MDR1特异性核酶逆转肝癌多药耐药的实验研究

目的探讨MDR1核酶（N2A＋tRNAi^met-iMDRl-sRz，sRz）在裸鼠体内逆转人肝癌组织多药耐药（MDR）的可行性。方法将原发性MDR人肝癌组织裸鼠原位移植模型第2代随机分为A组（空白对照组：生理盐水40μl＋Lipofect AMINE^TM2000 10μ1）、B组（阴性对照组：N2A＋tRNAi^met 10μg／40μl＋Lipofect AMINE^TM2000 10μl）和C组（核酶组：sRz 10μg／40μl＋LipofectAMINE^TM2000 10μl），均开腹瘤内注射。瘤内注药1周后用表阿霉素15mg／kg腹腔注射，每周1次，连续4周。彩色B超测量肿瘤体积。化疗结束后1周处死裸鼠，RT-PCR、Western blot法检测肿瘤中MDR1 mRNA及其蛋白P-gp的表达。结果C组每次化疗后肿瘤体积均较前缩小（F=659．99，P〈0．05）。除第1次化疗外，其余各次化疗后C组的抑制率均高于A、B组（F=35．36，12．77，97．60，P〈0．05）。化疗结束后，C组与瘤源以及A、B组相比，肿瘤组织中MDR1 mRNA和P-gp的表达明显降低（F=45．36，3590．40，P〈0．05）。结论sRz可有效降低肝癌细胞表达MDR1 mRNA和P-gp，一定程度上逆转MDR，提高E-ADM的化疗效果。单纯E-ADM化疗可使肝癌组织MDR1 mRNA和P-gp表达升高，诱导MDR的产生。     

人钠/二羧酸协同转运蛋白3基因调控肾小管上皮细胞线粒体膜电位的研究

目的 观察人钠／二羧酸协同转运蛋白3(hNaDC3，)对人肾脏近曲小管上皮细胞(HKC)线粒体膜电位的变化及其对细胞能量代谢的影响。方法 应用亚克隆技术构建正义pcDNA3-hNaDC3和反义pcDNA3-AhNaDC3两个真核表达载体，通过脂质体LipofectAMINE将pcDNA3-hNaDC3及pcDNA3-AhNaDC3转染至HKC细胞。克隆筛选后，用RT—PCR、Northern印迹及Western印迹鉴定外源基因的整合和表达。荧光探针JC-1观察各细胞系线粒体膜电位的变化。结果 外源hNaDC3基因稳定整合到HKC细胞基因组中，并获得高、低表达。转染正义hNaDC3cDNA的HKC细胞线粒体膜电位降低，JC-1在线粒体内形成单体，发出绿色荧光；而转染反义hNaDC3cDNA的HKC细胞线粒体膜电位略微升高，JC-1形成聚合体，发出红色荧光。结论 hNaDC3过表达引起线粒体膜电位降低，反义hNaDC3则使线粒体膜电位略微升高。提示NaDC3可能通过使线粒体膜电位下降，参与了细胞能量代谢。     

血清蛋白变化对鼻咽癌患者预后判断的意义

本文研究了155例鼻咽癌血清蛋白电泳α_2/β的比值变化。结果表明,正常组(α_2/β<1)5年生存率明显高于异常组(α_2/β≥1)。尽管两组在治疗结束时疗效相似(完全缓解率为66.1％和65.2％),但5年内复发率前者为30.6％.后者为80.0％。因此,我们认为血清蛋白电泳不同于临床分期或其他预后因素,对判断鼻咽癌病人的预后方面更有价值。     

地塞米松对哮喘豚鼠肺组织Giα、Gqα的抑制作用

目的　研究糖皮质激素对豚鼠哮喘模型肺组织G蛋白α亚族表达的影响。方法　 18只豚鼠随机分为正常对照组(NS) ,哮喘组 (AS)和地塞米松治疗组 (DEX)。AS组用卵蛋白皮下及腹腔注射致敏 ,卵蛋白重复雾化吸入激发复制豚鼠哮喘模型。DEX组在每次激发前腹腔内注射地塞米松 2mg/kg进行干预。用Westernblot分析法测定豚鼠肺组织G蛋白α亚族的表达水平。结果　三组豚鼠肺组织Giα水平分别为NS组 10 0 % ,AS组 (15 3± 18) % ,DEX组 (113± 18) % ,AS组与NS组比较、DEX组与AS组比较差别显著 (P <0 .0 5 )。三组豚鼠肺组织Gqα水平分别为NS组 10 0 % ,AS组 (15 1± 19) % ,DEX组 (98± 4 ) % ,AS组与NS组比较、DEX组与AS组比较差别显著 (P <0 .0 5 )。在同样的条件下Gsα水平无显著变化 (P >0 .0 5 )。地塞米松能够显著抑制哮喘豚鼠肺组织中Giα、Gqα的高表达。结论　肺组织Giα ,Gqα的高表达变化参与了豚鼠哮喘模型的病理性信号传导 ,抑制哮喘肺组织Giα、Gqα的高表达可能是糖皮质激素治疗哮喘的机制之一。     

The subdivisions of the intermediolateral nucleus in the sacral spinal cord of the cat

The subdivisions of the sacral intermediolateral nucleus (IML) of the cat have been studied by using a double-labeling technique of retrograde Fluoro-gold (FG) and wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) tracing. The parasympathetic preganglionic neurons (PGNs) that were labeled by the FG injected into the pelvic nerve formed a ‘V’-shaped column known as the sacral parasympathetic nucleus (SPN) in the sacral IML. The neurons that were labeled by the WGA-HRP applied to the lateral parabrachial nucleus (PBL) formed an elongated spindle-shaped column extending throughout the IML of the sacral segments. We designated it by the name of sacral visceral sensory nucleus (SVSN). These findings indicate that the sacral IML of the cat contain two distinct subdivisions, SPN and SVSN.     

