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D H Russell N E Zorn A R Buckley P D Crowe M D Sauro E M Hadden R V Farese H E Laird 《European journal of pharmacology》1990,188(2-3):139-152
Prolactin (PRL) and other trophic factors rapidly activate a nuclear pool(s) of protein kinase C (nPKC) in purified splenocyte nuclei. The PRL also enhanced [2-3H]glycerol incorporation into nuclear mono- and triacylglycerol. An assay was devised which not only probed the ability of the hormone to activate protein kinase C (PKC) but also demonstrated the presence of nuclear substrates. Using this methodology, a biphasic concentration-response curve to PRL was observed. Heterologous species of PRL and various growth factors also activated nPKC. The PRL-induced nPKC stimulation was antagonized by various immunomodulators, G protein-coupling inhibitors, PKC inhibitors, a calmodulin inhibitor, and a peripheral benzodiazepine agonist and antagonist. A monoclonal antibody to PKC, anti-rat PRL antiserum and a monoclonal anti-rat PRL receptor antibody antagonized PRL-induced PKC-dependent nuclear phosphorylation, further implicating nPKC and a PRL receptor-mediated activation process. Nuclear PKC may be a major target for trophic regulation in response to both positive and negative growth signals. 相似文献
3.
As knowledge of the human genome continues to grow, more progress is being made towards not only identifying the genes involved in disease susceptibility but also in defining the synergistic role genes play with environmental exposures. The detection of gene‐environment interactions is important as it can offer clinicians a potential means of intervention. The discovery of interactions relies heavily on powerful statistical methods. We present a test, FBAT‐I, that can be used to investigate gene‐environment interaction. The test uses the case‐parent triad design and protects the statistical inference from potential spurious results due to population admixture. 相似文献
4.
Ralls PW; Johnson MB; Kanel G; Dobalian DM; Colletti PM; Boswell WD Jr; Radin DR; Halls JM 《Radiology》1986,161(2):451-454
FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease. 相似文献
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顾性初 《中国医药工业杂志》1995,(11)
抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Berthelot试剂在96孔培养板上检测重组脲酶活性,其灵敏度指标酚红法每mg酶蛋白引起的每分钟吸光度变化。△A为6.9,而Berthelot法每mg酶蛋白引起的每分钟吸光度比值变化△A为313。结果表明用Berthelot试剂检测重组脲酶活性适宜在96孔培养板上大规模筛选天然产物中的脲酶抑制剂。 相似文献
7.
C. Laird Birmingham 《Canadian Medical Association journal》1994,150(8):1276-1277
8.
Gerald L DeNardo Arutselvan Natarajan Saphon Hok Julie Perkins Monique Cosman Sally J DeNardo Felice C Lightstone Gary R Mirick Laird A Miers Rodney L Balhorn 《Journal of nuclear medicine》2007,48(8):1338-1347
Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting. 相似文献
9.
Genotype-phenotype correlation for nucleotide substitutions in the IgII- IgIII linker of FGFR2 总被引:6,自引:3,他引:3