Magnetic resonance imaging of gadolinium-labeled monoclonal antibody polymers directed at human T lymphocytes implanted in canine brain

Two different murine monoclonal anti-human T cell antibodies, that were coupled to gadolinium (Gd), bind specifically to human T lymphocyte cells implanted in canine brain. This binding was at a concentration of Gd sufficient to detect the implanted cells and to distinguish them from the surrounding brain tissue with magnetic resonance imaging (MRI) at a field strength of 1.5 Tesla. These Gd-labeled immunoglobulin preparations did not bind bovine T cells at a concentration sufficient to be detected on MRI. A protein solution containing the immunoglobulins (100 micrograms), gelatin (2 mg), and bovine serum albumin (2.5 mg) was reacted with the dianhydride of diethylenetriaminepentaacetic acid (DTPA); the DTPA serves as a metal chelator and as a protein crosslinking agent. The DTPA-protein complex was reacted with Gd chloride. There were approximately 10 DTPA residues per protein molecule in the modified protein mixture. Isolated human or bovine monocytes (approximately 12 million cells) were implanted in the brains of anesthetized dogs in a volume of 40 microliters. The blood-brain barrier was then disrupted by the intra-arterial injection of hyperosmotic mannitol, and the Gd-labeled antibodies were injected through a catheter placed at the branch of the internal and external carotid arteries. The brains were imaged 48 to 72 hours later. The MRI scans revealed a markedly decreased T1 relaxation time with a high signal intensity (TE = 25 msec, TR = 200 msec) related to the human T cell implants. There was no evidence of decreased T1 at the site of the bovine T cells. Neither control murine gamma globulin coupled to Gd-DTPA nor anti-human T cell antibodies uncoupled to Gd modified the MRI contrast of the human T cells in the brain.     

苦楝化学成份的研究

从苦楝(Melia azedarach L.)果中分得苦楝新醇(Ⅰ),苦楝醇(Ⅱ)、苦楝酮(Ⅲ)、苦楝二醇(Ⅳ)、香草醛(Ⅴ)和香草酸(Ⅵ)。根据波谱(IR,MS,¹HNMR,¹³CNMR)分析和理化常数测定,确定了它们的结构。其中苦楝新醇(Ⅰ)为新化合物,对菜青小虫有一定的拒食活性。     

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Ohne ZusammenfassungSiehe Band 71, Heft 4/6 dieser Zeitschrift.     

骨髓间充质干细胞移植后脑梗死大鼠脑电图的变化

目的:对比观察骨髓间充质干细胞移植前后脑梗死大鼠脑电图的变化。方法:实验于2002-09/12在解放军第三军医大学中心实验室及西南医院神经内科肌电图室完成。①实验分组:选取清洁级健康成年Wistar大鼠15只,随机数字表法分为干细胞移植组、模型对照组、假手术组,5只/组。②实验方法:另取2只健康幼年Wistar大鼠用于骨髓间充质干细胞的提取,联合采用密度梯度离心及贴壁法分离培养大鼠骨髓间充质干细胞,选取生长良好的1～3代细胞用于移植实验。干细胞移植组、模型对照组大鼠建立大脑中动脉栓塞模型。假手术组仅分离颈总动脉、颈外动脉和颈内动脉,不予结扎和放置线栓。造模后1周,干细胞移植组、假手术组大鼠行细胞移植,在立体定向仪定位下于脑梗死区(壳核)直接注射骨髓间充质干细胞悬液5μL,细胞浓度1×104μL-1,移植坐标为前囟前1.0mm,右旁开3.0mm,硬膜下5.0mm。模型对照组大鼠于相同部位注射等量不含细胞的磷酸盐缓冲液。③实验评估:采用脑电图机分别于造模前、造模后1周(移植前)、细胞移植后4周对各组大鼠进行脑电图检测。结果:15只大鼠均进入结果分析。①造模前基本节律为8～11Hz、15～30μV的α波,间或少量θ波,双侧对称。②造模后1周,假手术组异常率为0;模型对照组20%(1/5)轻度异常,80%(4/5)中度异常;干细胞移植组20%(1/5)轻度异常,60%(3/5)中度异常,20%(1/5)重度异常。③细胞移植后4周,假手术组脑电图恢复正常;模型对照组随术后时间的延长慢波有所减少,但仍可见到δ波、棘波、棘慢波的发放,至细胞移植后4周60%(3/5)轻度异常,40%(2/5)中度异常;干细胞移植组术后局限性慢波逐渐减少,基本节律全部恢复为α波,不对称的情况明显好转,至细胞移植后4周60%(3/5)轻度异常,以病灶侧局限性θ波较多为主,另外40%(2/5)基本正常。结论:动物实验显示骨髓间充质干细胞移植对脑梗死大鼠的脑电图背景节律有改善作用,一定程度上促进了神经系统功能的恢复。     

