ; Lower Eukaryotes ; Higher Eukaryotes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The occurrence of basic chromosomal proteins in lower eukaryotes provides a useful approach to the study of histone evolution and function in higher eukaryotes. The histones of higher plants and animals are very similar and some are nearly identical, suggesting a high degree of evolutionary conservation within this group of proteins. However, a literature survey reveals that in the lower eukaryotes the histone situation is quite variable. The ciliates, and the true and cellular slime molds possess basic chromosomal proteins that are very similar to the histones of higher plants and animals. Various other lower eukaryotes possess basic chromosomal proteins that resemble at least some of the major histone fractions, and some microorganisms possess basic chromosomal proteins that bear little or no relationship to higher plant and animal histones. Since histones play a major role in the control of gene expression and the maintenance of chromosome structure in higher organisms, the evolution of these proteins represents a major change in the packaging of DNA and the mode of regulating gene expression in eukaryotes.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-1432
    Schlagwort(e): Evolution ; Expression patterns ; α-Amylase ; Glucose repression ; Starch induction ; Intra- and interspecific variation ; Drosophila ; Gene expression ; Regulatory genes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Intraspecific variation of α-amylase activity in D. melanogaster and D. immigrans, which is distantly related to D. melanogaster, and interspecific variation of α-amylase activity in 18 Drosophila species were examined. The amount of intraspecific variation of α-amylase activities measured in terms of coefficient of variation in D. melanogaster and D. immigrans was one-half and one-tenth or less, respectively, of the interspecific variation in 18 Drosophila species. We also surveyed the response patterns of α-amylase activity to dietary carbohydrates at the larval and adult stages. The levels of α-amylase activity depended on both repression by dietary glucose (glucose repression) and induction by dietary starch (starch induction). In general, our data suggest that glucose repression was conserved among species at both stages while starch induction was mainly observed in larvae, although the degree of the response depended on species. In D. lebanonensis lebanonensis and D. serrata, larvae expressed electrophoretically different α-amylase variants (isozymes) from those of adult flies. These results may suggest that the regulatory systems responsible both for the response to environment and developmental expression are different among species in Drosophila.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 8 (1976), S. 387-388 
    ISSN: 1432-1432
    Schlagwort(e): Nitrate Respiration ; Fermentation ; Energy Metabolism ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary E. Broda's recent argument against our concept that nitrate respiration antedated oxygen respiration is criticized.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1432
    Schlagwort(e): Evolution ; Repetitive DNA ; SI Nuclease ; Sequence Organization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The organization of repetitive and single copy DNA sequences in sea urchin DNA has been examined with the single strand specific nuclease Sl fromAspergillus. Conditions and levels of enzyme were established so that single strand DNA was effectively digested while reassociated divergent repetitive duplexes remained enzyme resistant. About 25% of sea urchin DNA reassociates with repetitive kinetics to form Sl resistant duplexes of two distinct size classes derived from long and short repetitive sequences in the sea urchin genome. Fragments 2,000 nucleotides long were reassociated to Cot 20 and subjected to controlled digestion with Sl nuclease. About half of the resistant duplexes (13% of the DNA) are short, with a mode size of about 300 nucleotide pairs. This class exhibits significant sequence divergence, and principally consists of repetitive sequences which were interspersed with single copy sequences. About one-third of the long duplexes (4% of the DNA) are reduced in size after extensive Sl nuclease digestion to about 300 nucleotide pairs. About two-thirds of the long resistant duplexes (8% of the DNA) remains long after extensive SI nuclease digestion. These long reassociated duplexes are precisely base paired. The short duplexes are imprecisely paired with a melting temperature about 9°C below that of precisely paired duplexes of the same length. The relationship between length of repetitive duplex and precision of repetition is confirmed by an independent method and has been observed in the DNA of a number of species over a wide phylogenetic area.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 8 (1976), S. 143-153 
    ISSN: 1432-1432
    Schlagwort(e): 5S rRNA ; Comparative Analysis ; Secondary Structure ; Evolution ; Tuned Helix
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The available comparative data on procaryotic 5S rRNA was extended through sequencing studies of eight gram positive procaryotes. Complete nucleotide sequences were presented for 5S rRNA fromBacillus subtilis, B. firmus, B.pasteurii, B.brevis, Lactobacillus brevis andStreptococcus faecalis. In addition, 5S rRNA oligonucleotide catalogs and partial sequence data were provided forB.cereus andSporosarcina ureae. These sequences and catalogs were discussed in terms of known features of procaryotic 5S rRNA architecture.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 9 (1976), S. 25-35 
    ISSN: 1432-1432
    Schlagwort(e): Genome organization ; Evolution ; Mitochondria
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The mitochondrial genome of yeast (S. cerevisiae orS. carlsbergensis) appears to be formed by 60–70 genetic units, each one of which is formed by (1) a GC-rich sequence, possibly having a regulatory role; (2) a gene, and (3) an AT-rich spacer, which probably is not transcribed. Recombination in this genome appears to underlie a number of important phenomena. The organization of the mitochondrial genome of yeast and these recombinational events are discussed in relationship with the organization and evolution of the nuclear genome of eukaryotes.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 40 (1995), S. 570-577 
    ISSN: 1432-1432
    Schlagwort(e): Alternate reading frames ; Evolution ; Overlapping frames ; Homology search ; Primary sequence analysis ; Polycistronic genes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Hypothetical Products from Noncoding Frames (i.e., HyPNoFs) are hypothetical, not-coded proteins, translated from alternate reading frames (i.e., coding+1 and coding+2) of cDNAs. HyPNoFs of CD4, PKC, oncostatin, bcl-2 proto-oncogene, tumor suppressor p53, cystic fibrosis transmembrane regulator (CFTR), and tumor necrosis factors a and β were searched as query sequences vs the SWISS-PROT data bank. Homology searches carried out revealed that hypothetical products (i.e., HyPNoFs) may share high similarity with real protein products actually coded. Sequence similarity of hypothetical products to real proteins is sometimes very high, suggesting common conformational features, according to the Sander and Schneider cutoff value. This finding supports the hypothesis that eukaryotic DNA, currently considered to be monocistronic, might occasionally have polycistronic regions, carrying different protein messages on overlapping frames. As yet, polycistronic genes have been observed in viral genomes only. The presence of polycistronic regions in eukaryotic genes is likely reminiscent of an ancient strategy, rather than a present feature of the genome in eukaryotes. These data suggest that thorough investigation of HyPNoFs is likely to improve our ability to trace genes' evolution and to investigate structure-function relationships of protein and DNA sequences.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 40 (1995), S. 601-607 
    ISSN: 1432-1432
    Schlagwort(e): Prolamine ; Sperm proteins ; Evolution ; Mammals
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Prolamine P1 genes have been sequenced following PCR amplification from 11 mammals representing five major mammalian orders: Rodentia (rat and guinea pig), Carnivora (cat and bear), Proboscidea (elephant), Perissodactyla (horse), and Artiodactyla (camel, deer, elk, moose, and gazelle). The predicted amino acid sequence for these genes together with previously reported sequences results in a data set of 25 different P1 genes and 30 different P1 amino acid sequences. The alignment of all these sequences reveals that prolamines are amongst the most rapidly diverging proteins studied. In spite of the large number of differences there are conserved motifs that are also common to birds such as the N-terminal ARYR followed by the triple alternating SRSRSR phosphorylation site. The central region contains 3 arginine clusters consisting of 5–6 arginines each. The C-terminus appears to be the most variable region of the protamines. Overall the molecular evolution of P1 genes is in agreement with the expected species evolution supporting that these genes have evolved vertically.
    Materialart: Digitale Medien
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  • 14
    ISSN: 1432-1432
    Schlagwort(e): Snake venom ; Bothrops ; Phospholipase ; Myotoxin ; Evolution ; cDNA ; Gene duplication ; Phylogeny
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The sequence coding for a snake venom phospholipase A2 (PLA2), BJUPLA2, has been cloned from a Bothrops jararacussu venom gland cDNA library. The cDNA sequence predicts a precursor containing a 16-residue signal peptide followed by a molecule of 122 amino acid residues with a strong sequence similarity to group II snake venom PLA2's. A striking feature of the cDNA is the high sequence conservation of the 5′ and 3′ untranslated regions in cDNAs coding for PLA2's from a number of viper species. The greatest sequence variation was observed between the regions coding for the mature proteins, with most substitutions occurring in nonsynonymous sites. The phylogenetic tree constructed by alignment of the amino acid sequence of BJUPLA2 with group II PLA2's in general groups them according to current taxonomical divisions and/or functional activity. It also suggests that gene duplications may have occurred at a number of different points during the evolution of snake venom group II PLA2's.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 238-246 
    ISSN: 1432-1432
    Schlagwort(e): Cellular slime molds ; Animals ; Fungi ; Plantae ; Maximum-likelihood method ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The phylogenetic position of Dictyostelium inferred from 18S rRNA data contradicts that from protein data. Protein trees always show the close affinity of Dictyostelium with animals, fungi, and plants, whereas in 18S rRNA trees the branching of Dictyostelium is placed at a position before the massive radiation of protist groups including the divergence of the three kingdoms. To settle this controversial issue and to determine the correct position of Dictyostelium, we inferred the phylogenetic relationship among Dictyostelium and the three kingdoms Animalia, Fungi, and Plantae by a maximum-likelihood method using 19 different protein data sets. It was shown at the significance level of 1 SE that the branching of Dictyostelium antedates the divergence of Animalia and Fungi, and Plantae is an outgroup of the Animalia-Fungi-Dictyostelium clade.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 293-298 
    ISSN: 1432-1432
    Schlagwort(e): β-tubulin ; Evolution ; Gene cluster ; Gene dispersion ; Drosophila montium subgroup
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The β1-, β2-, and β3-tubulin genes have been mapped by in situ hybridization on the polytene chromosomes of 11 selected species (15 strains) belonging to theDrosophila montium subgroup. Although the hybridization pattern among the strains of the same species does not differ, this pattern is significantly different among the species. The β-tubulin genes in themontium subgroup seem to be organized in a cluster, or in a semi-cluster, or are completely dispersed. The clustered arrangement is found in the North-Oriental sibling speciesD. auraria, D. triauraria, andD. quadraria. The semi-clustered arrangement, wherein the β1 and β2 genes are located at the same locus while β3 is at a different one, appears in the South-Oriental speciesD. bicomuta, D. serrata, andD. birchii, as well as in the Afrotropical speciesD. diplacantha andD. seguyi. The complete separation of the genes is observed in the Indian speciesD. kikkawai andD. jambulina and in the Afrotropical speciesD. vulcana. Based on the above results, a possible mode of evolution of the β-tubulin genes in the montium subgroup is attempted. In addition, phylogenetic relationships among themontium species are discussed.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 293-298 
    ISSN: 1432-1432
    Schlagwort(e): β-tubulin ; Evolution ; Gene cluster ; Gene dispersion ; Drosophila montium subgroup
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The β1-, β2-, and β3-tubulin genes have been mapped by in situ hybridization on the polytene chromosomes of 11 selected species (15 strains) belonging to the Drosophila montium subgroup. Although the hybridization pattern among the strains of the same species does not differ, this pattern is significantly different among the species. The β-tubulin genes in the montium subgroup seem to be organized in a cluster, or in a semi-cluster, or are completely dispersed. The clustered arrangement is found in the North-Oriental sibling species D. auraria, D. triauraria, and D. quadraria. The semi-clustered arrangement, wherein the β1 and β2 genes are located at the same locus while β3 is at a different one, appears in the South-Oriental species D. bicomuta, D. serrata, and D. birchii, as well as in the Afrotropical species D. diplacantha and D. seguyi. The complete separation of the genes is observed in the Indian species D. kikkawai and D. jambulina and in the Afrotropical species D. vulcana. Based on the above results, a possible mode of evolution of the β-tubulin genes in the montium subgroup is attempted. In addition, phylogenetic relationships among the montium species are discussed.
