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71.
Several procedures have been applied to the preparation of 5-alkyl analogues of araU and araC via condensation of the appropriate 2,4-bis-O-(trimethylsilyl)-5-alkylpyrimidine with 2,3,5-tri-O-benzyl-alpha-D-arabinofuranosyl chloride. The resulting O'-benzylated nucleosides were deblocked with the aid of BF3 . Et2O in C2H5SH. The araC analogues were also prepared by conversions of the corresponding 5-alkyl-araU derivatives. The chloromercuri derivatives of araU and araC, were reacted with allyl chloride in the presence of Li2PdCl4. The resulting 5-allyl derivatives were catalytically reduced to the corresponding 5-propyl analogues. Catalysed condensation of 2,4-bis-O-(trimethylsilyl)-5-vinyluracil with 2,3,5-tri-O-benzyl-alpha-D-arabinosyl chloride, as well as with 1-O-acetyl-2,3,5-tri-O-benzoylarabinofuranose, was carried out under a variety of different conditions. Deblocking of the benzylated nucleosides with various reagents led invariably to addition to the vinyl substituent. In the case of benzoylated nucleosides, deblocking yielded largely the alpha-anomers. The antiherpes activities of the 5-alkyl compounds have been evaluated, as well as the susceptibility of the araC analogues to enzymatic deamination. 相似文献
72.
73.
W. Szeszkowski J. Cieśla R. Stolarski W. Rode T. Kulikowski 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):865-866
Abstract Interactions of mammalian (rat hepatoma) thymidylate synthase with FdUMP and its 4-thio analogue were studied in solution with the use of 1H and 19F NMR. The results pointed to formation of ternary covalent complexes of TS with either nucleotide in the presence of N5, N10-methylenetetrahydrofolate and only noncovalent binary complexes in the absence of the cofactor. 相似文献
74.
Dobrzycka B Terlikowski SJ Kowalczuk O Kulikowski M Niklinski J 《European cytokine network》2011,22(1):45-51
Endometrial cancer (EC) is the most common type of uterine cancer. A dualistic model of endometrial tumorigenesis serves as a useful way of categorizing these cancers in terms of both etiology and clinical behavior. There are two types of EC: type I and type II. Type I is so-called estrogen-dependent, and appears mostly in pre- and perimenopausal women, it is well differentiated and therefore has a better prognosis. Type II EC is estrogen-independent, diagnosed mostly in postmenopausal women, thin and fertile women, or in women with normal menstrual cycles. It is aggressive and has a worse prognosis than type I. The aim of this study was to evaluate the relationship between the pretreatment serum levels of VEGF and VEGF-C and the outcome of EC patients. A total of 98 patients treated between 1999 and 2003 were included in this study. Circulating VEGF and VEGF-C levels were determined using ELISA kits. VEGF levels among the 76 patients with type I, and the 22 patients with type II EC were significantly higher than those found in the healthy control subjects (p?0.001). The differences in mean values of VEGF-C were highly significant in both types of tumor examined compared to the control (p?0.001). The results demonstrate that serum VEGF concentration correlated significantly with advanced FIGO stage in type II EC (p?0.001). The preoperative VEGF-C level correlated with advancing tumor stages in type I EC (p?0.05). An elevated preoperative VEGF-C was an independent risk factor for disease-specific survival in patients with type II tumors. Thus, in type II EC patients with high preoperative levels of VEGF-C, pelvic and para-aortic lymphadenectomy should be performed. However, the value of longitudinal measurements of the markers used is yet to be determined. 相似文献
75.
