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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of solution chemistry 6 (1977), S. 203-216 
    ISSN: 1572-8927
    Keywords: Glucose ; kinetics ; mixed solvent ; kinetic isotope effect ; enthalpy of activation ; entropy of activation ; tetrahydrofuran ; tert-butanol ; mutarotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The mutarotation rates of glucose in aqueous mixtures of tetrahydrofuran andtert-butanol in the mole fraction (xi) range 0〈xi〈0.2 have been measured at 5° intervals in the range 5–35°C. The kinetic deuterium isotope effects have been determined for the same solvent compositions at 25 and 35°C. A statistical analysis of the Arrhenius plots indicates that the experimental errors, although small, are too large for the establishment of any compensation behavior between ΔH
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  • 2
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    Journal of solution chemistry 5 (1976), S. 163-169 
    ISSN: 1572-8927
    Keywords: Solvent effects ; tetramethylurea ; hydrolysis ; hydrogen bonding ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Tetramethylurea was hydrolyzed in aqueous hydrochloric acid at temperatures of 80, 90, and 100°C. All reactions were carried out in an excess of both tetramethylurea and water, with first-order dependence on acid concentration being observed. As the concentration of water was increased, the rate of hydrolysis decreased until equimolar amounts of water and tetramethylurea were present. Subsequent addition of water had no effect on the observed rate.
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  • 3
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    Adsorption 6 (2000), S. 137-147 
    ISSN: 1572-8757
    Keywords: adsorption ; kinetics ; linear driving force model ; process design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The Linear Driving Force (LDF) model for gas adsorption kinetics is frequently and successfully used for analysis of adsorption column dynamic data and for adsorptive process designs because it is simple, analytic, and physically consistent. Yet, there is a substantial difference in the characteristics of isothermal batch uptake curves on adsorbent particles by the LDF and the more rigorous Fickian Diffusion (FD) model. It is demonstrated by using simple model systems that the characteristics of the adsorption kinetics at the single pore or the adsorbent particle level are lost in (a) evaluating overall uptake on a heterogeneous porous solid, (b) calculating breakthrough curves from a packed adsorbent column, and (c) establishing the efficiency of separation by an adsorptive process due to repeated averaging of the base kinetic property. That is why the LDF model works in practice.
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  • 4
    ISSN: 1572-879X
    Keywords: ammonia synthesis ; kinetics ; ruthenium catalysts ; promotional effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of NH3 synthesis over carbon-based ruthenium catalysts promoted with barium or alkali was studied. Both the ammonia partial pressure dependencies of the reaction rates (T = 400°C, p = 63 bar, H2 : N2 = 3 : 1) and the pressure variations of the activity (T = 370°C, p= 4–63 bar, H2 : NN2 = 3 : 1) were found to be different for Ba and for the alkali (K, Cs). Ba–Ru/C proved to be more sensitive to the NH3 content and to the total pressure. The rate of synthesis over the alkali-promoted catalysts is, in turn, much stronger influenced by the ruthenium dispersion. TOFs of NH3 synthesis for the promoted samples at 370°C and 4 bar (Ba 0.085 1/s, Cs 0.05 1/s, K 0.035 1/s) are significantly higher than that for the Ru(0001) basal plane (0.0085 1/s results from the literature data at 370°C, 2 bar). The most active Ru/C samples (Ba or Cs) exceed significantly the fused iron catalyst, especially at high conversions.
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  • 5
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    Topics in catalysis 11-12 (2000), S. 327-333 
    ISSN: 1572-9028
    Keywords: hydrodenitrogenation ; toluidine ; methylcyclohexylamine ; kinetics ; nickel-promoted molybdenum sulphide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The hydrodenitrogenation (HDN) of o-toluidine and its reaction intermediates was studied over a NiMo/γ-Al2O3 catalyst. The kinetics of the HDN of methylcyclohexylamine and of the hydrogenation of cyclohexene were also studied. Hydrogenation of o-toluidine alone produces methylcyclohexene and methylcyclohexane. When a sufficient quantity of cyclohexene is added during the HDN of toluidine, methylcyclohexylamine, the first intermediate in the hydrogenation of toluidine, becomes detectable. Because of its strong adsorption constant and high rate constant for reacting further to methylcyclohexene and methylcyclohexane, methylcyclohexylamine is not observed in the HDN of toluidine. Adding cyclohexene decreases the adsorption of methylcyclohexylamine, thus enabling its detection. The rate and adsorption constants of methylcyclohexylamine and cyclohexene in the HDN of methylcyclohexylamine were calculated by fitting the kinetic data to a Langmuir–Hinshelwood equation. A two-site model was used to describe the surface reactions, with one site for the methylcyclohexylamine reactions and the other for the cyclohexene reaction.
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  • 6
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    Adsorption 6 (2000), S. 349-357 
    ISSN: 1572-8757
    Keywords: sulfadiazene ; adsorption ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract To investigate the nature of interactive forces between sulfadiazene molecules and alumina surface the experiments were performed for the adsorption of sulfadiazene (SD) from its aqueous sulution onto the alumina surfaces at 25 ± 0.2°C and the influence of factors such as increasing concentration of SD (4.0–20.0 × 10−3 mol cm−3), the time required for adsorption equilibrium, pH (2.0–12.0) and temperature (5–45°C) of the adsorption medium, the presence of ions like Cl−, SO2− 4 and PO3− 4 (0.01–0.30 M) and organic solvents (5% v/v) were observed on the course of adsorption of SD. Various adsorption and kinetic parameters such as adsorption coefficient, the rate constants for adsorption and desorption were also evaluated. The results of the above cited studies facilitated to formulate the mechanisms of interaction between SD and alumina surfaces. From application view point the present work may be a potential tool for an effective chromatographic separation of sulfa drugs from industrial effluents.
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  • 7
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    Catalysis letters 64 (2000), S. 65-75 
    ISSN: 1572-879X
    Keywords: NO reduction ; CH3OH ; La2O3 ; methyl nitrite ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Nitric oxide (NO) reduction by methanol was studied over La2O3 in the presence and absence of oxygen. In the absence of O2, CH3OH reduced NO to both N2O and N2, with selectivity to dinitrogen formation decreasing from around 85% at 623 K to 50–70% at 723 K. With 1% O2 in the feed, rates were 4–8 times higher, but the selectivity to N2 dropped from 50% at 623 K to 10% at 723 K. The specific activities with La2O3 for this reaction were higher than those for other reductants; for example, at 773 K with hydrogen a specific activity of 35 μmol NO/s m2 was obtained whereas that for methanol was 600 μmol NO/s m2. The Arrhenius plots were linear under differential reaction conditions, and the apparent activation energy was consistently near 14 kcal/mol with CH3OH. Linear partial pressure dependencies based on a power rate law were obtained and showed a near‐zero order in CH3OH and a near‐first order in H2. In the absence of O2, a Langmuir–Hinshelwood type model assuming a surface reaction between adsorbed CH3OH and adsorbed NO as the slow step satisfactorily fitted the data, and the model invoking two types of sites provided the best fit and gave thermodynamically consistent rate constants. In the presence of O2 a homogeneous gas‐phase reaction between O2, NO, and CH3OH occurred to yield methyl nitrite. This reaction converted more than 30% of the methanol at 300 K and continued to occur up to temperatures where methanol was fully oxidized. Quantitative kinetic studies of the heterogeneous reaction with O2 present were significantly complicated by this homogeneous reaction.
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  • 8
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    Catalysis letters 69 (2000), S. 103-107 
    ISSN: 1572-879X
    Keywords: dicyclopentadiene ; Wacker oxidation ; Pd(AcO)2 ; benzoquinone ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The oxidation of dicyclopentadiene catalyzed by palladium(II) acetate and benzoquinone in the presence of perchloric acid was studied. Tricyclodecenone in high selectivity (85–98%) at a conversion of dicyclopentadiene up to 76% was obtained. The kinetic model assumed the significant inhibition complexation between dicyclopentadiene and tricyclodecenone with the catalytic species.
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  • 9
    ISSN: 1432-1211
    Keywords: Key words Antigen presentation ; Autoimmune disease ; Evolution ; MHC ; Self peptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Comparison of peptides eluted from human class I and class II major histocompatibility complex (MHC) molecules and the proteins from which they are derived (source proteins) revealed that class I MHC bind peptides derived from proteins that are highly conserved, hydrophilic, and universally expressed, while the peptides themselves are hydrophobic and even more conserved than their source proteins. In contrast, source proteins for class II-bound peptides were not significantly more conserved than a random sample of proteins. Class II-bound peptides were generally more conserved than their source proteins but were significantly less conserved than class I-bound peptides. The characteristics of class I-bound peptides can probably be explained by the selectivity of processing and transport of peptides for binding by class I, while the relative lack of selectivity of peptide binding for class II may explain the high incidence of autoimmune diseases associated with alleles of these molecules.
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  • 10
    ISSN: 1432-1211
    Keywords: Key words iNOS ; Fish ; Parasite ; Evolution ; Transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Using an oligonucleotide primer based on a partial goldfish inducible nitric oxide synthase (iNOS) sequence, a complete carp iNOS cDNA was isolated from an activated carp phagocyte cDNA library. Nucleotide and predicted amino acid sequence analysis indicate that carp iNOS encodes a 1127-amino acid protein with 57% sequence identity to human iNOS. Like mammalian NOSs, carp iNOS protein contains putative binding sites for heme, tetrahydrobiopterin, calmodulin, flavine mononucleotide, flavine adenine dinucleotide, and NADPH. Phylogenetic analysis, using neighbor joining, showed that the carp iNOS protein clustered together with the other vertebrate iNOS proteins. Inducibility of carp iNOS was confirmed by reverse transcription-polymerase chain reaction after stimulation of carp phagocytes with lipopolysaccharide or the protozoan blood flagellate Trypanoplasma borreli. These stimulators produced high amounts of nitric oxide that were toxic for T. borreli in vitro. The nuclear transciption factor NF-κB was shown to play a role in the induction of iNOS transcription.
