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41.
42.
Joanne I. Brodfuehrer Tracy J. Wilke David H. Kinder Garth Powis 《Cancer chemotherapy and pharmacology》1989,24(5):277-283
Summary The chemical breakdown of carmethizole [1-methyl-2-methylthio-4,5-bis-(hydroxymethyl)imidazole-4,5-bis(N-methylcarbamate)hydrochloride] and its pharmacokinetics in the mouse and beagle dog were studied. Carmethizole was relatively unstable in aqueous media, having a half-life of 1 h in 0.9% sodium chloride, human whole blood, human plasma, and dog urine at 37°C. Its major breakdown product in 0.9% sodium chloride and pH 5.0 sodium phosphate buffer was carmethizole diol. When carmethizole was added to pH 7.0 or pH 9.0 sodium phosphate buffer, the major breakdown product was carmethizole diol-4-monophosphate. Carmethizole reacted directly with glutathione at pH 8.0, forming a glutathione adduct of carmethizole monocarbamate. Elimination of the drug from the plasma of the beagle dog following i.v. bolus doses of 22.4 and 4.3 mg/kg was biphasic. At these doses the terminal half-life was 39 and 46 min, respectively, and the respective total body clearance was 4.6 and 7.7 ml/min per kg. The 22.4 mg/kg dose was lethal to the beagle dog by day 4. Elimination of carmethizole from the plasma of mice following an i. v. bolus dose of 115 mg/kg was monoexponential, with a half-life of 11.6 min and a total body plasma clearance of 43.6 ml/min per kg. When the drug was infused at 230 mg/kg over 8 h into mice, the total body clearance was 40.8 ml/min per kg. Following the i.v. bolus administration of carmethizole to mice, 30% of the total dose was excreted in urine over 3 h as carmethizole diol, 10%, as carmethizole diol-sulfate, 3.4%, as carmethizole 4-monocarbamate, and 2.4%, as unchanged drug. 相似文献
43.
Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks,chromosomal instability,and reduced life span in mice 总被引:1,自引:0,他引:1
Donoho G Brenneman MA Cui TX Donoviel D Vogel H Goodwin EH Chen DJ Hasty P 《Genes, chromosomes & cancer》2003,36(4):317-331
The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51. 相似文献
44.
We present the first case of Holt-Oram syndrome associated with the lethal congenital heart defect of hypoplastic left heart syndrome. The possible pathophysiological link is explored and the need for careful genetic and cardiologic evaluation in these patients is reiterated. 相似文献
45.
46.
Potent inhibition of HIV-1 entry by (s4dU)35 总被引:2,自引:0,他引:2
Horváth A Tokés S Hartman T Watson K Turpin JA Buckheit RW Sebestyén Z Szöllosi J Benko I Bardos TJ Dunn JA Fésüs L Tóth FD Aradi J 《Virology》2005,334(2):214-223
47.
Physical Deletion of the p53 Gene in Bladder Cancer: Detection by Fluorescence in Situ Hybridization 总被引:1,自引:6,他引:1
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Guido Sauter Guoren Deng Holger Moch Russell Kerschmann Kouji Matsumura Sandy De Vries Tracy George Jose Fuentes Peter Carroll Michael J. Mihatsch Frederic M. Waldman 《The American journal of pathology》1994,144(4):756-766
To understand better the role of physical p53 deletion in bladder cancer, 106 formalin-fixed and 45 unfixed bladder tumors were examined using fluorescence in situ hybridization. Probes for centromere 17 and the p53 locus were hybridized simultaneously to interphase tumor cells to analyze p53 and chromosome 17 copy number on a cell by cell basis. 17p deletion was found in four of 43 pTa tumors, 18 of 43 pT1 tumors and 29 of 58 pT2-4 tumors (P = 0.0001). 17p deletion was also highly correlated with grade (P = 0.0001) and with p53 immunostaining (P = 0.0005). Chromosome 17 polysomy was associated with stage, grade, 17p deletions, and p53 immunostaining (P = 0.0001). The strong difference in centromere 17 copy number and 17p deletions between pTa and pT1 tumors supports a relevant biological distinction between pTa and pT1 tumors. 相似文献
48.
Differential Effects of Clostridium difficile Toxins on Tissue-Cultured Cells 总被引:13,自引:4,他引:13
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![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sam T. Donta Nadine Sullivan Tracy D. Wilkins 《Journal of clinical microbiology》1982,15(6):1157-1158
Two immunologically distinct Clostridium difficile toxins elicited similar morphological changes on cultured cells, although there were differences in both toxin potency and cell sensitivities. 相似文献
49.
Somatostatin analogue (octreotide) inhibits bile duct epithelial cell proliferation and fibrosis after extrahepatic biliary obstruction. 总被引:2,自引:0,他引:2
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T. F. Tracy Jr A. J. Tector M. E. Goerke S. Kitchen D. Lagunoff 《The American journal of pathology》1993,143(6):1574-1578
Extrahepatic biliary obstruction leads to bile duct epithelial cell proliferation. Somatostatin and its analogue, octreotide, have been shown to inhibit DNA synthesis and proliferation in hepatocytes. We investigated the effect of octreotide on the biliary epithelial cell proliferative responses to biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial cells, and periportal connective tissue was performed by computerized point counting. Hepatocyte volume was preserved with octreotide treatment, which also significantly decreased bile duct proliferation and periportal extracellular matrix deposition in response to biliary obstruction compared with saline treated, duct-ligated animals. These results indicate that octreotide prevents the morphological changes that accompany extrahepatic biliary obstruction. 相似文献
50.
Regulated expression of the IL-31 receptor in bronchial and alveolar epithelial cells, pulmonary fibroblasts, and pulmonary macrophages. 总被引:1,自引:0,他引:1
Randeep S Jawa Souvik Chattopadhyay Erin Tracy Yanping Wang Kristin Huntoon Merril T Dayton Heinz Baumann 《Journal of interferon & cytokine research》2008,28(4):207-219
Interleukin-31 (IL-31), an IL-6 cytokine family member, is proposed to play a role in animal models of airway hyperreactivity. It is produced by activated T cells and signals via a heterodimeric receptor complex composed of IL-31Ralpha and OSMRbeta. Only low levels of IL-31Ralpha expression have been demonstrated in pulmonary epithelial cell lines, however, and little is known about the ability to regulate its expression and signaling. Therefore, primary cultures of human bronchial and alveolar epithelial cells, pulmonary fibroblasts, pulmonary macrophages, and established lines of immortalized bronchial epithelial cells (HBE) and alveolar carcinoma cells (A549) were analyzed by RT-PCR, immunoblotting, and thymidine incorporation. Distinct, cell type-specific regulation of IL-31Ralpha expression was detected. Transforming growth factor-beta (TGF-beta) enhanced IL-31Ralpha mRNA expression in primary cultures and established lines of epithelial cells, but not in macrophages. In contrast, interferon-gamma (IFN-gamma) induced IL-31Ralpha mRNA expression in macrophages. IL-31Ralpha protein expression was below detection threshold in primary epithelial cell cultures but was detectable in A549 cells and increased with TGF-beta treatment. In HBE and A549 cells, TGF-beta pretreatment increased IL-31-mediated Stat3 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. In A549 cells, TGF-beta magnified IL-31-dependent suppression of proliferation. The data suggest that increased IL-31Ralpha expression correlates with an enhanced response to IL-31. 相似文献