Differential Distribution of MAP1a and Aldolase c in Adult Mouse Cerebellum

MAP1a is a microtubule-associated protein with an apparent molecular weight of 360 kDa that is found in the axonal and dendritic processes of neurons. Two monoclonal anti-MAP1a antibodies, anti-A and anti-BW6, revealed different epitope distributions in the adult mouse cerebellum. Anti-A stained Purkinje and granule cells uniformly throughout the cerebellum. In contrast, anti-BW6 selectively stained the dendrites of a subset of Purkinje cells, revealing parasagittal bands of immunoreactivity in the molecular layer. The compartmentation of the BW6 epitope was compared to the Purkinje cells as revealed by immunostaining with anti-zebrin II, a well known antigen expressed selectively by bands of Purkinje cells. The anti-BW6 staining pattern was complementary to the zebrin II bands, the zebrin II^- Purkinje cells having BW6⁺ dendrites. These results demonstrate that MAP1a is present in two forms in the mouse cerebellum, one of which is segregated into parasagittal bands. This may indicate a unique MAP1a isoform or may reflect differences in the metabolic states of Purkinje cell classes, and regional differences in their functions.     

Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na⁺ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.     

Computer-Assisted Design of an Implantable, Intrathoracic Artificial Lung

Abstract: A semiempirical mathematical model of convective oxygen transport is used to design a new, low pressure loss, implantable artificial lung that could be used as a bridge to lung transplantation in patients with advanced respiratory failure. The mass transfer and flow friction relations pertinent to the design of a cross–flow hollow fiber membrane lung are described. The artificial lung is designed to transfer over 200 ml/min of oxygen at blood flow rates up to 5 L/min. A compact design and a blood-side pressure loss of <15 mm Hg allows the device to be implanted in the left chest without the need for a prosthetic blood pump. Surgical implantation of the artificial lung would require the creation of inflow and outflow anastomoses. Oxygen would be supplied via an external source. Blood properties, operating conditions, and empirically determined mass transfer and flow properties are all specified and input into a computer program that numerically solves the design equations. Computer–generated values for the device frontal area, blood path length, and fiber surface area are thereby obtained. The use of this computer–assisted design minimizes the need for extensive trial–and–error testing of prototype devices. Results from in vitro tests of a prototype implantable lung indicate that the mathematical model we describe is an accurate and useful tool in the design of hollow fiber artificial lungs.     

Impact of Ultrafiltration on Back-Diffusion in Hemodialyzer

Abstract: Ultrafiltration of water from blood to dialysate decreases the rate of back–diffusion of solutes from dialysate to blood. Therefore, back–clearance ( bK ) of hemodialyzers may be expressed as bK = bK _o – bTrQ _u, where bK _o is the diffusive back–clearance, bTr is the "back–"transmittance coefficient, and Qu is the net ultrafiltration rate. A formula for bK was derived from the one–dimensional theory of hemodialyzer, and bTr was described as a function of bK _o and the Staverman reflection coefficient. The transport parameters, bK _o and bTr , for creatinine and vitamin B₁₂ were measured in two types of hemodialyzers with negligible back–filtration, using water solutions, and compared with the transport parameters, K _o and Tr , for the case of both diffusion and ultrafiltration from blood to dialysate. bK _o was in general equal to K_o. bTr was not different from Tr for creatinine whereas bTr was lower than Tr for vitamin B₁₂. Experimental values of bTr for vitamin B₁₂ were in general agreement with theoretical predictions. However, experimental values of bTr for creatinine were lower than predicted values. We conclude that the impact of ultrafiltration on back–clearance for slowly diffusing solutes is weaker than on their clearance.     

核仁形成区嗜银蛋白定量对结肠癌分型、分级的诊断意义

对１１４例不同类型和级别的结肠癌进行银染核仁形成区嗜银蛋白（Ａｇ－ＮＯＲｓ）形态定量研究．结果表明，Ａｇ－ＮＯＲｓ数量、大小和分布在结肠未分化癌和印戒细胞癌组与管状腺癌和粘液腺癌组比较，有明显差异．管状腺癌随分化程度的降低，Ａｇ－ＮＯＲｓ的数量、形态、大小和分布也发生等级性变化．结果提示，Ａｇ－ＮＯＲｓ形态定量的数量、形态、大小和分布４项指标对结肠癌分型有一定意义，对管状腺癌分级有较好的诊断价值。