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  • 11
    ISSN: 1432-1211
    Keywords: Key words HLA ; Patr class I molecules ; Evolution ; Polymorphism ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Human immunodefiency virus (HIV) poses a major threat to humankind. And though, like humans, chimpanzees are susceptible to HIV infection, they are considered to be resistant to the development of the acquired immune deficiency syndrome (AIDS). Little is known about major histocompatibility complex (MHC) class I diversity in chimpanzee populations and, moreover, whether qualitative aspects of Patr class I molecules may control resistance to AIDS. To address these questions, we assayed MHC class I diversity in a West African chimpanzee population and in some animals from other subspecies of chimpanzee. Application of different techniques allowed the detection of 17 full-length Patr-A, 19 Patr-B, and 10 Patr-C alleles. All Patr-A alleles cluster only into the HLA-A1/A3/A11 family, which supports the idea that chimpanzees have experienced a reduction in their repertoire of A locus alleles. The Patr-B alleles do not cluster in the same lineages as their human equivalents, due to frequent exchange of polymorphic sequence motifs. Furthermore, polymorphic motifs may have been exchanged between Patr-A and Patr-B loci, resulting in convergence. With regard to evolutionary stability, the Patr-C locus is more similar to the Patr-A locus than it is to the Patr-B locus. Despite the relatively low number of animals analyzed, humans and chimpanzees were ascertained as sharing similar degrees of diversity at the contact residues constituting the B and F pockets in the peptide-binding side of MHC class I molecules. Our results indicate that within a small sample of a West African chimpanzee population, a high degree of Patr class I diversity is encountered. This is in agreement with the fact that chimpanzees display more mitochondrial DNA variation than humans. In addition, population analyses demonstrated that particular Patr-B molecules, with the capacity to bind conserved HIV-1 epitopes, are characterized by high gene frequencies. These findings have important implications for evaluating immune responses in HIV vaccine studies and, more importantly, may help in understanding the relative resistance of chimpanzees to AIDS.
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  • 12
    ISSN: 1432-1211
    Keywords: Key words HLA genes ; IgV genes ; Evolution ; Gene conversion ; Sheep ileal Peyer's patch
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Polymorphic sequence variation in the peptide-binding domains of MHC class I molecules appears to have been driven largely by the constructive action of natural selection on the specificity of the peptide-binding groove. Similar features are displayed by the variable domains of immunoglobulins generated in the sheep ileal Peyer's patch, but in this case there is evidence that the action of a targeted hypermutator acting on a selected substrate rather than antigen-driven selection is responsible for the pattern of variation in the system. Such a hypermutator acting in the germ line would not only mimic the action of natural selection but also, by convergent mutation, generate similar patterns of variation in unrelated alleles that could be interpreted as evidence for short-tract gene conversion. We analyzed human class I MHC alleles in the light of these data, but failed to find evidence of the action of a similar hypermutator. A search for other mutationally driven patterns of variation also failed, even in hypervariable residues from parsimonious phylogenies. Single-nucleotide variation at these residues is also frequent in recent allelic variants, but the data are as consistent with short-tract gene conversion as with base mutation. We conclude that the patterns of allelic variation in MHC molecules are not driven by mutational pressure, but rather by conventional mutational processes, accompanied by short-tract gene conversion and intense natural selection.
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  • 13
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    Immunogenetics 51 (2000), S. 587-590 
    ISSN: 1432-1211
    Keywords: Key words J chain ; Immunoglobulin ; Amphibian ; Evolution ; Comparative immunology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 14
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    Immunogenetics 51 (2000), S. 606-609 
    ISSN: 1432-1211
    Keywords: Key words MHC ; Evolution ; Primate ; Callithrix ; Callicebus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 15
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    Mycorrhiza 10 (2000), S. 145-149 
    ISSN: 1432-1890
    Keywords: Keywords Arbuscular mycorrhiza ; Pteridophyte ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The percentage of arbuscular mycorrhizal pteridophytes among 256 pteridophyte species distributed in Yunnan (southwest China) was found to be lower than that in angiosperms. In the pteridophytes, the occurrence of arbuscular mycorrhizas was low in sporophytes of fern-allies and leptosporangiates, whereas in the eusporangiates it was relatively high. From the standpoint of mycotrophism, the evolutionary trend in the Filicineae may be from constantly mycorrhizal to facultative mycorrhizal and finally to nonmycorrhizal plants.
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  • 16
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    Journal of molecular evolution 5 (1975), S. 187-197 
    ISSN: 1432-1432
    Keywords: Evolution ; Cytochrome C ; Substitution ; Covarion ; Monte-Carlo Simulations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A statistical analysis aimed at obtaining some informations on a possible correlation between simultaneous amino acid substitutions is proposed. This method is applied to a set of cytochromes C, at the level of tandem and triple substitutions separated along the peptide chain by 1 to 15 peptide bonds. Monte-Carlo simulations are performed and the results are compared. We find a significant occurence of three adjacent amino acid substitutions in which the first replacement requires a two nucleotide substitution. A possible explanation of this fact is proposed on the basis of covarions.
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  • 17
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    Journal of molecular evolution 7 (1976), S. 133-149 
    ISSN: 1432-1432
    Keywords: 5S rRNA ; Nucleotide Sequence Homology ; Evolution ; Mutation Frequencies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 18
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    Journal of molecular evolution 5 (1975), S. 47-55 
    ISSN: 1432-1432
    Keywords: Gene Duplication ; Dipeptides ; Posterior Pituitary Peptide ; Evolution ; Protein Sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have compiled the dipeptide frequencies in 100 known protein sequences. We suggest that dipeptides which occur with low frequencies can be used to locate proteins where partial gene duplication may have taken place. The 48 residue sequence of posterior pituitary peptide contains two Cys Trp pairs. The adjacent portions of the sequence are compatible with a partial gene duplication in the evolutionary history of posterior pituitary peptide.
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  • 19
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    Journal of molecular evolution 6 (1975), S. 309-320 
    ISSN: 1432-1432
    Keywords: Aminoacyl Transfer ; Amino Acid Adenylate ; Imidazole Catalysis ; Evolution ; Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Imidazole catalysis of phenylalanyl transfer from phenylalanine adenylate anhydride to the hydroxyl groups of homopolyribonucleotides was investigated as a chemical model of the biochemical aminoacylation of tRNA. Imidazole catalyzed transfer of phenylalanine to poly (U) increases from pH 6.5 to 7.7 and decreases above pH 7.7. At pH 7.7 approximately 10% of the phenylalanyl residues are transferred to poly (U). At pH 7.1, transfer to poly (U) was five times as great as to poly (A) and transfer to a poly (A) poly (U) double helix was negligible. At pH 7.1 approximately 45 mole percent linkages to poly (U) were monomeric phenylalanine; the remainder of the linkages were peptides of phenylalanine. The number of linkages and their lability to base and neutral hydroxylamine indicates that phenylalanine and its peptides are attached as esters to the 2′ hydroxyl groups throughout poly (U) and the 2′ (3) hydroxyl groups at the terminus of poly (U). These results do model the contemporary process of aminoacyl transfer to tRNA and continue to suggest that a histidine residue is in the active site of aminoacyl-tRNA-synthetases.
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  • 20
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    Journal of molecular evolution 7 (1976), S. 111-131 
    ISSN: 1432-1432
    Keywords: Crustacea ; Evolution ; Repeated DNA ; Molecular Hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 21
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    Journal of molecular evolution 7 (1976), S. 185-195 
    ISSN: 1432-1432
    Keywords: Evolution ; Randomicity ; Counter-Example
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Specific counter-examples are derived theoretically to the hypothesis that a random amino acid composition signifies a random evolutionary process.
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  • 22
    ISSN: 1432-1432
    Keywords: Bacilli, 16S rRNA ; Phylogeny ; Thermophile ; Evolution ; Oligonucleotide Fingerprint
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 23
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    Journal of molecular evolution 6 (1975), S. 149-163 
    ISSN: 1432-1432
    Keywords: Electrophoretic Detectability ; Neutral Mutation Theory ; Evolution ; Mutation Rates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Routine electrophoretic surveys for genetic variation in natural populations depend primarily upon detecting differences in the net charge carried by a protein. We have calculated the proportion of base substitutions which would yield an electrophoretically detectable mutant protein, and the relative mutation rates among different charge classes, under a variety of simplifying assumptions. These calculations indicate that: (i) only 25 per cent of all single base mutations would lead to a charge change on a protein molecule. (ii) five distinct classes of electrophoretic variants can be generated from a specified protein by single base substitutions. (iii) the relative mutation rates differ markedly among the different charge classes which can be generated by single base substitutions. The estimates of the proportion of electrophoretically detectable mutant proteins and relative mutation rates among charge classes were relatively robust to changes in assumptions concerned with the kind and site of base substitutions and the amino acid composition of the protein.
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  • 24
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    Journal of molecular evolution 8 (1976), S. 79-94 
    ISSN: 1432-1432
    Keywords: Histones ; Evolution ; Prokaryotes ; Lower Eukaryotes ; Higher Eukaryotes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 25
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    Journal of molecular evolution 8 (1976), S. 387-388 
    ISSN: 1432-1432
    Keywords: Nitrate Respiration ; Fermentation ; Energy Metabolism ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary E. Broda's recent argument against our concept that nitrate respiration antedated oxygen respiration is criticized.