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  • 18
    ISSN: 1432-1432
    Schlagwort(e): Giardia ; Trichomonas ; CDK ; CDC ; Unicellular ; Metazoa ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Cyclin-dependent kinase (CDK) and cell division control (CDC2) sequences are strongly conserved among eukaryotes and may complement the use of other sequence families in eukaryotic phylogenetic inference. We synthesized degenerate PCR primers to amplify the catalytic region of CDK homologs in representatives of the earliest available lineages of eukaryotes. CDK family sequence-based, maximum-likelihood distance measurements with neighbor joining, and Fitch-Margoliash least-squares analyses produced unrooted dendrograms that included protists, yeasts, and higher eukaryotes. Bootstrap confidence estimates supported CDK-based phylogenetic groupings among the protists, fungi, and vertebrates although resolution within these groups was often insignificant. However, Trichomonas vaginalis and Giardia lamblia exhibited two of the most divergent CDK-like sequences consistent with rRNA-phylogenetic inference of early divergence of these eukaryotic lineages. In the evolution from unicellular to multicellular organisms, a constellation of amino acid residues aligning with the human, CDK N-terminal β sheet may have undergone abrupt replacement.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 813-832 
    ISSN: 1432-1432
    Schlagwort(e): Phylogeny ; Evolution ; Carbamoylphosphate synthetase ; Dihydroorotase ; Aspartate transcarbamoylase ; Intron ; Exon ; Arginine biosynthesis ; Pyrimidine biosynthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Carbamoylphosphate is a common intermediate in the metabolic pathways leading to the biosynthesis of arginine and pyrimidines. The amino acid sequences of all available proteins that catalyze the formation of carbamoylphosphate were retrieved from Genbank and aligned to estimate their mutual phylogenetic relations. In gram-negative bacteria carbamoylphosphate is synthesized by a two-subunit enzyme with glutamiriase and carbamoylphosphate synthetase (CPS) activity, respectively. In gram-positive bacteria and lower eukaryotes this two-subunit CPS has become dedicated to arginine biosynthesis, while in higher eukaryotes the two subunits fused and subsequently lost the glutaminase activity. The CPS dedicated to pyrimidine synthesis is part of a multifunctional enzyme (CPS II), encoding in addition dihydroorotase and aspartate transcarbamoylase. Evidence is presented to strengthen the hypothesis that the two “kinas” subdomains of all CPS isozymes arose from a duplication of an ancestral gene in the progenote. A further duplication of the entire CPS gene occurred after the divergence of the plants and before the divergence of the fungi from the eukaryotec root, generating the two isoenzymes involved in either the synthesis of arginine or that of pyrimidines. The mutation rate was found to be five- to tenfold higher after the duplication than before, probably reflecting optimization of the enzymes for their newly acquired specialized function. We hypothesize that this duplication arose from a need for metabolic channeling for pyrimidine biosynthesis as it was accompanied by the tagging of the CPS gene with the genes for dihydroorotase and aspartate transcarbamoylase, and as the duplication occurred independently also in gram-positive bacteria. Analysis of the exon-intron organization of the two “kinase” subdomains in CPS I and II suggests that ancient exons may have comprised approx. 19 amino acids, in accordance with the prediction of the “intron-early” theory.
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 850-858 
    ISSN: 1432-1432
    Schlagwort(e): Ribonuclease ; Gene duplication ; Evolution ; Ruminants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Phylogenetic analysis, based on the primary structures of mammalian pancreatic-type ribonucleases, indicated that gene duplication events, which occurred during the evolution of ancestral ruminants, gave rise to the three paralogous enzymes present in the bovine species. Herein we report data that demonstrate the existence of the orthologues of the bovine pancreatic, seminal, and cerebral ribonucleases coding sequences in the genomes of giraffe and sheep. The “seminal” sequence is a pseudogene in both species. We also report an analysis of the transcriptional expression of ribonuclease genes in sheep tissues. The data presented support a model for positive selection acting on the molecular evolution of ruminant ribonuclease genes.
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 40 (1995), S. 482-486 
    ISSN: 1432-1432
    Schlagwort(e): Aminoacyl-tRNA synthetase ; Computer analysis ; Evolution ; Genetic code ; tRNA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract tRNA sequences were analyzed for sequence features correlated with known classes of aminoacyl-tRNA synthetase enzymes. The tRNAs were searched for distinguishing nucleotides anywhere in their sequences. The analyses did not find nucleotides predictive of synthetase class membership. We conclude that such nucleotides never existed in tRNA sequences or that they existed and were lost from many of the tRNA sequences during evolution.
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 40 (1995), S. 476-481 
    ISSN: 1432-1432
    Schlagwort(e): Aminoacylation ; Aminoacyl-tRNA synthetases ; tRNA ; GluRS ; GlnRS ; Glutamate ; Glutamine ; Evolution ; Mischarging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Aminoacyl-tRNA for protein synthesis is produced through the action of a family of enzymes called aminoacyl-tRNA synthetases. A general rule is that there is one aminoacyl-tRNA synthetase for each of the standard 20 amino acids found in all cells. This is not universal, however, as a majority of prokaryotic organisms and eukaryotic organelles lack the enzyme glutaminyl-tRNA synthetase, which is responsible for forming Gln-tRNAGln in eukaryotes and in Gram-negative eubacteria. Instead, in organisms lacking glutaminyl-tRNA synthetase, Gln-tRNAGln is provided by misacylation of tRNAGln with glutamate by glutamyl-tRNA synthetase, followed by the conversion of tRNA-bound glutamate to glutamine by the enzyme Glu-tRNAGln amidotransferase. The fact that two different pathways exist for charging glutamine tRNA indicates that ancestral prokaryotic and eukaryotic organisms evolved different cellular mechanisms for incorporating glutamine into proteins. Here, we explore the basis for diverging pathways for aminoacylation of glutamine tRNA. We propose that stable retention of glutaminyl-tRNA synthetase in prokaryotic organisms following a horizontal gene transfer event from eukaryotic organisms (Lamour et al. 1994) was dependent on the evolving pool of glutamate and glutamine tRNAs in the organisms that acquired glutaminyl-tRNA synthetase by this mechanism. This model also addresses several unusual aspects of aminoacylation by glutamyl- and glutaminyl-tRNA synthetases that have been observed.
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  • 23
    ISSN: 1432-1432
    Schlagwort(e): Aminoacyl-tRNA synthetases ; tRNA ; Genetic code ; RNA world ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Two aspects of the evolution of aminoacyl-tRNA synthetases are discussed. Firstly, using recent crystal structure information on seryl-tRNA synthetase and its substrate complexes, the coevolution of the mode of recognition between seryl-tRNA synthetase and tRNAser in different organisms is reviewed. Secondly, using sequence alignments and phylogenetic trees, the early evolution of class 2 Amnoacyl-tRNA synthetases is traced. Arguments are presented to suggest that synthetases are not the oldest of protein enzymes, but survived as RNA enzymes during the early period of the evolution of protein catalysts. In this view, the relatedness of the current synthetases, as evidenced by the division into two classes with their associated subclasses, reflects the replacement of RNA synthetases by protein synthetases. This process would have been triggered by the acquisition of tRNA 3′ end charging activity by early proteins capable of activating small molecules (e.g., amino acids) with ATP. If these arguments are correct, the genetic code was essentially frozen before the protein synthetases that we know today came into existence. Correspondence to: S. Cusack
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 996-1005 
    ISSN: 1432-1432
    Schlagwort(e): Repetitive DNA ; Tandem repeats ; Sequence analysis ; Phylogenetic tree ; Silent repeats ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Two different satellite DNAs exist in the genus Cucurbita which are different with respect to repeat length (350 by and 170 bp), array size, and sequence homogenization. Whereas the 350-bp satellite DNA is prominent and very homogeneous in all species investigated except for C. maxima and C. lundelliana, the 170-bp satellite is rather evenly distributed in all species. In C. maxima and C. lundelliana the 350-bp satellite is present only in small amounts, but detectable by the sensitive PCR method. These repeats are also very homogeneous, reflecting a silent stage of satellite DNA. In contrast, the 170-bp satellite DNA is intra- and interspecifically heterogeneous. It is striking that the species with no detectable amount of 350-bp satellite contain 170-bp satellite DNA clusters with the highest degree of homogeneity. The evolution of satellite DNA repeats within cultivated and wild species in the genus Cucurbita is elucidated using the sequence data of both satellite DNAs from all species investigated. The value of satellite DNA for phylogenetic analysis between closely related species is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 40 (1995), S. 120-126 
    ISSN: 1432-1432
    Schlagwort(e): Simple repetitive DNA ; Microsatellites ; Unstable triplets ; Database ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Simple repeats composed of tandemly repeated units 1–6 nucleotides (nt) long have been extracted from a selected set of primate genomic DNA sequences. Of the 501 theoretically possible, different types of repeats only 67 were present in the analyzed database in at least two different size ranges over 12 nt. They include all simple repeats known to be polymorphic in the primate genome. A list of moderately expanding and nonexpanding oligonucleotide patterns has also been included. Furthermore, we have compiled statistical data with emphasis on the overall variability of the most abundant 67 types of repeats. We have demonstrated that the expandability of at least some simple repeats may be affected by the overall base composition and by flanking sequences. In particular, the occurrence of tandemly repeated CAG and GCC triplets in exons positively correlates with their G+C content. We also noted that in the vicinity of Alu sequences tetrameric repeats are more abundant than in the total genomic DNA. This paper can be used as a comprehensive guide in identification of the most abundant and potentially polymorphic simple repeats. It is also of broader significance as a step toward understanding the contribution of flanking sequences and the overall sequence composition to variability of simple repeats.
    Materialart: Digitale Medien
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 457-466 
    ISSN: 1432-1432
    Schlagwort(e): Seed storage proteins ; Legumin ; Gene structure ; Evolution ; Gymnosperms ; Ginkgo biloba
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Legumin-like seed storage proteins have been intensively studied in crop plants. However, little is known about the molecular evolution of these proteins and their genes and it was assumed that they originated from an ancestral gene that already existed at the beginning of angiosperm evolution. We have evidence for the ubiquitous occurrence of homologous proteins in gymnosperms as well. We have characterized the major seed storage globulin from Ginkgo biloba by amino acid sequencing, which reveals clear homology to legumin-like proteins from angiosperms. The Ginkgo legumin is encoded by a gene family; we describe two of its members. The promoter regions contain sequence motifs which are known to function as regulatory elements involved in seed-specific expression of angiosperm legumins, although the tissues concerned are different in gymnosperms and angiosperms. The Ginkgo legumin gene structure is divergent from that of angiosperms and suggests that the evolution of legumin genes implicated loss of introns. From our data and from functional approaches recently described it becomes obvious that the posttranslational processing site of legumin precursors is less conserved than hitherto assumed. Finally, we present a phylogenetic analysis of legumin encoding sequences and discuss their utility as molecular markers for the reconstruction of seed plant evolution.
