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991.
Pettit GR Xu JP Chapuis JC Pettit RK Tackett LP Doubek DL Hooper JN Schmidt JM 《Journal of medicinal chemistry》2004,47(5):1149-1152
The Indo-Pacific marine sponge Ircinia ramosa has been found to contain two powerful (GI50 from 0.001 to <0.0001 microg/mL) murine and human cancer cell growth inhibitors. Both were isolated (10(-3)-10(-4)% yields) by cancer cell line bioassay-guided techniques and named irciniastatins A (1) and B (2). Structural elucidation by a combination of spectral analyses, primarily high resolution mass and 2D-NMR (principally APT, HMQC, HMBC, and ROESY) spectroscopy, revealed the unusual structures 1 and 2. 相似文献
992.
Substantial protection against the economically important nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of this parasite. This fraction has been termed Haemonchus galactose-containing glycoprotein complex (H-gal-GP) since it was originally isolated through its selective binding to lectins with a specificity for N-acetylgalactosamine. A major component of this highly protective antigen complex is a family of four zinc metalloendopeptidases, designated MEPs 1-4. Various combinations of these MEPs were evaluated in immunization-challenge trials in sheep. In two experiments a combination of all four MEPs, separated from the rest of the complex by gel filtration in 8 m urea, significantly reduced H. contortus egg counts by 45 and 50%, an effect not significantly different from that conferred by 8 m urea treatment of H-gal-GP itself. Similarly, MEP3 alone or MEPs 1, 2 and 4 in combination, electroeluted from the complex following SDS gel electrophoresis, each reduced egg counts by some 33%. The MEPs are therefore protective components of H-gal-GP and from previously published findings, it appears that MEP3 is the most effective member of this metalloendopeptidase family. However, there was no significant protection when sheep were immunized with fully reduced and denatured H-gal-GP or with bacterially expressed recombinant forms of MEP 1 or the principal domains of MEP3, suggesting that conformational epitopes on the MEPs are required for immunity. 相似文献
993.
Pettit GR Numata A Iwamoto C Usami Y Yamada T Ohishi H Cragg GM 《Journal of natural products》2006,69(3):323-327
Bioassay-guided (P388 lymphocytic leukemia cell line) separation of extracts prepared from the leaves, stems, and pods of Bauhinia purpurea, and, in parallel, its roots, led to the isolation of four new dibenz[b,f]oxepins (2a, 3-5) named bauhiniastatins 1-4, as well as the known and related pacharin (1) as cancer cell growth inhibitors. The occurrence of oxepin derivatives in nature is quite rare. Bauhiniastatins 1-4 were found to exhibit significant growth inhibition against a minipanel of human cancer cell lines, and bauhiniastatin 1 (2a) was also found to inhibit the P388 cancer cell line. Structures for these new cancer cell growth inhibitors were established by spectroscopic techniques that included HRMS and 2D NMR. 相似文献
994.
Pettit GR Melody N Simpson M Thompson M Herald DL Knight JC 《Journal of natural products》2003,66(1):92-96
An efficient procedure was found for synthetic conversion of the sparingly soluble anticancer isocarbostyril narciclasine (1), a component of various Narcissus species, to a cyclic phosphate designated narcistatin (3b). The reaction between narciclasine, tetrabutylammonium dihydrogen phosphate, and p-toluenesulfonic acid in pyridine afforded pyridinium narcistatin (3a) in reasonable yields. Transformation of narcistatin (3a) to, for example, the water-soluble prodrug sodium narcistatin (3d) was easily achieved by cation exchange chromatography. Narcistatin (3b) and 15 salt derivatives were evaluated against a panel of human cancer cell lines, and the range (0.1-0.01) of GI(50) values in micro g/mL was found to parallel that shown by the parent narciclasine. 相似文献
995.
Keen JC Yan L Mack KM Pettit C Smith D Sharma D Davidson NE 《Breast cancer research and treatment》2003,81(3):177-186
996.
Ali S Aranha O Li Y Pettit GR Sarkar FH Philip PA 《Cancer chemotherapy and pharmacology》2003,52(3):235-246
PURPOSE: Protein kinase C (PKC) plays an important role in cell proliferation, differentiation, and apoptosis. The interaction between the PKC modulator bryostatin 1 (BRYO), and gemcitabine in human breast cancer MCF-7 and MDA-MB-231 cells and in the non-transformed MCF-10A human breast epithelial cells was investigated. METHODS: Immunoblotting was used to determine the expression of PKC isoenzymes and proteins involved in the cell cycle and apoptosis. MTT, ELISA and flow cytometry assays were used to determine cell survival. RESULTS: Treatment of cells with BRYO 200 n M resulted in a significant downregulation of cytoplasmic PKC in all three cell lines. However, the expression of membranous PKC was differentially affected in these cells. BRYO (1-200 n M) had no significant effects on cell viability in any of the cell lines. Nevertheless, BRYO significantly enhanced the antiproliferative and apoptotic effects of gemcitabine in the MCF-7 and MDA-MB-231 cells, but not in the MCF-10A cells. This was associated with significant reduction in the bcl-2/bax ratio. There was a significant upregulation of p53, p21(waf1), and p27 in MCF7 and MCF-10A cells treated with the combination of gemcitabine and BRYO compared to gemcitabine-treated cells. CONCLUSIONS: The potentiation of the effect of gemcitabine by BRYO was demonstrated in MCF-7 and MDA-MB-231 cells and was associated with a specific pattern of PKC modulation. Further investigation of the role of specific isoforms of PKC in the downstream molecular events of gemcitabine-induced cytotoxicity is warranted. 相似文献
997.