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  • 26
    ISSN: 1432-1432
    Keywords: Evolution ; Repetitive DNA ; SI Nuclease ; Sequence Organization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 27
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    Journal of molecular evolution 9 (1977), S. 131-158 
    ISSN: 1432-1432
    Keywords: Parvalbumins ; Evolution ; Maximum parsimony ; Troponin-C ; Myosin alkali light chain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Phylogenetic trees requiring the lowest sum of nucleotide replacements and gene duplicative events were constructed from the amino acid sequence data on ten gnathostome parvalbumins (PAR) and two related myofibrillar proteins troponin-C (TNC) and myosin alkali-light-chain (ALC). The origin and differentiation of the structural domains within these proteins were also investigated by the maximum parsimony method and by an alignment statistic for identifying evolutionarily related protein sequences. The results suggest, in agreement with the Weeds-McLachlan model, that tandem duplications in a precursor gene caused a primordial one-domain polypeptide (consisting of two helices with a calcium binding region in between) to double and then quadruple in size. Duplications of the gene coding for this four domain (I–II–III–IV) protein in an early metazoan, pre-gnathostome lineage gave rise to the separate loci for TNC, ALC, and PAR. TNC, which alone retained the Ca-binding function in each of its four domains, evolved much more slowly than either the ALC or PAR lineages. In the PAR lineage the I–II–III–IV structure was degraded, presumably by a partial gene deletion, to the II–III–IV structure during descent to the gnathostome ancestor of parvalbumins. Also during this period the mid region in domain II lost its Ca-binding function and, as it did so, evolved at an accelerated rate over other regions, a pattern indicative of positive selection for a change in function. In turn, from the gnathostome ancestor to the present, the mid regions of domains III and IV, which each retained Ca-bindung function, evolved much more slowly than other regions, a pattern indicative of stabilizing selection for preservation of function. Between the gnathostome and teleost-tetrapod ancestor a gene duplication separated the parvalbumins into anα-lineage and aβ-lineage. During this early vertebrate period PAR genes evolved at the extremely fast rate of 89 nucleotide replacements per 100 codons per 108 years (i.e. 89 NR %), but from the teleost-tetrapod ancestor to the present, bothα- andβ-PAR lineages evolved at a much slower rate, about 8 NR %. The use ofβ-parvalbumins as phylogenetic markers was complicated by presumptive evidence that paralogous (i.e. duplication dependent) gene lineages occur within this group. As a final point, in the genealogy of TNC, ALC, and PAR lineages, a non-random pattern of nucleotide replacements was observed between the reconstructed ancestral and descendant mRNA sequences. The pattern was similar to that observed for other protein genealogies and seems to reflect a bias in the genetic code for guanine to adenine and adenine to guanine transitions (especially at the first nucleotide position of the RNA codons) to produce amino acid substitutions which are compatible with the preservation of protein three-dimensional structure.
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    Journal of molecular evolution 6 (1975), S. 61-76 
    ISSN: 1432-1432
    Keywords: 5S ribosomal RNA ; Translation ; Evolution ; Molecular Architecture ; Conformational Changes
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    Topics: Biology
    Notes: Summary An extensive comparative analysis of the available primary sequence data on 5S rRNA has been made. A universal secondary structure is presented for procaryotic 5S rRNA which contains four helical regions. Eucaryotic 5S rRNAs are found to have only three of these helices and thus have a somewhat different architecture. In addition, a highly conserved segment of more than thirty nucleotides is identified in the 5′ half of the procaryotic molecule. This segment includes the oligonucleotide-CGAAC- which presumably binds to the t-RNA “common” sequence-GTΨCG-. Among the eucaryotes, the plants display a procaryotic nature in this region, but no eucaryote has the sequence -CGAAC- in this segment. A functional role for the procaryotic 5S rRNA molecule is discussed in which it is envisioned to undergo conformational change, i.e., coiling and uncoiling of one of the helices, which can result in a cyclic interaction of the 5S rRNA molecule with two t-RNA molecules. A general principle also emerges: the natural rotational motion inherent in coiling and uncoiling of nucleic acid helices can be converted quite simply to linear mechanical motion.
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    Journal of molecular evolution 5 (1975), S. 279-290 
    ISSN: 1432-1432
    Keywords: E.coli ; Mutagenesis ; Evolution ; Gene Transposition
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    Topics: Biology
    Notes: Summary The lactose fermenting genes inE.coli have been transposed to various chromosomal locations. The bacterial strains were mutagenized with different chemical mutagens and the frequency of Lac negative mutant colonies was measured as a function of lactose gene location in the chromosome. There appears to be a highly mutable location between 58–60 minutes on theE.coli map. This region does not appear to be correlated with the origin of DNA replication or with the terminus. The possible significance of this mutable region in the evolution of new bacterial genes is discussed.
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    Journal of molecular evolution 8 (1976), S. 143-153 
    ISSN: 1432-1432
    Keywords: 5S rRNA ; Comparative Analysis ; Secondary Structure ; Evolution ; Tuned Helix
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    Topics: Biology
    Notes: 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.
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    Journal of molecular evolution 9 (1976), S. 25-35 
    ISSN: 1432-1432
    Keywords: Genome organization ; Evolution ; Mitochondria
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    Notes: 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.
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    Journal of molecular evolution 9 (1977), S. 343-347 
    ISSN: 1432-1432
    Keywords: Evolution ; Haemoglobin ; Cooperativity ; Lamprey ; Maximum parsimony
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    Notes: Summary The sequences ofPetromyzon andAplysia globins are compared with the postulated vertebrate and mollusc-vertebrate ancestors to see if differences exist in the rates of evolution of different types of residue positions. Between the mollusc-vertebrate ancestor andAplysia globin there is no very striking pattern of changes except that the interior positions are relatively conserved. In the evolution ofPetromyzon haemoglobin, theα 1 β 2 contact area is relatively conserved. The homopolymeric binding of lamprey Hb seems to be a primitive function.
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    Journal of molecular evolution 9 (1977), S. 369-371 
    ISSN: 1432-1432
    Keywords: Methanogenic bacteria ; Primitive atmosphere ; Evolution ; Ecology ; Methane-carbon dioxide cycle
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    Topics: Biology
    Notes: Summary The phenotype and antiquity of methanogenic bacteria suggest them to have been one of the major factors determining a dynamic balance between CO2 and CH4 in the primitive atmosphere.
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  • 34
    ISSN: 1432-1432
    Keywords: Ribosome ; 5S RNA ; Conformation ; Evolution
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    Notes: Summary Fox and Woese (1975a) have shown that a model of 5S RNA secondary structure similar to the one originally derived forChlorella 5S RNA can be generalized with relatively minor variations to all sequenced 5S RNA molecules, i.e. that corresponding base paired regions can be formed at approximately the same positions. We present experimental data in favour of this hypothesis and show that the points at which ribonucleases T1, T2 and pancreatic ribonuclease cleave six different 5S RNA molecules under ‘mild’ conditions (high ionic strength, low temperature, low RNAase concentration) nearly always fall in the proposed single-stranded regions. We conclude that this model is a good approximation to the conformation of 5S RNA in solution.
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    Journal of molecular evolution 10 (1977), S. 123-135 
    ISSN: 1432-1432
    Keywords: Ancestral sequence ; Eye lens protein ; Evolution ; Phylogenetic tree
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    Notes: Summary The sequences of the A chains of the eye lens proteinα-crystallin from seventeen mammalian species were compared. They showed a generally slow rate of evolution, but with marked variations in different lineages. Most substitutions have occurred in the C-terminal part of the chain, which probably forms part of the surface of theα-crystallin aggregate. The ancestral sequence method of Dayhoff revealed interesting indications about the phylogenetic relationships between the eleven mammalian orders that were represented by the investigated species. Most evident was the divergence of marsupial and placental orders. A notable resemblance between the hyrax and elephant sequences was observed, setting them apart from the ungulates, including whale. Primates, rodents, lagomorphs, insectivores and tupaiids seem to derive from a common stem group. These phylogenetic inferences are discussed in relation to current palaeontological and taxonomical opinions, and compared to evidence from other protein sequence data.
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    Journal of molecular evolution 11 (1978), S. 109-120 
    ISSN: 1432-1432
    Keywords: Origin of Life ; Genetic code ; Protein synthesis ; Evolution ; Prebiotic reactions
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    Notes: Summary The fact that proteins contain onlya-amino acids and that protein structure is determined by 3′ → 5′ linked ribonucleotides is postulated to be the result of the copolymerization of these molecules in the prebiotic environment. Ribonucleotides therefore represent partial degradation products and proteins represent a side reaction developing from copolymerization. The basic structural unit of copolymerization is a nucleotide substituted with an amino acid at the 2′ position. Characteristics of modern amino and ribonucleic acid structure are all consistent with and necessary for this hypothesis. The characteristics and individual base assignments of the code also provide strong support for origin from the postulated copolymers. All characteristics of the code can be accounted for by this single hypothesis.
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    Journal of molecular evolution 11 (1978), S. 225-231 
    ISSN: 1432-1432
    Keywords: Phylogenetic denseness ; Phylogenetic trees ; Topology ; Molecular reconstructions ; Evolution ; Paleogenetics
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    Notes: Summary The concept of phylogenetic denseness bears critically on the accuracy of evolutionary pathways inferred from experimentally sequenced proteins isolated from extant species. In this paper I develop an objective measure,ρ, of denseness to supplement previous intuitive concepts and which permits one to use this concept in comparing the quality of different evolutionary reconstructions. This measure is used to examine several published phylogenetic trees: insulin, a-hemoglobin,β-hemoglobin, myoglobin, cytochromec, and the parvalbumin family. The paper emphasizes 1) the importance of denseness in accurately estimating the number of nucleotide replacements which separate homologous sequences when this estimation is made by the method of parsimony, 2) the value of this concept in assessing the quality of those estimates, and 3) the use of this concept as a biologically practical heuristic method for identifying poorly studied regions in a phylogenetic tree, whether or not the tree was obtained by the parsimony method.