    Materialart: Digitale Medien
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 492-497 
    ISSN: 1432-1432
    Schlagwort(e): Primate ; Microsatellite ; Evolution ; Mutation process
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Dimeric short tandem repeats are a source of highly polymorphic markers in the mammalian genome. Genetic variation at these hypervariable loci is extensively used for linkage analysis, for the identification of individuals, and may be useful for interpopulation and interspecies studies. In this paper, we analyze the variability and the sequences of a segment including three microsatellites, first described in man, in several species of primates (chimpanzee, orangutan, gibbon, and macaque) using the heterologous primers (man primers). This region is located on the human chromosome 6p, near the tumor necrosis factor genes, in the major histocompatibility complex. The fact that these primers work in all species studied indicates that they are conserved throughout the different lineages of the two superfamilies, the Hominoidea and the Cercopithecidea, represented by the macaques. However, the intervening sequence displays intraspecific and interspecific variability. The sites of base substitutions and the insertion/ deletion events are not evenly distributed within this region. The data suggest that it is necessary to have a minimal number of repeats to increase the rate of mutation sufficiently to allow the development of polymorphism. In some species, the microsatellites present single base variations which reduce the number of contiguous repeats, thus apparently slowing the rate of additional slippage events. Species with such variations or a low number of repeats are monomorphic. These microsatellite sequences are informative in the comparison of closely related species and reflect the phylogeny of the Old World monkeys, apes, and man.
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    Standort Signatur Erwartet Verfügbarkeit
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Journal of comparative physiology 183 (1998), S. 635-650 
    ISSN: 1432-1351
    Schlagwort(e): Key words Olfactory receptors ; Multigene families ; Pseudogenes ; Vertebrate species ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract In species representing different levels of vertebrate evolution, olfactory receptor genes have been identified by molecular cloning techniques. Comparing the deduced amino-acid sequences revealed that the olfactory receptor gene family of Rana esculenta resembles that of Xenopus laevis, indicating that amphibians in general may comprise two classes of olfactory receptors. Whereas teleost fish, including the goldfish Carassius auratus, possess only class I receptors, the `living fossil' Latimeria chalumnae is endowed with both receptor classes; interestingly, most of the class II genes turned out to be pseudogenes. Exploring receptor genes in aquatic mammals led to the discovery of a large array of only class II receptor genes in the dolphin Stenella Coeruleoalba; however, all of these genes were found to be non-functional pseudogenes. These results support the notion that class I receptors may be specialized for detecting water-soluble odorants and class II receptors for recognizing volatile odorants. Comparing the structural features of both receptor classes from various species revealed that they differ mainly in their extracellular loop 3, which may contribute to ligand specificity. Comparing the number and diversity of olfactory receptor genes in different species provides insight into the origin and the evolution of this unique gene family.
    Materialart: Digitale Medien
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 40 (1995), S. 405-412 
    ISSN: 1432-1432
    Schlagwort(e): Primate ; Evolution ; Heterochromatin ; Repetitive sequences ; β Satellite sequences ; L1 transposon ; Polymerase chain reaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The genomes of four primate species, belonging to the families Pongidae (chimpanzee, gorilla, and orangutan) and Hylobatidae (gibbons), have been analyzed for the presence and organization of two human GC-rich heterochromatic repetitive sequences: βSatellite (βSat) and LongSau (LSau) repeats. By Southern blot hybridization and PCR, both families of repeats were detected in all the analyzed species, thus indicating their origin in an ape ancestor. In the chimpanzee and gorilla, as in man, βSat sequences showed a 68-bp Sau3A periodicity and were preferentially organized in large clusters, whereas in the orangutan, they were organized in DNA fragments of 550 bp, which did not seem to be characterized by a tandem organization. On the contrary, in each of the analyzed species, the bulk of LSau sequences showed a longer Sau3A periodicity than that observed in man (450–550 bp). Furthermore, only in the chimpanzee genome some of LSau repeats seemed to be interspersed within blocks of βSat sequences. This sequence organization, which also characterizes the human genome, is probably absent in the gorilla. In fact, the analysis of a gorilla genomic library suggested that LSau repeats are not preferentially in linkage with βSat sequences. Moreover, LSau sequences were found in a genomic sector characterized by the simultaneous presence of L1 and (CA) repeats, as well as of anonymous sequences and known genes. In spite of the different sequence organization, the nucleotide differences between complete human and gorilla LSau repeats were very few, whereas one gorilla LSau repeat, interrupted by a probably-truncated L1 transposon, showed a higher degree of divergence. Besides the gorilla, this unusual sequence organization was detected in man, and, to a lesser extent, in the chimpanzee.
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  • 30
    ISSN: 1432-1432
    Schlagwort(e): Chloroplasts ; Evolution ; Rubisco ; Picoplankton ; Prochloron ; Prochlorothrix ; Prochlorococcus ; Prochlorales
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The prochlorophytes, oxygenic photosynthetic prokaryotes having no phycobiliprotein but possessing chlorophylls a and b, have been proposed to have a common ancestry with green chloroplasts, yet this is still controversal. We report here that partial sequence comparisons of the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, including sequence data from two prochlorophytes, Prochlorococcus and Prochloron, indicate that Prochlorococcus is more closely related to a photosynthetic bacterium, Chromatium vinosum (γ-purple bacteria), than to cyanobacteria, while Prochloron is closely related to the prochlorophyte Prochlorothrix and to cyanobacteria. The molecular phylogenetic tree indicates that a common ancestor of Prochlorococcus and γ-purple bacteria branched off from the land plant lineage earlier than Prochloron, Prochlorothrix, and cyanobacteria.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 41 (1995), S. 46-53 
    ISSN: 1432-1432
    Schlagwort(e): Alcohol dehydrogenase ; Caenorhabditis elegans ; Evolution ; Gene families
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract We have characterized two cDNA clones from the nematode Caenorhabditis elegans that display similarity to the alcohol dehydrogenase (ADH) gene family. The nucleotide sequences of these cDNAs predict that they encode Zn-containing long-chain ADH enzymes. Phylogenetic analysis suggests that one is most similar to dimeric class III ADHs found in diverse taxa; the other is most similar to the tetrameric forms of ADH previously described only in fungi.
    Materialart: Digitale Medien
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  • 32
    ISSN: 1432-1432
    Schlagwort(e): Cyanelles ; Cyanophora paradoxa ; Endosymbiosis ; Evolution ; Glaucocystophyta ; Glaucophyta ; Phylogeny ; Plastid ; 16S ribosomal RNA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Glaucocystophyte algae (sensu Kies, Berl. Deutsch. Bot. Ges. 92, 1979) contain plastids (cyanelles) that retain the peptidoglycan wall of the putative cyanobacterial endosymbiont; this and other ultrastructural characters (e.g., unstacked thylakoids, phycobilisomes) have suggested that cyanelles are “primitive” plastids that may represent undeveloped associations between heterotrophic “host” cells (i.e., glaucocystophytes) and cyanobacteria. To test the monophyly of glaucocystophyte cyanelles and to determine their evolutionary relationship to other plastids, complete 16S ribosomal RNA sequences were determined for Cyanophora paradoxa, Glaucocystis nostochinearum, Glaucosphaera vacuolata, and Gloeochaete wittrockiana. Plastid rRNAs were analyzed with the maximum-likelihood, maximumparsimony, and neighbor joining methods. The phylogenetic analyses show that the cyanelles of C. paradoxa, G. nostochinearum, and G. wittrockiana form a distinct evolutionary lineage; these cyanelles presumably share a monophyletic origin. The rDNA sequence of G. vacuolata was positioned within the nongreen plastid lineage. This result is consistent with analyses of nuclear-encoded rRNAs that identify G. vacuolata as a rhodophyte and support its removal from the Glaucocystophyta. Results of a global search with the maximumlikelihood method suggest that cyanelles are the first divergence among all plastids; this result is consistent with a single loss of the peptidoglycan wall in plastids after the divergence of the cyanelles. User-defined tree analyses with the maximum-likelihood method indicate, however, that the position of the cyanelles is not stable within the rRNA phylogenies. Both maximumparsimony and neighbor-joining analyses showed a close evolutionary relationship between cyanelles and nongreen plastids; these phylogenetic methods were sensitive to inclusion/exclusion of the G. wittrockiana cyanelle sequence. Base compositional bias within the G. wittrockiana 16S rRNA may explain this result. Taken together the phylogenetic analyses are interpreted as supporting a near-simultaneous radiation of cyanelles and green and nongreen plastids; these organelles are all rooted within the cyanobacteria.
    Materialart: Digitale Medien
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    Surveys in geophysics 16 (1995), S. 533-591 
    ISSN: 1573-0956
    Schlagwort(e): Satellites ; Giant planets ; Origin ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geologie und Paläontologie , Physik
    Notizen: Abstract The paper reviews the problem of formation and evolution of the so-called “regular satellites “ of the giant planets, and it consists of two parts: the first describes the possible origin of the satellites, the second studies their evolution, attempting to stress the relations of the present status of the satellites with their evolutionary history. The formation of regular satellite systems around giant planets is probably related to the formation of the central planet. Some characteristics of regular satellite systems are quite similar, and suggest a common origin in a disk present around the central body. This disk can originate through different mechanisms which we will describe, paying attention to the so-called “accretion disk” model, in which the satellite-forming material is captured. The disk phase links the formation of the primary body with the formation of satellites. The subsequent stages of the disk's evolution can lead first to the formation of intermediate size bodies, and through the collisional evolution of these bodies, to the birth of satellite “embryos” able to gravitationally capture smaller bodies. Given the scenario in which icy satellites may be formed by homogeneous accretion of planetesimals made of a mixtures of ice and silicates, if no melting occurs during accretion, the satellites have a homogeneous ice-rock composition. For the smaller satellites this homogeneous structure should not be substantially modified; only sporadic local events, such as large impacts, can modify the surface structure of the smaller satellites. For the larger satellites, if some degree of melting appears during accretion, a differentiation of the silicate part occurs, the amount of differentiation and hence the core size depending on the fraction of gravitational potential energy retained during the accumulation process. Melting and differentiation soon after the accretion, for the larger satellites, could also depend on the convective evolution in presence of phase transitions and generate an intermediate rock layer, considerably denser than the underlying, still homogeneous core, and unstable to overturning on a geologic time scale. Moreover the liquid water mantle could be a transient feature because the mantle would freeze over several hundred million years. For these large bodies the stable configuration is expected to be one consisting of a silicate core and a mantle of mixed rock and ice.