Design,synthesis, and evaluation of novel boronic-chalcone derivatives as antitumor agents 总被引:4,自引:0,他引:4
Kumar SK Hager E Pettit C Gurulingappa H Davidson NE Khan SR 《Journal of medicinal chemistry》2003,46(14):2813-2815
A series of boronic-chalcone derivatives were synthesized and tested for antitumor activity against human breast cancer cell lines. The results show the boronic-chalcones are more toxic to breast cancer cells compared to normal breast cells than other known chalcones. 相似文献
998.
In a prospective study 26 of the 116 consecutive neonates suffering from respiratory distress survived on varying concentrations of humidified oxygen. Continuous positive airway pressure (CPAP) of 4-12 cm of water was applied through short nasal prongs to 90 neonates. Haemoglobin oxygen saturation (SaO2) rose in all and it was maintained steadily above 85% in 46 (51%) infants who survived. The mean duration of CPAP among the survivors was 61 hours (range 8-190 hours). Common indications of CPAP ventilation were hyaline membrane disease (HMD) (27.7%), meconium aspiration syndrome (MAS) (20%), apnea of prematurity (18.8%) and asphyxia (17.7%). Neonates weighing >1000 gm faired well with overall survival of 60 to 82.35%. However, among the 16 babies weighing <1000 gm, only 3 (18.75%) survived. 4 infants on CPAP died due to pneumothorax, none had complications of oxygen toxicity. The 44 CPAP failures, fared poorly even when shifted to intermittent positive pressure ventilation (IPPV) regardless of their weight and 1 among the 5 survivors developed grade 1 intraventricular haemorrhage. It was concluded that nasal CPAP ventilation with pulse oximetry is a simple and efficient method of treating respiratory distress in newborns. This technique can be adopted even by smaller hospitals where the equipment and expertise for IPPV and arterial blood gas (ABG) monitoring are not feasible.Key Words: Nasal continuous positive airway pressure, Neonates, Respiratory distress 相似文献
999.
As is the case for all retroviruses, the protease of HIV-1 is only functional as a homodimer; dimerization of two protease monomers results in the formation of the enzyme active site. This dimer structure is supported primarily by interactions between the first four amino-terminal and the last four carboxy-terminal amino acids. These eight amino acids form a beta-sheet in which hydrophobic residues are oriented towards the core of the molecule and polar residues are directed towards the solvent. Although the structure of the dimer interface has been determined, the forces that support dimerization have not been fully characterized. Here, we describe a tethered construct in which two protease monomers are joined by a 5 amino acid linker. We evaluate the relative role of each dimer interface residue in functional homo- and heterodimers. Our studies indicate that the hydrophobic residues of the dimer interface are particularly important in maintaining enzyme activity and that enzyme activity is more sensitive to substitutions of the C-terminal amino acids. Further, we demonstrate that the presence of the tether is able to compensate for mutations within the dimer interface that inactivate the enzyme. 相似文献
1000.
Comparison of a new rapid plasma reagin card test with the standard rapid plasma reagin 18-mm circle card test and the venereal disease research laboratory slide test for serodiagnosis of syphilis. 总被引:1,自引:0,他引:1 下载免费PDF全文
E A Hambie S A Larsen M W Perryman D E Pettit R L Mullally W Whittington 《Journal of clinical microbiology》1983,17(2):249-254
The rapid plasma reagin (RPR) card test manufactured by Beckman Instruments, Inc., was compared, qualitatively and quantitatively, with the Venereal Disease Research Laboratory (VDRL) slide test and the standard RPR 18-mm circle card tests for the serodiagnosis of syphilis. Sera from 638 individuals were used in this study. Two pilot lots and two production lots of antigen were submitted by Beckman Instruments, Inc., for evaluation. Qualitative agreement among the three RPR card tests was 98.1%; between the Beckman RPR card and the VDRL slide tests, 95.0%; and between the reference RPR card and the VDRL slide tests, 95.5%. The Beckman RPR card test was 95.3% specific, whereas the specificities of the reference RPR card and the VDRL slide tests were 98.8% and 96.1%, respectively. Sensitivities of the three nontreponemal tests were: Beckman RPR card test production lots, 94.7%; reference RPR card test, 96.8%; and VDRL slide test, 90.6%. Quantitative agreement +/- 1 dilution among the three RPR card tests was 93.0%, whereas quantitative agreement was approximately 40% when both RPR card tests were compared with the VDRL slide test. We found the Beckman RPR card test comparable to the standard RPR card tests. Therefore, the decision of which test to use for the serodiagnosis of syphilis is at the discretion of the user. 相似文献