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    Journal of molecular evolution 13 (1979), S. 95-101 
    ISSN: 1432-1432
    Keywords: Oparin Ocean ; Origin of Life ; Evolution ; Runaway greenhouse ; Photosynthesis ; Methanogenesis
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    Notes: Summary The widely accepted Oparin thesis for the origin and early evolution of life seems sufficiently far from the true state of affairs as to be considered incorrect. It is proposed that life on earth actually arose in the planet's atmosphere, however an atmosphere very different from the present one. Because of an extremely warm surface, the early earth may have possessed no liquid surface water, its water being partitioned between a molten crust and a fairly dense atmosphere. Early preliving systems are taken to arise in the droplet phase in such an atmosphere. The early earth, which resembled Venus then and to some extent now, underwent a transition to its present condition largely as a result of the evolution of methanogenic metabolism.
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    Journal of molecular evolution 10 (1977), S. 93-96 
    ISSN: 1432-1432
    Keywords: Evolution ; Endosymbiosis ; Mitochondrion ; Photosynthetic
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    Notes: Summary The possibility is put forth that the mitochondrion did not originate from an endosymbiosis, 1–2 billion years ago, involving an aerobic bacterium. Rather, it arose by endosymbiosis in a much early, anaerobic period, and was initially a photosynthetic organelle, analogous to the modern chloroplast. This suggestion arises from a reconsideration of the nature of endosymbiosis. It ex-plains the remarkable diversity in mitochondrial information storage and processing systems.
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  • 40
    ISSN: 1432-1432
    Keywords: Lysozyme ; Insect ; Lepidoptera ; Evolution ; Sequence
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    Notes: Summary Sequence studies of the N-terminal halves of the lysozymes isolated fromBombyx mori, Galleria mellonella andSpodoptera littoralis (Lepidoptera) allow us to classify these enzymes among the c (chicken) type lysozymes.
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    Journal of molecular evolution 14 (1979), S. 287-300 
    ISSN: 1432-1432
    Keywords: Phenylalanine tRNA ; Methionine initiator tRNA ; Evolution ; Mutations ; Conformation
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    Notes: Summary Sequence data from methionine initiator and phenylalanine transfer RNAs were used to construct phylogenetic trees by the maximum parsimony method. Although eukaryotes, prokaryotes and chloroplasts appear related to a common ancestor, no firm conclusion can be drawn at this time about mitochondrial-coded transfer RNAs. tRNA evolution is not appropriately described by random hit models, since the various regions of the molecule differ sharply in their mutational fixation rates. ‘Hot’ mutational spots are identified in the TψC, the amino acceptor and the upper anticodon stems; the D arm and the loop areas on the other hand are highly conserved. Crucial tertiary interactions are thus essentially preserved while most of the double helical domain undergoes base pair interchange. Transitions are about half as costly as transversions, suggesting that base pair interchanges proceed mostly through G-U and A -C intermediates. There is a preponderance of replacements starting from G and C but this bias appears to follow the high G + C content of the easily mutated base paired regions.
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    Journal of molecular evolution 5 (1975), S. 25-34 
    ISSN: 1432-1432
    Keywords: Rhodopseudomonas spheroides ; 16S Ribosomal RNA ; T1 Ribonuclease Digest ; Phylogeny ; Evolution
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    Notes: Summary The 16S ribosomal RNA (30S subunit) ofRhodopseudomonas spheroides has been characterized in terms of T1 ribonuclease digestion products. This “fingerprint” ultimately permits the placement ofR. spheroides into a detailed procaryotic phylogenetic tree. Given the number of major procaryotic lines that have been characterized in these terms to date, one can tentatively place the Athiorhodaceae closer to the Vibrio-Enteric group than to the Bacillaceae or Cyanophyta.
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    Journal of molecular evolution 5 (1975), S. 35-46 
    ISSN: 1432-1432
    Keywords: Photobacter Strain 8265 ; 5S Ribosomal RNA ; Primary Structure ; Comparative Characterization ; Evolution ; Energetically Constrained Helix
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    Notes: Summary Comparative sequencing studies provide powerful insights into molecular function and evolution. The sequence for 5S ribosomal RNA from Photobacter strain 8265 is eighteen base replacements removed from that ofEscherichia coli. Of these, the vast majority involve a G or C becoming an A or U. These variations also define unequivocally a hexanucleotide base paired region, which appears to be a universal feature of the 5S RNA molecule. The base composition of this helix seems to be under rather stringent, and so unusual, energetic constraints. The possible implications of this are discussed - in particular the prospect of a 5S RNA molecule that undergoes conformational transitions as a part of the overall state changes that constitute the function of the ribosome.
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    ISSN: 1432-1432
    Keywords: 5S RNA ; Drosophila ; Evolution ; Secondary structure ; Development
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    Notes: Summary The nucleotide sequence ofDrosophila melanogaster 5S RNA has been determined and appears to be homogeneous both in the KC cell line and in the insect at different developmental stages. Experimental evidence on the conformation of this molecule is in agreement with a general class of 5S RNA models.
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    Journal of molecular evolution 9 (1977), S. 305-311 
    ISSN: 1432-1432
    Keywords: Comparative cataloging ; Methanogenic bacteria ; Phylogeny ; 16S ribosomal RNA ; Evolution
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    Notes: Summary The 16S ribosomal RNAs from two species of methanogenic bacteria, the mesophileMethanobacterium ruminantium and the thermophileMethanobacterium thermoautotropbicum, have been characterized in terms of the oligonucleotides produced by digestion withT 1 ribonuclease. These two organisms are found to be sufficiently related that they can be considered members of the same genus or family. However, they bear only slight resemblance to “typical” Procaryotic genera; such asEschericbia, Bacillus andAnacystis. The divergence of the methanogeinc bacteria from other bacteria may be the most ancient phylogenetic event yet detected — antedating considerably the divergence of the blue green algal line for example, from the main bacterial line.
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    Journal of molecular evolution 14 (1979), S. 13-31 
    ISSN: 1432-1432
    Keywords: Mars ; Evolution ; Planetary geochemistry ; Soil ; Ionizing radiation ; Exobiology
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    Notes: Summary Physical and chemical considerations permit the division of the near-surface regolith on Mars into at least six zones of distinct microenvironments. The zones are euphotic, duricrust/peds, tempofrost, permafrost, endolithic, and interfacial/transitional. Microenvironments vary significantly in temperature extremes, mean temperature, salt content, relative pressure of water vapor, UV and visible light irradiance, and exposure to ionizing radiation events (100 Mrad) and oxidative molecular species. From what is known of the chemistry of the atmossphere and regolith fines (soil), limits upon the aqueous chemistry of soil pastesmay be estimated. Heat of wetting could reach 45 cal/g dry soil; initial pH is indeterminate between 1 and 10; ionic strength and salinity are predicted to be extremely high; freezing point depression is inadequate to provide quantities of liquid water except in special cases. The prospects for biotic survival are grim by terrestrial standards, but the extremes of biological resiliency are inaccessible to evaluation. Second-generation in situ experiments which will better define Martian microenvironments are clearly possible. Antarctic dry valleys are approximations to Martian conditions, but deviate significantly by at least half-a-dozen criteria.
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    Journal of molecular evolution 10 (1977), S. 155-160 
    ISSN: 1432-1432
    Keywords: Cysteine ; Cystine ; Protein ; Evolution
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    Notes: Summary Analysis of published data on the cysteine and half-cystine content of proteins indicates that most intracellular proteins may be classified as sulfhydryl proteins (those containing cysteine but little or no half-cystine) and that such sulf-hydryl proteins have a low cysteine content. The mean cysteine content found for 32 intracellular mammalian proteins was 1.6 % and intracellular proteins of many bacteria have similar or lower values. Extracellular mammalian proteins are primarily disulfide proteins (those containing half-cystine but little or no cysteine) and have a high half-cystine content, the mean value found for some 34 extracellular mammalian proteins being 4.1 %. This is contrasted with many of the extracellular proteins from facultative bacteria which are cyst(e)ine-free proteins, being lacking in both cysteine and half-cystine. These and related observations are interpreted in terms of the evolution of life in a reducing atmosphere and the subsequent transition to an oxidizing environment. It is suggested that disulfide proteins evolved primarily after the accumulation of oxygen in the atmosphere.
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    Journal of comparative physiology 186 (2000), S. 105-118 
    ISSN: 1432-1351
    Keywords: Key words Stomatogastric nervous system ; Penaeus ; Motor pattern ; Neural network ; Evolution
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    Topics: Biology , Medicine
    Notes: Abstract  Motor patterns of the cardiac sac, the gastric and the pyloric network in the stomatogastric nervous system of the shrimp Penaeus japonicus, the most primitive decapod species, were studied. Single neurons can switch from the gastric or the pyloric pattern to the cardiac sac pattern. Some of the pyloric neurons fire with the gastric pattern. All of the gastric neurons fire with the pyloric pattern, unlike those in reptantians. Proctolin activates and modulates the cardiac sac and the pyloric rhythm, and promotes reconfiguration of the networks. Neurons of the three networks have so many interconnections that they construct a multifunctional neural network like those in Cancer. This network may function in different configurations under the appropriate conditions. Several modes of interactions between the networks found in different reptantian species can apply to the penaeidean shrimp. Such interactions are general features of the stomatogastric nervous system in decapods. Phylogenetic differences among the decapod infraorders are seen in the number and orientation of muscles and the innervation pattern of muscles. The multifunctional networks have existed in the most primitive decapod species, and types of configurations of the networks would have evolved to produce a wide range of motor patterns as the foregut structure has become complex.
