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61.
WD Morgan B Birdsall VI Polshakov D Sali I Kompis J Feeney 《Canadian Metallurgical Quarterly》1995,34(37):11690-11702
Two-dimensional (2D) double-quantum-filtered correlation spectroscopy (DQF-COSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), and rotating-frame NOESY (ROESY) spectra were used to assign essentially all the protons in a 1:1 complex of Lactobacillus casei dihydrofolate reductase formed with an analogue of the antibacterial drug brodimoprim [2,4-diamino-5-(3',5'-dimethoxy-4'-bromobenzyl)pyrimidine]. The analogue has a 4,6-dicarboxylic acid side chain substituted on the 3'-O position designed to interact with the Arg 57 and His 28 residues in L. casei dihydrofolate reductase; it binds a factor of 10(3) more tightly to the enzyme than does the parent compound. Thirty-eight intermolecular and 11 intramolecular NOEs were measured involving the bound brodimoprim-4,6-dicarboxylic acid analogue. These provided the distance constraints used in conjunction with an energy minimization and simulated annealing protocol (using Discover from Biosym Ltd.) to dock the brodimoprim analogue into dihydrofolate reductase. In calculations where side chains and backbone fragments for binding-site residues were allowed flexibility, 90% of the 40 calculated structures had reasonable covalent geometry and none of them had NOE distance violations of greater than 0.36 A. The conformations of the aromatic rings in the bound ligand were well-defined in all the structures, with torsion angles tau 1 = -153 degrees +/- 4 degrees (C4-C5-C7-C1') and tau 2 = 53 degrees +/- 4 degrees (C5-C7-C1'-C2'): the aromatic rings of the ligand occupied essentially the same space in all the calculated structures (root mean square deviation value 1.83 A). Inclusion of the electrostatic interactions into the energy minimizations indicated that structures in which the 4,6-dicarboxylate group of the ligand interacts with the side chains of Arg 57 and His 28 are of low energy. Significant differences in side-chain and backbone conformations were detected between binding-site residues in the enzyme complexes with the brodimorpim analogue and methotrexate. 相似文献
62.
The clinical picture and cytostatic treatment of solitary subconjunctival cysts of filtration pad after fistula-forming antiglaucoma surgery are described. Twenty-seven eyes with hypertension which developed as a result of subconjunctival cysts formed in the early postoperative period in 7% of patients operated on for open-angle glaucoma. Probable mechanisms of the pathogenesis of the formation of solitary cysts are discussed and 3-staged therapy proposed, including beta-blockers, perforation of the cyst wall by YAG laser, and, in 10% of cases with rigid cysts, microsurgical revision of filtration pad. 相似文献
63.
With the purpose of detecting long-term somatic effects of incorporated iodine, an analysis was performed of health disorders in those subjects (n = 1040) who received 131 I in therapeutic dosages 25 to 30 years ago. Discordances in pituitary-thyroid- and pituitary-adrenal axes were found to result in excessive metabolic-degenerative and vegetovascular type morbidity rates compared with the general population. Mortality index exceeds that of in the population 2.1-fold. No one of the deceased had reached the average length of human life. Halt the cases died of ischemic heart disease, 6 patients developed carcinoma of endocrine organs; these were all females, who had taken radioactive iodine prior to the age of 30 years. Thus, in remote time periods after incorporation, there develop a number of those disorders leading ultimately to reduction of the length of human life, which is believed to be one of the universal effects of irradiation. 相似文献
64.