    Materialart: Digitale Medien
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Journal of statistical physics 90 (1998), S. 191-210 
    ISSN: 1572-9613
    Schlagwort(e): Evolution ; birth/death processes ; mean-field ; population dynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Physik
    Notizen: Abstract The role of mutational bias in evolution on a smooth landscape is investigated. We consider both a finite-length genome where the bias increases linearly with the fitness, and an infinite genome with a fixed bias. We present simulations of finite populations in a waiting time model, showing both the nonequilibrium dynamics and the equilibrium fitness distributions that are reached. We compute the equilibrium analytically in several cases, using approximate direct solution of the master equations and truncated hierarchies.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Development genes and evolution 208 (1998), S. 591-594 
    ISSN: 1432-041X
    Schlagwort(e): Key words Arthropod ; Hox ; Evolution ; Development ; Chelicerate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  We have cloned, from an oribatid mite, a gene homologous to the zerknült (zen) genes of insects and the Hox 3 genes of vertebrates. Hox genes specify cell fates in specific regions of the body in all metazoans studied and are expressed in antero-posteriorly restricted regions of the embryo. This is true of the vertebrate Hox 3 but not of the zen genes, the insect homologs, and it has been proposed that the zen genes have lost their Hox-like function in the ancestor of the insects. We studied expression of a mite Hox 3/zen homolog and found that it is expressed in a discrete antero-posterior region of the body with an anterior boundary coinciding with that of the chelicerate homolog of the Drosophila Hox gene, proboscipedia, and propose that its loss of Hox function in insects is due to functional redundancy due to this overlap with another Hox gene.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Development genes and evolution 208 (1998), S. 113-116 
    ISSN: 1432-041X
    Schlagwort(e): Key words TALE homeobox gene ; MEINOX domain ; Hox cluster ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  A recent survey of TALE superclass homeobox genes revealed a new domain upstream of the homeodomain that is conserved between the plant KNOX genes and the animal MEIS genes. At the same time, another paper identified the Drosophila gene homothorax (hth) as a homologue of the vertebrate MEIS genes, which prompted a reexamination of the sequences of the MEIS, KNOX (collectively named MEINOX) and PBC domains. Similarity of the complete MEINOX domain was found within the PBC domain. This suggests that the PBC class genes were also derived from the ancient MEINOX genes. Recently, it has been shown that the MEIS genes can interact with the Abd-B genes, whilst previous results have shown that the PBC genes interact with anterior Hox genes. This leads to the hypothesis that the duplication of an ancestral MEINOX gene into the PBC and MEIS genes happened at a point in time when the first two Hox cluster genes, an anterior one and a posterior one, emerged, and that subsequently these gene classes coevolved.
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  • 37
    ISSN: 1432-041X
    Schlagwort(e): Key words Amphioxus ; Snail ; Neural crest ; Evolution ; Chordate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  Homologs of the Drosophila snail gene have been characterized in several vertebrates. In addition to being expressed in mesoderm during gastrulation, vertebrate snail genes are also expressed in presumptive neural crest and/or its derivatives. Given that neural crest is unique to vertebrates and is considered to be of fundamental importance in their evolution, we have cloned and characterized the expression of a snail gene from amphioxus, a cephalochordate widely accepted as the sister group of the vertebrates. We show that, at the amino acid sequence level, the amphioxus snail gene is a clear phylogenetic outgroup to all the characterized vertebrate snail genes. During embryogenesis snail expression initially becomes restricted to the paraxial or presomitic mesoderm of amphioxus. Later, snail is expressed at high levels in the lateral neural plate, where it persists during neurulation. Our results indicate that an ancestral function of snail genes in the lineage leading to vertebrates is to define the paraxial mesoderm. Furthermore, our results indicate that a cell population homologous to the vertebrate neural crest may be present in amphioxus, thus providing an important link in the evolution of this key vertebrate tissue.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    Development genes and evolution 208 (1998), S. 94-99 
    ISSN: 1432-041X
    Schlagwort(e): Key words T-box ; Evolution ; Zebrafish ; Paraxial mesoderm ; Tail bud
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  We report on a new zebrafish T-box-containing gene, tbx16. It encodes a message that is first detected throughout the blastoderm soon after the initiation of zygotic gene expression. Following gastrulation, expression becomes restricted to paraxial mesoderm and later primarily to the developing tail bud. To gain an evolutionary prospective on the potential function of this gene, we have analyzed its phylogenetic relationships to known T-box genes from other species. Zebrafish tbx16 is likely orthologous to the chicken Tbx6L and Xenopus Xombi/Antipodean/Brat/VegT genes. Our analysis also shows that zebrafish tbx6 and mouse Tbx6 genes are paralogous to zebrafish tbx16. We present evidence which argues, that despite the same name and similar expression, zebrafish tbx6 and mouse Tbx6 genes are not orthologous to each other but instead represent relatively distant paralogs. The expression patterns of all genes are discussed in the light of their evolutionary relationships.
    Materialart: Digitale Medien
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  • 39
    ISSN: 1432-041X
    Schlagwort(e): Key words Tooth morphogenesis ; Evolution ; Mouse ; Microtus rossiaemeridionalis ; Enamel knot
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  While the evolutionary history of mammalian tooth shapes is well documented in the fossil record, the developmental basis of their tooth shape evolution is unknown. We investigated the expression patterns of eight developmental regulatory genes in two species of rodents with different molar morphologies (mouse, Mus musculus and sibling vole, Microtus rossiaemeridionalis). The genes Bmp-2, Bmp-4, Fgf-4 and Shh encode signal molecules, Lef-1, Msx-1 and Msx-2, are transcription factors and p21 CIP1/WAF1 participates in the regulation of cell cycle. These genes are all known to be associated with developmental regulation in mouse molars. In this paper we show that the antisense mRNA probes made from mouse cDNA cross-hybridized with vole tissue. The comparisons of gene expression patterns and morphologies suggest that similar molecular cascades are used in the early budding of tooth germs, in the initiation of tooth crown base formation, and in the initiation of each cusp’s development. Furthermore, the co-localization of several genes indicate that epithelial signalling centres function at the three stages of morphogenesis. The earliest signalling centre in the early budding epithelium has not been reported before, but the latter signalling centres, the primary and the secondary enamel knots, have been studied in mouse. The appearance of species-specific tooth shapes was manifested by the regulatory molecules expressed in the secondary enamel knots at the areas of future cusp tips, whilst the mesenchymal gene expression patterns had a buccal bias without similar species-specific associations.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 40
    ISSN: 1432-041X
    Schlagwort(e): Key words Astacin ; Metalloproteinase ; Toxin ; Cnidaria ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  Metalloproteinases of the astacin family such as tolloid play major roles in animal morphogenesis. Cnidarians are thought to be evolutionary simple organisms and, therefore, a metalloproteinase from the marine hydrozoan Podocoryne carnea was analysed to evaluate the role of this conserved gene familiy at the base of animal evolution. Surprisingly, the proteinase domain of Podocornyne PMP1 is more similar to human meprin than to HMP1 from another hydrozoan, the freshwater polyp Hydra vulgaris. However, PMP1 and HMP1 both contain a small C-terminal domain with six cysteines that distinguishes them from other astacin-like molecules. Similar domains have been described only recently from sea anemone toxins specific for potassium channels. This toxin homology (Tox1) domain is clearly distinct from epidermal growth factor (EGF)-like domains or other cysteine-rich modules and terminates with the characteristic pattern CXXXCXXC with three out of six cysteines in the last eight residues of the protein. PMP1 is transiently expressed at various sites of morphogenetic activity during medusa bud development. In the adult medusa, however, expression is concentrated to the manubrium, the feeding organ, where the PMP1 gene is highly induced upon feeding. These disparate expression patterns suggest a dual role of PMP1 comparable to tolloid in development and, like astacin in the crayfish, also for food digestion. The Tox1 domain of PMP1 could serve as a toxin to keep the pray paralysed after ingestion, but as a sequence module such Tox1 domains with six cysteines are neither restricted to cnidarians nor to toxins.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    Development genes and evolution 205 (1995), S. 160-170 
    ISSN: 1432-041X
    Schlagwort(e): Drosophila ; Evolution ; fz ; Homeodomain ; Plasticity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The Drosophila melanogaster segmentation gene fushi tarazu (ftz) encodes a homeodomain-type transcription factor involved in the control of larval pattern formation. Loss of function mutations cause an embryonic lethal, pair-rule phenotype. The segmentation defects, but not the lethality, can be partially rescued by the ftz orthologue from Drosophila hydei. In this work, the primary structure, expression and regulation of the D. hydei ftz gene was characterized. Sequence comparisons classify ftz as a rather fast evolving gene. However, since the homeodomain of the D. hydei FTZ protein is highly similar to that of D. melanogaster, proper regulation of D. melanogaster ftz downstream genes would be expected. In D. melanogaster embryos, a D. hydei ftz transgene is expressed normally, independent of endogenous ftz gene activity, suggesting that D. hydei ftz regulatory sequences are correctly recognized by D. melanogaster transcription factors. Accordingly, lacZ fusion constructs driven by the D. hydei ftz upstream element are expressed normally in D. melanogaster embryos. Altogether, the similarities between the two ftz orthologues by far outweigh the differences. The limited success of the trans-species rescue might be, therefore, a consequence of the accumulation of too many subtle changes in gene function, exceeding the limits of developmental plasticity during fly embryogenesis.
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  • 42
    ISSN: 1432-1211
    Schlagwort(e): Key words β2-microglobulin ; Primates ; Evolution ; Diversity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Nucleotide sequences for the three exons of the β2-microglobulin (β2m) gene (B2m) were determined for 135 animals representing 37 species and all 16 genera of neotropical primates (Platyrrhini). Twenty-eight different nucleotide sequences, encoding for 26 different proteins, were obtained. In comparison with those of other primate species, the β2-microglobulins of the Platyrrhini form a distinct clade. Individual genera of neotropical primates have distinctive B2m sequences, but within a genera species can have either the same or different B2m sequences. B2m polymorphism was found within three of the species sampled: Callicebus personatus, Saguinus midas, and Aotus azarae. Of these only the polymorphism in A. azarae has an effect upon the mature, functional β2m protein: residue 4 being either alanine or threonine. The A. azarae B2m allele encoding alanine at position 4 is shared with another species of Aotus (A. infulatus). In pairwise comparison the mature β2m proteins of neotropical primates differ by 1–9 amino acid substitutions which can occur at 18 positions within the sequence. The substitutions are distributed throughout the primary structure but are more commonly found in loops rather than β strands of the tertiary structure. Of 17 residues of β2m which hydrogen-bond with the class I heavy chain in human MHC class I molecules, 13 are conserved in the neotropical primates. The overall pattern of sequence variation in the B2m genes of the Platyrrhini is consistent with an evolution by successive selectively neutral events.