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    Journal of molecular evolution 10 (1977), S. 1-6 
    ISSN: 1432-1432
    Keywords: Evolution ; Ribosomes ; Genotype-Phenotype ; Cytoplasm ; Endosymbiosis ; Procaryote ; Eucaryote ; Progenote
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    Notes: Summary A central evolutionary question is whether the eucaryotic cytoplasm represents a line of descent that is separate from the typical bacterial line. It is argued on the basis of differences between their respective translation mechanisms that the two lines do represent separate phylogenetic trees in the sense that each line of descent independently evolved to a level of organization that could be called procaryotic. The two lines of descent, nevertheless shared a common ancestor, that was far simpler than the procaryote. This primitive entity is called a progenote, to recognize the possibility that it had not yet completed evolving the link between genotype and phenotype. This concept changes considerably the view one takes toward cellular evolution.
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    Journal of molecular evolution 10 (1977), S. 261-264 
    ISSN: 1432-1432
    Keywords: Lysozyme ; Tortoise ; Evolution ; Reptile
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    Topics: Biology
    Notes: Summary A first series of structural studies allowed a reptilian egg-white lysozyme isolated fromTrionyx gangeticus to be classified among the c (chicken) type lysozymes
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    Journal of molecular evolution 11 (1978), S. 1-8 
    ISSN: 1432-1432
    Keywords: Halobacteria ; Archaebacteria ; Phylogeny ; 16S rRNA catalog ; Evolution
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    Topics: Biology
    Notes: Summary Comparative cataloging of the 16S rRNA ofHalobacterium halobium indicates that the organism did not arise, as a halophilic adaptation, from some typical bacterium. Rather,H. halobium is a member of the Archaebacteria, an ancient group of organisms that are no more related to typical bacteria than they are to eucaryotes.
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    Journal of molecular evolution 11 (1978), S. 47-56 
    ISSN: 1432-1432
    Keywords: Genome duplication ; Genome topography ; Evolution ; Gene expression
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    Notes: Summary Genes ofEscherichia coli were grouped according to the “biochemical relatedness” of the enzymes they specifiy, using two schemes to determine relatedness: similarity of reaction or similarity of reactants. The tendency of biochemically related genes as so defined to lie approximately 90° or 180° from one another on the circular genetic map was analyzed statistically. Of the classes analyzed, only the genes for the enzymes of glucose catabolism showed a significant departure from random distribution in this respect. The glucose catabolism genes showed a pronounced tendency to lie either 90° or 180° from one another (P = ca. 10−9), and, furthermore, most of these genes were found to lie in only four gene clusters on theE. coli genome. The significance of this observation is discussed in relation to evolutionary mechanisms and to mechanisms of gene expression.
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    Journal of molecular evolution 11 (1978), S. 313-332 
    ISSN: 1432-1432
    Keywords: Evolution ; Optical activity ; Photolysis ; Circularly ; polarized radiation ; Selection
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    Topics: Biology
    Notes: Summary Stereoselective physical phenomena and their possible importance for the prevalence of D-sugars and L-aminoacids in living matter are reviewed. A classification is presented according to which a selective force provides a microscopic or macroscopic selection depending on its generality when taken over a macrosystem (a ‘unitary biosphere’ such as the Earth). The microscopic ‘selections’ are not genuine selections because the final sense of asymmetry is here determined by chance, in other words the initial choice is ‘random’, while it is ‘directed’ in the macroscopic selection. Two macroscopic selections appear possible: 1. selection due to an intrinsic energy difference between enantiomorph configurations, 2. selection accomplished by elliptically polarised radiation.
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    Journal of molecular evolution 13 (1979), S. 295-304 
    ISSN: 1432-1432
    Keywords: Evolution ; Restriction endonuclease mappings and mitochondrial DNA
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    Notes: Summary A new estimate of the sequence divergence of mitochondrial DNA in related species using restriction enzyme maps is constructed. The estimate is derived assuming a simple Posisson-like model for the evolutionary process and is chosen to maximize an expression which is a reasonable approximation to the true likelihood of the restriction map data. Using this estimate, four sets of mitochondrial DNA data are analyzed and discussed.
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    Development genes and evolution 210 (2000), S. 644-650 
    ISSN: 1432-041X
    Keywords: Keywords Pax protein ; Paired domain ; Homeobox ; Transposase ; Evolution
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    Topics: Biology
    Notes: Abstract  Pax proteins play a diverse role in early animal development and contain the characteristic paired domain, consisting of two conserved helix-turn-helix motifs. In many Pax proteins the paired domain is fused to a second DNA binding domain of the paired-like homeobox family. By amino acid sequence alignments, secondary structure prediction, 3D-structure comparison, and phylogenetic reconstruction, we analyzed the relationship between Pax proteins and members of the Tc1 family of transposases, which possibly share a common ancestor with Pax proteins. We suggest that the DNA binding domain of an ancestral transposase (proto-Pax transposase) was fused to a homeodomain shortly after the emergence of metazoans about one billion years ago. Using the transposase sequences as an outgroup we reexamined the early evolution of the Pax proteins. Our novel evolutionary scenario features a single homeobox capturing event and an early duplication of Pax genes before the divergence of porifera, indicating a more diverse role of Pax proteins in primitive animals than previously expected.
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    Development genes and evolution 210 (2000), S. 82-91 
    ISSN: 1432-041X
    Keywords: Key words T-box genes ; Zebrafish ; Fins ; Evolution ; Gene duplication
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    Topics: Biology
    Notes: Abstract  The presence of two sets of paired appendages is one of the defining features of jawed vertebrates. We are interested in identifying genetic systems that could have been responsible for the origin of the first set of such appendages, for their subsequent duplication at a different axial level, and/or for the generation of their distinct identities. It has been hypothesized that four genes of the T-box gene family (Tbx2–Tbx5) played important roles in the course of vertebrate limb evolution. To test this idea, we characterized the orthologs of tetrapod limb-expressed T-box genes from a teleost, Danio rerio. Here we report isolation of three of these genes, tbx2, tbx4, and tbx5. We found that their expression patterns are remarkably similar to those of their tetrapod counterparts. In particular, expression of tbx5 and tbx4 is restricted to pectoral and pelvic fin buds, respectively, while tbx2 can be detected at the anterior and posterior margins of the outgrowing fin buds. This, in combination with conserved expression patterns in other tissues, suggests that the last common ancestor of teleosts and tetrapods possessed all four of these limb-expressed T-box genes (Tbx2–Tbx5), and that these genes had already acquired, and have subsequently maintained, their gene-specific functions. Furthermore, this evidence provides molecular support for the notion that teleost pectoral and pelvic fins and tetrapod fore- and hindlimbs, respectively, are homologous structures, as suggested by comparative morphological analyses.
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    Development genes and evolution 187 (1979), S. 105-127 
    ISSN: 1432-041X
    Keywords: Drosophila ; Pattern formation ; Leg ; Bristle ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The bristle pattern of the second-leg basitarsus inDrosophila melanogaster was studied as a function of the number and size of the cells on this segment in well-fed and starved wild-type flies, in triploid flies, and in two mutants (dachs andfour-jointed) that have abnormally short basitarsi. The second-leg basitarsi of well-fed, wild-type flies from 22 otherDrosophila species were studied in a similar manner. There are typically 8 longitudinal rows of evenly-spaced bristles on the second-leg basitarsus, and in each row the number of bristles was consistently found to vary in proportion to the estimated number of cells along the segment, and the interval between bristles was found to vary in proportion to the average cell diameter on the segment. These correlations are interpreted to mean that the spacing of the bristles within each row is controlled developmentally, whereas the number of bristles is not. The interval between bristles is evidently measured either as a fixed number of cells or as a distance which indirectly depends upon cell diameter.
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    Development genes and evolution 210 (2000), S. 329-336 
    ISSN: 1432-041X
    Keywords: Key words Development ; Evolution ; Notch ; Insect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Studies of somitogenesis in vertebrates have identified a number of genes that are regulated by a periodic oscillator that patterns the pre-somitic mesoderm. One of these genes, hairy, is homologous to a Drosophila segmentation gene that also shows periodic spatial expression. This, and the periodic expression of a zebrafish homologue of hairy during somitogenesis, has suggested that insect segmentation and vertebrate somitogenesis may use similar molecular mechanisms and possibly share a common origin. In chicks and mice expression of the lunatic fringe gene also oscillates in the presomitic mesoderm. Fringe encodes an extracellular protein that regulates Notch signalling. This, and the finding that mutations in Notch or its ligands disrupt somite patterning, suggests that Notch signalling plays an important role in vertebrate somitogenesis. Although Notch signalling is not known to play a role in the formation of segments in Drosophila, we reasoned that it might do so in other insects such as the grasshopper, where segment boundaries form between cells, not between syncytial nuclei as they do in Drosophila. Here we report the cloning of a single fringe gene from the grasshopper Schistocerca. We show that it is not detectably expressed in the forming trunk segments of the embryo until after segment boundaries have formed. We conclude that fringe is not part of the mechanism that makes segments in Schistocerca. Thereafter it is expressed in a pattern which shows that it is a downstream target of the segmentation machinery and suggests that it may play a role in segment morphogenesis. Like its Drosophila counterpart, Schistocerca fringe is also expressed in the eye, in rings in the legs, and during oogenesis, in follicle cells.
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  • 59
    ISSN: 1432-0819
    Keywords: Stratigraphy ; Evolution ; El Chichón ; México
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: 2 abundance and depletion in MgO, CaO, TiO2, as well as trace and rare earth elements. This suggests segregation of olivine and orthopyroxene from the melt. Since human settlements in southeast Mexico and Central America can be traced as far back as approximately 2500 years BP, most of these events probably affected human activity. In fact, there are reports of pottery shards and other artifacts in deposits from the eruption of 1250 BP. Pottery fragments in deposits of an eruption that took place 2500 BP are also reported in this paper. Thus, the impact of the volcano on human activities has been frequent, with most of the repose intervals lasting between 100 to 600 years. The impact of the eruptions was probably of greater than local extent, because airfall tephra could reach distant sites and possibly even affect weather. The eruptive history of El Chichón also offers clues in the investigation of the Maya civilization. Several researchers have considered the volcano as an important factor in the answer to some intriguing questions such as the extensive use of volcanic ash in Late Classic Maya ceramics or, of greater importance, the causes of the collapse of the Classic Maya civilization.
