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排序方式: 共有241条查询结果,搜索用时 15 毫秒
51.
Lisiane B. Meira Catherine A. Moroski-Erkul Stephanie L. Green Jennifer A. Calvo Roderick T. Bronson Dharini Shah Leona D. Samson 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(3):888-893
Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype. 相似文献
52.
Improved synthesis and application of [11C]benzyl iodide in positron emission tomography radiotracer production
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Aleksandra Pekošak Ulrike Filp Lonneke Rotteveel Alex J. Poot Albert D. Windhorst 《Journal of labelled compounds & radiopharmaceuticals》2015,58(8):342-348
Positron emission tomography has increased the demand for new carbon‐11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is [11C]benzyl iodide ([11C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [11C]BnI has received little attention, resulting in limited application. Therefore, we investigated the synthesis in order to significantly improve, automate, and apply it for labeling of the dopamine D2 antagonist [11C]clebopride as a proof of concept. [11C]BnI was synthesized from [11C]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one‐pot procedure, [11C]BnI was synthesized in 11 min from [11C]CO2 with high yield, purity, and specific activity, 52 ± 3% (end of the cyclotron bombardment), 95 ± 3%, and 123 ± 17 GBq/µmol (end of the synthesis), respectively. Changes in the [11C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid‐phase intermediate purification. [11C]Clebopride was synthesized within 28 min from [11C]CO2 in an isolated decay‐corrected yield of 11 ± 3% (end of the cyclotron bombardment) with a purity of >98% and specific activity (SA) of 54 ± 4 GBq/µmol (n = 3) at the end of the synthesis. Conversion of [11C]BnI to product was 82 ± 11%. The reliable synthesis of [11C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
53.
O6-methylguanine repair in liver cells in vivo: Comparison between G1- and S-phase of the cell cycle
H. M. Rabes R. Kerler G. Rode C. Schuster R. Wilhelm 《Journal of cancer research and clinical oncology》1984,108(1):36-45
Summary To compare the formation and persistance of alkylated DNA bases in the G1- and S-phase compartments in liver in vivo, regnerating rat liver was exposed to [14C]dimethylnitrosamine (0.57 mg/kg, IP injection) or N-[methyl 14C]-N-nitrosourea (3.3 mg/kg, intraportal injection) during the G1 phase of the cell cyle (12 h after partial hepatectomy), or at 24 h after partial hepatectomy with 30% hepatocytes in DNA synthesis, or at 43 h after partial hepatectomy, 4 h after an hydroxyurea block from 14 to 39 h after operation with 80% hepatocytes in DNA synthesis. At 120 min after dimethylnitrosamine and 90 s, 5, 10, or 60 min after the intraportal pulse of N-methyl-N-nitrosourea the molar fractions of 7-methylguanine (7megua), O6-methylguanine (O6megua), and 3-methyladenine (3mead) and of metabolically labeled guanine were determined from DNA hydrolysates by Sephadex-G10 radiochromatography. After dimethylnitrosamine only minor differences were observed for 7megua formation in the three groups; the 3mead/7megua ratio remained constant irrespective of the number of cells in S phase. In contrast, the O6megua/7megua ratio revealed a loss of O6megua, the extent of which appeared proportional to the fraction of DNA-synthesizing cells in the liver. The rapid loss of O6megua in S-phase cells was confirmed after intraportal administration of N-methyl-N-nitrosourea. During the first 10 min after the methylnitrosourea pulse the O6megua/7megua ratio was constant in G1 cells and dropped from 90 s to 10 min by about 15% in liver containing 30% S-phase cells and by about 40% with 80% cells in DNA synthesis. DNA-synthesizing hepatocytes are apparently endowed with a higher O6megua DNA transferase activity than nonproliferating liver cells. The rapid, though exhaustible elimination of O6megua during S-phase might result in partial protection of DNA-synthesizing cells from base-mispairing and/or from hypomethylation at G-C sites.Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthdaySupported by grants from the Deutsche Forschungsgemeinschaft and the Dr. Mildred Scheel-Stiftung 相似文献
54.
