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111.
Schröder C Pierson RN Nguyen BN Kawka DW Peterson LB Wu G Zhang T Springer MS Siciliano SJ Iliff S Ayala JM Lu M Mudgett JS Lyons K Mills SG Miller GG Singer II Azimzadeh AM DeMartino JA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(4):2289-2299
Pharmacologic antagonism of CCR5, a chemokine receptor expressed on macrophages and activated T cells, is an effective antiviral therapy in patients with macrophage-tropic HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this regard, the recruitment of CCR5-bearing cells into clinical allografts is a hallmark of acute rejection and may anticipate chronic rejection, whereas conventionally immunosuppressed renal transplant patients homozygous for a nonfunctional Delta32 CCR5 receptor rarely exhibit late graft loss. Therefore, we explored the effects of a potent, highly selective CCR5 antagonist, Merck's compound 167 (CMPD 167), in an established cynomolgus monkey cardiac allograft model. Although perioperative stress responses (fever, diminished activity) and the recruitment of CCR5-bearing leukocytes into the graft were markedly attenuated, anti-CCR5 monotherapy only marginally prolonged allograft survival. In contrast, relative to cyclosporine A monotherapy, CMPD 167 with cyclosporine A delayed alloantibody production, suppressed cardiac allograft vasculopathy, and tended to further prolong graft survival. CCR5 therefore represents an attractive therapeutic target for attenuating postsurgical stress responses and favorably modulating pathogenic alloimmunity in primates, including man. 相似文献
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Vilotti S Biagioli M Foti R Dal Ferro M Lavina ZS Collavin L Del Sal G Zucchelli S Gustincich S 《Cell death and differentiation》2012,19(3):488-500
TRAF and TNF receptor-associated protein (TTRAP) is a multifunctional protein that can act in the nucleus as a 5'-tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling. In this paper we show that in response to proteasome inhibition TTRAP accumulates in nucleolar cavities in a promyelocytic leukemia protein-dependent manner. In the nucleolus, TTRAP contributes to control levels of ribosomal RNA precursor and processing intermediates, and this phenotype is independent from its 5'-tyrosyl DNA phosphodiesterase activity. Our findings suggest a previously unidentified function for TTRAP and nucleolar cavities in ribosome biogenesis under stress. 相似文献
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Transactivation properties of c-Myb are critically dependent on two SUMO-1 acceptor sites that are conjugated in a PIASy enhanced manner. 总被引:4,自引:0,他引:4
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The mono- (2) and bis-phosphate (3) derivatives of D-threo-2,5-hexodiulose (1) (5-keto-D-fructose) were synthesized enzymically and purified by anion-exchange chromatography. The proportions, sizes of ring, and anomeric configurations were determined by F.t. 31P- and 13C-n.m.r. spectroscopy. Compound 2 was found to exist preponderantly (70-78%) in the beta-pyranose form with the remainder existing in the 2R,5R-furanose form. Compound 3 assumes two different furanose forms in solution, one (77-84%) being the 2R,5R-furanose form and the other the 2S,5R-furanose form. 相似文献
120.
Masahiro Yao Farida Latif Mary Lou Orcutt Igor Kuzmin Thomas Stackhouse Fang wei Zhou Kalman Tory Fuh mei Duh Frances Richards Eamonn Maher Sal LaForgia Kay Huebner Denis Le Pasilier Marston Linehan Michael Lerman Berton Zbar 《Human genetics》1993,92(6):605-614
Von Hippel-Lindau disease (VHL) is an inherited multisystem neoplastic disorder. We prepared a 2.5-megabase (Mb) restriction map of the region surrounding the VHL gene and identified and characterized overlapping deletions in three unrelated patients affected with VHL. The smallest nested deletion (100 kb) was located within a 510-kb NruI fragment detected by 19–63. The rearrangements detected will be useful in isolating and evaluating candidate cDNAs for the VHL gene. The detailed physical map will be useful in studying the organization and structure of genes in the VHL region. 相似文献