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  • 60
    ISSN: 1432-1211
    Keywords: Key words KIR ; Multigene family ; Gene duplication ; Evolution
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    Topics: Biology , Medicine
    Notes: Abstract. Natural killer (NK) immunoglobulin-like receptors (KIRs) are a family of polymorphic receptors which interact with specific motifs on HLA class I molecules and modulate NK cytolytic activity. In this study, we analyzed a recently sequenced subgenomic region on chromosome 19q13.4 containing eight members of the KIR receptor repertoire. Six members are clustered within a 100-kb continuous sequence. These genes include a previously unpublished member of the KIR gene family 2DS6, as well as 2DL1, 2DL4, 3DL1, 2DS4, 3DL2, from centromere to telomere. Two additional KIR genes, KIRCI and 2DL3, which may be located centromeric of this cluster were also analyzed. We show that the KIR genes have undergone repeated gene duplications. Diversification between the genes has occurred postduplication primarily as a result of retroelement indels and gene truncation. Using pre- and postduplication Alu sequences identified within these genes as evolutionary molecular clocks, the evolution and duplication of this gene cluster is estimated to have occurred 30–45 million years ago, during primate evolution. A proposed model of the duplication history of the KIR gene family leading to their present organization is presented.
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    Immunogenetics 51 (2000), S. 69-74 
    ISSN: 1432-1211
    Keywords: Key words MHC class I ; Pseudogene ; Evolution ; Gorilla ; Chimpanzee
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 62
    ISSN: 1432-1211
    Keywords: Key words Immunoglobulin ; Fugu ; VH family ; Teleosts ; Evolution
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    Topics: Biology , Medicine
    Notes: Abstract. The variable region of the immunoglobulin heavy chain is created by a somatic rearrangement of a limited number of germline genes. This mechanism of gene assembly [V(D)J recombination] has been found to take place only in jawed vertebrates (gnathostomes). To understand how this mechanism evolved and diversified it is necessary to study the genomic organization of the heavy-chain gene in different vertebrate lineages. Since there is scant sequence information on the VH locus in fish, shotgun sequencing of a cosmid clone containing part of the VH genomic region of the Japanese pufferfish, Fugu rubripes, was undertaken. Eight full-length VH genes were isolated and characterized. They have higher homology to trout genes, but show the same structural features as VHs found in other vertebrates. Two VH subgroups have been identified whose members are interspersed. The frequency of synonymous and nonsynonymous substitution for VH comparisons between family members was found to be higher in the complementarity-determining regions than in the framework regions. Finally, there are four other genes interspersed with the VH genes, one of which is the first full-length retrotransposon element characterized in vertebrates.
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  • 63
    ISSN: 1432-1211
    Keywords: Key words J chain ; Polymeric immunoglobulin ; Ontogeny ; Evolution ; Comparative immunology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The J chain is a component of polymeric immunoglobulin (Ig) molecules and may play an important role in their polymerization and the transport of polymeric Ig across epithelial cells. In this study, the primary structure of the chicken J chain was determined by sequencing cDNA clones. The cDNA had an open reading frame of 476 nucleotides encoding a putative protein of 158 amino acid residues including the signal sequence. The 3′ untranslated region consisted of 1216 nucleotides and a poly(A) tail. The deduced amino acid sequence of the chicken J chain had a high degree of homology to that of human, cow, rabbit, mouse, frog, and earthworm, with eight conserved Cys residues identical to the mammalian J chains. Northern blot hybridization performed with total RNA from various chicken tissues revealed high levels of J-chain mRNA expression in spleen, intestine, Harderian gland, and bursa of Fabricius, and low levels in the thymus. The J chain was expressed in the bursa as early as day 15 of embryogenesis. These data indicated that the chicken J-chain gene displays a high degree of homology with that of other species, and is expressed at an early stage of development of the chicken immune system.
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    Oecologia 123 (2000), S. 330-341 
    ISSN: 1432-1939
    Keywords: Key words  Arabidopsis thaliana ; Carbon dioxide ; Evolution ; Reproduction ; Selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Atmospheric CO2 partial pressure (pCO2) was as low as 18 Pa during the Pleistocene and is projected to increase from 36 to 70 Pa CO2 before the end of the 21st century. High pCO2 often increases the growth and reproduction of C3 annuals, whereas low pCO2 decreases growth and may reduce or prevent reproduction. Previous predictions regarding the effects of high and low pCO2 on C3 plants have rarely considered the effects of evolution. Knowledge of the potential for evolution of C3 plants in response to CO2 is important for predicting the degree to which plants may sequester atmospheric CO2 in the future, and for understanding how plants may have functioned in response to low pCO2 during the Pleistocene. Therefore, three studies using Arabidopsis thaliana as a model system for C3 annuals were conducted: (1) a selection experiment to measure responses to selection for high seed number (a major component of fitness) at Pleistocene (20 Pa) and future (70 Pa) pCO2 and to determine changes in development rate and biomass production during selection, (2) a growth experiment to determine if the effects of selection on final biomass were evident prior to reproduction, and (3) a reciprocal transplant experiment to test if pCO2 was a selective agent on Arabidopsis. Arabidopsis showed significant positive responses to selection for high seed number at both 20 and 70 Pa CO2 during the selection process. Furthermore, plants selected at 20 Pa CO2 performed better than plants selected at 70 Pa CO2 under low CO2 conditions, indicating that low CO2 acted as a selective agent on these annuals. However, plants selected at 70 Pa CO2 did not have significantly higher seed production than plants selected at 20 Pa CO2 when grown at high pCO2. Nevertheless, there was some evidence that high CO2 may also be a selective agent because changes in development rate and biomass production during selection occurred in opposite directions at low and high pCO2. Plants selected at high pCO2 showed no change or reductions in biomass relative to control plants due to a decrease in the length of the life cycle, as indicated by earlier initiation of flowering and senescence. In contrast, selection at low CO2 resulted in an average 35% increase in biomass production, due to an increase in the length of the life cycle that resulted in a longer period for biomass accumulation before senescence. From the Arabidopsis model system we conclude that some C3 annuals may have produced greater biomass in response to low pCO2 during the Pleistocene relative to what has been predicted from studies exposing a single generation of C3 plants to low pCO2. Furthermore, C3 annuals may exhibit evolutionary responses to high pCO2 in the future that may result in developmental changes, but these are unlikely to increase biomass production. This series of studies shows that CO2 may potentially act as a selective agent on C3 annuals, producing changes in development rate and carbon accumulation that could not have been predicted from single-generation studies.
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    European journal of clinical pharmacology 8 (1975), S. 97-105 
    ISSN: 1432-1041
    Keywords: Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
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  • 66
    ISSN: 1432-1041
    Keywords: Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy untrained volunteers the increase in plasma dopamine-β-hydroxylase (DBH) activity during graded physical exercise has been examined as a true measure of increased activity of the sympathetic nervous system. The correlation between DBH activity, catecholamine concentration (CA) in plasma and heart rate was studied. When work on an electrically braked bicycle ergometer was gradually increased from 12.5 to 100, 200 and 300 watts there was a linear increase in DBH activity and heart rate; the increase in CA concentrations followed an exponential function. The peak values for DBH activity and CA concentration in plasma after the 300 watt work load (as percentages of the resting levels) were 130±3% and 820±71%, respectively; the adrenaline concentration in plasma increased only to 150±19% (p〉0.05). There were significant correlations between heart rate and work load, DBH and work load and log CA and work load. The data imply direct correlations between heart rate and DBH, heart rate and log CA and DBH and log CA. The exponential increase in noradrenaline concentration in plasma might be due either to a greater net “overflow” from sympathetic nerve endings, and/or to increased secretion by the adrenal medulla. In the latter case, the release of noradrenaline would not be accompanied by secretion either of adrenaline or DBH. After work ceased there were sharp falls in heart rate and CA concentration, which indicate an immediate drop in sympathetic activity. DBH activity in plasma returned to normal very slowly; it reached half maximum values after 20 – 22 min. It is concluded that increased sympathetic activity in man can be estimated in vivo as changes in DBH and/or CA concentration in plasma. In contrast, a rapid decrease in sympathetic activity is directly reflected only by a rapid fall in the plasma concentrations of CA.
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    European journal of clinical pharmacology 8 (1975), S. 33-39 
    ISSN: 1432-1041
    Keywords: m-octopamine ; metabolism ; first-pass effect ; man ; enteric absorption ; monohydroxylated phenylalkylamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The diminished sympathomimetic pressor activity of monohydroxylated phenylalkylamines after oral administration has been attributed to incomplete enteric absorption. Therefore, urinary excretion of the unchanged drug and its metabolites has been compared after intravenous and oral administration of3H-m-octopamine to eight patients. Identical amounts of3H-activity (80% of the dose) were excreted after the two routes of dosing, so enteric absorption has been assumed to be complete. Significant differences were found in the fraction of free urinarym-octopamine, which amounted to 10.5% of the dose after infusion and 0.58% after oral administration. The only metabolic pathways form-octopamine are deamination and conjugation. Following oral administration the percentage of conjugates was considerably higher than after intravenous infusion. This metabolic pattern appears typical of all phenylalkylamines with a hydroxyl group in themeta position. Ring hydroxylation to catecholamines was not observed. The enzymes mainly responsible for conjugation after oral administration are located in the gut wall. The resulting “first pass effect”, i.e. metabolism prior to the access to the central compartment, can account for the diminished pharmacodynamic effect after dosing by this route.
