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5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase. 相似文献
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Endothelin-1 (ET-1) is a potent, vasoconstrictive peptide isolated from culture media of vascular endothelial cells. The binding of ET-1 to membrane preparations from rat and bovine lung was studied using radioiodinated ET-1 (125I-ET-1). With both membrane preparations, 125I-ET-1 showed saturable binding to a single class of high affinity sites. Scatchard analysis of the binding data gave dissociation constants (Kd) for ET-1 of 0.22 nM and 0.15 nM, and receptor densities (Bmax) of 6.1 pmol/mg and 2.7 pmol/mg for rat and bovine lung membranes, respectively. Photo-reactive radioiodinated ET-1, N epsilon 9-azidobenzoyl-125I-ET-1, was synthesized and purified as a mono-reactive affinity labeling reagent. This reagent was used for affinity labeling of ET-1 receptor in bovine and rat lung membranes. Photoaffinity labeling followed by sodium dodecyl sulfate gel electrophoresis and autoradiography gave a radiolabeled protein band with an apparent Mr of 34,000 in both membrane preparations. The labeling of this protein band was inhibited by cold ET-1 in a concentration-dependent manner. Labeling was not abolished by unrelated peptides such as angiotensin II and [Arg8]-vasopressin, or by structurally related bee venom apamin. These results indicate that the ET-1 receptor or its ligand binding subunit consists of a 34,000 Da polypeptide. 相似文献
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The propagation speed (C) of surface acoustic waves (SAW), e.g. Rayleigh (R-waves) and longitudinal lateral waves (L-waves), the latter being the surface manifestation of the longitudinal waves, strongly reflect mechanical properties of materials. In view of an increasing interest in ultrasonic methodology in the field of bone biomechanics, we tested the hypothesis that both R- and L-waves can be excited in trabecular bone using an acoustic microscope at 1 GHz and that their speeds (C(R) and C(L)) can be extracted from V(z)-curves, i.e. plots of lens output voltage as a function of the lens focal point position with respect to the specimen surface. In accordance with V(z)-curves theoretically synthesized on the basis of incident field theory, experimental curves for canine femoral trabecular bone showed evidence of both R- and L-waves in almost all regions of recording. The measured CR ranged between 1.93 and 2.07 km/s (mean +/- SD.: 2.00=0.06 km/s) and the C(L) ranged between 2.33 and 4.33 km/s (3.37+/-0.61 km/s). Knowledge of both speeds allowed computation of a number of material constants by means of simple theory of elasticity and assumptions of the material density. We found values of Poisson ratio (v) ranging from 0.14 to 0.32 (0.23+/-0.07). Young's modulus (E) from 15 to 22.8 GPa (19.9+/-2.5 GPa) and the shear modulus (G) from 7.6 to 8.9 GPa (8.4+/-0.5 GPa). Anisotropy in the trabecular bone material was clearly detected at the micrometer level. In conclusion, the V(z)-curve method was successfully used to determine the distribution of material elastic constants of trabecular bone with micrometer resolution. 相似文献
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Singh P Mathur SK Kundu ZS Singh S Marwah N Arora B 《Indian journal of pathology & microbiology》2005,48(2):206-208
Extraskeletal chondroma is a rare entity. A fairly benign condition, it is usually seen in adults. It presents as an enlarging mass, most commonly in the hand. Local excision is the treatment of choice. We present a case of extraskeletal chondroma of hand in a 12 year male child. Its variable histological appearance not infrequently leads to a mistaken diagnosis of chondrosarcoma. 相似文献
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Detection of beet yellows virus by RT-PCR and immunocapture RT-PCR in Tetragonia expansa and Beta vulgaris 总被引:1,自引:0,他引:1
Two sensitive methods, RT-PCR with phenol-extracted RNA or Triton X-100-released RNA and immunocapture RT-PCR (IR-RT-PCR) were used for the detection of Beet yellows virus (BYV) in young and old leaves of Tetragonia expansa and sugar beet (Beta vulgaris) and in sugar beet roots. Four oligonucleotide primer pairs proved suitable for the detection of BYV. The release of BYV RNA with Triton X-100 was shown to be a very effective and easy as compared to isolation of total RNA by phenol extraction with the same or higher sensitivity of subsequent PCR. Using the Triton X-100 release of RNA and IC-RT-PCR the sensitivity of detection was so high that pg amounts of BYV RNA occurring in dilutions up to 10(-6) of saps from young Tetragonia and sugar beet leaves could be detected. 相似文献
9.
Kundu Abhishake Feijoo Felipe Martinez Diego A. Hermosilla Manuel Matis Timothy 《Health care management science》2022,25(1):89-99
Health Care Management Science - Proactive and objective regulatory risk management of ongoing clinical trials is limited, especially when it involves the safety of the trial. We seek to... 相似文献
10.
Ali A. Rabaan Abdul Hawil Abas Trina Ekawati Tallei Mona A. Al-Zaher Noor M. Al-Sheef Fatimawali Esraa Z. Al-Nass Eba A. Al-Ebrahim Yunus Effendi Rinaldi Idroes Mather F. Alhabib Hussain A. Al-Fheid Ahmad Akroman Adam Talha Bin Emran 《Journal of medical virology》2023,95(1):e28306
Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future. 相似文献