    Materialart: Digitale Medien
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  • 43
    ISSN: 1432-1211
    Schlagwort(e): Key words MHC class I ; Chimpanzee ; Inter-species allele ; Intron ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Immunoglobulin heavy chain (IgH) genes in representative chondrichthyan fishes (sharks and skates) consist of independently functioning clusters, containing separate variable (V H ), diversity (D H ), and joining (J H ) region elements and constant (C H ) region exons. IgH loci have been characterized in Hydrolagus colliei (spotted ratfish), a modern representative of a major independent chondrichthyan lineage. Three distinct families of IgH gene clusters were identified. The most numerous genes consist of unjoined V H -D 1 -D 2 -J H segments that correspond to the most abundant Hydrolagus spleen (cDNA) transcripts which apparently arise from a diversified gene family. In the second cluster type, V H , D H , and J H segments are germline-joined, whereas the C H exons exhibit typical organization. This gene type is found in only a few copies per haploid genome and both transmembrane and secretory transcripts have been identified. A third cluster type has been identified that consists of unjoined V H elements but lacks a typical C H 1 exon, which is substituted with a second C H 2-like exon. Transcripts from this third cluster type also appear to derive from a diversified gene family. Genomic D regions of the two unjoined clone types exhibit structural differences that are consistent with incorporation of recombination machinery-mediated events. Genomic library screening indicates that 90% of V H + clones are truncated, nearly identical pseudogenes (lacking J H and C H ). These studies demonstrate an early phylogenetic origin for the cluster type of gene organization and document extensive organizational diversification within an apparent single class of IgH genes.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 47 (1998), S. 272-277 
    ISSN: 1432-1211
    Schlagwort(e): Key words Immunoglobulin ; Evolution ; Arctic charr ; Rainbow trout ; VH gene familiy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  A comparison between related species would allow us to study the evolutionary changes in complex gene families. To investigate the evolution of immunoglobulin VH gene families in lower vertebrates, we compared cDNA VH clones from two related teleost fish species, Arctic charr (Salvelinus alpinus) and rainbow trout (Oncorhynchus mykiss), which are separated from their common ancestor by 12–20 million years (MY). The results showed that randomly isolated charr VH genes could be closely grouped to known VH genes of rainbow trout, suggesting that the VH family structure is stable during 12–20 MY and that the total number of VH families changes only gradually over a longer period. This finding also led us to define eight VH gene families of Arctic charr, designated Salalp VH I, VH II, and so on. The presence of species-specific amino acids suggests that non-reciprocal genetic exchanges (e.g., gene duplication) play an important role in shaping the evolution of the V gene family.
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  • 45
    ISSN: 1432-1211
    Schlagwort(e): Key words Mice ; Immunoglobulins ; Canonical ; structures Igk-V ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Although human and mouse antibodies are similar when one considers their diversification strategies, they differ in the extent to which kappa and lambda light chains are present in their respective variable light chain repertoires. While the Igk-V germline genes are preponderant in mice (95% or more), they comprise only 60% in humans. This may account for differences in the structural repertoire encoded in the Igk-V germline genes of these species. However, this subject has not been properly investigated, partially because a systematic structural characterization of the mouse Igk-V germline genes has not been undertaken. In the present study we compiled all available information on mouse Igk-V germline genes to characterize their structural repertoire. As expected, comparison with the structural repertoire of human Igk-V germline genes indicates differences. The most interesting is that the mouse Igk-V germline gene repertoire is more diverse in structural terms than its human counterpart: the mouse encodes seven canonical structure classes (combination of canonical structures in L1 and L3). In contrast, the human encodes only four. Analysis of the evolutionary relationships of human and mouse Igk-V germline genes led us to propose that the difference reflects a strategy of mice to compensate for the small lambda chain contribution to the repertoire of their variable light chains.
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  • 46
    ISSN: 1432-1211
    Schlagwort(e): Key words Major histocompatibility complex (MHC) ; Sequence tagged sites (STS) ; Physical mapping ; Evolution ; HLA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  A yeast artificial chromosome (YAC) contig from the C57BL/6 (H2 b ) mouse was created from the major histocompatibility complex (Mhc, H2 in mouse) class Ib subregion, H2-M. It spans approximately 1.2 megabase (Mb) pairs and unites the previous 〉1.5-Mb YAC contigs (Jones et al. 1995) into a single contig, which includes 21 Mhc class I genes distal to H2-T1. A bacterial artificial chromosome (BAC) contig from the 129 (H2 bc ) mouse, spanning approximately 600 kilobases, was also built from Znf173 (Afp, a gene for acid finger protein), through Tctex5 (t-complex testis expressed-5) and Mog (myelin oligodendrocyte glycoprotein), to H2-M2. Twenty-four sequence-tagged site (STS) markers were newly developed, and 35 markers were mapped in the YAC/BAC contigs, which define the marker order as Cen –Znf173–Tctex5 – Mog–D17Tu42–D17Mit232–H2-M3–D17Leh525–H2-M2– Tel. The gene order of Znf173 – Tctex5 – Mog – D17Tu42 is conserved between mouse and human, showing that the middle H2-M region corresponds to the subregion of the human Mhc surrounding HLA-A.
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 47 (1998), S. 477-482 
    ISSN: 1432-1211
    Schlagwort(e): Key words Rat ; Major histocompatibility complex class I ; Mr1 ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  We isolated and analyzed a new rat gene which is homologous to the recently described human major histocompatibility complex class I-related gene MR1. The deduced amino acid sequence of the rat Mr1 gene shows conserved cysteine residues typical of class I genes as well as conserved β2-microglobulin and CD8 contact sites. Analysis of partial DNA sequences and restriction fragment length polymorphism patterns of several inbred rat strains indicate that Mr1 is not polymorphic. Mr1 is a single-copy gene, which could be mapped to rat chromosome 13 by co-segregation analysis of Mr1 and a microsatellite marker in the renin (Ren) gene in double-backcross hybrids. The recombination frequency between both genes was determined to be 14.7% (4.9–31.1, 95% confidence limits). Expression analysis revealed various Mr1 transcripts in each organ tested and occurrence of alternative splicing.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 48 (1998), S. 82-86 
    ISSN: 1432-1211
    Schlagwort(e): Key words MHC ; H2 ; Kinases ; Alternative splicing ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 49
    ISSN: 1432-1211
    Schlagwort(e): Key words Major histocompatibility complex (Uhc) ; Retinoid receptor genes ; Evolution ; Linkage ; Zebrafish
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    International journal of game theory 27 (1998), S. 21-35 
    ISSN: 1432-1270
    Schlagwort(e): Evolution ; games ; multilevel ; group selection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Mathematik , Wirtschaftswissenschaften
    Notizen: Abstract In this paper, we analyze a generalization of the evolutionary model of Kandori, Mailath, & Rob (1993) where the population is partitioned into groups and evolution takes place “in parallel” at the following two levels: (i) within groups, at the lower level; among groups, at the higher one. Unlike in their context, efficiency considerations always overcome those of risk-dominance in the process of selecting the long-run equilibrium. This provides an explicitly dynamic basis for a conclusion reminiscent of those put forward in the biological literature by the so-called theories group selection. From a normative viewpoint, it suggests the potential importance of “decentralization”, here understood as local and independent interaction.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 48 (1998), S. 372-382 
    ISSN: 1432-1211
    Schlagwort(e): Key words Immunoglobulin ; Heavy chain ; VH gene ; Diversity ; Evolution ; Sturgeon
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  To investigate the gene organization of the IGH locus, and the VH diversity of the Siberian sturgeon, a cDNA library was constructed and screened with VH-specific probes from two holostean fish. Isolated clones were analyzed and domain-specific probes used in rescreening of the library, Southern blot analysis, and northern blots. It was concluded that the Siberian sturgeon has one IGH locus with a translocon type of organization. Two allelic variants of the mu gene were found, with identities ranging from 80 to 100% for the different domains (highest for CH4 and lowest for CH2). Sturgeon CH sequences are most closely related to those of holostean fish. There are three distinct VH families, VHI grouping with mammalian clan III, VHII grouping with the teleost clan, and VHIII grouping with the archaic clan. The variability of the CDR 3 region is substantial, and we identified a number of conserved motifs in the D segment. Further, we deduced that there are at least nine different JH segments in the locus, contributing to the antibody repertoire of the sturgeon. The variable segments of the three families can be associated with any of the D or JH segments in the rearrangement. Sturgeon, in addition to the random rearrangement of VH, D, and JH segments, have exonuclease activity, and an introduction of N and probably P nucleotides at the site of rearrangement.
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  • 52
    ISSN: 1432-1939
    Schlagwort(e): Key words Chemo-taxonomy ; Isoprenoid emission ; Evolution ; Quercus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract We show that Mediterranean oaks that emit isoprene, monoterpenes or no isoprenoids belong to different subgenera as indicated by morpho-taxonomy and molecular genetics. On the other hand, oaks from North America and Asia that are taxonomically similar to the Mediterranean monoterpene emitter Q. ilex emit isoprene only. We surmise that isoprene emission is a genetic character which evolved ancestrally in the oak genus since this is the prevalent emission type in oaks widespread around the world and adapted to different environments. This ancestral character may have been either lost or modified in more recent clades such as those originating the Mediterranean oaks. If our hypothesis is correct then the taxonomy of European oaks is validated by this independent trait. Isoprenoid emission could serve as a chemo-taxonomical marker and could be used to reconstruct the phylogeny of oaks in association with molecular markers.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    Sexual plant reproduction 8 (1995), S. 189-196 
    ISSN: 1432-2145
    Schlagwort(e): Endosperm balance number ; Congruity ; Imprinting ; Evolution ; Lycopersicon ; Triploid block
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Success of seed development following sexual crosses is primarily dependent on proper endosperm function and development. The failure to produce triploids, or “triploid block” in 4x×2x crosses served as the impetus for numerous studies of embryo and endosperm to attempt to explain cross failure. Early explanations were based upon a concept of a 2∶3∶2 ploidy balance between maternal tissue, endosperm, and embryo. Subsequent studies done with maize demonstrated that normal endosperm development in intraspecific maize crosses is dependent solely on having a 2∶1 maternal to paternal genome dosage in the endosperm. These results have been modified and extended to solanaceous species in the form of an endosperm dosage system in which empirically determined factors must bear the same 2∶1 relationship for crosses to succeed. Crossing behavior of these species suggest that the system is polygenically controlled and regulates both interspecific and intraspecific crosses. Endosperm dosage systems explain many aspects of species evolution, but the system appears to have originated as an ancient means of ensuring diploid fidelity.
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 47 (1995), S. 507-511 
    ISSN: 1432-1041
    Schlagwort(e): Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5–16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg·kg−1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 47 (1995), S. 525-530 
    ISSN: 1432-1041
    Schlagwort(e): Antipyrine disposition ; Obesity ; pharmacokinetics ; oxidative metabolism ; weight reduction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg · m−2 and 181vs 106 % respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t 1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t 1/2 15.5 vs 12.0 h respectively), but its clearance rate (CLo) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l · kg−1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t 1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CLo. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t 1/2 whereas its CLo is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.
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  • 56
    ISSN: 1432-1041
    Schlagwort(e): Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract CHF1194 is an inclusion complex of β-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, β-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-β-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of β-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5′-hydroxypiroxicam and β-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80–125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5′-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with β-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain relief. The pharmacokinetics of piroxicam was linear after the doses used here, suggesting that long term treatment with CHF1194 should not require any change in dosing regimen. Even after 14 days of repeated administration of CHF1194, β-cyclodextrin could not be detected in plasma or urine, suggesting that in man the unchanged oligosaccharide was absorbed to a very small extent.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 385-390 
    ISSN: 1432-1041
    Schlagwort(e): Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
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  • 58
    ISSN: 1432-1041
    Schlagwort(e): Caffeine ; Cardio-green ; Indocyanine Green ; altitude ; metabolism ; pharmacokinetics ; hypoxia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardiogreen (ICG) were examined in eight healthy males (23–35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg · kg−1) was administered as an intravenous bolus and caffeine (4 mg · kg−1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in the caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g · 1−1 · min−1), and increased clearance (117 vs 86 ml · min−1 · 70 kg−1). In ALT the area under the curve of ICG significantly decreased (85 vs 207 mg · 1−1 · min−1) and the volume of distribution and clearance increased (5.2 vs 2.41 and 532 vs 234 ml · min−1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.
