Bibliothek

Notizen: Translational fusions between a mutant phoA (lacking its promoter, ribosomal binding site and signal peptide sequence) and Rhizobium‘symbiotic’ genes were isolated. Since these fusions expressed alkaline phosphatase (AP), the product of phoA, the genes into which phoA was inserted apparently specify proteins located in the bacterial periplasm or cell membrane, the compartment in which AP has activity. These genes were psiA and genes upstream of psiA (psiA is required for normal nodule development and strains with multicopy psiA fall to make exopolysaccharide (EPS) and to nodulate). Fusions between phoA and pss (exo) genes, which are required for EPS production, also resulted in the expression of AP indicating that products of these pss genes were located at the cell surface. Using grus fusions to psiA and pssA, we found that the former was expressed in N2-fixing bean root nodules but the latter was not.

Notizen: Summary Marked interindividual variation has been observed in the pharmacokinetics of the antiarrhythmic agent mexiletine. The fact that its urinary excretion is dependent on urinary pH may account, in part, for such variation. The influence that genetic differences in hepatic metabolism of the debrisoquine-type may have on mexiletine pharmacokinetics was considered in this study. The pharmacokinetics and urinary excretion of mexiletine (250 mg administered intravenously) were investigated in 5 rapid extensive metabolisers (EM), 5 slow EM and 5 poor metabolisers (PM) of debrisoquine, under conditions of controlled urinary pH. Mexiletine disposition kinetics was found to be altered in PM individuals. These subjects showed higher total area under the curve (AUC), (15.7 versus 8.16 μg · h · ml−1) prolonged elimination half-lives (in serum and urine) (serum: 18.5 versus 11.6 h, urine: 19.2 versus 11.7 h) and lower total clearance values compared with EM (216 versus 450 ml · min−1). In this respect, slow EM individuals generally presented intermediate values of those pharmacokinetic parameters. A higher incidence of adverse-effects was also observed among slow EM and PM subjects. It is concluded that genetic differences in mexiletine oxidation of the debrisoquine-type have an influence on its observed pharmacokinetic variability. The clinical consequences are discussed.

Notizen: Abstract Peraluminous granitoid magmas are a characteristic product of ultrametamorphism leading to anatexis of aluminous metasedimentary rocks in the continental crust. The mechanisms and characteristic length-scales over which these magmas can be mobilized depend strongly on their melt fraction, because of their high viscosities. Thus, it is of fundamental importance to understand the controls exerted by pressure, temperature and bulk composition of the source material on melt productivity. We have studied experimentally the vapour-absent melting behaviour of a natural metapelitic rock and our results differ greatly from those of previous experimental and theoretical investigations of melt productivity from metamorphic rocks. Under H2O-undersaturated conditions, bulk composition of the source material is the overriding factor controlling melt fraction at temperatures on the order of 850–900° C. Granitoid melts formed in this temperature interval by the peritectic dehydration-melting reaction: $$\begin{gathered} Biotite + plagioclase + aluminosilicate + quartz \hfill \\ = melt + garnet \hfill \\ \end{gathered} $$ have a restricted compositional range. As a consequence, melt fractions will be maximized from protoliths whose modes coincide with the stoichiometry of the melting reaction. This “optimum mode” (approximately 38% biotite, 32% quartz, 22% plagioclase and 8% aluminosilicate) reflects the fact that generation of low-temperature granitoid liquids requires both fusible quartzo-feldspathic components and H2O (from hydrous minerals). Metapelitic rocks rich in mica and aluminosilicate and poor in plagioclase contain an excess of refractory material (Al2O3, FeO, MgO) with low solubility in low-temperature silicic melts, and will therefore be poor magma sources. Melt fraction varies inversely with pressure in the range 7–13 kbar, but the effect is not strong: the decrease (at constant temperature) over this pressure range is of at most 15 vol% (absolute). The liquids produced in our experiments are silicarich (68–73 wt% SiO2), strongly peraluminous (2–5 wt% normative corundum) and very felsic (MgO+FeO* +TiO2 less than 3 wt%, even at temperatures above 1000° C). The last observation suggests that peraluminous granitoids with more than 10% mafic minerals (biotite, cordierite, garnet) contain some entrained restite. Furthermore, because liquids are also remarkably constant in composition, we believe that restite separation is more important than fractional crystallization in controlling the variability within and among peraluminous granitoids. We present liquidus phase diagrams that allow us to follow the phase relationships of melting of silica-and alumina-saturated rocks at pressures corresponding to the mid- to deep-continental crust. Garnet, aluminosilicate, quartz and ilmenite are the predominant restitic phases at temperatures of about 900° C, but Ti-rich biotite or calcic plagioclase can also be present, depending on the bulk composition of the protolith. At temperatures above 950–1050° C (depending on the pressure) the restitic assemblage is: hercynitic spinel+ilmenite+quartz±aluminosilicate. Our results therefore support the concept that aluminous granulites (garnet-spinel-plagioclase-aluminosilicate-quartz) can be the refractory residuum of anatectic events.

