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11.
Michon J; Moutel S; Barbet J; Romet-Lemonne JL; Deo YM; Fridman WH; Teillaud JL 《Blood》1995,86(3):1124-1130
Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo. 相似文献
12.
目的:检测转化生长因子β1在腹膜透析大鼠腹膜内表达,并探讨其在腹膜纤维化中的意义。方法:实验于2005-06/2006-03在中南大学湘雅二医院肾内科实验室完成。①实验材料:雄性SD大鼠,体质量180~240g,由中南大学湘雅二医院动物实验中心提供。②实验方法:将28只大鼠按随机数字表随机分为4组,每组7只。正常对照组不予任何干预;生理盐水组腹腔注射20mL生理盐水;低糖透析液组腹腔注射20mL1.5%葡萄糖透析液;高糖透析液组腹腔注射20mL4.25%葡萄糖透析液,均为1次/d。4周后,向大鼠腹腔注射4.25%葡萄糖腹膜透析液20mL,4h后于大鼠右下腹缓慢插入带有多个侧孔的10号静脉留置针,缓慢低位引流腹透液,量取引流液。③实验评估:取大鼠壁层腹膜组织,以苏木素-伊红染色,镜下测量腹膜厚度,采用免疫组织化学方法检测大鼠腹膜中转化生长因子β1及纤连蛋白。结果:28只大鼠均进入结果分析。①高糖透析液组、低糖透析液组超滤量均明显低于正常对照组与生理盐水组,并且高糖透析液组超滤量明显少于低糖透析液组(P均<0.05)。②高糖透析液组腹膜明显增厚,表面粗糙,间皮细胞肿胀,脱落,间皮下有大量血管生成以及胶原纤维沉积,还可见单核细胞等炎症细胞浸润,与其他组比较,腹膜厚度明显增加(P<0.05)。③高糖透析液组转化生长因子β1、纤连蛋白表达量均明显高于其他组;低糖透析液组转化生长因子β1、纤连蛋白表达量均明显高于正常对照组与生理盐水组(P<0.05)。④大鼠腹膜组织转化生长因子β1蛋白与纤连蛋白表达量、腹膜厚度之间呈明显的正相关(r=0.86,0.83,P<0.05)。结论:葡萄糖透析液可诱导腹膜组织转化生长因子β1明显上调,腹膜转化生长因子β1高表达与腹膜透析腹膜纤维化密切相关。 相似文献
13.
We report a case of cerebral dural sinus thrombosis presenting as acute subarachnoid haemorrhage and clinically mimicking an aneurysmal bleed. Awareness of this rare initial presentation of cerebral venous thrombosis is important and should be considered in the diagnostic work‐up of acute subarachnoid haemorrhage. The radiologist plays a crucial role in making this often unsuspected but important diagnosis to enable prompt appropriate treatment. 相似文献
14.
Wu DC; Liu JM; Chen YM; Yang S; Liu SM; Chen LT; Whang-Peng J 《Japanese journal of clinical oncology》1997,27(2):115-118
Hemolytic uremic syndrome spontaneously arises in a few patients with
advanced cancer, but it is more commonly related to the use of certain
chemotherapeutic agents. Mitomycin-C is, etiologically, the most common
causative agent inducing hemolytic uremic syndrome, in a dose dependent
manner. We report this syndrome, attributable to mitomycin-C at a
cumulative dose of 40 mg/m2, in a gastric cancer patient. A 42-year-old
female with stage III gastric cancer underwent radical gastrectomy and was
given mitomycin-C at 10 mg/m2 intravenously every four weeks as adjuvant
therapy. Hemolytic uremic syndrome was diagnosed three months after the
last dose of mitomycin-C administration. The most prominent symptoms
included pallor, hypertension and anasarca, with laboratory evidence of
microangiopathic hemolytic anemia, azotemia and hyperkalemia. Her disease
was progressive, but fortunately stabilized after staphylococcus column A
dialysis. Her disease remained in remission for 24 months from the time of
diagnosis, and then relapsed in the form of peritoneal carcinomatosis with
partial intestinal obstruction.
相似文献
15.
Prevalence and aetiology of neurological impairment in extremely low birthweight infants 总被引:2,自引:0,他引:2
J WAUGH MJ O'CALLAGHAN DI TUDEHOPE HA MOHAY YR BURNS PH GRAY YM ROGERS 《Journal of paediatrics and child health》1996,32(2):120-124
Objective : To determine the prevalence and perinatal predictors of cerebral palsy, intellectual impairment, visual impairment and deafness in a cohort of extremely low birthweight (ELBW) infants at two years of age.
Methodology : The study population comprised 199 of the 224 (89%) ELBW infants managed at the Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who survived to two years. The prevalence of cerebral palsy, intellectual impairment, blindness and deafness was measured by clinical, psychometric and audiological assessment and the association with 24 risk factors examined.
