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排序方式: 共有560条查询结果,搜索用时 31 毫秒
91.
István Gyertyán Béla KissKatalin Sághy Judit LaszyGyörgyi Szabó Tamás SzabadosLarisza I. Gémesi Gabriella PásztorMária Zájer-Balázs Margit KapásÉva Ágai Csongor György DományKároly Tihanyi Zsolt Szombathelyi 《Neurochemistry international》2011,59(6):925-935
We investigated the in vivo effects of orally administered cariprazine (RGH-188; trans-N-{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-N′,N′-dimethyl-urea), a D3/D2 dopamine receptor partial agonist with ∼10-fold preference for the D3 receptor. Oral bioavailability of cariprazine at a dose of 1 mg/kg in rats was 52% with peak plasma concentrations of 91 ng/mL. Cariprazine 10 mg/kg had good blood-brain barrier penetration, with a brain/plasma AUC ratio of 7.6:1. In rats, cariprazine showed dose-dependent in vivo displacement of [3H](+)-PHNO, a dopamine D3 receptor-preferring radiotracer, in the D3 receptor-rich region of cerebellar lobules 9 and 10. Its potent inhibition of apomorphine-induced climbing in mice (ED50 = 0.27 mg/kg) was sustained for 8 h. Cariprazine blocked amphetamine-induced hyperactivity (ED50 = 0.12 mg/kg) and conditioned avoidance response (CAR) (ED50 = 0.84 mg/kg) in rats, and inhibited the locomotor-stimulating effects of the noncompetitive NMDA antagonists MK-801 (ED50 = 0.049 mg/kg) and phencyclidine (ED50 = 0.09 mg/kg) in mice and rats, respectively. It reduced novelty-induced motor activity of mice (ED50 = 0.11 mg/kg) and rats (ED50 = 0.18 mg/kg) with a maximal effect of 70% in both species. Cariprazine produced no catalepsy in rats at up to 100-fold dose of its CAR inhibitory ED50 value. Cariprazine 0.02-0.08 mg/kg significantly improved the learning performance of scopolamine-treated rats in a water-labyrinth learning paradigm. Though risperidone, olanzapine, and aripiprazole showed antipsychotic-like activity in many of these assays, they were less active against phencyclidine and more cataleptogenic than cariprazine, and had no significant effect in the learning task. The distinct in vivo profile of cariprazine may be due to its higher affinity and in vivo binding to D3 receptors versus currently marketed typical and atypical antipsychotics. 相似文献
92.
Szilvia Ecsedi Hector Hernandez-Vargas Sheila C. Lima Laura Vizkeleti Reka Toth Viktoria Lazar Viktoria Koroknai Timea Kiss Gabriella Emri Zdenko Herceg Roza Adany Margit Balazs 《PloS one》2014,9(5)
In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and associated with the BRAFV600E mutation, gradually decreased in the medium and late stages of the disease. An inverse relationship among the other predefined groups and promoter methylation was also revealed except for histologic subtype, whereas the more aggressive, nodular subtype melanomas exhibited hypermethylation as well. The Breslow thickness, which is a continuous variable, allowed for the most precise insight into how promoter methylation decreases from stage to stage. Integrating our methylation results with a high-throughput copy number alteration dataset, local correlations were detected in the MYB and EYA4 genes. With regard to the effects of DNA hypermethylation on melanoma patients'' survival, correcting for clinical cofounders, only the KIT gene was associated with a lower overall survival rate. In this study, we demonstrate the strong influence of promoter localized DNA methylation changes on melanoma initiation and show how hypermethylation decreases in melanomas associated with less favourable clinical outcomes. Furthermore, we establish the methylation pattern as part of an integrated apparatus of somatic DNA alterations. 相似文献
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Of all known ribosomal proteins, the 40S ribosomal protein S6 is by far the most extensively studied. Still, little is known about some basic aspects of S6 regulation including its cell cycle-related expression and localization. Using a flow cytometric single cell approach applied to whole cells and isolated nuclei, we monitored nucleocytoplasmic expression of total and S240/4 phosphorylated S6 during unperturbed cell cycle progression, providing first evidence for a S6-specific spatiotemporal pattern and its deregulation under conditions of hyperactivated mTOR. 相似文献
96.
TraM of plasmid R1 regulates its own expression 总被引:7,自引:2,他引:5
Regulation of the traM gene, which encodes a factor essential for conjugation of resistance plasmid R1, was studied in vivo using translational gene fusions. tram″lacZ fusion constructs were transferred to the chromosome via the recombinant phage λRZ5. The level of β-galactosidase expressed by the lysogens indicates that the traM promoters are very active. Expression of traM was diminished five- to sixfold when the single-copy plasmids R1 or R1-19 were present in trans. When recombinant plasmids carrying traM were present at higher copy numbers, traM expression was reduced as much as 45-fold. The negative effect of R1 plasmids on traM expression in trans, which we interpret as autoregulation, was observed regardless of whether the plasmids were conjugatjvely repressed or derepressed. Site-specific mutagenesis of the region encoding the N-terminus of the TraM protein eliminated the autoregulative effect indicating that the N-terminal amino acids of the protein are important to its DNA-binding function. The autoregulatory behaviour of TraM is allele specific. R1- or P307-encoded TraM molecules were found to recognize only the cognate DNA. 相似文献
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Gyrgy Vereb Lszl Mtyus Lszl Bene Gyrgy Panyi Zsolt Bacs Margit Balzs Jnos Matk Jnos Szllsi Rezs Gspr Sndor Damjanovich Robert E. Dale Carlo Pieri Marcel Ameloot 《Journal of molecular recognition : JMR》1995,8(4):237-246
Molecular recognition processes between cell surface elements are discussed with special reference to cell surface pattern formation of membrane-bound integral proteins. The existence, as detected by flow cytometric resonance energy transfer (Appendix), and significance of cell surface patterns involving the interleukin-2 receptor, the T-cell receptor–CD3 system, the intercellular adhesion molecule ICAM-1, and the major histocompatilibilty complex class I and II molecules in the plasma membrane of lymphocytes are described. The modulation of antigen presentation by transmembrane potential changes is discussed, and a general role of transmembrane potential changes, and therefore of icon channel activities, adduced as one of the major regulatory mechanisms of cell–cell communications. A general role in the mediation and regulation of intercellular interactions is suggested for cell-surface macromolecular patterns. The dynamic pattern of protein and lipid molecules in the plasma membrane is generated by the genetic code, but has a remarkable flexibility and may be one of the major instruments of accomodation and recognition processes at the cellular level. 相似文献