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Mycosis fungoides (MF) is a malignant T-cell lymphoma that primarily involves the skin, but may, in its advanced stages, metastasize to internal organs. From autopsy series, CNS involvement of MF can be seen in 14% of patients. We describe the CT and MR findings in three patients with CNS metastases. The images showed various manifestations of CNS MF, including parenchymal homogeneously intensely enhancing masses and ependymal enhancement. The CSF and biopsy results were eventually diagnostic in all three cases. One patient was treated prior to pathologic diagnosis, the other two were treated after diagnosis. The tumor improved following treatment in two patients. Although the imaging findings of CNS MF are nonspecific, they can be the first evidence of the disease. 相似文献
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Human nm23 has been implicated in suppression of metastasis in various cancers, but the underlying mechanism of such activity has not been fully understood. Using Drosophila tracheal system as a genetic model, we examined the function of the Drosophila homolog of nm23, the awd gene, in cell migration. We show that loss of Drosophila awd results in dysregulated tracheal cell motility. This phenotype can be suppressed by reducing the dosage of the chemotactic FGF receptor (FGFR) homolog, breathless (btl), indicating that btl and awd are functionally antagonists. In addition, mutants of shi/dynamin show similar tracheal phenotypes as in awd and exacerbate those in awd mutant, suggesting defects in vesicle-mediated turnover of FGFR in the awd mutant. Consistent with this, Btl-GFP chimera expressed from a cognate btl promoter-driven system accumulate at high levels on tracheal cell membrane of awd mutants as well as in awd RNA duplex-treated cultured cells. Thus, we propose that awd regulates tracheal cell motility by modulating the FGFR levels, through a dynamin-mediated pathway. 相似文献
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Prasad V. Jallepalli Grant W. Brown Marco Muzi-Falconi Deborah Tien Thomas J. Kelly 《Genes & development》1997,11(21):2767-2779
Cyclin-dependent kinases (CDKs) promote the initiation of DNA replication and prevent reinitiation before mitosis, presumably through phosphorylation of key substrates at origins of replication. In fission yeast, the p65cdc18 protein is required to initiate DNA replication and interacts with the origin recognition complex (ORC) and the p34cdc2 CDK. Here we report that p65cdc18 becomes highly phosphorylated as cells undergo the G1→S phase transition. This modification is dependent on p34cdc2 protein kinase activity, as well as six consensus CDK phosphorylation sites within the p65cdc18 polypeptide. Genetic interactions between cdc18+ and the S-phase cyclin cig2+ suggest that CDK-dependent phosphorylation antagonizes cdc18+ function in vivo. Using site-directed mutagenesis, we show that phosphorylation at CDK consensus sites directly targets p65cdc18 for rapid degradation and inhibits its replication activity, as strong expression of a constitutively hypophosphorylated mutant form of p65cdc18 results in large amounts of DNA over-replication in vivo. Furthermore, the over-replication phenotype produced by this mutant p65cdc18 is resistant to increased mitotic cyclin/CDK activity, a known inhibitor of over-replication. Therefore, p65cdc18 is the first example of a cellular initiation factor directly regulated in vivo by CDK-dependent phosphorylation and proteolysis. Regulation of p65cdc18 by CDK phosphorylation is likely to contribute to the CDK-driven “replication switch” that restricts initiation at eukaryotic origins to once per cell cycle. 相似文献
7.
Biochemical and biophysical analysis of heptad repeat regions from the fusion protein of Menangle virus,a newly emergent paramyxovirus 总被引:4,自引:0,他引:4
E. coli in vitro expression system. The GST-removed purified 2-Helix protein could form a stable trimer in vitro judging by gel-filtration and chemical cross-linking. CD spectra showed that the 2-Helix protein had a high percentage of
α-helix and was very thermo-stable. Crystals of the 2-Helix protein preparations have been obtained in many conditions with
hanging-drop diffusion method. These results indicated that Menangle virus has the common features of the fusion protein for
other paramyxoviruses and should adopt a similar fusion mechanism to other members. As the HR regions of Menangle virus F
protein could form stable six-helix bundle coiled coil structure, they should be used as drug target for the design of fusion
inhibitors, as successfully used for other parmyxoviruses. This is especially relevant to such a newly emergent virus with
zoonotic potentials.
Received January 23, 2003; accepted February 28, 2003
Published online April 28, 2003 相似文献
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Huang Tien L. Székács András Uematsu Tamon Kuwano Eiichi Parkinson Andrew Hammock Bruce D. 《Pharmaceutical research》1993,10(5):639-648
Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of -naphthol, -naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of -naphthol were cleaved more rapidly than the corresponding -naphthol isomers by the mammalian liver esterases. -Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis–Menten constant (K
m) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of - and -naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of -naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the - and -naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the -naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a log P value of about 4.0 was observed, after which the enzyme activity decreased. 相似文献
10.
Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection 相似文献