Results : Cerebral palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis and multiple birth, though only ventricular dilatation (OR 4.41; 95% Cl 1.32-14.8) remained significant in the adjusted analysis. Intellectual impairment occurred in 20 children (10%) and was independently associated with ventricular dilatation (OR 15.0; 95% Cl 2.2-102.8), ventilation Fi O2 >80% (OR 3.4; 95% Cl 1.01-11.5), vaginal delivery (OR 3.5; 95% Cl 1.09-11.4) and male sex (OR 6.1; 95% Cl 1.67-22.3). No perinatal predictor was statistically associated with risk of deafness. Retinopathy of prematurity (OR 36.9; 95% Cl 2.8-495.5) was associated with risk of later visual impairment.
Conclusions : Intellectual impairment was associated with a broad range of perinatal variables. Cerebral palsy was associated with fewer variables, all of which were also associated with intellectual impairment. Neurologic injury was associated with male sex and multiple birth, which are not biological insults themselves, but may be markers of susceptibility to injury. 相似文献
Methodology : The study population comprised 199 of the 224 (89%) ELBW infants managed at the Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who survived to two years. The prevalence of cerebral palsy, intellectual impairment, blindness and deafness was measured by clinical, psychometric and audiological assessment and the association with 24 risk factors examined.
Results : Cerebral palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis and multiple birth, though only ventricular dilatation (OR 4.41; 95% Cl 1.32-14.8) remained significant in the adjusted analysis. Intellectual impairment occurred in 20 children (10%) and was independently associated with ventricular dilatation (OR 15.0; 95% Cl 2.2-102.8), ventilation F
Conclusions : Intellectual impairment was associated with a broad range of perinatal variables. Cerebral palsy was associated with fewer variables, all of which were also associated with intellectual impairment. Neurologic injury was associated with male sex and multiple birth, which are not biological insults themselves, but may be markers of susceptibility to injury. 相似文献
16.
17.
Tousled-like kinase functions with the chromatin assembly pathway regulating nuclear divisions
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Carrera P Moshkin YM Gronke S Sillje HH Nigg EA Jackle H Karch F 《Genes & development》2003,17(20):2578-2590
Tousled-like kinases (TLKs) constitute a family of serine/threonine kinases conserved in plants and animals that act in a cell cycle-dependent manner. In mammals, their activity peaks during S phase, when they phosphorylate the antisilencing function protein 1 (ASF1), a histone chaperone involved in replication-dependent chromatin assembly. Here, we show that Drosophila ASF1 is also a phosphorylation target of TLK, and that the two components cooperate to control chromatin replication in vivo. By altering TLK activity through loss-of-function mutations, we show that nuclear divisions are arrested at interphase, followed by apoptosis. Overexpression of TLK alters the chromatin structure, suggesting that TLK mediates the activity of chromatin proteins. These results suggest that TLK coordinates cell cycle progression through the regulation of chromatin dynamics. 相似文献
18.
Moshkin YM Armstrong JA Maeda RK Tamkun JW Verrijzer P Kennison JA Karch F 《Genes & development》2002,16(20):2621-2626
De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophila asf1 gene derepress silencing at heterochromatin and that the ASF1 protein has a cell cycle-specific nuclear and cytoplasmic localization. Furthermore, using both genetic and biochemical methods, we demonstrate that ASF1 interacts with the Brahma (SWI/SNF) chromatin-remodelling complex. These findings suggest that ASF1 plays a crucial role in both chromatin assembly and SWI/SNF-mediated chromatin remodelling. 相似文献
19.
Automated reinfusion of autoerythrocytes prepared from blood lost during removal of tumors was the main component of transfusion therapy in 49 patients (52 operations) with brain tumors. All patients developed massive blood loss of 0.5-5 TCB during the intervention, reinfusion device cell saver C.A.T.S 2-02 (Fresenius, Germany) was used. Various aspects of clinical application of this method are discussed, its efficiency and factors affecting it are analyzed. Special attention is paid to time course of hemostasis values during automated reinfusion and the problem of tumor contamination of reinfused suspension. This latter problem was solved by using the last-generation leukocyte filter RC-400 Klev (Pall, Germany). Automated reinfusion of autoerythromass effectively compensated for massive intraoperative blood loss, on condition of correction of hemostasis disorders by fresh frozen plasma and purification of reinfused suspension from tumor cells by filtering through leukocytic filters. Moreover, our results indicate that utilization of cell saver is obligatory for some patients with supermassive hemorrhages. 相似文献
20.
The bithorax complex of Drosophila melanogaster: Underreplication and morphology in polytene chromosomes
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