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31.
The binding of dapsone, 4,4'-sulfonylbis(aniline)(1), and its diacetylated derivative, 4,4"'-sulfonylbis(acetanilide)(2), to human serum albumin is reported. To assess the ability of these compounds to displace 4'-[(4-aminophenyl)sulfonyl]acetanilide (3) from albumin, a dialysis rate technique was used. Competition for the bilirubin binding site on albumin was measured with the peroxidase assay. Compounds 1 and 2 strongly displaced both 3 and bilirubin from human serum albumin. The association constants for 1 and 2 with respect to bilirubin binding were 1.29 X 10(3) and 1.15 X 10(4) M-1, respectively. These results suggest that the binding site for 3 and the bilirubin binding site are similar with respect to 1 and 2 and that the binding of dapsone and its derivatives probably does not involve the amino function. 相似文献
32.
Effect of muscle activity immediately after botulinum toxin injection for writer's cramp. 总被引:1,自引:0,他引:1
R Chen B I Karp S R Goldstein W Bara-Jimenez Z Yaseen M Hallett 《Movement disorders》1999,14(2):307-312
Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections. 相似文献
33.
Kieszak SM Flanders WD Kosinski AS Shipp CC Karp H 《Journal of clinical epidemiology》1999,52(2):137-142
The objective of this article is to compare the Charlson comorbidity index derived from medical record data (Chart Index) with the same index derived from billing data (ICD-9 Index) to determine how well each predicted inpatient and 30-day mortality, length of stay, and complications among Medicare beneficiaries hospitalized for carotid endarterectomy. Economic and time constraints have increased the need for risk adjusters derived from administrative data, yet few studies have compared these measures with those derived from chart review. Using logistic regression, the Chart Index was found to be a significant predictor of inpatient mortality, 30-day mortality, length of stay, and complications, after controlling for age, gender, and neurologic and medical risk factors (P values = 0.004, 0.056, 0.0001, and 0.042, respectively). The ICD-9 Index approached significance as a predictor of the outcomes (P values = 0.092, 0.100, 0.093, and 0.080, respectively). The Chart Index was shown to be superior to the ICD-9 Index within this patient sample. 相似文献
34.
Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy 总被引:1,自引:0,他引:1
Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have "secondary" acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of "primary" acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively. 相似文献
35.
Characterization of the Mr difference between secreted murine fourth component of complement and the major plasma form: evidence for carboxyl-terminal cleavage of the alpha chain. 总被引:5,自引:3,他引:2 下载免费PDF全文
D R Karp D C Shreffler J P Atkinson 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(21):6666-6670
The alpha-chain of murine fourth component of complement (C4) secreted by cells in vitro and in vivo has a Mr that is larger by approximately equal to 4,000 than that of the alpha-chain of the principal form of C4 in plasma. By using in vivo labeling of C4 with [35S]methionine, C4 was shown to be first synthesized with the higher Mr ("secreted") alpha-chain, which was then quickly processed (t1/2 approximately equal to 1 hr) extracellularly to the mature ("plasma") C4 possessing the lower Mr alpha-chain. Both forms of C4 were functional as assayed by the ability of their alpha-chains to be cleaved by the protease C1, to bind methylamine, and to undergo denaturation-dependent autolysis. When secreted C4 and plasma C4 were activated to C4b, the Mr difference of 4,000 was maintained in the alpha'-chains. The Mr difference was localized to the carboxyl-terminal autolytic fragment of the alpha-chain and was unaffected by the removal of carbohydrate. C4 from resident peritoneal macrophage cultures could be converted to the plasma form by incubation with heparin/plasma. This conversion could be blocked by EDTA or 1,10-phenanthroline. These data suggest that an enzyme, presumably a neutral proteinase present in mouse plasma, cleaves the carboxyl terminus of newly synthesized C4 alpha-chains, thereby creating the major form of C4 in plasma. 相似文献
36.
