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排序方式: 共有978条查询结果,搜索用时 30 毫秒
1.
Judith Brock Andreas Schmid Thomas Karrasch Petra Pfefferle Jutta Schlegel Inga Busse Annette Hauenschild Barbara Schmidt Maria Koukou Efthymia Arapogianni Andreas Schultz Miriam Thomalla Secil Akinci Johannes Kruse Winfried Padberg Andreas Schffler Jens Albrecht 《Clinical endocrinology》2019,91(3):400-410
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Claudia Linde Cornelia Löffler Christina Kessler U. Quast 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(4):467-474
In vascular smooth muscle, openers of ATP-dependent potassium channels (K
ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the
binding of P1075 and on the 86Rb+ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in 86Rb+ efflux induced by P1075 was taken as a qualitative measure of K+ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [3H]-P1075 with an IC50 value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic
acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond
reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [3H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In 86Rb+ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated
tracer efflux with an IC50 value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT.
In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting
the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups
interferes with the binding of the K
ATP channel opener, P1075; concomitantly, the 86Rb+ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects
on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the
KATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated 86Rb+ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their
reactivity.
Received: 7 April / Accepted: 9 July 1997 相似文献
4.
Cranial computed tomography (CCT) findings for 37 patients with cycloid psychosis and 19 patients with DSM-III-R schizophrenia were compared with findings for age- and sex-matched controls. Schizophrenic patients showed enlarged ventricles compared both to controls and to patients suffering from cycloid psychosis. In patients with cycloid psychosis, neither at the first episode nor after many years (mean 16.6 years) of disease were significant differences found compared to control subjects. Over the course of the illness, patients with cycloid psychosis showed ventricular enlargement which was correlated with age but not with the duration of illness. The morphological differences provide further evidence for the proposed nosological distinction between cycloid psychosis and schizophrenia. 相似文献
5.
To verify the assumption of a specific and potent drug action on de novo pyrimidine biosynthesis, isolated dihydroorotate dehydrogenase (DHO-DH) (EC 1.3.3.1) was exposed to Brequinar Sodium (6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline carboxylic acid sodium salt, NSC 368 390) (Brequinar). The membrane-bound DHO-DH was purified to apparent homogeneity (25,000-fold) from rat liver mitochondria in six steps via detergent extraction and subsequent chromatography using the dye ligand Matrex Gel Orange A. Using molecular mechanistic studies (MM2) this ligand was found to mimic closely the stereochemical conformation of Brequinar. SDS-PAGE revealed two protein bands for the purified enzyme with apparent molecular masses of 58 (major) and 68 kDa (minor). In vitro, two modes of action of the DHO-DH are possible: (i) acting as a dehydrogenase in the presence of ubiquinone as proximal electron acceptor and (ii) direct reaction with oxygen as oxidase. A novel assay for the measurement of the oxidase activity was adapted using leuco-dichlorofluorescein-diacetate. Inhibition experiments revealed a striking difference in the susceptibility of DHO-dehydrogenase/oxidase to Brequinar: apparent Ki = 6.09 +/- 0.05 (SD) nM (DHO; ubiquinone n = 10), but Ki = 3.10 +/- 0.09 (SD) mM (DHO; O2). Analyses of initial velocity experiments showed non-competitive inhibition of Brequinar with respect to the substrate dihydroorotic acid in both assays (dehydrogenase and oxidase). The inhibitory effect of the latter was compared to that of the competitive inhibitor 5-aza-dihydroorotate (apparent Ki = 15 +/- 0.25 (SD) microM). The present kinetic data on the action of the purified rodent DHO-DH with Brequinar and computer-aided analyses provide a better insight into the drug-enzyme interaction. 相似文献
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R. Gottschalk C. Seidl T. Löffler E. Seifried D. Hoelzer J.P. Kaltwasser 《Tissue antigens》1998,51(3):270-275
Abstract: Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and Bcll/Mbo 1 for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P >0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P =NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients. 相似文献
8.
Precipitable immune complexes in healthy homosexual men, acquired immune deficiency syndrome and the related lymphadenopathy syndrome. 总被引:6,自引:0,他引:6
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Increased levels of 3% PEG precipitable circulating immune complexes (CIC) were found in healthy homosexual men, in homosexual patients with the acquired immune deficiency syndrome (AIDS), and in the AIDS related lymphadenopathy syndrome (LAS). The degree of CIC elevation increases from healthy homosexual men to LAS and AIDS. Patients suffering from AIDS associated with opportunistic infections had a more pronounced increase in CIC than patients with AIDS associated Kaposi's sarcoma. In LAS and AIDS the amount of CIC correlated with the degree of inversion of the T4/T8 lymphocyte ratio, whereas in healthy homosexual men with increased levels of CIC the T4/T8 ratio was not significantly altered. Laser nephelometric partial components analysis revealed that these complexes were of a complement poor subtype with low component levels of C4, C1q and C3c. IgM and IgG were found to be the major components. It is suggested that these CIC might represent a marker of the total antigenic burden of the immune system. Possibly, they are of prognostic and monitoring value for clinical handling of patients at risk for AIDS. 相似文献
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Zusammenfassung Mit cytochemischer Methodik wurde die Aktivität von saurer Phosphatase, bei pH 7,2 wirksamen Phosphatasen, alkalischer Phosphatase, unspezifischen Esterasen und Aminopeptidase in Knochenmarkausstrichen von 200 Patienten mit verschiedenen Erkrankungen und reaktiven Knochenmarksveränderungen sowie 38 Patienten mit Plasmocytom, darunter ein Fall von Plasmazellenleukämie, untersucht.
Normale Plasmazellen zeichnen sich durch deutliche ATPase-Aktivität, eine mäßige Aktivität von saurer Phosphatase und durch schwache Esteraseaktivität aus. Keine Fermentreaktion fand sich bei Verwendung der Substrate Glycerophosphat, Adenosin-5- und Adenosin-3-monophosphat, beim Nachweis der alkalischen Phosphatase, der Aminopeptidase und bei Benutzung von Naphthol-AS-D-chloracetat als Substrat für den Esterasenachweis.
Myelomzellen zeichnen sich durch verstärkte Aktivität von saurer Phosphatase und unspezifischer Naphthol-Esterase aus. Die ATPase-Aktivität ist im Vergleich zu normalen Plasmazellen deutlich vermindert oder fehlt völlig.Die mögliche Bedeutung der Befunde wird erörtert.Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献