Sumatriptan - Nonresponders: A Survey in 366 Migraine Patients

Sumatriptan, notably after subcutaneous administration, is highly effective in the acute treatment of migraine in the majority of patients. The response is consistent within patients and over time. To determine risk factors for nonresponse to sumatriptan, we compared clinical characteristics. In responders and nonresponders and, within patients, between attacks with and without response. We found no differences at the strict level of significance (P<0.001 because of multiple comparisons), but only tendencies for differences (0.001相似文献   

Radiation-induced red cell damage: role of reactive oxygen species

BACKGROUND: Cellular blood components are irradiated to prevent graft- versus-host disease in transfusion recipients at risk for this syndrome. Because gamma radiation can result in the production of reactive oxygen species, the role of reactive oxygen species was investigated in radiation-induced red cell damage. STUDY DESIGN AND METHODS: Whole blood from normal donors was exposed to various doses of t-butyl hydroperoxide (0-1 mM) and/or to gamma-radiation (0-50 Gy). Oxidative damage was assessed by the extent of lipid peroxidation (measured by thiobarbituric acid-reactive substances [TBARS]) and hemoglobin oxidation. Fresh blood was divided into three parts-one initially irradiated and stored, another stored with portions irradiated weekly, and a third stored without irradiation. TBARS and hemoglobin oxidation were measured weekly. RESULTS: As expected, t- butyl hydroperoxide induced TBARS formation and hemoglobin oxidation in a dose-dependent fashion. The gamma-radiation not only increased hemoglobin oxidation and TBARS formation, but also enhanced the t-butyl hydroperoxide effect on red cells. Red cell storage increased TBARS generation and hemoglobin oxidation in a time-dependent fashion. When radiation was administered either initially or after weekly storage, TBARS production and hemoglobin oxidation were increased over that measured in unirradiated paired controls. CONCLUSION: Gamma radiation at clinically used doses increases lipid peroxidation and hemoglobin oxidation in human red cells. The effect of gamma-radiation is accentuated by blood storage and induces damage independent of time of storage.     

蒿甲醚对大鼠肺泡Ⅱ型上皮细胞DNA的影响

目的:蒿甲醚除了具有良好的临床治疗作用外,对正常组织有极大的副作用。实验拟观察蒿甲醚对大鼠肺泡Ⅱ型上皮细胞的影响。方法:实验于2005-09-20/2007-03-10在山东省泰山医学院生命科学研究所、中心实验室和机能实验室完成。①实验材料:蒿甲醚购自昆明制药厂,分析纯,使用前先进行预处理,处理方法:研磨后用溶液配成1g/L的母液,超声助溶解后供实验用。Wistar大鼠70只,体质量(70±15)g,雌雄不拘,由山东大学医学院实验动物中心提供。实验过程中对动物处置符合动物伦理学标准。②实验方法:将大鼠随机分为普通饲料对照组(n=10)和实验组(n=60),实验组分6个亚组,分别在饲料中加入0.1,0.2,0.4,0.8,1.6,3.2mg/kg的蒿甲醚。采用单细胞凝胶电泳技术观察大鼠肺泡Ⅱ型上皮细胞DNA的改变。结果:70只大鼠,饲养过程中实验组死亡6只,死亡原因为饲料添加蒿甲醚造成。当饲料中的蒿甲醚浓度为0.1mg/kg时,大鼠肺泡Ⅱ型上皮细胞DNA损伤率与对照组相比,差异无统计学意义;饲料中的蒿甲醚浓度超过0.2mg/kg时,大鼠肺泡Ⅱ型上皮细胞DNA损伤率明显增加,与对照组相比,差异有统计学意义。且损伤程度与饲料中蒿甲醚含量呈正相关。结论:当饲料中的蒿甲醚浓度超过0.2mg/kg时,蒿甲醚可在一定程度上改变肺泡Ⅱ型上皮细胞的DNA生物学特性。且随着蒿甲醚浓度的升高,这种损害更为明显。