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81.
AW Minto R Kalluri M Togawa EC Bergijk PD Killen DJ Salant 《Canadian Metallurgical Quarterly》1998,110(3):207-217
The swelling, erosion and solvent front penetration properties of mini-matrices containing xanthan (X), locust bean (LB) and karaya (K) gums were examined, analysed and related to the overall in vitro release kinetics of diclofenac sodium, used as a model drug. Mini-matrices were produced with drug:gum ratios of 1:1 as well as formulations of drug and X in combinations of 2:1, 2:3 and 1:2. The rank order of decreasing swelling index (SI) in both axial and radial dimensions was X?K?LB and each gum showed almost Fickian swelling behaviour. The solvent front penetration rates were consistent with the rates of swelling. However, the order of decreasing drug release and erosion rates was LB>X>K and all formulations demonstrated anomalous (non-Fickian) drug release kinetics. Therefore Fickian drug diffusion and polymer erosion were both occurring simultaneously. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution time period. There was a loss of matrix integrity in formulations containing a high drug:gum ratio. 相似文献
82.
83.
EC Griffith Z Su S Niwayama CA Ramsay YH Chang JO Liu 《Canadian Metallurgical Quarterly》1998,95(26):15183-15188
Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Fumagillin and ovalicin compose a class of structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. A synthetic analog of fumagillin, TNP-470, is currently undergoing clinical trials for treatment of a variety of cancers. A common target for fumagillin and ovalicin recently was identified as the type 2 methionine aminopeptidase (MetAP2). These natural products bind MetAP2 covalently, inhibiting its enzymatic activity. The specificity of this binding is underscored by the lack of inhibition of the closely related type 1 enzyme, MetAP1. The molecular basis of the high affinity and specificity of these inhibitors for MetAP2 has remained undiscovered. To determine the structural elements of these inhibitors and MetAP2 that are involved in this interaction, we synthesized fumagillin analogs in which each of the potentially reactive epoxide groups was removed either individually or in combination. We found that the ring epoxide in fumagillin is involved in the covalent modification of MetAP2, whereas the side chain epoxide group is dispensable. By using a fumagillin analog tagged with fluorescein, His-231 in MetAP2 was identified as the residue that is covalently modified by fumagillin. Site-directed mutagenesis of His-231 demonstrated its importance for the catalytic activity of MetAP2 and confirmed that the same residue is covalently modified by fumagillin. These results, in agreement with a recent structural study, suggest that fumagillin and ovalicin inhibit MetAP2 by irreversible blockage of the active site. 相似文献
84.
Benign peptic stricture of the esophagus is a complex disorder which results from persistent gastroesophageal reflux. Its successful management depends on an accurate preoperative evaluation of the stricture and the patient. Surgical management of peptic strictures can be quite effective in relieving the symptoms and halting the pathologic gastroesophageal reflux that accompanies this disorder. This article reviews the general principles of evaluation and surgical treatment of benign peptic esophageal strictures. 相似文献
85.
86.
The arabidopsis ACT7 actin gene is expressed in rapidly developing tissues and responds to several external stimuli 总被引:1,自引:0,他引:1
JM McDowell YQ An S Huang EC McKinney RB Meagher 《Canadian Metallurgical Quarterly》1996,111(3):699-711
ACT7 encodes one of the six distinct and ancient subclasses of actin protein in the complex Arabidopsis actin gene family. We determined the sequence and structure of the Arabidopsis thaliana ACT7 actin gene and investigated its tissue-specific expression and regulation. The ACT7 mRNA levels varied by 128-fold among several different tissues and organs. The highest levels of aCT7 mRNA were found in rapidly expanding vegetative organs, the lowest in pollen. A translational fusion with the 5' end of ACT 7 (1.9 kb) joined to the beta-glucuronidase reporter gene was strongly and preferentially expressed in all young, developing vegetative tissues of transgenic Arabidopsis plants. ACT7 was the only Arabidopsis actin gene strongly expressed in the hypocotyl and seed coat. Although no beta-glucuronidase expression was seen in developing ovules or immature seeds, strong expression was seen in dry seeds and immediately after imbibition in the entire seedling. ACT7 was the only Arabidopsis actin gene to respond strongly to auxin, other hormone treatments, light regime, and wounding, and may be the primary actin gene responding to external stimuli. The ACT7 promoter sequence contains a remarkable number of motifs with sequence similarity to putative phytohormone response elements. 相似文献
87.
88.
EC Todoroff M Sevcik DC Villeneuve WG Foster JF Jarrell 《Canadian Metallurgical Quarterly》1998,12(3):305-316
We describe the cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73. p63 was detected in a variety of human and mouse tissues, including proliferating basal cells of epithelial layers in the epidermis, cervix, urothelium, and prostate. Unlike p53, the p63 gene encodes multiple isotypes with remarkably divergent abilities to transactivate p53 reporter genes and induce apoptosis. Importantly, the predominant p63 isotypes in many epithelial tissues lack an acidic N terminus corresponding to the transactivation domain of p53. We demonstrate that these truncated p63 variants can act as dominant-negative agents toward transactivation by p53 and p63, and we suggest the possibility of physiological interactions among members of the p53 family. 相似文献
89.
We herein report a simple method using intestinal clamps to prevent intraoperative contamination during an immediate mucocutaneous suture of the intestinal stoma. Using this technique, a protruded intestinal stoma can be constructed reliably without soiling. The technique can be used both for constructing an end as well as a loop intestinal stoma. 相似文献
90.
Escherichia coli senses and signals anoxic or low redox conditions in its growth environment by the Arc two-component system. Under those conditions, the tripartite sensor kinase ArcB undergoes autophosphorylation at the expense of ATP and subsequently transphosphorylates its cognate response regulator ArcA through a His --> Asp --> His --> Asp phosphorelay pathway. In this study we used various combinations of wild-type and mutant ArcB domains to analyze in vitro the pathway for signal decay. The results indicate that ArcA-P dephosphorylation does not occur by direct hydrolysis but by transfer of the phosphoryl group to the secondary transmitter and subsequently to the receiver domain of ArcB. This reverse phosphorelay involves both the conserved His-717 of the secondary transmitter domain and the conserved Asp-576 of the receiver domain of ArcB but not the conserved His-292 of its primary transmitter domain. This novel pathway for signal decay may generally apply to signal transduction systems with tripartite sensor kinases. 相似文献