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L D Nord R C Willis T S Breen T L Avery R A Finch Y S Sanghvi G R Revankar R K Robins 《Biochemical pharmacology》1989,38(20):3543-3549
The basis for the antitumor activities of the exocyclic amino nucleosides 4-amino-(ARPP) and 4-methoxy-8-(D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP) was investigated. The primary target of these nucleosides appeared to be 5-phospho-alpha-D-ribofuranose-1-pyrophosphate (PRPP) synthetase. MRPP-5'-monophosphate was a competitive inhibitor (Ki = 40 microM) of the activation of this enzyme by the cofactor inorganic phosphate (K alpha = 2.2 mM). Consequently, ARPP and MRPP treatment of WI-L2 cultures rapidly inhibited both de novo pyrimidine and purine synthesis as well as the nucleotide salvage reactions dependent on PRPP, ARPP or MRPP treatment completely prevented [14C]bicarbonate incorporation into acid-soluble pyrimidine and purine nucleotides. The rate of salvage of [8-14C]hypoxanthine to form IMP was decreased by 85%. Treatment of cells with these agents caused a 50% reduction in the steady-state level of PRPP. When the capacity of the treated cells for sustained synthesis of PRPP was examined by adenine incorporation, the rate of adenine uptake was inhibited by greater than 50%. In vivo treatment of BDF1 mice with a single dose of ARPP (173 mg/kg) or MRPP (62 mg/kg) extended the mean life span of the mice, which had been inoculated intraperitoneally 1 day earlier with 1 x 10(6) L1210 murine leukemia cells, by 62 and 82% respectively. These studies indicate that MRPP and ARPP inhibit PRPP synthetase, and that PRPP synthetase may be a viable target in the development of certain antitumor agents. 相似文献
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K Ramasamy B S Sharma W B Jolley R K Robins G R Revankar 《Journal of medicinal chemistry》1989,32(8):1905-1909
Several amino acid and peptide conjugates of 6-azacadeguomycin (6-amino-1-beta-D-ribofuranosyl-4,5-dihydro-4-oxopyrazolo[3,4-d]py rimidine- 3-carboxylic acid, 2) have been prepared in good yields, via a two-step procedure involving 1-hydroxybenzotriazole and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride mediated coupling of 2 with an appropriately protected amino acid or peptide, followed by ammonolysis. Thus, condensation of 2 with L-phenylalanine methyl ester, glycine ethyl ester, and L-glutamic acid diethyl ester gave the corresponding protected linear nucleoside peptides (3, 5 and 7, respectively). Subsequent ammonolysis of 3, 5 and 7 furnished L-phenylalanine amide (4), glycine amide (6) and L-glutamic acid diamide (8) conjugates of 6-azacadeguomycin, respectively. Saponification of 7 gave the corresponding L-glutamic acid derivative 9. A similar coupling of 2 with L-phenylalaninyl-N epsilon-nitro-L-arginine methyl ester trifluoroacetate and subsequent ammonolysis (after catalytic hydrogenation) gave L-phenylalaninyl-L-arginine amide conjugate (12) of 6-azacadeguomycin. Compounds 2, 4, 6, 8, 9, and 12 were evaluated for their ability to potentiate T-cell responses to plant mitogens, in comparison with cadeguomycin (1). Compounds 4, 6, and 9 exhibited an increase in the T-cell proliferation in a dose-dependent manner. 相似文献
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Background
Bone density at the interradicular area plays an important role during orthodontic treatment. In view of this fact, the study was designed to quantitatively evaluate the bone density at the interradicular areas of the alveolar and basal bones of maxilla and mandible by computed tomography.Methods
One hundred and nine computed tomographic images were randomly selected, and bone density was measured in Hounsfield units (HU) with bone mineral density software (Siemens VA20A_SP3A). The sample consisted of 78 males (mean age 29.5 years, range 20 to 40 years) and 31 females (mean age 27.6 years, range 20 to 40 years). Cortical and cancellous bone density was measured at the interradicular areas at the alveolar and basal bone levels of the maxilla and mandible, and the data was subjected to statistical analysis for comparisons.Results
The highest cortical bone density was observed between the second premolar and first molar at the alveolar bone level and between the first and second molars at the basal bone level in the maxilla. Maxillary tuberosity showed the least bone density. The density of the cortical bone was greater in the mandible than in the maxilla and showed a progressive increase from the incisor to the retromolar area. The basal bone showed a higher density thanthe alveolar bone.Conclusion
Different qualities of the bone were found in the anatomic regions studied, which confirms the importance of knowledge of site-specific bone tissue density to correlate with various clinical findings. 相似文献7.
Smith HO Leslie KK Singh M Qualls CR Revankar CM Joste NE Prossnitz ER 《American journal of obstetrics and gynecology》2007,196(4):386-9; discussion 386.e9-11
8.
Sensitisation by mycobacteria and the effects of BCG on children attending schools in the slums of Bombay 总被引:1,自引:0,他引:1
J L Stanford R Ganapati C R Revankar D Lockwood J Price P Ashton L Ashton R J Rees 《Tubercle》1988,69(4):293-298
Quadruple skin testing with new tuberculins was used to evaluate the effects of previously administered BCG Madras in children attending schools in the slums, or living in Kopri Leprosy Colony in Bombay. There were differences between schools both in the level of sensitisation of children without BCG scars and in the effects of BCG vaccination. Results obtained at one school resembled those obtained in a previous study in Agra, where BCG was thought to be ineffective. Results from the other schools and Kopri were more like those previously reported from Ahmednagar, where BCG was considered to be much more effective. Thus within the same city groups of children of the same social status may vary widely both in their contact with mycobacteria and in their capacity to benefit from BCG vaccination. 相似文献
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