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91.
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Steroid metabolites in urine from neonates with 21-hydroxylase deficiency are predominantly polyhydroxylated 17-hydroxyprogesterone and androgen metabolites, and most have incompletely defined structure. This study forms part of a comprehensive project to characterize and identify these in order to enhance diagnosis and to further elucidate neonatal types of steroid metabolism.Steroids were analyzed, after extraction and enzymatic conjugate hydrolysis, as methyloxime-trimethylsilyl ether derivatives on gas-chromatographs coupled to quadrupole and ion-trap mass-spectrometers. GC-MS and GC-MS/MS spectra, obtained with constant excitation conditions, were used together to determine the structure of the D-ring and the side chain of 20-oxo and 20-hydroxy pregnane(ene)s without oxo groups on the A-, B-, and C-ring.All possible combinations of D-ring and side chain configuration were considered. Most fragmentations could be interpreted as partial or complete D-ring cleavages with loss of the side chain, aided by comparison with spectra of deuterated derivatives and of borohydride reduced metabolites. Possible rearrangement ions are also discussed. More than 140 endogenous metabolites were characterized.GC-MS/MS was especially beneficial for characterization of compounds with 16,17-dihydroxy-20-oxo structure, interpreted as markers of intra-uterine enzyme induction. It also assisted the differentiation of 16-hydroxy-20-oxo metabolites, present in urine of non-affected neonates, from the diagnostic 17-hydroxy-20-oxosteroids and enabled the detection of 15,17-dihydroxy-20-oxo compounds in low concentrations. The presence of 17,21-dihydroxylated pregnane(ene)s despite the deficit in CYP21A2 is discussed.We conclude that GC-MS combined with GC-MS/MS allows reliable identification of the structure of the D-ring and side chain of pregnane(ene)s without prior isolation, even when in low concentrations in urine. 相似文献
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A 71-year-old female with a widespread double mycotic infection caused byC. Albicans andT. rubrum was discovered to be suffering from mycosis fungoides. Clinically she was found to have large, polycyclic erythematous plaques with scaly, slightly infiltrated borders, covering almost all areas of the glabrous skin, and also involving the scalp (with no hair penetration), the soles and palms, toe-webs, finger and toe nails; there was also perleche and oral thrush. Cultures yieldedC. albicans from most of the skin lesions, from the scalp, mouth, finger nails and urine and stool specimens, andT. rubrum from intermingled skin specimens, from the palms and soles and toe-nails. Blood culture was negative as were intracutaneous tests with fungal antigens and tuberculin. Histological examination confirmed the fungal invasion of the horny layer and at the same time revealed an underlying pathologic picture of mycosis fungoides, the lesions having been masked by the mycotic eruption. Intensive cytostatic and antifungal therapy led to a transient improvement but shortly thereafter there was a relapse of the fungal and lymphoproliferative manifestations and the patient died in septic shock.
Résumé Une femme, agée 71 ans, ayant une double infection mycosique due àC. albicans et auT. rubrum, a été décélée qu'elle souffrait aussi d'un mycosis fungoïde. Au point de vue clinique elle avait de larges plaques érythémato-squameuses, polycicliques, aux bords légèrement infiltrés, répandues sur une grande partie de la peau glabre, paumes et plantes inclus, et affectant aussi le cuir chevelu (sans pénétration des poils), les ongles des doigts et des orteils. Les cultures ont permis d'isoler leC. albicans à partir de la majorité des lésions de la peau et du cuir chevelu, des ongles des doigts, ainsi que de la bouche, de l'urine et des selles. On a trouvé aussiT. rubrum dans des lésions cutanées entremêlées aux precedentes, dans la région palmaire et plantaire et dans les ongles des orteils. Les testes intradermiques aux antigens fongiques et à tuberculine ont été négatifs, ainsi que les hémocultures. L'examen histologique a montré l'invasion de la couche cornée par les champignons et en même temps a découvert un tableau pathologique sous-jacent d'un mycosis fungoïde, ayant été masqué par l'éruption fongique. Un traitement intensif par des produits cytostatiques et antifongiques a mené à une amélioration temporaire, mais brièvement après on a assisté à une réchute rapide des manifestations lymphoprolifératives et fongiques et la malade a décédé à la suite d'un état septique.相似文献
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David Houle Alexey S Kondrashov 《Proceedings. Biological sciences / The Royal Society》2002,269(1486):97-104
Females often choose their mates, instead of mating at random, even when a father contributes nothing but genes to his offspring. Costly female preferences for males with exaggerated traits that reduce viability, such as the peacock's tail, are particularly puzzling. Such preferences can evolve if directly favoured by natural selection or when the exaggerated trait, although maladaptive per se, indicates high overall quality of the male's genotype. Two recent analyses suggested that the advantage to mate choice based on genetic quality is too weak to explain extreme cases of exaggeration of display traits and the corresponding preferences. We studied coevolution of a female mate-preference function and a genotype-dependent male display function where mutation supplies variation in genotype quality and mate preference is costly. Preference readily evolves, often causing extreme exaggeration of the display. Mate choice and trait expression can approach an equilibrium, or a limit cycle, or exaggeration can proceed forever, eventually causing extinction. 相似文献
97.
98.
Interaction of gentamicin and spermine with bilayer membranes containing negatively charged phospholipids 总被引:12,自引:0,他引:12
We measured the electrophoretic mobility of multilamellar phospholipid vesicles, the 31P NMR spectra of both sonicated and multilamellar vesicles, and the conductance of planar bilayer membranes to study the binding of spermine and gentamicin to membranes. Spermine and gentamicin do not bind significantly to the zwitterionic lipid phosphatidylcholine. We measured the concentrations of gentamicin and spermine that reverse the charge on vesicles formed from a mixture of phosphatidylcholine and either phosphatidylserine or phosphatidylinositol. From these measurements, we determined that the intrinsic association constants of the cations with these negative lipids are all about 10 M-1. This value is orders of magnitude lower than the apparent binding constants reported in the literature by other groups because the negative electrostatic surface potential of the membranes and the resultant accumulation of these cations in the aqueous diffuse double layer adjacent to the membranes have not been explicitly considered in previous studies. Our main conclusion is that the Gouy-Chapman-Stern theory of the aqueous diffuse double layer can describe surprisingly well the interaction of gentamicin and spermine with bilayer membranes formed in a 0.1 M NaCl solution if the negative phospholipids constitute less than 50% of the membrane. Thus, the theory should be useful for describing the interactions of these cations with the bilayer component of biological membranes, which typically contain less than 50% negative lipids. For example, our results support the suggestion of Sastrasinh et al. [Sastrasinh, M., Krauss, T. C., Weinberg, J. M., & Humes, H. D. (1982) J. Pharmacol. Exp. Ther. 222, 350-358] that phosphatidylinositol is the major binding site for gentamicin in renal brush border membranes. 相似文献
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W J Koopman M H Gillis J R David 《Journal of immunology (Baltimore, Md. : 1950)》1973,110(6):1609-1614