Interactive suppression of aberrant crypt foci induced by azoxymethane in rat colon by phytic acid and green tea 总被引:1,自引:2,他引:1
Several epidemiological studies point to a strong correlation between
nutrient composition of the diet and cancer of the colon. Phytic acid,
present in grains, has been credited with reducing the risk of cancer of
the colon. A number of reports are available indicating the benefits of
green tea consumption in reducing the risk of stomach, lung and skin
cancer, but little data are available on the effect of green tea in
reducing the risk of colon cancer. Also, there are no studies on the
combined effect of these compounds on colon tumorigenesis. Thus the primary
objective of this investigation was to elucidate the combined effects of
green tea and phytic acid on colonic preneoplastic lesions and the Phase II
enzyme glutathione S-transferase. Fisher 344 male weanling rats were
divided into nine groups of 15 rats each and fed the experimental diet for
13 weeks. Rats received two s.c. injections of azoxymethane in saline at 16
mg/kg body wt at 7 and 8 weeks of age. Rats received three levels (0, 1 and
2%) of phytic acid with three levels (0, 1 and 2%) of green tea within each
phytic acid level in a 3 x 3 factorial experiment. Results indicate that
while green tea had a marginal effect (P < 0.14), phytic acid
significantly reduced the incidence of aberrant crypt foci (P < 0.008).
The interaction between green tea and phytic acid was significant (P <
0.029 for distal and < 0.0168 for entire colon) and positive, pointing
to a synergistic effect of green tea and phytic acid.
相似文献
37.
Hellman Richard Neuberg Donna S. Wagner Henry Grunnet Margaret Robins H. Ian Karp Daniel Flynn Patrick Adams George 《Journal of neuro-oncology》1998,37(1):55-62
This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas. 相似文献
38.
39.
Scott H Kaufmann Judith E Karp Louis Letendre Timothy J Kottke Stephanie Safgren Jackie Greer Ivana Gojo Pamela Atherton Phyllis A Svingen David A Loegering Mark R Litzow Jeff A Sloan Joel M Reid Matthew M Ames Alex A Adjei Charles Erlichman 《Clinical cancer research》2005,11(18):6641-6649
PURPOSE: To assess the maximum tolerated dose, toxicities, pharmacokinetics, and antileukemic activity of topotecan and carboplatin in adults with recurrent or refractory acute leukemias. EXPERIMENTAL DESIGN: Patients received topotecan and carboplatin by 5-day continuous infusion at nine dose levels. Patients achieving a complete remission received up to two additional courses for consolidation. Plasma topotecan and ultrafilterable platinum were assayed on days 1 to 5. In addition, pretreatment levels of various polypeptides in leukemic cells were examined by immunoblotting to assess possible correlations with response. RESULTS: Fifty-one patients received a total of 69 courses of therapy. Dose-limiting toxicity consisted of grade 4/5 typhlitis and grade 3/4 mucositis after one course of therapy or grade 4 neutropenia and thrombocytopenia lasting >50 days when a second course was administered on day 21. Among 45 evaluable patients, there were 7 complete remissions, 2 partial remissions, 1 incomplete complete remission, and 1 reversion to chronic-phase chronic myelogenous leukemia. Topotecan steady-state plasma concentrations increased with dose. No accumulation of topotecan or ultrafilterable platinum occurred between days 1 and 5 of therapy. Leukemic cell levels of topoisomerase I, checkpoint kinase 1, checkpoint kinase 2, and Mcl-1 correlated with proliferating cell nuclear antigen but not with response. In contrast, low Bcl-2 expression correlated with response (P = 0.014, Mann-Whitney U test). CONCLUSIONS: The maximum tolerated dose was 1.6 mg/m(2)/d topotecan plus 150 mg/m(2)/d carboplatin. The complete remission rate in a heavily pretreated population was 16% (33% at the highest three dose levels). Responses seem to correlate with low pretreatment blast cell Bcl-2 expression. 相似文献
40.