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  • 59
    ISSN: 1432-1041
    Schlagwort(e): Diltiazem ; sustained-release formulation ; pharmacokinetics ; bioavailability ; bioequivalence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3–4 times a day. A sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in order to allow a single daily administration. Two repeated dosing studies were performed in healthy volunteers. The absolute bioavailability of sustained-release diltiazem LP 300 mg was investigated using concomitant i.v. administration of 13C-labelled drug: absolute bioavailability of the “once a day” formulation was 35%. The second study compared sustained-release diltiazem LP 300 mg with the standard formulation of diltiazem. The results showed that the diltiazem plasma concentrations obtained after the LP formulation remained stable between 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release diltiazem LP 300 mg was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard diltiazem formulation.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 253-258 
    ISSN: 1432-1041
    Schlagwort(e): Diabetes ; Human insulin ; Lorazepam ; pharmacokinetics ; glucuronidation ; enterohepatic circulation ; animal insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml·min−1·kg−1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 273-277 
    ISSN: 1432-1041
    Schlagwort(e): Mesalamine ; 5-aminosalicylic acid ; controlled release capsules ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 μg · ml−1 and 1.33 μg · ml−1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 49 (1995), S. 127-137 
    ISSN: 1432-1041
    Schlagwort(e): Thiopental ; Pharmacokinetic modelling ; pharmacokinetics ; single dose ; multiple dosing ; neurosurgical patients ; variability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg−1, and the steady-state volume of distribution (Vss) was 2.16 1·kg−1. The distribution (t1/2α) and elimination (t1/2β) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min−1·kg−1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg·1−1 (mean 16.0 mg·1−1 and median 14.3 mg·1−1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg·1−1 (25.4 mg·1−1, and median 23.3 mg·1−1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg−1. The mean Vss was 2.68 1·kg−1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2α was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2β and the mean residence time became longer due to a decrease in clearance. For t1/2β the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml·min−1·kg−1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose. Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 49 (1995), S. 139-143 
    ISSN: 1432-1041
    Schlagwort(e): Intestinal absorption ; Amoxicillin ; pharmacokinetics ; maximum entropy ; input rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract A computer program applying the principle of maximum entropy to the analysis of drug absorption rate has been developed. Plasma concentrations of amoxicillin obtained after oral and intravenous dosing have been analysed, together with simulated data corresponding to a complex input. Amoxicillin absorption rates devised by the program were similar to those obtained by a standard deconvolution method, although they were displayed as an almost continuous profile. However, improbable fluctuations were obtained with some data sets and the fraction absorbed was underestimated by 13%. With the simulated data, the maximum entropy program did not provide a better solution than the standard deconvolution procedure, and it was sensitive to the addition of random error and to the number of samples. The maximum entropy principle, as implemented in our computer program, may not have a better performance than standard deconvolution procedures, especially in human experiments where the number of blood samples is usually limited.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 327-332 
    ISSN: 1432-1041
    Schlagwort(e): Antipyrine ; pharmacokinetics ; half-life ; blood ; plasma ; saliva ; individual variation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). The levels in blood and saliva were comparable to those in plasma at every time studied. The half life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n=5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva and capillary blood.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 319-325 
    ISSN: 1432-1041
    Schlagwort(e): Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
    ISSN: 1432-1041
    Schlagwort(e): Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 443-450 
    ISSN: 1432-1041
    Schlagwort(e): Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 47 (1995), S. 543-548 
    ISSN: 1432-1041
    Schlagwort(e): Sumatriptan ; pharmacokinetics ; single dose ; bioavailability ; dose proportionality ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavilability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 1) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.
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  • 69
    ISSN: 1432-1041
    Schlagwort(e): Granisetron ; pharmacokinetics ; elderly ; tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 70
    ISSN: 1432-1041
    Schlagwort(e): Growth hormone ; Jet-injection ; pharmacokinetics ; pharmacodynamics ; Somatomedin C ; free fatty acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108 – 142). The AUC0−∞ for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93 – 103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.
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  • 71
    ISSN: 1432-1041
    Schlagwort(e): Losartan ; Cimetidine ; pharmacokinetics ; plasma renin activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I·ml−1·h−1 without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 501-504 
    ISSN: 1432-1041
    Schlagwort(e): Quinidine ; CYP2D6 ; Sparteine oxidation polymorphism ; (3S)-3OH-quinidine ; quinidine-N-oxide ; dihydroquinidine ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l·h−1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l·h−1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 49 (1995), S. 221-228 
    ISSN: 1432-1041
    Schlagwort(e): Nefazodone ; Geriatric assessment ; Hepatic cirrhosis ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The single-dose pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were examined in 12 healthy younger subjects ≤55 years of age (YNG), 12 elderly subjects ≥65 years of age (ELD), 12 patients with biopsy proven hepatic cirrhosis (HEP) and 12 patients with moderate renal impairment (REN), ClCR 20–60 ml·min−1. The study was of parallel group design, with each of the four subject groups receiving escalating single oral doses of 50, 100 and 200 mg of nefazodone at 1 week intervals. Serial blood samples for pharmacokinetic analysis were collected for 48 h following each dose and plasma samples were assayed for NEF, HO-NEF and mCPP by a validated HPLC method. Single oral doses up to 200 mg of nefazodone were well tolerated by all subjects. Maximum plasma levels of NEF and HO-NEF were generally attained within 1 h after administration of nefazodone. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively. There were no apparent gender-related pharmacokinetic differences in any group of subjects. NEF and HO-NEF pharmacokinetics were dose dependent in all four subject groups; a superproportional increase in AUC and an increase in t1/2 with increasing dose was obtained, indicative of nonlinear pharmacokinetics. Relative to normal subjects, elderly and cirrhotic subjects exhibited increased systemic exposure to NEF and HO-NEF, as reflected by AUC, at all doses of nefazodone; subjects with moderate renal impairment did not. Elderly and cirrhotic patients may require lower doses of NEF to achieve and maintain therapeutic effectiveness.
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 49 (1995), S. 229-235 
    ISSN: 1432-1041
    Schlagwort(e): Nefazodone ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The steady-state pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were compared in subjects with normal and impaired renal function. Patients: The Study was of parallel group design which included 7 subjects with normal (NOR) renal function, CLCR≥72 ml·min−1·1.73 m−2, 6 with moderate (MOD) renal impairment, CLCR 31–60 ml·min−1·1.73 m−2 and 9 with severe (SEV) renal impairment, CLCR≤30 ml·min−1·1.73 m−2. Subjects in each renal function group received a 100-mg oral dose of nefazodone hydrochloride BID for 7 days and a single morning dose on day 8. Starting 48 h after the last 100-mg dose, 200-mg doses were administered on a similar schedule to 3, 4 and 3 subjects from each renal function group (NOR, MOD and SEV, respectively). Single trough blood samples just prior to each morning dose (Cmin) and serial samples after the dose on day 8 were obtained at each dose level for pharmacokinetic analysis. Plasma samples were assayed by a specific HPLC method for NEF, HO-NEF and mCPP. The CMIN data indicated that steady state was attained by the third day of BID administration of both the 100- and 200-mg doses of nefazodone, regardless of degree of renal function. Both NEF and HO-NEF attained steady-state Cmax within 2 h after administration of nefazodone; tmax for mCPP was less defined and more delayed. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively, regardless of the status of renal function. Steady-state systemic exposure of NEF and HO-NEF, as reflected by AUC and Cmax, and elimination t1/2 values did not differ significantly among renal function groups. Conclusion: The study results suggest that dose adjustments may not be necessary, but nefazodone should be used with caution in the presence of severe renal impairment.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 49 (1995), S. 203-210 
    ISSN: 1432-1041
    Schlagwort(e): Felodipine ; pharmacokinetics ; haemodynamics ; congestive heart failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract In congestive heart failure patients the kinetics of felodipine, a dihydropyridine calcium antagonist, show interpatient differences after acute i.v. administration that disappear after 8 weeks oral treatment with a change in kinetics in the patients with the largest clearances (CL) and the smallest volumes of distribution (V SS). Pharmacokinetic and haemodynamic data were combined to construct a haemodynamic-pharmacokinetic model. This model shows that the differences between the patients in i.v. pharmacokinetics are consistent with a difference in plasma flow distribution between liver and poorly perfused tissues. In patients in whom kinetics changed, felodipine treatment is supposed to cause a redistribution of flow from liver to peripheral tissues, accompanied by a decreased work load of the heart and a larger increase in VO2max during therapy than in the other patients, whose workload increased. This suggests a better therapeutic response in the patients whose kinetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might be predictive for the therapeutic effect of felodipine.
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  • 76
    ISSN: 1432-1041
    Schlagwort(e): Cholesterol acyltransferase ; Hypocholesterolaemic ; 447C88 ; volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract 447C88 (N-Heptyl-N′-(2,4 difluoro-4-6-(2(-4-(2,2 dimethylpropyl)phenyl)ethyl)phenyl)urea) is an inhibitor of human microsomal AcylCoA:Cholesterol acyltransferase (ACAT) with an IC50 of 10.2 ng·ml−1 (23 nM). It is poorly absorbed but 5 mg·kg−1·day−1 completely abolishes the rise in plasma cholesterol in cholesterol-fed rats. In this study, twelve healthy, male volunteers received single, oral doses of 25, 50, 100, 200, 400 and 800 mg of 447C88 (n+8) or placebo (n+4) with food in a double-blind study with at least a week between occasions. The 400 mg dose was repeated after an overnight fast. Subsequently, fourteen different volunteers received a single 200 mg dose of 447C88 (n+8) or placebo (n+6) with food and, a week later, the same dose twice daily for 10 days; all doses were given with food. All doses were well tolerated with no significant changes in vital signs, full blood counts or plasma biochemical profiles. Plasma concentrations of 447C88 were unquantifiable after the fasting dose and low after all other doses. Mean Cmax and AUC were 1.8 ng·ml−1 and 9.0 ng·ml−1·h after 200 mg rising to 5.4 ng·ml−1 and 23.8 ng·ml−1·h respectively after 800 mg; t1/2 was 1.3 to 5.2 h. After 10 days dosing, plasma 447C88 concentrations were higher in the evening than the morning probably due to administration of the evening dose with more food. There were no significant changes in plasma triglcerides or total, LDL- or HDL-cholesterol after dosing with 447C88.
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  • 77
    ISSN: 1432-1017
    Schlagwort(e): Key words Sequence similarity ; Glyceraldehyde-3-phosphate dehydrogenase ; Phosphoglycerate kinase ; Pyruvate kinase ; Evolution ; Phylogeny
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Physik
    Notizen: Abstract Data are presented that suggest enzyme sequence similarities among species are not solely a function of their evolutionary relationship. It is demonstrated that sequence similarities of glyceraldehyde-3-phosphate dehydrogenases, phosphoglycerate kinases, and pyruvate kinases from yeast, bacteria, mammals and a bird possess a significant species optimal thriving temperature dependence that crosses through conventional phylogenetic divisions. It is therefore suggested that species which are distantly related evolutionarily may possess some degree of enzyme sequence similarity if they happen to thrive at near the same optimal temperature; conversely, organisms which are closely related evolutionarily but function at radically different temperatures will possess a sequence dissimilarity that may mask the close relatedness.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 251-256 
    ISSN: 1432-1041
    Schlagwort(e): Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 311-317 
    ISSN: 1432-1041
    Schlagwort(e): Hydralazine ; instability of impaired renal function ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Following a single 50 mg dose of hydralazine (Apresoline®) in 13 patients with impaired renal function, a decrease in glomerular filtration rate (GFR) was correlated with an increase in serum half-life (T1/2) of the drug (r=−0.69; p〈0.01). The T1/2 was 15.8 h in one patient with a GFR of 16 ml·min−1, as compared to a T1/2 of 1.7–3.0 h found previously in 16 healthy volunteers. In 49 patients on long-term antihypertensive treatment with hydralazine, the ratio between the minimum steady-state drug concentration and the daily dose of hydralazine (C SS min : Dose) increased as the GFR decreased. This accumulation of the drug was particularly evident in patients with a GFR less than 30 ml·min−1 (r=−0.63; p〈0.01; n=19). As renal excretion of unchanged hydralazine is generally regarded as unimportant, the slower elimination rate in chronic renal failure was probably caused by a slower rate of metabolic conversion. It was found, however, that the renal excretion of hydralazine could easily have been underestimated, as only 12.7% of an initial hydralazine concentration of 200 ng·ml−1 in urine could be recovered after storage of the samples at room temperature for 24 h.