Objective: To evaluate the ethyl acetate, methanol and aqueous extracts of dried fruiting bodies of Pleurotus eous for its anti-platelet activity on human volunteer''s blood. And also to analyze the free radical scavenging property of the extracts of P.eous by using various in vitro models. Methods: Anti-platelet activity of dried fruiting bodies of P.eous was evaluated by in vitro model using blood platelets. Inhibition of platelet aggregation was monitored after pre-incubation of platelets with the crude extracts of mushroom P.eous. Antioxidant activities of extracts of P.eous were evaluated by different in vitro experiments, namely, 1, 1-diphenyl- 2-picryl hydrazyl (DPPH), superoxide, hydroxyl radical and lipid peroxide radical models. Results: Crude extracts of mushroom P.eous inhibited platelet aggregation dose-dependently which was induced by adenosine diphosphate (ADP). At a maximum concentration of 10 mg/mL, methanol extract effected 64.02% inhibition of lipid per-oxidation and 50.12% scavenging effect on superoxide anion radical. Aqueous extract of P.eous have shown 69.43% chelating ability on ferrous ions, 24.27% scavenging effect on hydroxyl radical and 49.57% scavenging effect on DPPH radical at 10 mg/mL. Increasing concentrations of the extract were found to cause progressively decreasing of the intensity of absorbance. Conclusions: Anti-platelet effects could be related in part to the polyphenolic compounds present in the extracts. Antioxidant activity results indicated the free radical scavenging property of the extracts of P.eous which might be due to the high content of phenolic compounds and flavonoids. 相似文献
55.
马兜铃酸广泛存在于马兜铃科马兜铃属中草药中,具有。肾毒性和致癌致突变性。其在体内经一系列硝基还原酶代谢活化后与DNA共价结合形成加合物而诱发癌变,并通过诱导肾小管上皮细胞凋亡及间质纤维化而导致马兜铃酸肾病。综述马兜铃酸体内毒性产生的分子机制和防治研究进展,探讨相关药物的研发,为马兜铃酸肾病的治疗提供新思路。 相似文献
56.
复方甘草酸苷治疗抗结核药物性肝炎的临床疗效分析 总被引:1,自引:1,他引:0
目的观察复方甘草酸苷治疗抗结核药物性肝炎的临床疗效。方法将65例由应用抗结核药物所引起的药物性肝损伤患者随机分为治疗组和对照组,治疗组给予复方甘草酸苷(复方甘草酸苷注射液60 ml加5%葡萄糖注射液250 ml,静脉滴注,每日1次)治疗4周,对照组给予还原型谷胱甘肽(还原型谷胱甘肽1.2 g加入5%葡萄糖注射液250 ml中静脉滴注,每日1次)治疗4周,对两组进行疗效比较。结果治疗组在肝功能恢复,症状、体征的改善方面差异均有显著性(P0.05)。结论复方甘草酸苷治疗药物性肝炎疗效可靠,值得临床推广。 相似文献
57.
The MNNG hyper-resistance of yeast transformants containing multiple copies of the SNQ3/YAP1 yeast gene is not caused by lowered MNNG activation due to depleted pools of glutathione. On the contrary, the SNQ3/YAP1-encoded protein stimulates production of GSH, apparently by promoter activation due to the AP-1 recognition element. Expression of at least one further gene, encoding a protein with a strong detoxifying activity, must also be stimulated to explain the MNNG hyper-resistance phenotype. 相似文献
58.
F.F.G. Rommerts A.J. Grootenhuis J.W. Hoogerbrugge H.J. van der Molen 《Molecular and cellular endocrinology》1985,42(2):105-111
Effects of ethane dimethane sulphonate (EDS) on the pattern of protein synthesis, steroid production and ATP levels in isolated Leydig cells have been investigated. After incubation of Leydig cells isolated from mature rats with EDS (75 μg/ml) for 3–5 h, the synthesis of a 33 kDA and 50 dKa protein and LH stimulated steroid production was inhibited, but the LH stimulated cAMP production and conversion of 22 R-hydroxycholesterol to testosterone were not affected. Busulphan or ethyl methyl sulphonate (EMS) at similar molar concentrations had no effect on steroid production. After 24 h incubation with EDS Leydig cells were detached from the plastic surface and had rounded up, but the cellular ATP levels were the same as in control cells. Leydig cells were destroyed after incubation with EMS 2000 μg/ml for 24 h. EDS had no detectable effects on steroid production by isolated Leydig cells from mice, from Leydig cell tumour tissue or from immature rats, nor on rat adrenal cells or on LH and FSH secreting pituitary cells. The data indicate that EDS specifically inhibits LH regulated functional properties of mature Leydig cells possibly via alkylation of proteins. EDS could be a valuable tool to study possible regulator proteins for control of steroidogenesis in Leydig cells from adult rats. 相似文献
59.
60.