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    European journal of clinical pharmacology 8 (1975), S. 161-166 
    ISSN: 1432-1041
    Keywords: Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75–100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2–4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30–150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the directβ-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.
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    European journal of clinical pharmacology 8 (1975), S. 249-254 
    ISSN: 1432-1041
    Keywords: Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
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    European journal of clinical pharmacology 8 (1975), S. 343-347 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
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    European journal of clinical pharmacology 8 (1975), S. 285-285 
    ISSN: 1432-1041
    Keywords: Lithium ; intoxication ; man ; delayed absorption ; gastric contents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A 55-year old man with lithium intoxication showed increasing serum concentrations in spite of forced diuresis and dialysis. A high lithium content was found in gastric juice three days after the compound had been taken. The serum lithium level began to fall after gastric lavage.
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    European journal of clinical pharmacology 8 (1975), S. 277-282 
    ISSN: 1432-1041
    Keywords: QX-572 ; quaternary ammonium compound ; plasma level ; urinary excretion ; man ; anti-arrhythmic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N, N-bis (phenylcarbamoylmethyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0±1.1 µg/ml (mean ± SE) at the end of infusion to 3.5±0.5 µg/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7±0.1 µg/ml. In these patients 22±2% (mean±SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.
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    European journal of clinical pharmacology 9 (1975), S. 135-145 
    ISSN: 1432-1041
    Keywords: Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
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    European journal of clinical pharmacology 9 (1975), S. 155-159 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
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    European journal of clinical pharmacology 9 (1975), S. 193-198 
    ISSN: 1432-1041
    Keywords: (−)-[14C]-ephedrine ; metabolism ; urinary excretion ; tolerance ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate of orally administered (−)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 µCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53–74%), with N-demethylation occurring to a variable extent (8–20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4–13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.
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    European journal of clinical pharmacology 9 (1975), S. 219-227 
    ISSN: 1432-1041
    Keywords: Rifampicin ; induction of drug metabolism ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.
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    European journal of clinical pharmacology 9 (1975), S. 229-234 
    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
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  • 78
    ISSN: 1432-1041
    Keywords: Aldosterone ; renin ; aldosterone antagonist ; canrenone ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Canrenone was administered in doses of 2×82 mg and 2×164 mg per day over a period of 10 days to diabetic patients without cardiovascular, liver or kidney involvement. Aldosterone excretion and plasma aldosterone increased only slightly during both regimes. There was a clear-cut increase in aldosterone excretion only after discontinuation of carenone. Excretion of sodium potassium and fluid was not significantly changed either during or after treatment. The lack of effect of canrenone on the kidney was in contrast to the significant decrease in serum sodium and increase in serum potassium, and the significant, dose-dependent rise in plasma renin activity following canrenone administration. The increased plasma renin activity persisted for some days after discontinuation of canrenone. It is suggested that canrenone primarily exerted its effect in the distal part of the large intestine where ionic movements are most affected by aldosterone. The disproportionately slight increase in plasma aldosterone concentration and aldosterone excretion, in spite of the greatly elevated plasma renin activity and serum potassium level, is considered to be due to a direct inhibitory effect of canrenone on aldosterone production in the adrenals.
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  • 79
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    European journal of clinical pharmacology 9 (1976), S. 291-298 
    ISSN: 1432-1041
    Keywords: Tricyclic antidepresent ; lofepramine ; single- and multiple-dose kinetics ; noradrenaline and 5-hydroxytryptamine uptake ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lofepramine, an imipramine analogue, have been studied by administering single oral doses to volunteers, determination of plasma levels of lofepramine and desmethylimipramine after ten days of oral administration to patients, and by relating plasma levels to the effect on uptake of noradrenaline by isolated rat irides and brain slices of plasma samples collected during treatment. The results indicate that lofepramine undergoes pronounced first pass elimination and that desmethylimipramine is a major metabolite of it. During steady-state conditions the plasma level of lofepramine fluctuates considerably between doses. A linear relation was found between inhibition of neuronal uptake of noradrenaline and the plasma concentration of desmethylimpramine. No effect was seen on the uptake of 5-hydroxytryptamine in brain slices incubated in patients' plasma which suggests that neither lofepramine nor its metabolites formedin vivo in man affect neuronal uptake of this amine. Lofepramine belongs to the group of tricyclic anti-depressants which preferentially inhibit noradrenaline uptake.
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  • 80
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    European journal of clinical pharmacology 9 (1976), S. 307-314 
    ISSN: 1432-1041
    Keywords: Absorption ; man ; β-methyl-digoxin ; serum concentration ; urinary excretion ; radio-immunoassay
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of β-methyl-digoxin 0.4 mg were given to groups of 17 – 18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum® or Lanitop® tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of β-methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with β-methyl-digoxin steady state glycoside concentrations were compared in a cross-over study of intravenous maintenance therapy with Lanitop® ampoules or oral treatment with Lanitop® tablets. For a standard daily dose of 0.2 mg β-methyl-digoxin the serum concentrations were 1.35±0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.
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  • 81
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    European journal of clinical pharmacology 9 (1976), S. 345-354 
    ISSN: 1432-1041
    Keywords: 3H-digitoxin ; metabolism ; spironolactone ; enzyme induction ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of spironolactone on the metabolism of intravenously administered3H-digitoxin (80 µCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79 % was unaltered drug and 12 % consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (〈2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p〈0.05). In addition spironolactone caused a 20 % reduction in the half-life of serum radioactivity (p〈0.01) and a 16 % reduction in the volume of distribution (p〈0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.
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  • 82
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    European journal of clinical pharmacology 9 (1976), S. 423-428 
    ISSN: 1432-1041
    Keywords: Serum zinc concentration ; intestinal absorption ; portal vein ; transumbilical catheterization ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum zinc concentrations in peripheral venous blood were determined in 8 healthy volunteers at various times after oral administration of 50 mg Zn++. The same dose was given to 6 patients surgically treated for obesity by jejuno-ileostomy. In the healthy volunteers the mean serum zinc concentration before dosing was 0.89 µg/ml and a mean peak concentration of 2.39 µg/ml was found after 3 h. In the patients the starting level was lower, 0.67 µg/ml, and a mean peak concentration of 1.31 µg/ml was found 90 min after treatment. In the patients the areas under the serum concentration-time curve was approximately 1/3 of that in the healthy subjects. Zn++ 50 mg was also given to 3 patients undergoing transumbilical catheterization of the portal vein for diagnostic purposes and serum zinc concentrations were measured in portal and peripheral venous blood sampled simultaneously. No significant differences were found between the concentration of zinc in portal and peripheral venous blood during absorption, which suggests slow passage of zinc across the intestinal wall.
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  • 83
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    European journal of clinical pharmacology 8 (1975), S. 227-231 
    ISSN: 1432-1041
    Keywords: Dixyrazine ; methaqualone ; etodroxizine ; Isonox® ; sleep stages ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox® (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox® (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.
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  • 84
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    European journal of clinical pharmacology 8 (1975), S. 91-96 
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
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  • 85
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    European journal of clinical pharmacology 8 (1975), S. 167-173 
    ISSN: 1432-1041
    Keywords: Disopyramide ; haemodynamic effect ; negative inotropic effect ; anticholinergic effect ; hear failure ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of disopyramide have been studied in 11 patients with manifest or imminent heart failure. Disopyramide, 2 mg per kg body weight, was given intravenously during right and left heart catheterisation. The cardiac index decreased by an average of 28% (p〈0.01); mean maximal left and right ventricular end-diastolic pressures were increased by 5.0±0.9 mm Hg (〈0.01) and 5.0±0.6 mm Hg (p〈0.05), respectively; and left ventricular systolic pressure fell slightly but significantly (p〈0.05). No significant change in right ventricular systolic pressure was seen. Pulmonary wedge pressure rose on average by 2.7 mm Hg (p〈0.05). No significant change in heart rate was observed in 5 patients with sinus rhythm. In 6 patients with atrial fibrillation, there was a significant (p〈0.01) increase in heart rate; the average increase in heart rate for the entire group was 19,6 heats per minute. The maximum effect on all the parameters occurred 7–11 minutes after the injection, and it gradually subsided during the following 10 minutes. It was concluded that disopyramide had a potentially serious myocardial depressant effect.
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  • 86
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    European journal of clinical pharmacology 8 (1975), S. 353-357 
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
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  • 87
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    European journal of clinical pharmacology 8 (1975), S. 371-376 
    ISSN: 1432-1041
    Keywords: Digoxin ; bioavailability ; plasma levels ; cumulative urinary excretion ; particle size ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz® tablets have been compared with Lanoxin® manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to “new” Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.
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  • 88
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    European journal of clinical pharmacology 8 (1975), S. 421-425 
    ISSN: 1432-1041
    Keywords: Proscillaridin ; enteric-coated tablets ; plasma levels ; urine excretion ; 86Rb-erythrocyte assay ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration of proscillaridin was measured by a modified86Rd method during treatment with multiple doses of a commercial preparation of proscillaridin. Despite high doses, very low plasma levels were found, and there were only minute amounts of glycoside activity in urine and faeces. Administration of an enteric-coated proscillaridin preparation gave higher plasma levels, which raises the possibility of inactivation of the glycoside by acid gastric juice. The results suggest that proscillaridin has low biological availability when given orally, and that it is extensively metabolised in the body.