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 325-330 
    ISSN: 1432-1041
    Schlagwort(e): Flutiorex ; pharmacokinetics ; sex ; anorectic agent ; sympathetic stimulation ; CNS stimulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of flutiorex, a new anorectic agent, and of a placebo on food intake and the activity of the sympathetic and central nervous systems have been compared in a double blind trial in two groups of healthy volunteers, one of five males and the other of five females. Flutiorex 20 mg orally had a significant anorectic effect both in males and females, the observed reduction in food intake being 34.0 and 27.5%, respectively. It caused α-adrenergic stimulation (blood pressure and pupil diameter) and central nervous system excitation (critical flicker frequency), both of which were more marked in males than in females. Flutiorex was better tolerated by women than by men. Measurement of the blood level of flutiorex and its de-ethylated metabolite, norflutiorex, showed that both compounds were detectable in four of the five male subjects, but in only one of the five females. Sex-linked differences in the pharmacokinetics of flutiorex may explain the greater intensity of its effects in males.
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 343-347 
    ISSN: 1432-1041
    Schlagwort(e): Methaqualone ; hypnotic ; pharmacokinetics ; combination formulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 µg/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and there-after more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 µg/ml; 1.5 µg/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 µg/ml – 0.6 µg/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.
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  • 82
    ISSN: 1432-0983
    Schlagwort(e): Green algae ; Volvox ; Transcription signals ; Gene expression ; Intron ; Evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A–H2B and H3–H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox the 3′ untranslated regions contain no poly A signal, but a palindromic sequence (3′ palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A–H2B pair. The H1 upstream region contains the octameric promoter element GGTTGA-CC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intronfree. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II (66% identity). Organization of the core histone gene in pairs, and non-polyadenylation of mRNAs are features shared with animals, whereas peptide sequences and enhancer elements are shared with higher plants, assigning the volvocalean histone genes a position intermediate between animals and plants.
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
    ISSN: 1432-1041
    Schlagwort(e): Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 25-29 
    ISSN: 1432-1041
    Schlagwort(e): Digoxin ; exchange transfusion ; pharmacokinetics ; neonates ; 86Rb assay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary By means of an86Rb-uptake inhibition assay, changes in the plasma concentration of digoxin and the amount of the glycoside removed during exchange transfusion have been studied in two newborns. For comparison, the exchange procedure was simulated by a computer on the basis of a two-compartment open model and available pharmacokinetic constants. A rapid decrease in plasma digoxin concentration during exchange transfusion was found when the glycoside was administered intravenously or intramuscularly within 60 min before the procedure. The amount of digoxin removed by the exchange was less than 6 per cent of the given dose. Computer simulation of the procedure also showed removal of only a minor amount of digoxin. It is concluded that the decrease in plasma concentration and the removal of only a small amount of glycoside by the exchange transfusion can be attributed mainly to extensive tissue distribution of digoxin. The results imply that replacement of digoxin after an exchange transfusion seems unnecessary.
    Materialart: Digitale Medien
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 121-126 
    ISSN: 1432-1041
    Schlagwort(e): Diazepam ; pharmacokinetics ; subchronic dosage in man ; desmethyldiazepam
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In seven healthy male volunteers the effects of the pattern of dosing on the pharmacokinetics of diazepam have been studied. A cross-over design was employed that consisted of three parts: a single intravenous dose (0.1 mg/kg), and oral dosing (10 mg/day) for six days followed by an intravenous bolus (0.1 mg/kg) on the seventh day, followed by re-examination of a single intravenous dose after diazepam (D) and its major metabolite desmethyldiazepam (DD) had been completely eliminated. Plasma levels of D and DD were monitored by a specific, sensitive GLC-method. In younger patients (n=5, age 29 – 35 years) the elimination half-life, T1/2 (β), of D was 33.9±10.6 h (mean±S.D.) after the single dose. The control study gave an almost identical result (35.7±12.1). After subchronic dosage in all patients T1/2 (β) showed a modest but significant prolongation (paired t-test p〈0.01) to 52.9±17.4 h. It was caused by a significant decrease (p=0.016) in total plasma clearance ( $$\overline {\user1{Cl}} $$ ), from 26.0±10.8 ml/min to 18.2±7.0 ml/min. Older patients (age 43–60 years) showed the same phenomenon. Blood/plasma ratios remained constant indicating no change in protein binding. Biliary excretion of D was measured in five patients with a T-tube. Only negligible amounts (0.3–0.4%) of administered D were excreted within 3 days after subchronic dosage, which demonstrates a lack of enterohepatic cycling of D. After multiple administration of D, there was accumulation of DD to levels approximately five times higher than after a single dose. The possibility that the slower elimination of D after subchronic treatment might be caused by DD was also supported by experiments in dogs and rabbits. After pretreating rabbits with DD and maintaining a high DD plasma level, there was prolongation of T1/2 (β) from 2.7 h to 5.2 h, with a corresponding decrease of $$\overline {\user1{Cl}} $$ from 101.6 ml/min to 23.4 ml/min. Similar results were obtained in dogs. It is concluded that the disposition of D is altered by subchronic use and may be regulated by the plasma DD concentration.
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  • 86
    ISSN: 1432-1041
    Schlagwort(e): Dorzolamide ; Glaucoma ; carbonic anhydrase ; pharmacokinetics ; renal effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Following a single-dose, open-label, pilot pharmacokinetic study in six subjects, the systemic pharmacokinetics and metabolic effects of dorzolamide after topical ocular administration were investigated in a double-blind, randomised, placebo-controlled study in 12 healthy volunteers. The subjects received a controlled diet on the 5 days before treatment initiation and throughout the study. For 14 days, a bilateral q.i.d. regimen of 3% dorzolamide, consisting of approximately 7.7 μg per day (21.3 μmol) dorzolamide hydrochloride, or placebo was given. Blood and urine electrolytes and acid-base profiles were measured 1 day prior to treatment and on days 1, 7 and 14 of treatment, and 24-h urine samples were collected daily. Topically applied dorzolamide was slowly taken up in erythrocytes and eliminated with a half life of approximately 120 days. Compared to the pre-study values, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium and citrate excretions. Two other volunteers given acetazolamide (125 mg q.i.d.) and assessed with the identical set of observations demonstrated marked metabolic changes. In spite of the prolonged and marked inhibition of carbonic anhydrase in red blood cells by dorzolamide, clinically significant metabolic and renal effects were not observed. The ocular tolerability profile was acceptable to all subjects.
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 57-59 
    ISSN: 1432-1041
    Schlagwort(e): Amrinone ; continuous veno-venous haemofiltration ; drug monitoring ; pharmacokinetics ; low cardiac output syndrom ; elimination ; renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract We studied the elimination of amrinone during continuous veno-venous haemofiltration (CVVHF) in three anuric patients after cardiac surgery. The patients had developed low cardiac output followed by acute prerenal failure. Plasma amrinone levels measured by HPLC were fitted to a two-compartment model. We found significant amrinone clearance, with a mean sieving coefficient (S) of 0.44%, which correlates with the protein-unbound, pharmacologically effective fraction of amrinone. The AUC of the arterial plasma concentration-time curve was decreased by 49.8%. All pharmacokinetic parameters showed wide interindividual variation. To ensure the therapeutic effect of amrinone and to avoid toxic adverse effects monitoring of plasma amrinone levels is necessary.
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 65-69 
    ISSN: 1432-1041
    Schlagwort(e): Paracetamol ; Malaria ; pharmacokinetics ; phase II conjugation ; glucuronidation ; sulphation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Investigations in animals have suggested that conjugation of paracetamol may be reduced in malaria. We have measured plasma concentrations and the urinary excretion of paracetamol and its phase II metabolites in eight Thai patients during uncomplicated falciparum malaria and in convalescence, following a 1000 mg single oral dose. The apparent oral clearance (Malaria, 3.6; Convalescence, 3.9; ml·min−1·kg−1), the elimination half-life (Malaria, 3.8; Convalescence, 3.7 h) and apparent volume of distribution (Malaria, 1.2; Convalescence, 1.2; l·kg−1) of paracetamol were similar during malaria and convalescence. In addition, the urinary excretion of paracetamol and its major phase II metabolites and their formation clearances from paracetamol were not significantly different between the two study phases. These data show that clinical malaria infection has no effect on the conjugation of paracetamol in man.
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 79-80 
    ISSN: 1432-1041
    Schlagwort(e): Metamizol ; Acetylation phenotype ; metabolites ; pharmacokinetics ; dose-linearity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 71-75 
    ISSN: 1432-1041
    Schlagwort(e): Nicotine ; Rhinitis ; pharmacokinetics ; nasal spray ; xylometazoline ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state. Applying strict bioequivalence criteria, we found that common cold/rhinitis slightly reduced the bioavailability of nicotine, both in its rate and extent; the geometric mean of the ratio of Cmax, AUC and tmax were 0.81, 0.93 and 1.36, respectively. The nasal vasoconstrictor, xylometazoline, normalised the extent of the bioavailability of nicotine, but further prolonged the time for absorption to almost twice that measured in the disease-free state, increasing the tmax ratio to 1.72. The results suggest that a minor proportion of people stopping smoking with the help of a nicotine nasal spray may experience a minor reduction in the effect of the spray during common cold/rhinitis. However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect.
    Materialart: Digitale Medien
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 265-268 
    ISSN: 1432-1041
    Schlagwort(e): Chlordesmethyldiazepam ; Liver disease ; pharmacokinetics ; i.v./p.o. administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract We studied the pharmacokinetics of a single 0.5-mg i.v. dose of chlordesmethyldiazepam in 8 patients with liver disease and in 12 age-matched healthy controls. The kinetics were also studied of a single 1-mg oral dose in the patients with liver disease. After i.v. administration the kinetics of total chlordesmethyldiazepam in patients with liver disease differed from those in controls: elimination half-life was almost twice that in controls (395 and 204 h), as a consequence of a marked reduction in total clearance (0.13 and 0.25 ng·ml−1·h−1), whereas the apparent volume of distribution was similar in patients and controls (4.7 and 3.9 1/kg−1). The free fraction of the drug in patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed clearance in the patients was one-fifth (1.8 and 10.5 ng ml−1·kg−1) and volume of distribution one-half (65.0 and 118.4 1·kg−1) that in controls. The systemic availability of oral chlordesmethyldiazepam was high (110%) in spite of a relatively slow absorption rate. These results indicate a need for caution in the administration of chlordesmethyldiazepam to patients with liver disease.