Cytogenetic instability of dental pulp stem cell lines 总被引:1,自引:0,他引:1
Duailibi MT Kulikowski LD Duailibi SE Lipay MV Melaragno MI Ferreira LM Vacanti JP Yelick PC 《Journal of molecular histology》2012,43(1):89-94
Human adult stem cells (hASCs) offer a potentially renewable source of cell types that are easily isolated and rapidly expanded
for use in regenerative medicine and cell therapies without the complicating ethical problems that are associated with embryonic
stem cells. However, the eventual therapeutic use of hASCs requires that these cells and their derivatives maintain their
genomic stability. There is currently a lack of systematic studies that are aimed at characterising aberrant chromosomal changes
in cultured ASCs over time. However, the presence of mosaicism and accumulation of karyotypic abnormalities within cultured
cell subpopulations have been reported. To investigate cytogenetic integrity of cultured human dental stem cell (hDSC) lines,
we analysed four expanded hDSC cultures using classical G banding and fluorescent in situ hybridisation (FISH) with X chromosome
specific probe. Our preliminary results revealed that about 70% of the cells exhibited karyotypic abnormalities including
polyploidy, aneuploidy and ring chromosomes. The heterogeneous spectrum of abnormalities indicates a high frequency of chromosomal
mutations that continuously arise upon extended culture. These findings emphasise the need for the careful analysis of the
cytogenetic stability of cultured hDSCs before they can be used in clinical therapies. 相似文献
76.
77.
78.
M Szamatowicz M Kulikowski D Grochowski S Wo?czyński W Kuczyński I Tomaszewska E Sola J Radwan 《Polski tygodnik lekarski (Warsaw, Poland : 1960)》1991,46(50-52):1007-1010
The authors survey available publications dealing with the indications for in vitro fertilization, ovary stimulation technique, control of the ovary stimulation, oocytes collection, and transfer of the embryo in human. The authors personal experience with in vitro fertilization is also discussed. 相似文献
79.
W Rode Z Zieliński J M Dzik T Kulikowski M Bretner B Kierdaszuk J Cie?la D Shugar 《Biochemistry》1990,29(48):10835-10842
N4-Hydroxy-dCMP (N4-OH-dCMP), N4-methoxy-dCMP (N4-OMe-dCMP), and their 5-fluoro congeners (syntheses of which are described) were all slow-binding inhibitors of Ehrlich carcinoma thymidylate synthase (TS), competitive with respect to dUMP, and had differing kinetic constants describing interactions with the two TS binding sites. N4-OH-dCMP was not a substrate (no dihydrofolate produced; no tritium released with 5-3H-labeled molecule), and its inactivation of TS was methylenetetrahydrofolate-dependent, hence mechanism-based, with arrest of a step posterior to addition of cofactor and blocking abstraction of the C(5) hydrogen. Ki values for N4-OH-dCMP and its 5-fluoro analogue were in the range 10(-7) - 10(-8) M, 2-3 orders of magnitude higher for the corresponding N4-OMe analogues. The 5-methyl analogue of N4-OH-dCMP was 10(4)-fold less potent, pointing to the anti rotamer of the imino form of exocyclic N4-OH, relative to the ring N(3), as the active species. This is consistent with weaker slow-binding inhibition of the altered enzyme from 5-FdUrd-resistant, relative to parent, L1210 cells by both FdUMP and N4-OH-dCMP, suggesting interaction of both N4-OH and C(5)-F groups with the same region of the active center. Kinetic studies with purified enzyme from five sources, viz., Ehrlich carcinoma, L1210 parental, and 5-FdUrd-resistant cells, regenerating rat liver, and the tapeworm Hymenolepis diminuta, demonstrated that addition of a 5-fluoro substituent to N4-OH-dCMP increased its affinity from 2- to 20-fold for the enzyme from different sources.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
80.
RR Lew 《Fungal genetics and biology : FG & B》1998,24(1-2):69-76
Ion channel mapping techniques are described and the results for two fungal organisms, Saprolegnia ferax and Neurospora crassa, are presented. In these species, two channel types have been characterized, stretch-activated channels exhibiting significant calcium permeability and spontaneous channels having significant potassium permeability. Two distinct analyses of patch clamp data, analysis of channel self-clustering and association between different channel types, and localization along the hyphae, reveal significant differences between the two organisms. S. ferax maintains a tip-high gradient of both channel types which is lost after disruption of the actin cytoskeleton. There is significant self-clustering of the channels, as well as interactions between channel types. N. crassa on the other hand does not maintain tip-high gradients, and clustered distributions are observed only for the stretch-activated channels. In terms of physiological roles, evidence is quite strong that the stretch-activated channels function as a growth sensor in S. ferax, but have an unknown function in N. crassa. In both organisms, the potassium permeable channels presumably function in potassium uptake. The differences between these two organisms may be due, in part, to differences in their normal environment: aquatic versus terrestrial. Copyright 1998 Academic Press. 相似文献