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  • 89
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    European journal of clinical pharmacology 10 (1976), S. 251-256 
    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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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  • 90
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    European journal of clinical pharmacology 11 (1977), S. 141-147 
    ISSN: 1432-1041
    Keywords: Phenothiazine ; thioridazine ; plasma level ; metabolic pattern ; half life ; man ; schizophrenia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma-levels of thioridazine, mesoridazine, sulphoridazine and two other metabolites were determined in ten older chronic psychotic patients on thioridazine therapy. The plasma-level before the morning dose of thioridazine was the most reliable parameter for clinical studies. An intra-individual relationship between lower doses of thioridazine and plasma-levels was found. The percentage contribution of psychoactive compounds to the total sum of “thioridazine plus metabolites” ranged from 43–74%. The mean “early disappearance half-life” of thioridazine was 5 hours, and its mean “late disapperance half-life” was 26 hours.
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  • 91
    ISSN: 1432-1041
    Keywords: cyproheptadine ; metergoline ; glucose tolerance ; insulin secretion ; chemical diabetes ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.
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  • 92
    ISSN: 1432-0983
    Keywords: Key words Arbuscular mycorrhizas ; Evolution ; Glomus mosseae ; Plasma membrane H+-ATPase genes
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    Topics: Biology
    Notes: Abstract  To identify genes that encode plasma membrane H+-ATPases in the arbuscular mycorrhizal fungus Glomus mosseae two sets of degenerate primers matching highly conserved motifs present in all plant and fungal ATPases were designed. Nested PCR-amplification of G. mosseae genomic DNA using the designed degenerate primers was carried out. Sequence analysis of the cloned PCR products identified five different clones (GmHA1, GmHA2, GmHA3, GmHA4 and GmHA5) encoding putative plasma membrane H+-ATPases. Comparison of the deduced amino-acid sequences of GmHA1–GmHA5 indicate that GmHA1, GmHA3 and GmHA4 are highly identical, while GmHA2 and GmHA5 are more divergent. The evolutionary and functional significance of the divergence found among the different members of the H+-ATPase gene family in G. mosseae is discussed.
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  • 93
    ISSN: 1432-1041
    Keywords: Acetylsalicylic acid ; surgery ; man ; bleeding ; pain ; wound-healing
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetylsalicylic acid (ASA) was tested against placebo in a double-blind crossover study, in which essentially the same operation was performed twice on 23 healthy patients who required surgical removal of bilateral “identically” impacted wisdom teeth. On the evening before one operation they received ASA 1.0 g (Globentyl®) followed by ASA 2.0 g daily for the next 3 days, and at the other operation placebo tablets. A number of objective and subjective parameters were recorded for paired comparison of the pre-, per-, and post-operative courses, including bleeding, pain, wound-healing, and preference. Tests of platelet aggregation before each operation indicated whether or not ASA had been taken. Pre-operative bleeding time was significantly increased (from 4.4 to 6.9 min) by ASA, as well as the per-operative blood loss (about 30%), and the post-operative bleeding tendency. Episodes of profuse post-operative haemorrhage were reported by 5 patients, always after the operation for which ASA had been given. ASA also significantly promoted the occurrence of ecchymosis and haematoma. The pre-operative bleeding time was not a reliable predictor for these complications. The drug was very well tolerated with respect to side effects such as abdominal discomfort. The post-operative pain scores were neither reduced nor increased significantly by ASA, and the preference scores were not in favour of the drug. The present patients were all young and denied any previous bleeding disorders; nevertheless, ASA resulted in post-operative haemorrhage, ecchymosis and haematoma formation in several cases.
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  • 94
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    European journal of clinical pharmacology 10 (1976), S. 257-262 
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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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  • 95
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    European journal of clinical pharmacology 10 (1976), S. 43-48 
    ISSN: 1432-1041
    Keywords: Spironolactone ; acetylsalicylic acid ; fludrocortisone ; kinetics ; pharmacology ; interaction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of 600 mg acetylsalicylic acid (ASA) on the renal excretion and clearance of canrenone, the principal unconjugated metabolite of spironolactone, was examined in a double-blind crossover study in six healthy subjects. ASA significantly reduced the urinary excretion, and the fractional excretion, of canrenone between 4 — 6 hours after administration of 50 mg spironolactone. The pharmacological activity of spironolactone, assessed simultaneously by alterations in fludrocortisone-induced urinary electrolyte changes, was slightly but not significantly reduced. The reductions in urinary canrenone excretion correlated with changes in the urinary log 10 Na/K ratio. The results suggest that canrenone may be actively secreted at the proximal renal tubule, and that secretion is blocked by ASA or its conjugates. This is a possible mechanism for the pharmacological interaction between ASA and spironolactone which has been described previously.
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  • 96
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    European journal of clinical pharmacology 10 (1976), S. 59-62 
    ISSN: 1432-1041
    Keywords: Tetracycline absorption ; zinc sulphate ; zinc citrate ; complex formation ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of zinc on the gastrointestinal absorption of tetracycline has been investigated in 7 healthy volunteers. Zinc (45 mg Zn++) was given as a solution of zinc sulphate and as a zinc citrate complex; tetracycline (500 mg) was administered as a commercially available preparation. Serum tetracycline concentrations and the area under the serum tetracycline concentration-time curve (up to 6 h) were significantly reduced when tetracycline was taken with either zinc sulphate or the zinc citrate complex. Although the reduction of absorption seemed more pronounced after zinc sulphate, the difference between the inhibitory effects of the two forms of zinc was not significant. It is concluded that simultaneous administration of zinc and tetracycline may reduce absorption of tetracycline.
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  • 97
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    European journal of clinical pharmacology 10 (1976), S. 127-131 
    ISSN: 1432-1041
    Keywords: Gallbladder emptying ; analgesics ; indoprofen ; pentazocine ; morphine ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A controlled study of the clinical pharmacology of the biliary tract has been made. The rate of gallbladder emptying induced by a fatty meal was taken as a parameter for assessment of the inhibitory effect of indoprofen, a new analgesic-anti-inflammatory drug, pentazocine and morphine. The compounds were administered as single doses by iv (indoprofen and pentazocine) or im (morphine) injection. Indoprofen up to 400 mg had no effect, whereas morphine and pentazocine exerted a significant inhibitory effect on emptying of the gallbladder. Adverse reactions of clinical significance were associated with morphine and pentazocine, but were negligible with indoprofen.
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  • 98
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    European journal of clinical pharmacology 10 (1976), S. 197-200 
    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; dopamine infusion ; blood pressure ; plasma ; man ; inter-individual variation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the function of dopamine-β-hydroxylase (DBH) in human plasma, dopamine, its natural substrate, was infused intravenously in 22 healthy volunteers. Their plasma DBH activities showed great interindividual variations (31–301 units/ml). The infusion rates of dopamine required to increase systolic blood pressure (BP) by 30 mm Hg differed considerably between the subjects, and ranged from 3,0 to 11,6 µg/kg/min. No correlation could be shown between the various dopamine doses and individual plasma levels of DBH. It was concluded, therefore, that plasma DBH in the blood stream was enzymatically inactive. Experiments with human plasma DBH in vitro also support this interpretation. Consequently, interindividual differences in the effects on BP during dopamine infusion cannot be due to pressor effects of noradrenaline synthesized by plasma DBH.
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  • 99
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    European journal of clinical pharmacology 11 (1977), S. 337-344 
    ISSN: 1432-1041
    Keywords: Twin study ; ethanol metabolism ; intra-individual variation ; pharmacogenetics ; plasma level ; man ; heritability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of genetic and environmental factors on the metabolism of a single oral dose of ethanol 1.2 ml per kg body weight was analysed in 19 identical and 21 fraternal healthy, adult, un-selected male twin pairs. The heritability values of the rates of absorption, degradation and elimination of ethanol were 0.57, 0.41 and 0.46 respectively. Environmental factors, such as daily alcohol intake and smoking, increased the rate of elimination of blood alcohol. Intrasubject variation in ethanol metabolism was studied by repeated tests in 11 male volunteers at intervals of at least 2 months, under the same conditions as in the twins; the coefficients of variation for parameters of metabolism was about 8%. The results demonstrate both genetic control of ethanol absorption, degradation and elimination and the appreciable influence of environmental factors. The almost total genetic control of ethanol metabolism postulated by Vesell et al. (1971) could not be confirmed.
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  • 100
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    European journal of clinical pharmacology 11 (1977), S. 359-366 
    ISSN: 1432-1041
    Keywords: Phenylbutazone ; 14C-label ; oxyphenbutazone ; gas chromatography ; disposition ; oxidative metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and elimination of orally administered14C-phenylbutazone and the role of oxidation in its metabolism have been studied. The main routes of excretion of14C-phenylbutazone and its metabolites were investigated in 3 patients with rheumatoid arthritis, and in 1 patient with a T-tube in the common bile duct. Up to 9 days after an oral dose of14C-phenylbutazone 600 mg (30 µCi) 63% of the radioactivity was found in the urine and 14% had appeared in the faeces. The cumulative excretion of radioactivity in bile amounted to 9.5% of the dose in 4 days. Only 1% of the radioactivity in the urine and bile was due to unchanged phenylbutazone. The role of oxidative metabolism of phenylbutazone in healthy human subjects was studied by gas chromatography. In 3 subjects given a single dose of phenylbutazone 600 mg, only 8.3% of the dose was excreted in urine as oxidized metabolites after 5 days. However, in 5 patients who had taken phenylbutazone for more than 5 weeks, these metabolites accounted for 23.4% of the dose. These results suggest that oxidative metabolism becomes more important after continued administration of the drug. After a single dose of phenylbutazone, the side-chain oxidized metabolite (II) was the major free derivative excreted in urine, but the ring oxidized metabolite, oxyphenbutazone (I), was much more important than the former in plasma. However, after prolonged treatment there was little difference between the concentration of the two metabolites in plasma. This finding suggests that side-chain oxidation is increased relative to ring oxidation on prolonged treatment with phenylbutazone. A third derivative containing hydroxyl groups both in the phenyl ring and in the side-chain (metabolite III) was found in urine in experiments with phenylbutazone, but in only one out of 3 volunteers given repeated doses of oxyphenbutazone.
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