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排序方式: 共有1767条查询结果,搜索用时 15 毫秒
1.
Holly A. Ingraham Mehran Goulian 《Biochemical and biophysical research communications》1982,109(3):746-752
Deoxyuridine triphosphatase has been purified from cultured human lymphoid cells in high yield and stable form by a relatively simple procedure. The properties differed somewhat from those reported previously, e.g. apparent Km, molecular weight, and effects of divalent metals. No other naturally occurring dNTP or NTP serves as substrate, however, the enzyme may be an important site of interaction with intracellular derivatives of analogues of dUrd. It is shown here that deoxyuridine triphosphatase acts on araUTP, 6-azadUTP, 2′-FdUTP, and 2′,3′-dideoxyUTP, but the enzyme has no effect on 5-C1dUTP, 5-BrdUTP, 5-HgdUTP and dUrd-5′[α-thio]triphosphate. For the preparation of one of the analogues, the enzyme, trans-N-deoxyribosylase, from Lactobacillus, was used to prepare the deoxynucleoside from the base, a procedure that may have general usefulness. 相似文献
2.
Jonathan T. Sims Sourik S. Ganguly Holly Bennett J. Woodrow Friend Jessica Tepe Rina Plattner 《PloS one》2013,8(1)
Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression. In this report, we demonstrate that the c-Abl/Arg inhibitor, imatinib (imatinib mesylate, STI571, Gleevec), reverses intrinsic and acquired resistance to the anthracycline, doxorubicin, by inducing G2/M arrest and promoting apoptosis in cancer cells expressing highly active c-Abl and Arg. Significantly, imatinib prevents intrinsic resistance by promoting doxorubicin-mediated NF-κB/p65 nuclear localization and repression of NF-κB targets in a STAT3-dependent manner, and by preventing activation of a novel STAT3/HSP27/p38/Akt survival pathway. In contrast, imatinib prevents acquired resistance by inhibiting upregulation of the ABC drug transporter, ABCB1, directly inhibiting ABCB1 function, and abrogating survival signaling. Thus, imatinib inhibits multiple novel chemoresistance pathways, which indicates that it may be effective in reversing intrinsic and acquired resistance in cancers containing highly active c-Abl and Arg, a critical step in effectively treating metastatic disease. Furthermore, since imatinib converts a master survival regulator, NF-κB, from a pro-survival into a pro-apoptotic factor, our data suggest that NF-κB inhibitors may be ineffective in sensitizing tumors containing activated c-Abl/Arg to anthracyclines, and instead might antagonize anthracycline-induced apoptosis. 相似文献
3.
Retrovirus-induced feline pure red cell aplasia: the kinetics of erythroid marrow failure 总被引:2,自引:0,他引:2
Cats viremic with feline leukemia virus subgroup C (FeLV-C) develop pure red cell aplasia (PRCA) characterized by the loss of detectable late erythroid progenitors (CFU-E) in marrow culture. Normal numbers of early erythroid progenitors (BFU-E) and granulocyte-macrophage progenitors (CFU-GM) remain, suggesting that the maturation of BFU-E to CFU-E is impaired in vivo. We have examined the cell cycle kinetics of BFU-E and their response to hematopoietic growth factor(s) to better characterize erythropoiesis as anemia develops. Within 3 weeks of FeLV-C infection, yet 6-42 weeks before anemia, the traction of BFU-E in DNA synthesis as determined by tritiated thymidine suicide increased to 43 +/- 4% (normal 23 +/- 2%) while there was no change in the cell cycle kinetics of CFU-GM. In additional studies, we evaluated the response of marrow to the hematopoietic growth factor(s) present in medium conditioned by FeLV-infected feline embryonic fibroblasts (FEA/FeLV CM). With cells from normal cats or cats viremic with FeLV-C but not anemic, a 4-fold increase in erythroid bursts was seen in cultures with 5% FEA/FeLV CM when compared to cultures without CM. However, just prior to the onset of anemia, when the numbers of detectable CFU-E decreased, BFU-E no longer responded to FEA/FeLV CM in vitro. BFU-E from anemic cats also required 10% cat or human serum for optimal in vitro growth. These altered kinetics and in vitro growth characteristics may relate to the in vivo block of BFU-E differentiation and PRCA. Finally, when marrow from cats with PRCA was placed in suspension culture for 2 to 4 days in the presence of cat serum and CM, the numbers of BFU-E increased 2- to 4-fold although no CFU-E were generated. By 4 to 7 days, CFU-E were detected, suggesting that conditions contributing to the block of erythroid maturation did not persist. The suspension culture technique provides an approach to study further the defect in erythroid differentiation characteristic of feline PRCA. 相似文献
4.
Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins 总被引:301,自引:0,他引:301
T R Mosmann H Cherwinski M W Bond M A Giedlin R L Coffman 《Journal of immunology (Baltimore, Md. : 1950)》1986,136(7):2348-2357
A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed. 相似文献
5.
