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301.
Kitova EN Kitov PI Paszkiewicz E Kim J Mulvey GL Armstrong GD Bundle DR Klassen JS 《Glycobiology》2007,17(10):1127-1137
The binding stoichiometry and affinities of the Shiga toxins, Stx1 and Stx2, for a series of uni- and oligovalent analogs of the Pk-trisaccharide were measured using the direct electrospray ionization mass spectrometry (ES-MS) assay. Importantly, it is shown that, for a given ligand, Stx1 and Stx2 exhibit similar affinities. The binding data suggest a high degree of similarity in the spatial arrangement and structural characteristics of the Pk binding sites in Stx1 and Stx2. The results confirm that both toxins recognize the alpha-D-Galp(1-->4)-beta-D-Galp(1-->4)-beta-D-Glcp carbohydrate motif of the cell surface glycolipid Gb3. This, taken together with the results of the chemical mapping study, suggests that the nature of the Pk binding interactions with Stx1 and Stx2 are similar. The affinities of Stx1-B(5) and Stx2 for the multivalent ligands reveals that site 2 of Stx2, which shares the same spatial arrangement as site 2 in Stx1, is the primary Pk binding site and that site 1 of Stx1 and of Stx2 can also participate in Pk binding. 相似文献
302.
Spácilová L Dzubák P Hajdúch M Krupková S Hradil P Hlavác J 《Bioorganic & medicinal chemistry letters》2007,17(23):6647-6650
The preparation of various 5-[alkoxy-(4-nitro-phenyl)-methyl]-uracils with alkyl chain lengths C(1)-C(12) is described. The synthesis is based on the preparation of 5-[chloro-(4-nitro-phenyl)-methyl]-uracil and subsequent substitution of chlorine with appropriate alcohols. The resulting ethers were tested for their cytotoxic activity in vitro against five cancer cell lines. The compounds were less active in lung resistance protein expressing cell lines, suggesting the involvement of this multidrug resistant protein in control of the biological activity. Cytotoxic substances induced rapid inhibition of DNA and modulation of RNA synthesis followed by induction of apoptosis. The data indicate that the biological activity of 5-[alkoxy-(4-nitro-phenyl)-methyl]-uracils depends on the alkyl chain length. 相似文献
303.
Wimmer Z Pechová L Sīle L Saman D Jedlicka P Wimmerová M Kolehmainen E 《Bioorganic & medicinal chemistry》2007,15(22):7126-7137
A series of the protected alkyl glycosides 5a/5b-12a/12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4'-(2'-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester (1a/1b-4a/4b; racemic structures) and (1a-4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs-Knorr reaction, and the products were obtained in 82-92% yields. Deprotection of the carbohydrate functionality of 5a/5b-12a/12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/13b-20a/20b (diastereoisomeric mixtures) and 13a-20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82-93% yields. Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of the respective enantiomers 13b-20b of the alkyl glycosides for their structure elucidation and (13)C chemical shift assignment by (1)H and (13)C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/13b-20a/20b were performed on the red firebug (Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which results in liberation of the biologically active juvenoid in the insect organism. 相似文献
304.
305.
The vegetation of natural fir-beech forests on the western edge of the Carpathians was repeatedly surveyed in 1972(4) and 1994(5) on 34 plots in the Razula and Salajka reserves. Concurrently repeated whole-area dendrometric measurements of all live and dead trees were made together with maps of forest development stages. The maps were used to compare vegetation changes. The objective was to assess the tree layer dynamics, to discern vegetation development trends from cyclical changes, and to assess the changes of site conditions through phytoindication. The fir (Abies alba) population showed disrupted continuity of development associated with its pronounced withdrawal and replacement by beech (Fagus sylvatica). Rather than a cyclical change, the phenomenon is a trend that can be expected to become more dominant in the future. The reason for the interchange of the two species is seen in a fading response to the medieval colonization of Carpathian ridges connected with the exploitation of local forests for grazing and intensive litter raking. The herb layer was significantly modelled by changes occurring over time and by the dynamics of forest development stages. Species diversity in Razula was observed to increase. Salajka exhibited an invasion of acidophilous taxa (Luzula luzuloides, Vaccinium myrtillus) and decreased frequency of demanding taxa (Galeobdolon montanum, Dentaria enneaphyllos, Galium odoratum). Changes in the coverage ofDryopteris filixmas, Rubus idaeus andSenecio ovatus were interpreted as cyclical changes. No significant shifts were found in the species diversity between the stages. The herb layer at a disintegration stage was homogenized and exhibited the lowest tendency to gain relative control of the undergrowth; the tendency was highest at the optimum stage. The stages of forest development exhibited changes in soil nitrogen and soil reaction. 相似文献
306.
Mendoza L Begany P Dyrhonova M Emritte N Svobodova X 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2007,151(1):65-67
AIM: A randomized, two-way, crossover, bioequivalence study was conducted in 25 fasting, healthy, male volunteers to compare two brands of fexofenadine 180 mg tablets, FEXOFENADINE 180 mg Film Tablet (Drogsan A.S., Ankara, Turkey) as test and Telfast 180 mg Tablet (Aventis Pharma, Frankfurt am Main, Germany) as a reference product. METHOD: One tablet of either formulation was administered after 10 h of overnight fasting. After dosing, serial blood samples were collected during a period of 48 hours. Plasma samples were analysed for fexofenadine by a validated HPLC method. The pharmacokinetic parameters AUC(0-48), AUC(0-alpha), C(max), T(max), K(el), T(1/2), and CL were determined from plasma concentration-time profiles for both formulations and were compared statistically. RESULTS AND CONCLUSIONS: The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range, satisfying the bioequivalence criteria of the FDA. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetics profiles and that Drogsan's Fexofenadine is equivalent to Telfast of Aventis Pharma, Frankfurt am Main, Germany. 相似文献
307.