Notizen: Abstract We report the result of H2O-undersaturated melting experiments on charges consisting of a layer of powdered sillimanite-bearing metapelite (HQ36) and a layer of powdered tonalitic gneiss (AGC150). Experiments were conducted at 10 kbar at 900°, 925° and 950°C. When run alone, the pelite yielded ∼40 vol% strongly peraluminous granitic melt at 900°C while the tonalite produced only ∼5 vol% weakly peraluminous granitic melt. At 950°C, the pelite and the tonalite yielded ∼50 vol% and ∼7 vol% granitic melt, respectively. When run side by side, the abundance of melt in the tonalite was ∼10 times higher at all temperatures than when it was run alone. In the pelite, the melt abundance increased by ∼25 vol%. When run alone, biotite dehydration-melting in the tonalite yielded orthopyroxene and garnet in addition to granitic melt. When run side by side only garnet was produced in addition to granitic melt. Experiments of relatively short duration, however, also contained Al-rich orthopyroxene. We suggest that the large increase in melt fraction in the tonalite is mainly a result of increased activity of Al2O3 in the melt, which lowers the temperature of the biotite dehydration-melting reaction. In the pelite, the increase in the abundance of melt is caused by transport of plagioclase component in the melt from the tonalite-layer to the pelite-layer. This has the effect of changing the bulk composition of this layer in the direction of “minimum-temperature” granitic liquids. Our results show that rocks which are poor melt-producers on their own can become very fertile if they occur in contact with rocks that contain components that destabilize the hydrous phase(s) and facilitate dehydration-melting. Because of this effect, the continental crust may have an even greater potential for granitoid melt production than previously thought. Our results also suggest that many anatectic granites most likely contain contributions from two or more different source rocks, which will be reflected in their isotopic and geochemical compositions.

Notizen: Abstract The effects of 5-hydroxytryptamine (5-HT) and related compounds on the discharge rate of tonically active medial vestibular nucleus (MVN) neurones were studied in an in vitro slice preparation of the dorsal brainstem of the rat. The majority (87 of 107, 82%) of MVN neurones were excited by 5-HT. Nine cells (8%) showed a biphasic response to 5-HT, which consisted of a brief inhibition followed by excitation. Eleven cells (10%) were inhibited by 5-HT. The excitatory effects of 5-HT were mimicked by alpha-methyl-5-HT and antagonised by ketanserin and ritanserin, indicating the involvement of the 5-HT2 subtype of 5-HT receptor. In biphasic cells, blockade of 5-HT2 receptors by ketanserin reduced the excitatory component of the response and revealed an enhanced initial inhibition. The inhibitory effects in biphasic cells, and in cells that showed a pure inhibition in response to 5-HT, were blocked by pindobind-5-HT and mimicked by 8-hydroxy-2-(di-n-propylamino)-tetralin indicating the involvement of 5-HT1A receptors. The significance of these findings in relation to the effects of 5-HT on vestibular reflex function is discussed.

Notizen: Summary Pedigrees of all known cases, on Shetland, of Down's syndrome, cytogenetically confirmed as trisomy 21, and of a control for each patient matched by birth date, sex and birth place, were traced over a minimum of eight generations. Mean kinship coefficients in all pairs of Down's syndrome patients and in all pairs of controls were similar. The kinship between the father and mother of each case shows that the parents are more closely related than the general level of relationship in the population, suggesting some recessive element in the etiology. It is argued that the effect of the resulting increased homozygosity would be to prevent the loss of the conceptus that occurs in the majority of trisomy 21 conceptions.