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排序方式: 共有191条查询结果,搜索用时 56 毫秒
11.
Z F Su X Zhang J R Ballinger A M Rauth A Pollak J R Thornback 《Bioconjugate chemistry》1999,10(5):897-904
The presence of hypoxic cells in solid tumors is a marker for therapy-resistant, aggressive disease. The noninvasive detection of hypoxic cells in tumors by radiolabeled 2-nitroimidazoles is a diagnostic technique under current evaluation. Two peptidic agents, dimethylglycyl-L-seryl-L-cysteinyl-lysyl{N(epsilon)-[1-(2-nitro-1H -im idazolyl)acetamido]}glycine (RP435) and dimethylglycyl-tert-butylglycyl-L-cysteinyl-glycine-[2-(2-ni tro-1H-im idazolyl)ethyl]amide (RP535) have been synthesized. Both agents contain an N(3)S class chelator for (99m)Tc and Re and a 2-nitroimidazole group which can be enzymatically reduced and selectively trapped in cells under hypoxic conditions. Two isomers of (99m)TcO-RP435, which are assumed to be syn and anti conformations, were observed on HPLC analysis. The interconversion of the two isomers in aqueous solution was investigated. In contrast, RP535 chelated (99m)Tc to form a single isomer and no conversion to its counterpart has been observed on HPLC analysis. The tert-butyl group on the chelator may inhibit the formation and interconversion of the syn and anti isomers of (99m)TcO-RP535. Both tracers showed a significant degree of hypoxia-specific accumulation in an in vitro assay, with (99m)TcO-RP535 showing higher selectivity for hypoxic cells than (99m)TcO-RP435. These results suggest that (99m)TcO-RP535 represents a lead compound worthy of further investigation as an agent for imaging hypoxia in tumors. 相似文献
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Isolated pancreatic islets from Lewis rats were stored at 4 °C for periods up to 96 hr. A normal pattern of insulin secretion in response to high glucose concentrations was demonstrated in islets stored for up to 48 hr but not in islets stored for longer than this time. The 4 °C environment may be adequate for temporary storage of isolated pancreatic islets but is not suitable for their long-term preservation. 相似文献
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Aronoff DM Peres CM Serezani CH Ballinger MN Carstens JK Coleman N Moore BB Peebles RS Faccioli LH Peters-Golden M 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(3):1628-1634
PGI(2) (prostacyclin) is a lipid mediator with vasodilatory and antithrombotic effects used in the treatment of vasoconstrictive/ischemic diseases including pulmonary artery hypertension. However, emerging research supports a role for PGs, including PGI(2), in the regulation of both innate and acquired immunity. As PGI(2) is unstable, we sought to define the effects of various PGI(2) analogs on resident alveolar macrophage (AM) and peritoneal macrophage (PM) innate immune functions. The effects of iloprost, carbaprostacyclin, and treprostinil on the regulation of phagocytosis, bacterial killing, and inflammatory mediator production were determined in both macrophage populations from rats. Iloprost failed to suppress AM functions to the same degree that it did in PMs, a characteristic shared by carbaprostacyclin. This difference reflected greater expression of the G(alphas) protein-coupled I prostanoid receptor and greater cAMP generation in PMs than AMs. Treprostinil inhibited phagocytosis, bacterial killing, and cytokine generation in AMs to a much greater degree than the other PGI(2) analogs and more closely resembled the effects of PGE(2). Studies with the E prostanoid (EP) 2 receptor antagonist AH-6809 and EP2-null macrophages indicated that this was due in part to the previously unknown ability of treprostinil to stimulate the EP2 receptor. The present investigation for the first time identifies differences in immunoregulatory properties of clinically administered PGI(2) analogs. These studies are the first to explore the capacity of PGI(2) to regulate bacterial killing and phagocytosis in macrophages, and our findings may hold important consequences regarding the risk of infection for patients receiving such agents. 相似文献
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Azooz OG Farthing MJ Savage MO Ballinger AB 《American journal of physiology. Regulatory, integrative and comparative physiology》2001,281(5):R1483-R1491
Delayed puberty is a frequent complication of inflammatory bowel disease. The precise etiological mechanisms are not known. In this study, we wanted to determine the relative contribution of undernutrition and inflammation to delayed puberty and the effect of inflammation on the reproductive axis. Puberty was assessed in rats with 2,4,6-trinitrobenzenesulfonic acid induced-colitis, healthy controls, and animals pair fed to match the food intake of the colitic group. The response to testosterone administration was assessed in colitic rats. We found that induction of colitis was associated with hypophagia and reduced weight gain, and undernutrition in healthy females (i.e., pair fed) resulted in a delay in the onset (by 4.8 days, P < 0.001) and progression of puberty (normal estrous cycles in 42%, P = 0.04) compared with controls. However, puberty was further delayed in the colitic group (1.4 days after pair fed) with the absence of normal estrous cycling in all rats. In males, the onset of puberty was also delayed, and weights of accessory sex organs were reduced compared with pair-fed controls. Plasma testosterone concentrations were low, and gonadotropin concentrations were normal in colitic rats. Testosterone treatment normalized puberty in male rats with colitis. In conclusion, in rats with experimental colitis, inflammation appears to potentiate the effect of undernutrition on puberty. The weights of secondary sex organs and the onset of puberty were normalized by testosterone treatment. 相似文献
18.
