Construction of bacteriophage expressing mouse monoclonal Fab fragments directed against the human MN glycophorin blood group antigens

BACKGROUND: The MN human blood group antigens are complex glycopeptide antigens at the amino terminus of glycophorin A. Many different mouse monoclonal antibodies to these antigens have been produced and characterized. The construction of combinatorial immunoglobulin libraries displaying antibody Fab fragments on the surface of bacteriophage (Fab-phage) represents a novel approach for developing monoclonal reagents, for exploring the diversity of the immune response to specific antigens, and for understanding the molecular basis of the interaction of an antibody with its antigen. However, it is necessary to determine whether Fab fragments displayed on bacteriophage surfaces retain immunologic characteristics similar to the intact antibodies. STUDY DESIGN AND METHODS: Fab-phage were constructed from three anti-N (AH7, N61, and N92) and two anti-M (425/2B and M2A1) murine hybridomas. The Fab-phage and parental hybridomas were compared by enzyme-linked immunosorbent assay, Western blotting, and flow cytometry. RESULTS: In each case, the Fab-phage and its parental hybridoma antibody had similar immunologic characteristics. In particular, their dependence on the pH of the buffer and on sialylation of the target antigen was similar. CONCLUSION: These results suggest that Fab-phage may provide novel reagents with applications in immunohematology and may be useful in the study of the immune response to human blood group antigens.     

N-甲基(3,4-亚甲二氧基苯甲酰)甲基-乙酰胺(SY-640)对化学致癌剂苯并芘与小鼠肝细胞核DNA共价结合的抑制作用

用小鼠肝细胞核制备和肝微粒体制备,研究了化合物SY-640对致癌剂苯并芘(BP)损伤肝细胞核的保护作用及与P-450的关系。结果表明,SY-640可显著抑制³H-BP与小鼠肝细胞核的DNA共价结合。SY-640连续po 3 d,可显著诱导小鼠肝微粒体细胞色素P-450含量及氨基比林脱甲基酶活性;给药1次2h内却只抑制氨基比林脱甲基酶活性。体外温孵实验表明,SY-640对小鼠肝微粒体氨基比林脱甲基酶活性也具有明显的抑制作用。差示光谱分析表明,SY-640可与细胞色素P-450形成络合物。提示该化合物对肝微粒体细胞色素P-450酶系的影响与其对化学致癌剂BP所致肝细胞毒性的保护作用有关。     

Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver

Superparamagnetic iron oxide (ferrite) particles were evaluated as a contrast agent for magnetic resonance (MR) imaging. In this pilot study, doses ranging from 10 to 50 mumol/kg were administered intravenously to 15 patients. Ferrite-enhanced images of the liver obtained with standard pulse sequence techniques significantly increased the number of hepatic lesions detected (P less than .01) and reduced the threshold size for detection to 3 mm (P less than .01). The improved clinical performance of ferrite-enhanced images correlated with significant increases in measured contrast-to-noise ratios (P less than .01). Degradation of superparamagnetic activity and/or clearance of ferrite from the liver was demonstrated as early as 12 hours after injection, suggesting that the lack of chronic toxicity observed in animal studies may be reproduced in humans. These initial clinical results appear to confirm extensive preclinical data indicating that ferrite administered at a dose of 20 mumol/kg has the potential to significantly improve the performance of abdominal MR imaging.     

A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group

The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient- years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)     

抗真菌药物的研究Ⅱ．C－端含氧代赖氨酸二肽的合成及抗白念珠菌活性

引用违法传递概念设计合成了１１个Ｃ－末端含氧代赖氨酸二肽，进行抗深部致病菌－白念珠菌活性试验，体外实验结果显示极强的抑菌活性，ＭＩＣ在１２．５～０．８μｇ／ｄｉｓｋ之间，较母体氧化赖氨酸大５０～１３５倍（克分子比）。