Jiraskova N Rozsival P Kadlecova J Nekolova J Pozlerova J Dubravska Z 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2007,151(2):311-314
Aims: To compare the metrics and surgical outcome when using Infiniti AquaLase and NeoSoniX cataract removal modalities. Methods: This prospective clinical study involved 50 patients with bilateral cataracts and lens removal using AquaLase in the right eye and NeoSoniX in the left eye. Best corrected visual acuity (BCVA), endothelial cell density and pachymetry were evaluted pre- and postoperatively. Statistical analysis was performed using the Wilcoxon Signed- Rank Test. Results: Preoperative mean pachymetry was 569 +/- 31 mu in the right eye (RE) and 560 +/- 37 mu in the left eye (LE), mean endothelial cell density 2744 +/- 418 cells/mm(2) (RE) and 2730 +/- 472 cells/mm(2) (LE). One week after operation pachymetry was 576 +/- 52 mu (RE) and 583 +/- 72 mu (LE) and endothelial cell density 2388 +/- 586 cells/mm(2) (RE) and 2463 +/- 615 cells/mm(2) (LE). One month after surgery pachymetry was 556 +/- 43 mu (RE) and 559 +/- 44 mu (LE) and endothelial cell density 2368 +/- 52 cells/mm(2) (RE) and 2495 +/- 548 cells/mm(2) (LE). BCVA improved in all eyes and was 0.8 or better on the first postoperative day. Conclusions: Both the NeosoniX and AquaLase minimize intraoperative damage to ocular structures. 相似文献
308.
Bouwer S Angelicheva D Chandler D Seeman P Tournev I Kalaydjieva L 《Genetic testing》2007,11(4):455-458
Mutations in the GJB2 gene are the most common cause of autosomal recessive nonsyndromic hearing loss and occur in approximately 20% of all cases of prelingual deafness. Previous studies of Roma/Gypsies in Slovakia, the Czech Republic, and Spain have shown that W24X, the most common GJB2 mutation in India, is also the prevalent molecular defect in the Gypsy population. The reported W24X frequencies vary broadly from 23% to 93% of Gypsy mutant alleles, likely reflecting local founder effects, drift, and differential admixture in the subisolates of this genetically structured population. Our goal was to provide more representative data on W24X carrier rates in European Gypsies, which can inform individual diagnostic investigations and public health initiatives across countries. Mutation testing in 603 control subjects of Gypsy ethnicity, representing 8 traditional subisolates in southeastern Europe and 4 additional European regions revealed that W24X is spread across subisolates, as expected for an ancestral founder mutation. While variation between subisolates does exist, the average carrier rates, overall and in the major linguistic/migrational categories of Balkan Gypsies, Vlax Roma, and west European Gypsies, are consistently in the 4%-5% range. The results place W24X among the three most common founder mutations in the Gypsies, and classify them as one of the high-risk populations for prelingual deafness. Higher demands on language acquisition in this bilingual population, together with poorer quality of health care compared to autochthonous Europeans, make the consequences of congenital deafness even more damaging than is usually the case. Neonatal screening for W24X among Gypsies would be a justified and cost-effective public health intervention. 相似文献
309.
Gene delivery properties of end-modified poly(beta-amino ester)s 总被引:4,自引:0,他引:4
Zugates GT Tedford NC Zumbuehl A Jhunjhunwala S Kang CS Griffith LG Lauffenburger DA Langer R Anderson DG 《Bioconjugate chemistry》2007,18(6):1887-1896
Here, we present the synthesis of a library of end-modified poly(beta-amino ester)s and assess their utility as gene delivery vehicles. Polymers were synthesized using a rapid, two-step approach that involves initial preparation of an acrylate-terminated polymer followed by a postpolymerization amine-capping step to generate end-functionalized polymers. Using a highly efficient poly(beta-amino ester), C32, we show that the terminal amine can greatly affect and improve polymer properties relevant to gene delivery. Specifically, the in vitro transfection levels can be increased by 30% and the optimal polymer:DNA ratio lowered 5-fold by conjugation of the appropriate end group. The most effective modifications were made by grafting primary diamine molecules to the chain termini. The added charge and hydrophobicity of some derivatives enhanced DNA binding and resulted in the formation of polymer-DNA complexes less than 100 nm in diameter. In addition, cellular uptake was improved 5-fold over unmodified C32. The end-modified poly(beta-amino ester)s presented here are some of the most effective gene-delivery polycations, superior to polyethylenimine and previously reported poly(beta-amino ester)s. These results show that the end-modification of poly(beta-amino ester)s is a general strategy to alter functionality and improve the delivery performance of these materials. 相似文献
310.
We compared morphometric parameters of the contours of cells in four pairs of non-transformed mouse and rat lines and of the same lines transformed by oncogenes of the RAS family. As expected, the mean areas of all RAS-transformed lines were much smaller than those of their non-transformed counterparts. At the same time the average length of cell projection did not regularly decrease after transformation. These results show that transformation induced by expression of RAS oncogene selectively affect only one component of spreading, namely transversal spreading and not longitudinal spreading; these changes result in an increase of antero-posterior polarity of transformed fibroblasts. 相似文献