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To pursue structure-function relationships of heme enzymes in the activation of peroxides, we have chosen to use myoglobin as the framework for our molecular engineering studies. Comparison of the crystal structures of myoglobin and peroxidases reveals differences in the arrangement of amino acid residues in heme active sites. On the basis of these structural differences and the reaction mechanisms of peroxidases, we have converted myoglobin into a peroxidase-like enzyme by alternation of the heme distal pocket via site-directed mutagenesis. The replacement of the proximal histidine with cysteine and the exogenous substituted imidazoles slightly accelerates the peroxide O-O bond cleavage due to the electron donor characteristics. However, we have not observed an enhancement in the activation of peroxide by the proximal mutant with tyrosine, the exogenous phenolate, and benzoate. A clear understanding of the absolute role of the proximal ligand remains elusive. 相似文献
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WP Su 《Canadian Metallurgical Quarterly》1987,35(17):9245-9246
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We report a case of neurosarcoidosis, which simulated a cerebral tumor located at the floor of the III ventricle, associated to an aseptic meningitis and diabetes insipidus. It was the first and only manifestation of the illness. The response to steroid therapy was very favourable, with complete clinical recuperation and radiological resolution. 相似文献
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WP Anderson 《Canadian Metallurgical Quarterly》1997,167(11-12):608-609
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R Pazdur E Diaz-Canton WP Ballard JE Bradof S Graham SG Arbuck JL Abbruzzese R Winn 《Canadian Metallurgical Quarterly》1997,15(8):2905-2909
PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS: Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease. 相似文献
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The problem of finding the shape of a perfectly conducting cylinder when illuminated by an E-polarized incident electromagnetic wave is considered. The given problem is cast in the form of a penalized optimization problem in which we seek a surface in some suitably constrained class which minimizes a functional involving two terms. The first term measures the mean square deviation of the far field of the solution to the direct scattering problem for a surface in the admissible class from given, measured, far field data whilst the second term, penalty, measures the error in satisfying the imposed boundary conditions. An optimisation algorithm is used which does not require that a direct problem be solved in the updating process. Explicit reconstructions are presented which illustrate the effectiveness of the method. Some results indicating the sensitivity of the algorithm to the choice of penalty parameter and the number of incident waves are also given. 相似文献