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121.
Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent's use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere(R)) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. 相似文献
122.
Goslinski T Wenska G Golankiewicz B Balzarini J De Clercq E 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):911-914
Tricyclic (T) analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) carrying the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system [i.e., 6-(4-BrPh)TACV, 5 and 6-(4-BrPh)TGCV, 6] were transformed into 6-[(4'-R2)-4-biphenylyl] derivatives of TACV (7-9) and TGCV (10-12) by Suzuki cross coupling with 4-substituted phenylboronic acids. Compound 11 (R2 = CH2OH) showed a high (approximately 1000) selectivity index against herpes simplex virus type 1 (HSV-1) together with advantageous fluorescence properties (emission in visible region, little overlap with absorption and moderate intensity). 相似文献
123.
Morkunas I Garnczarska M Bednarski W Ratajczak W Waplak S 《Journal of plant physiology》2003,160(3):311-319
Embryo axes isolated from germinating lupine seeds were cultivated in vitro for 24-96 h over media containing either 60 mmol/L sucrose or no sucrose. Ultrastructural studies showed that large vacuoles were accumulating in a central region of primary parenchyma cells in sucrose starved lupine embryo axes, whereas cytoplasm along with organelles were forced to a periphery of the cells. We suggest that the autolysis of cytoplasmic proteins contributes to the accumulation of the vacuoles and this suggestion is consistent with the results of the characterisation of protein content. The level of cytosolic proteins was reduced by 50% and the activity of cytosolic marker enzyme, PEP carboxylase, was reduced by 46% in starved embryos as compared to control. The mitochondria from starved tissues were not degraded. The level of mitochondrial proteins was reduced by only 10% and the activity of mitochondrial NAD-isocitrate dehydrogenase decreased by 8% as a result of starvation. As demonstrated by the results of Percoll density gradient centrifugation, sucrose starvation caused an increase of 49% in many of the higher density mitochondria fractions, whereas many of the lower density mitochondria fractions were decreased by 33%. The samples of mitochondria from starved embryo axes were determined to have higher respiration activity in the presence of glutamate and malate as compared to control samples. EPR-based analyses of free radicals showed the presence of free radicals with a signal at g = 2.0060 in embryo axes. The level of the radical was two times higher in sucrose-starved embryo axes than in control (the level of this radical increased in senescing plant tissues as well). The results of EPR-based quantitation of Mn2+ ions revealed that the level was a few times higher in starved material than in control. Starved embryo axes, however, do possess a number of adaptive mechanisms protecting them from oxidative damage. Densitometric analyses of gels revealed an increase in the activity of SOD in sugar-starved embryos, whereas CAT and POX activities were lower in axes grown without sucrose as compared to control. Superoxide dismutase, catalase and peroxidase zymogram analyses showed that synthesis of new isoforms was not induced by sugar starvation. An accumulation of phytoferritin was found in plastids of sucrose starved embryos. These results are discussed in relation to the metabolic changes observed in senescing plant tissues. 相似文献
124.
Mieszała M Lipiński T Kocharova NA Zatonsky GV Katzenellenbogen E Shashkov AS Gamian A Knirel YA 《FEMS immunology and medical microbiology》2003,36(1-2):71-76
Serological studies using SDS-PAGE and immunoblotting revealed that from five strains that are ascribed to Citrobacter serogroup O2, four strains, PCM 1494, PCM 1495, PCM 1496 and PCM 1507, are reactive with specific anti-Citrobacter O2 serum. In contrast, strain PCM 1573 did not react with anti-Citrobacter O2 serum and, hence, does not belong to serogroup O2. The LPS of Citrobacter youngae O2a,1b (strain PCM 1507) was degraded under mild acidic conditions and the O-specific polysaccharide (OPS) released was isolated by gel chromatography. Sugar and methylation analyses along with (1)H- and (13)C-NMR spectroscopy, including two-dimensional (1)H,(1)H COSY, TOCSY, NOESY and (1)H,(13)C HSQC experiments, showed that the repeating unit of the OPS has the following structure: [structure: see text]. NMR spectroscopic studies demonstrated that Citrobacter werkmanii O20 and C. youngae O25 have the same OPS structure as C. youngae O2. Sugar and methylation analyses of the core oligosaccharide fractions demonstrated structural differences in the lipopolysaccharide core regions of these strains, which may substantiate their classification in different serogroups. 相似文献
125.
Lukasiewicz J Jachymek W Niedziela T Dzieciatkowska M Lakomska J Miedzybrodzki R Fortuna W Szymaniec S Misiuk-Hojlo M Lugowski C 《FEMS immunology and medical microbiology》2003,37(1):59-67
The covalent conjugate of oligosaccharide core of Escherichia coli type R4 with tetanus toxoid was prepared using reaction of reductive amination. The neoglycoconjugate was a good immunogen in rabbits yielding a high level of anti-lipopolysaccharide (LPS) antibodies of the IgG class. It was found that antiserum was able to react with the smooth LPS molecules of identical (R4) or related (R1) core type. The reactions were shown in the enzyme-linked immunosorbent assay and the immunoblotting test. Flow cytometry showed that anti-core antibodies reacted with LPS present on intact, live, smooth bacteria labelling more than 90% of cells. The anti-OS R4-TT serum used for in vitro studies showed high endotoxin neutralization activity. The serum inhibited endotoxin-induced tumor necrosis factor alpha and nitric oxide synthesis by the J-774A.1 cell line and attenuated pulmonary retention of YAC-1 cells. 相似文献
126.
Analytical work on the fractionation of the glycan strands of Streptococcus pneumoniae cell wall has led to the observation that an unusually high proportion of hexosamine units (over 80% of the glucosamine and 10% of the muramic acid residues) was not N-acetylated, explaining the resistance of the peptidoglycan to the hydrolytic action of lysozyme, a muramidase that cleaves in the glycan backbone. A gene, pgdA, was identified as encoding for the peptidoglycan N-acetylglucosamine deacetylase A with amino acid sequence similarity to fungal chitin deacetylases and rhizobial NodB chitooligosaccharide deacetylases. Pneumococci in which pgdA was inactivated by insertion duplication mutagenesis produced fully N-acetylated glycan and became hypersensitive to exogenous lysozyme in the stationary phase of growth. The pgdA gene may contribute to pneumococcal virulence by providing protection against host lysozyme, which is known to accumulate in high concentrations at infection sites. 相似文献
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130.
K. J. Rakowski M. Behzadipour R. Ratajczak M. Kluge 《Plant biology (Stuttgart, Germany)》1998,111(3):236-240
Norway spruce (Picea abies Karst.) seeds were frozen and stored for 15 months at + 3, ? 25, ? 75 or ? 196°C. After storage, seeds were germinated for 9?14 days to determine viability and plasma membrane protein composition, H+-ATPase activity and fluidity. The results indicate no significant differences in viability of seed 14 days after germination. Biochemical analyses revealed increased plasma membrane fluidity in 9-day-old Norway spruce seedlings raised from seeds pretreated at ? 75 °C. and changes in the temperature profile of membrane fluidity in seedlings after pre-treatment of seeds at ? 25 °C. On the other hand, the same treatments did not result in changes in plasma membrane protein content, protein composition or ATPase activity. There was also no difference in plasma membrane H+-ATPase activity assayed in the presence of different ATP hydrolysis inhibitors. Based on the presented results, and other experimental data, we suggest that during early seedling growth, adaptation of seeds to ? 25 and ? 75°C freezing and/or storage temperature results in stability of the plasma membrane protein function and composition and increased fluidity or changes in the temperature-dependent fluidity profile of these membranes. 相似文献