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The common B-chronic lymphocytic leukemia (B-CLL) antigen (cCLLa) appears to be ideal for targeted immunotherapy in that it is the most prevalent and disease-restricted marker in B-CLL. To assess this potential, we developed four immunotoxins (ITs) of anti-cCLLa monoclonal antibody CLL2m (an IgG2a kappa), using ricin chain A (RTA) or its deglycosylated derivative (dgA), each conjugated to either the whole IgG molecule or its Fab' fragment. Each IT was tested in vitro for specificity and cytotoxic activity (assessed by protein synthesis inhibition [PSI] and by cell kill [CK] in the clonogenic assay) against B-CLL cells. RTA-based anti-CD5 ITs and enriched normal B and T lymphocytes were used as controls. Each IT exhibited antigen-specific, dose-dependent activity. Thus, whereas B-CLL cells exhibited dose- dependent PSI and CK (whether the B-CLL clone was CD5+ or CD5-), normal B (cCLLa-/CD5-) and T lymphocytes (cCLLa-/CD5+) remained unaffected. IT potency was independent of toxin glycosylation, but was slightly influenced by antibody valence; divalent ITs were twice as potent as monovalent ITs (IC50, 2.3 v 7.1 x 10(-11) mol/L; CK, 2.6- v 2.0-log reached with 524 v 1,072 IT molecules bound/cell, respectively). In the presence of ammonium chloride or Verapamil, IT-induced CK was enhanced 10- to 80-fold. These data suggest that the cCLLa is a promising target for IT-based immunotherapy of B-CLL in vivo and ex vivo. 相似文献
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Features of Aicardi's syndrome include infantile spasms associated with pathognomonic chorioretinopathy, abnormalities of the corpus callosum with heterotopia of gray matter, and characteristic electroencephalographic findings. Vertebral abnormalities are also part of the syndrome, which is apparently limited to female infants. Subnormal mental development appears in all cases. It was first described in 1969 in French. Isolated cases in the literature have been associated with facial asymmetry, plagiocephaly, and the Dandy-Walker syndrome. Experience with two patients suggests that a search for cases among patients with chorioretinopathy and infantile spasms will show the syndrome to be more common than currently reported. 相似文献
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血浆中去甲地西泮及代谢物奥沙西泮的HPLC测定方法和大鼠口服药代动力学 总被引:2,自引:0,他引:2
采用高效液相色谱法测定去甲地西泮(去甲安定)及其代谢产物奥沙西泮。以RP-C18为固定相,乙腈—0.01mol·L-1醋酸钠(pH3.8,33.3:66.6)为流动相,地西泮为内标物,紫外波长240nm处定量测定。去甲地西泮、奥沙西泮和内标物的保留时间分别为2.8min,4.85min和8.5min;绝对回收率分别为74%,86%和86%。奥沙西泮在35.3~2260ng·ml-1,去甲地西泮在20~2560ng·ml-1血浆浓度范围内线性关系良好,r=0.9997和r=0.9998。二药的最低检测浓度分别为10ng·ml、和7ng·ml-1;日内和日间相对标准偏差(RSD)均分别小于6%和10%(n=5)。多种常用药物对样品的色谱峰无干扰。并用此法研究了大鼠单次口服去甲地西泮的药代动力学。 相似文献
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Intra-articular calcification in scleroderma 总被引:1,自引:0,他引:1