EE Miniat EB Khomiakova MV Petrova MZ Gorgoshidze VI Ivanov 《Canadian Metallurgical Quarterly》1998,32(6):1013-1019
A HPLC method was developed and validated for the quantitation of 9-cis-retinoic acid (ALRT1057) and its major metabolite, 4-oxo-9-cis-retinoic acid (LG100182) in human plasma. Samples were buffered and extracted with methyl-tert-butyl-ether. The analytes and an I.S. were separated on a C18 HPLC column using a shallow gradient of 70-89% organic solvent. The analytes were quantitated by UV detection at 348 nm. Selectivity against endogenous compounds and potential metabolites (retinol, all trans-, 13-cis-, and 4-hydroxy-9-cis-retinoic acid) was demonstrated. The run time was 29 min. The standard curve was linear from 2.5 to 450 ng ml-1. Interassay precision for both analytes in quality control samples was less than 5.0% RSD. Accuracy was within 11.0% RE for both compounds. Analyte stability during sample storage, extraction processing, and chromatography was established. Method ruggedness was tested by two analysts and on two HPLC systems. This method has been applied to the quantitation of clinical samples. 相似文献
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66.
NM Nasybullina VP Zherdev VI Gunar VM Kopelevich GS Kozlova 《Canadian Metallurgical Quarterly》1997,60(6):52-54
The authors studied the permeability of the blood-brain barrier (CEB) to two nootropics: calcium ketogomopantothenate (KRA-Ca), a GABA derivative, and and calcium salt of oxybutyrate (OB-Ca), a derivative of GOBA. It was established that both preparations penetrate the CEB easily and are found in the brain at different intervals after their administration. However, essential differences in the distribution constant of these drugs were disclosed: KPA-Ca permeated the CEB more intensively and was accumulated in larger amounts in the late-term intervals. 相似文献
67.
VI Mitashov SA Luk'ianov OV Kazanskaia IuV Markitantova SM Dolgilevich IIu Snegovaia SL Zno?ko AS Mikaélian 《Canadian Metallurgical Quarterly》1995,(3):276-280
This paper constitutes a review of the methodical approaches allowing analysis of the mechanisms underlying development and differentiation. Progress in investigation of the mechanisms underlying embryogenesis is related to the discovery of genic families in the Drosophila genome, which are responsible for different periods of embryogenesis. The true revolution in studies of developmental mechanisms began with the application of molecular-genetic methods for analysis of Drosophila mutant lines. The clarification and analysis of the genes controlling regeneration is one of the most effective paths toward an understanding of the mechanisms underlying regeneration. No mutations affecting regeneration are, and the development of alternative (i.e., not based on mutation analysis) methods of discovery of the genes controlling regeneration is necessary for investigation of the genetic mechanisms of regeneration. The advantages and drawbacks of the two main approaches for discovery of the genes controlling regeneration are considered. The first approach is based on the production of a bank of sequences expressed in the regenerating structures and subsequent screening of the bank by the known probes. This approach also involves analysis of the structure, function, and expression pattern of the obtained homologs. The second approach is based on subtractive hybridization, which allows identification of the genes specifically expressed in the regenerating structures. This approach was made it possible to identify, for the first time, new genes specifically expressed during lens and retina regeneration in amphibians. 相似文献
68.
VI Tsirkin 《Canadian Metallurgical Quarterly》1997,23(3):88-96
The conventional analysis and design of highway bridges ignore the contribution of sidewalks and∕or railings in a bridge deck when calculating the flexural strength of superstructures. The presence of sidewalks and railings or parapets acting integrally with the bridge deck have the effect of stiffening the outside girders and attracting more load while reducing the load effects in the interior girders. This paper presents the results of a parametric study showing the influence of typical sidewalks and railings on wheel load distribution as well as on the load-carrying capacity of highway bridges. A typical one-span, two-lane, simply supported, composite steel girder bridge was selected in order to investigate the influence of various parameters such as: span length, girder spacing, sidewalks, and railings. A total of 120 bridges were analyzed using three-dimensional finite-element analysis. American Association of State Highway and Transportation Officials (AASHTO) HS20 design trucks were positioned in both lanes to produce the maximum moments. The finite-element analysis results were also compared with AASHTO wheel load distribution factors. The AASHTO load and resistance factor design (LRFD) wheel load distribution formula correlated conservatively with the finite-element results and all were less than the typical empirical formula (S∕5.5). The presence of sidewalks and railings were shown to increase the load-carrying capacity by as much as 30% if they were included in the strength evaluation of highway bridges. 相似文献
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