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To combine the cytotoxic activity of cisplatin and the phototoxicicity of hematoporphyrin derivatives in the same molecule, hematoporphyrin was derivatized at the two secondary alcohol positions by etherification with oligo- and poly(ethylene glycol) units. The two carboxylic acid groups of the propionate side chains were used to bind platinum fragments. The antiproliferative activity of 35 platinum complexes (0.5, 1, and 5 microM) differing in solubility and type of the platinum fragment and the corresponding porphyrin ligands were studied in tests with TCC-SUP and J82 transitional bladder cancer cells in the dark and after irradiation (lambda = 600-730 nm, 24 J/cm(2)). The most active compounds were found among the porphyrin-platinum conjugates bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligand. These porphyrin-platinum conjugates, especially the water-soluble species, such as diammine(7,12-bis[1-(poly(ethylene glycol)-750-monomethyl ether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato)platinum(II), are promising candidates for the development of a novel type of photosensitizers with intrinsic cytotoxicity, which due to the porphyrin constituent may selectively enrich in tumor tissues. 相似文献
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Bernhardt ES Likens GE Buso DC Driscoll CT 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(18):10304-10308
Between January 4 and 10, 1998, a severe ice storm impacted large areas of northern New York, New England, and eastern Canada. This storm struck the Hubbard Brook Experimental Forest in New Hampshire on January 7-8, 1998, and caused extensive forest crown damage (>30%) in a narrow elevation band (600-740 m) across the south-facing experimental watersheds. Stream water has been collected and chemically analyzed since 1963 in six experimental watersheds at Hubbard Brook Experimental Forest; thus, we were able to examine the effect of this severe natural disturbance on watershed nutrient export and changes in instream nitrate (NO3-) processing. The ice storm caused large increases in watershed export of NO3- for 2 years after the disturbance, but our examination of in-stream processing suggests that NO3- losses would have been much more dramatic had there not been an increase in in-stream, nitrogen-processing efficiency after the ice storm. The canopy damage that resulted from the ice storm led to increased light availability and large inputs of woody debris to the stream. We suspect that increases in algal production and storage and processing of terrestrial litter account for the increase in inorganic nitrogen processing in these streams. Our results indicate that, without in-stream processing, export of NO3- from the damaged watersheds would have been 80-140% higher than was observed. These results point to an intriguing negative feedback mechanism whereby the same disturbance that causes watershed NO3- loss may simultaneously lead to increased in-stream retention and transformation. 相似文献
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Sonography is a valuable method for imaging superficial tendons and ligaments. The ability to obtain comparison images easily with dynamic stress allows assessment of ligament and tendon integrity. We studied the medial elbow joints of two baseball pitchers using MR imaging and dynamic sonography. Both sonography and MR imaging identified the ulnar collateral ligament tears. Dynamic sonography uniquely demonstrated the medial joint instability. 相似文献
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Friebel TM Beutler RA Lee SM Bernhardt BA Helzlsouer KJ Griffin CA 《Journal of clinical epidemiology》2004,57(11):1172-1176
BACKGROUND AND OBJECTIVE: The Mid-Atlantic Cancer Genetics Network (MACGN) targets individuals from cancer risk assessment clinics for recruitment into a national hereditary cancer registry. We sought to determine whether different recruitment methods used in a high-risk breast and ovarian cancer clinic yielded differences into enrollment into MACGN. METHODS: Two methods of recruitment were compared over an 8-month period. A passive recruitment technique, used during the first 4 months of recruitment, involved distribution of a brochure. An active recruitment method, used during the second 4-month period, required a MACGN recruiter to approach patients and initiate a brief discussion of the registry. RESULTS: During the first 4-month period, 158 eight patients were seen in the clinic and 142 were seen in the second 4-month period. During passive recruitment, 20% of available patients were approached, compared with 63% during active recruitment. Active recruitment also resulted in fourfold increase over passive recruitment in enrollment (from 15.6% to 67.4%). CONCLUSION: Allocating research staff specifically for recruitment and personal contact with potential participants is effective in achieving increased enrollment into a national hereditary cancer research registry. 相似文献