Elisabeth Steichen-Gersdorf Holly H. Gallion Deborah Ford Catherine Girodet Douglas F. Easton Richard A. DiCioccio Gareth Evans Margaret A. Ponder Carole Pye Sylvie Mazoyer Tetsuro Noguchi Fabienne Karengueven Hagay Sobol A. Hardouin Yves-Jean Bignon M. Steven Piver Simon A. Smith Bruce A. J. Ponder 《American journal of human genetics》1994,55(5):870-875
In a study of nine families with “site-specific” ovarian cancer (criterion: three or more cases of epithelial ovarian cancer and no cases of breast cancer diagnosed at age <50 years) we have obtained evidence of linkage to the breast-ovarian cancer susceptibility gene, BRCA1 on 17q12-21. If the risk of cancer in these families is assumed to be restricted to the ovary, the best estimate of the proportion of families linked to BRCA1 is .78 (95% confidence interval .32–1.0). If predisposition to both breast and ovarian cancer is assumed, the proportion linked is 1.0 (95% confidence interval .46–1.0). The linkage of familial site-specific ovarian cancer to BRCA1 indicates the possibility of predictive testing in such families; however, this is only appropriate in families where the evidence for linkage to BRCA1 is conclusive. 相似文献
6.
M. Hollsi Zs. Majer A. Z. Rnai A. Magyar K. Medzihradszky S. Holly A. Perczel G. D. Fasman 《Biopolymers》1994,34(2):177-185
Comparative CD and Fourier transform ir (FTIR) spectroscopic data on N-Boc protected linear peptides with or without the (Pro-Gly) β-turn motif (e.g., Boc-Tyr-Pro-Gly-Phe-Leu-OH and Boc-Tyr-Gly-Pro-Phe-Leu-OH) are reported herein. The CD spectra, reflecting both backbone and aromatic contributions, were not found to be characteristic of the presence of β-turns. In the amide I region of the FTIR spectra, analyzed by self-deconvolution and curve-fitting methods, the β-turn band shewed up between 1639 and 1633 cm?1 in trifluoroethanol (TFE) but only for models containing the (Pro-Gly) core. This band war-also present in the spectra in chloroform but absent in dimethylsulfoxide. These findings, in agreement with recent ir data on cyclic models and 310-helical polypeptides and protein in D2O [see S. J. Prestrelski, D. M. Byler, and M. P. Thompson (1991), International Journal of Peptide and Protein Research, Vol. 37, pp. 508–512; H. H. Mantsch, A. Perczel. M. Hollósi, and G. D. Fasman (1992), FASEB Journal, Vol. 6, p. A341; H. H. Mantsch. A. Perczel, M. Hollósi, and G. Fasman (1992), Biopolymers. Vol. 33, pp. 201–207; S. M. Miick, G. V. Martinez, W. R. Fiori, A. P. Tedd, and G. L. Millhauser (1992). Nature, Vol. 359, pp. 653–655], suggest that the amide I band, with a major contribution from the acceptor C ? O of the 1 ← 4 intramolecular H bond of β-turns, appears near or below 1640 cm?1, rather than above 1660 cm?1. In TFE, bands between 1670 and 1660 cm?1 are mainly due to “free” carbonyls, that is, C ? O's of amides that are solvated but not involved in the characteristic H bonds of periodic secondary structures or β-turns. © 1994 John Wiley & Sons, Inc. 相似文献
7.
8.
Galls produced by the cecidomynd Lastoptera ephedncola on Ephedia trifurca always have a black ring associated with them while galls produced by the congener L ephedrae never do Black ring material after microscopic examination and culture proved to be Aureobasidium pullulans In addition to lacking black ring material neither L ephedrae galls nor healthy stems consistently yielded Aureobasidium on culture Gall and larva size measurements indicated that continued larval presence is not necessary for gall development, suggesting fungus initiated gall formation However inoculation of healthy stems with Aureobasidium caused lesions hut not galls The mycelium m galls did not appear grazed and neither larvae nor pupae contained Aureobasidium propagules suggesting that larvae do not feed directly on fungi These data also suggest that there is no trans-pupal passage of fungus from larvae or pupae to adults Newly emerged females do not carry fungal propagules suggesting that thcy are not inoculated upon exiting the gall Gall position leaf culture and stem culture data suggest that the fungus is picked up from leaves prior to oviposition 相似文献
9.
Holly L. Neibergs Daniel S. Gallagher Michel Georges Leslie S. Sargeant Allan B. Dietz James E. Womack 《Mammalian genome》1993,4(6):328-332
The gene for the -A subunit of inhibin (INHBA) was assigned to bovine syntenic group U13 by bovine x rodent hybrid somatic cells and the polymerase chain reaction (PCR). A 482-bp PCR fragment was used to clone a 37-kb cosmid. This cosmid was assigned to bovine Chromosome (Chr) 4 (BTA 4) by fluorescence in situ hybridization (FISH). This is the first assignment of a U13 marker to a bovine chromosome. A restriction fragment length polymorphism (RFLP) was detected with PstI within the INHBA cosmid. 相似文献
10.
Three loci in the genome of the white-footed mouse, Peromyscus leucopus, were examined for the presence or absence of orthologous copies of the retrovirus-like element mys using polymerase chain reaction. We examined these loci in 28 mice collected throughout the P. leucopus species range. Mys insertions were present in only one of the individuals examined at the mys-1 and mys-7 loci. Conversely, the mys-6 element was found in several individuals, but the presence of this element was limited to northern latitudes. Because the
long terminal repeats (LTRs) of a given element are expected to be identical at the time of retrotransposition into the genome,
and to accumulate changes over evolutionary time, within-element LTR sequence comparisons can be used to estimate the relative
age of insertions. Within-element LTR differences are greater in mys-6 than in mys-1 or mys-7. The LTRs from orthologous mys-6 elements of six mice were sequenced. The alignment revealed 13 of the 22 differences between the right and left LTRs that
were shared by all orthologous mys-6 sites, suggesting that relative to its time of insertion into the genome, mys-6 has only recently spread across the northern part of the species range.
Received: 23 January 1996 / Accepted: 24 April 1996 相似文献