The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins 总被引:1,自引:0,他引:1
Connell P Ballinger CA Jiang J Wu Y Thompson LJ Höhfeld J Patterson C 《Nature cell biology》2001,3(1):93-96
To maintain quality control in cells, mechanisms distinguish among improperly folded peptides, mature and functional proteins, and proteins to be targeted for degradation. The molecular chaperones, including heat-shock protein Hsp90, have the ability to recognize misfolded proteins and assist in their conversion to a functional conformation. Disruption of Hsp90 heterocomplexes by the Hsp90 inhibitor geldanamycin leads to substrate degradation through the ubiquitin-proteasome pathway, implicating this system in protein triage decisions. We previously identified CHIP (carboxyl terminus of Hsc70-interacting protein) to be an interaction partner of Hsc70 (ref. 4). CHIP also interacts directly with a tetratricopeptide repeat acceptor site of Hsp90, incorporating into Hsp90 heterocomplexes and eliciting release of the regulatory cofactor p23. Here we show that CHIP abolishes the steroid-binding activity and transactivation potential of the glucocorticoid receptor, a well-characterized Hsp90 substrate, even though it has little effect on its synthesis. Instead, CHIP induces ubiquitylation of the glucocorticoid receptor and degradation through the proteasome. By remodelling Hsp90 heterocomplexes to favour substrate degradation, CHIP modulates protein triage decisions that regulate the balance between protein folding and degradation for chaperone substrates. 相似文献
19.
Cloning and sequencing of the peroxisomal amine oxidase gene from Hansenula polymorpha 总被引:7,自引:0,他引:7
P G Bruinenberg M Evers H R Waterham J Kuipers A C Arnberg G AB 《Biochimica et biophysica acta》1989,1008(2):157-167
We have cloned the AMO gene, encoding the microbody matrix enzyme amine oxidase (EC 1.4.3.6) from the yeast Hansenula polymorpha. The gene was isolated by differential screening of a cDNA library, immunoselection, and subsequent screening of a H. polymorpha genomic library. The nucleotide sequence of a 3.6 kilobase stretch of DNA containing the amine oxidase (AMO) gene was determined. The AMO gene contains an open reading frame of 692 amino acids, with a relative molecular mass of 77,435. The 5' and 3' ends of the gene were mapped and show that the transcribed region measures 2134 nucleotides. The derived amino-acid sequence was confirmed by sequencing an internal proteolytic fragment of the purified protein. Amine oxidase contains the tripeptide sequence Ser-Arg-Leu, located 9 residues from the carboxy terminus, which may represent the topogenic signal for protein import into microbodies. 相似文献
20.
The structure of human mitochondrial DNA variation 总被引:20,自引:0,他引:20
D. Andrew Merriwether Andrew G. Clark Scott W. Ballinger Theodore G. Schurr Himla Soodyall Trefor Jenkins Stephen T. Sherry Douglas C. Wallace 《Journal of molecular evolution》1991,33(6):543-555
Summary Restriction analysis of mitochondrial DNA (mtDNA) of 3065 humans from 62 geographic samples identified 149 haplotypes and 81 polymorphic sites. These data were used to test several aspects of the evolutionary past of the human species. A dendrogram depicting the genetic relatedness of all haplotypes shows that the native African populations have the greatest diversity and, consistent with evidence from a variety of sources, suggests an African origin for our species. The data also indicate that two individuals drawn, at random from the entire sample will differ at approximately 0.4% of their mtDNA nucleotide sites, which is somewhat higher than previous estimates. Human mtDNA also exhibits more interpopulation heterogeneity (GST=0.351±0.025) than does nuclear DNA (GST=0.12). Moreover, the virtual absence of intermediate levels of linkage disequilibrium between pairs of sites is consistent with the absence of genetic recombination and places constraints on the rate of mutation. Tests of the selective neutrality of mtDNA variation, including the Ewens-Watterson and Tajima tests, indicate a departure in the direction consistent with purifying selection, but this departure is more likely due to the rapid growth of the human population and the geographic heterogeneity of the variation. The lack of a good fit to neutrality poses problems for the estimation of times of coalescence from human mtDNA data. 相似文献