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 133-137 
    ISSN: 1432-1041
    Schlagwort(e): Sauna ; Propranolol ; Captopril ; pharmacokinetics ; blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The effects of a Finnish sauna on propranolol pharmacokinetics and on the pharmacodynamics of propranolol and captopril were studied in healthy, young volunteers (2 males, 6 females) in a double-blind, cross-over trial. The subjects received single oral doses of placebo. propranolol (40 mg) or captopril (12.5 mg) in sauna and control sessions at a one-week interval. The sauna sessions consisted of three repetitive 10-min stays in a sauna (85–100°C, relative humidity 25–35%) separated by two 5-min rest periods in a cool room. Sauna bathing started 35, 50 and 65 min after ingestion of the drugs. Venous blood for plasma propranolol measurement were collected before and 15, 30, 45, 60, 75, 90 min and 2, 3, 4, 5, 7 and 24 h after drug intake. The sauna significantly increased the maximum concentration (Cmax 41 vs. 28 ng·ml−1) of propranolol and the mean plasma propranolol concentration 60 and 90 min, and 2 and 3 h after drug administration. It also significantly increased the AUC0–5h (119 vs 71 μg·h·l-1) of propranolol from 0 to 5 hours tmax, t1/2β and AUC0–24h of propranolol did not differ between the control and sauna sessions. The higher propranolol levels during and after the cessation of sauna bathing did not lead to significant changes in blood pressure or heart rate compared to the control period. Captopril had no major effects on these parameters during the post-sauna phase. The results suggest that a sauna may increase the plasma propranolol concentration, but that did not notably affect the blood pressure or heart rate in healthy, young volunteers during the post-sauna phase.
    Materialart: Digitale Medien
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 151-153 
    ISSN: 1432-1041
    Schlagwort(e): Ethanol ; Acetylsalicylic acid ; ibuprofen ; paracetamol ; non-steroidal anti-inflammatory drugs ; interactions ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract This study assessed the influence of acetylsalicylic acid (ASA, 1.0 g), ibuprofen (0.8 g) and paracetamol (1.0 g) on the single-dose kinetics of ethanol in 12 healthy volunteers ingesting the drug and a standardised 1840-kJ breakfast 1 h before intake of ethanol. It also assessed the influence of ethanol on the single-dose kinetics of 1.0 g ASA in ten fasting healthy volunteers. Plasma concentrations of ethanol were measured by gas chromatography, and those of the drugs by liquid chromatography. There was no effect of ASA, ibuprofen or paracetamol on the single-dose kinetics of ethanol, but concurrent intake of ethanol reduced the peak concentration of ASA by 25%.
    Materialart: Digitale Medien
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  • 94
    ISSN: 1432-1041
    Schlagwort(e): Recombinat hirudin ; Piroxicam ; activated partial thromboplastin time ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Recombinant hirudins are currently under investigation for use in myocardial infarction and unstable angina. In this study the influence of piroxicam on the pharmacodynamics and pharmacokinetics of a recombinant hirudin preparation (CGP 39393) administered intravenously was determined. Twelve healthy, male volunteers received piroxicam 10 mg and matching placebo once daily for 12 days according to a double-blind, randomised cross-over design. On the 12th day, the dose of piroxicam was followed by a 6-hour infusion of hirudin 0.1 mg·kg−1·h−1. Plasma concentrations and urinary excretion of hirudin and repeated measurements of the activated partial thromboplastin time (APTT), bleeding time and platelet adhesion index were assessed up to 24 h after the start of the infusion. The maximum APTT was 83 s (placebo) and 84 s (piroxicam), 3 to 4 h after the start of the infusion, and was comparable on both study days. The AUD0–24 (APTT) came to 913 s·h·kg−1 under placebo and it was slightly increased to 1,017 s·h·kg−1 after piroxicam; the 95%-confidence interval according to MOSES ranged from 0.97 to 1.24, and the point estimator was 1.10. Bleeding time was significantly prolonged from 290 s under placebo to 345 s under piroxicam before the start of the infusion of hirudin. No further prolongation was found during or after the infusion. No change was observed in the platelet adhesion index. Responsiveness parameters according to a sigmoidal Emax-model were obtained from the hirudin-plasma concentration/effect (i.e. APTT-prolongation)-curves after placebo and piroxicam. Maximal APTT-prolongation (Emax; i.e. peak APTT minus the baseline value) was 53 s after placebo and 52 s after piroxicam. The EC50 was 34 nmol·l−1 after placebo and 40 nmol·h·l−1 after piroxicam. The AUC0 of hirudin was to 539 nmol·h·l−1·kg−1 under placebo and 557 nmol·h·l−1·kg−1 after piroxicam coadministration; the 95%- confidence interval according to MOSES ranged from 0.95 to 1.14, and the point estimator was 1.03. No period effect was detected. There were no significant differences between the other pharmacokinetic parameters except Vss, which was increased slightly from 0.23 l to 0.27 l under piroxicam. The results do not show a clinically relevant pharmacodynamic and/or pharmacokinetic interaction between hirudin and piroxicam.
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  • 95
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 291-293 
    ISSN: 1432-1041
    Schlagwort(e): Fluconazole ; absorption ; pharmacokinetics ; HIV infection ; children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The objective of this study was to determine the pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus (HIV) infection. After an overnight fast, a single dose of either 2 mg·kg−1 or 8 mg·kg−1 was administered in a suspension; five children received 2 mg·kg−1 and four 8 mg·kg−1 (ages 5–13 years). Blood samples were collected at various times on day 1, and once daily on days 2–7 after the dose. Fluconazole serum concentrations were measured by gas chromatography. At the dose of 2 mg·kg−1, the Cmax, AUC (0–∞), and t1/2 ranged from 2.3–4.4 μg·ml−1, 84.9–136 μg·h·ml−1, and 19.8–34.8 h, respectively. At the dose of 8 mg·kg−1 the Cmax, AUC (0–∞), and t1/2 ranged from 5.4–12.1 μg·ml−1, 330–684 μgh·ml−1, and 25.6–42.3 h, respectively. When compared with published data in healthy adults, fluconazole achieved similar serum concentrations in the present group of children, indicating a nearly complete degree of absorption.
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  • 96
    ISSN: 1432-1041
    Schlagwort(e): Idrapril ; ACE-inhibition ; Hypertension ; essential ; active renin ; angiotensin II ; blood pressure ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum ACE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 μ·ml−1), and by 12 hours the compound had al most disappeared (67 ng·ml−1). Derived t1/2 was 1.4–2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol−1·min−1·ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 12 hours) pg·ml−1] for up to 12 h, while active renin rose up to 24 h [from 12.3 to 20.1 (after 8 hours) and 17.5 (after 24 hours) pg·ml−1]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg) up to 24 hours (idrapril calcium 142/91 mmHg; placebo: 155/97 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.
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  • 97
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporin ; Cystic fibrosis ; pharmacokinetics ; bioavailability ; formulation ; transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have compared the relative bioavailability of cyclosporin from conventional and microemulsion formulations in 5 adult heart-lung transplant candidates with cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg and 800 mg). A randomized 4-period cross-over study was performed with at least a 7 days washout period between each single dose pharmacokinetic study. Blood cyclosporin concentrations were measured by a selective monoclonal antibody-based radioimmunoassay. The bioavailability of cyclosporin from the microemulsion formulation was 1.84 (95% C.I. 1.05 to 3.22; P−0.04) and 2.09 (95% C.I. 0.95 to 4.61; P−0.06) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. Cmax following the microemulsion formulation was 3.38 (C.I. 1.14 to 10.59; P−0.04) and 2.77 (C.I. 1.48 to 5.19; P−0.01) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. The higher Cmax following the microemulsion formulation was accompanied by shorter tmax. An enhancement of cyclosporin absorption with the microemulsion formulation was demonstrated in each patient for at least one dose level. We conclude that rate and extent of cyclosporin absorption from the microemulsion formulation is greater compared with the conventional formulation in patients with cystic fibrosis. The potential therapeutic and economic benefits of the micro-emulsion formulation should be evaluated in cystic fibrosis patients following heart-lung transplantation.
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  • 98
    ISSN: 1432-1041
    Schlagwort(e): Atrial natriuretic peptide ; Hypertension ; SCH 42354 ; blood pressure ; neutral metalloendopeptidase ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the “link” model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid Emax PD model. For the 300 mg BID dose, PD parameters were: maximum effect (Emax), 8.1mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC50), 0.87 μg·ml−1; and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple Emax PD model. PD parameters obtained over the dose range were: Emax, 10.3 mmHg; Eo, 2.0 mmHg; and EC50, 0.7 μg·ml−1. These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 μg·ml−1.
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 48 (1995), S. 373-379 
    ISSN: 1432-1041
    Schlagwort(e): Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The effect of pH on the buccal and sublingual absorption of captopril was evaluated using in vitro techniques and human studies. Partitioning of captopril into n-octanol was lowest over the pH range 5 to 8 and highest at pH values 3, 4 and 9. Using the buccal absorption technique, the partitioning of captopril (2 mg) was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8, and 9). Lowest buccal partitioning occurred at pH 3 while maximal buccal partitioning occurred at pH 7. These data clearly indicated that the buccal absorption of captopril did not obey the classical pH/partition hypothesis suggesting that mechanisms other than passive diffusion were involved in its absorption. Captopril pharmacokinetic and pharmacodynamic parameters were determined after administration of buffered sublingual captopril (pH 7, optimal pH for absorption as determined from the buccal partitioning data) and unbuffered sublingual captopril. The study was performed in eight healthy volunteers in a randomised single-blind cross-over fashion. The tmax for captopril was found to be approximately 11 minutes earlier after buffered versus unbuffered sublingual administration and AUC0–30 min increased by approximately 30% in the case of buffered captopril. Cpmax, AUC0–180 min and relative bioavailability did not differ between the buffered and unbuffered administration. Pharmacodynamic parameters (BP, heart rate and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration. The increased rate of captopril absorption after buffered sublingual administration was small and is likely to offer little therapeutic advantage over conventional sublingual formulation.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    ISSN: 1432-0983
    Schlagwort(e): RNA editing ; Group-II intron ; Gene transfer ; Evolution ; tRNA genes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract A novel group II intron has been identified in the pea (Pisum sativum) mitochondrial genome. The gene harbouring this intron is identified as rps10 (encoding protein S10 of the small ribosomal subunit) by similarity to its known homologues in bacteria and in the mitochondrion of the liverwort Marchantia polymorpha. The rps10 gene is transcribed in pea, the intron is removed, and RNA editing in the rps10 reading frame increases similarity to its homologue in the M. polymorpha mitochondrion. Contrary to the situation in bacteria and Marchantia, rps10 is not part of a ribosomal-protein gene cluster in pea. It is flanked upstream by the genes trnF and trnP, encoding phenylalanine-and proline-accepting tRNAs, and downstream by cox1, encoding subunit 1 of the cytochrome-c-oxidase. Southern hybridization shows that sequences homologous to rps10 exist in potato mitochondria but not in mitochondria of Oenothera berteriana and Arabidopsis thaliana. The pea rps10 intron is homologous to introns in rrn26 and cox3 in the Marchantia mitochondrial genome, while the Marchantia rps10 gene lacks an intron.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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