Spectrin-alpha I/61: a new structural variant of alpha-spectrin in a double-heterozygous form of hereditary pyropoikilocytosis

Recent biochemical studies have led to the identification of abnormal spectrins in the erythrocytes of patients with hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis (HE). In this report we describe the biochemical characterization of the erythrocytes from a proband with severe HPP who is doubly heterozygous for two mutant spectrins (Sp): Sp alpha I/74 and a new, previously undetected, mutant of alpha-spectrin designated Sp alpha I/61. The proband's erythrocytes are unstable when exposed to 45 degrees C, and her membrane skeletons exhibit instability to shear stress. The content of spectrin in the proband's erythrocyte membranes is decreased to 75% of control values. The amount of spectrin dimers in crude 4 degrees C spectrin extracts is increased (58%) as compared with control values (6% +/- 4%). Limited tryptic digestion reveals a marked decrease in the normal 80,000-dalton alpha I domain, an increase in the 74,000-dalton fragment that is characteristic of Sp alpha I/74, and an increase in a series of new fragments of 61,000, 55,000, 21,000, and 16,000 daltons. Both parents are asymptomatic, but they have increased amounts of spectrin dimers (17% to 25%). Limited tryptic digestion of the father's spectrin demonstrates the presence of a previously identified abnormal spectrin (Sp alpha I/74) that is characterized by a decrease in content of the 80,000-dalton peptide and an increase in concentration of the 74,000-dalton peptide. The mother's spectrin digests show a decrease in the amount of 80,000-dalton peptide and the formation of new peptides of 61,000, 55,000, 21,000, and 16,000 daltons. The data indicate that this severe form of HPP is due to the inheritance of two distinct abnormal spectrins, Sp alpha I/74 and a new spectrin mutant, Sp alpha I/61.     

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.      

Antiestrogenic effects of Z-1, 1-dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane(5a) on human breast cancer cells in culture.

Compound 5a ([Z]-1, 1-Dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane) is a novel cyclopropyl compound which was shown to be a pure antiestrogen. In the present study, the antiproliferative activity of 5a was examined on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and A-549 human lung cancer cells using the hemocytometric trypan blue exclusion method. Compound 5a inhibited the growth of MCF-7 cells in a dose-related manner over a concentration range of 10(-9) to 10(-5) M, but did not alter the growth of MDA-MB-231 or A-549 cells. Co-administration of estradiol (10(-8) M) reversed the antiproliferative activity of 5a (10(-7) M) on MCF-7 cells. Further, an ER-dependent mechanism of action is supported by the specific ER binding of 5a in MCF-7 cells observed in this study. The influence of 5a on the cell surface morphology of MCF-7 and MDA-MB-231 cells was studied using scanning electron microscopy (SEM). Compound 5a at 10(-6) M reduced the length and density of microvilli (MV) on MCF-7 cells, which was reversed by co-administration of estradiol (10(-8) M). This compound did not alter the cell surface morphology of ER-negative MDA-MB-231 cells. In conclusion, 5a and tamoxifen inhibited the growth of ER-prositive MCF-7 cells in an estradiol-reversible manner, and had no effect on ER-negative MDA-MB-231 cells. The results of this study with human breast cancer cells suggest that 5a may be highly effective in the treatment of estrogen-dependent breast cancer and/or in the prophylactic treatment of women with a high risk of breast cancer development.     

溃结Ⅰ号的制备与稳定性考察

目的提高医院临时处方溃结Ⅰ号保留灌肠剂的稳定性,并对其中的主要成分含量进行控制。方法制备时加入助悬剂,用沉降容积比和再分散性选择适宜的助悬剂及其最佳助悬浓度,并用紫外分光光度法对主要成分柳氮磺吡啶的含量进行测定。结果在制剂中加入卡波母作为助悬剂0.15%就可以达到良好的助悬效果,而且制备的制剂再分散性好。结论加入卡波母作为助悬剂制备的制剂稳定,再分散性好,便于使用和保存。     

Biological evaluation of novel cyclopropyl analogues of stilbene, stilbenediol, and phenanthrene for estrogenic and antiestrogenic activity

The triphenylethylene-type antiestrogens, such as tamoxifen, are known to be useful in the treatment of estrogen-dependent tumors. However, these compounds display mixed estrogen agonist/antagonist activity which may limit their therapeutic effectiveness. This problem of mixed activity led to the synthesis and identification of a cyclopropyl derivative of cis-stilbene which we have named Analog I. This compound (1,1-dichloro-cis-2,3-diphenylcyclopropane) displayed only antiestrogenic activity in the mouse. The present study was designed to evaluate cyclopropyl derivatives of Analog II for estrogenic and antiestrogenic activity in the rat using the standard 3-d uterotropic assay and the uterine cytoplasmic estrogen receptor assay. Five compounds (B-F) which are cyclopropyl derivatives of stilbene, stilbenediol, and phenanthrene were evaluated in this study. Three of the compounds (B-D) displayed neither estrogenic nor antiestrogenic activity in the rat. The relative estrogenic activities of E and F were 11.3 and 1.5%, respectively, of diethylstilbestrol in the uterotropic assay, and 39 and 6.2%, respectively, of estradiol in the estrogen receptor assay. Neither E nor F was found to display antiestrogenic activity in the rat. The results indicate that the relative estrogenic and receptor binding activities of E and F are similar to those previously observed in the mouse, while B-D appear to be inactive in both species.     

人参皂甙Rb1和Rg1对小鼠中枢神经递质受体和脑内蛋白质合成的影响

应用放射配基结合法测定了人参皂甙Rb₁和Rg₁对α₁,α₂,β肾上腺素能受体、M胆碱能受体、5-羟色胺、多巴胺及GABA等七种受体的作用。结果均不能证明它们对这七种受体有亲和力。但给动物ip药物连续5天,Rb₁和Rg₁均能使中枢M胆碱受体密度显著增高。Rb₁及Rg₁还能显著增加脑内蛋白质的含量。上述实验结果对解释人参的中枢作用提供了重要证据。     

关于人眼视力发展的非线性成长率理论

目的使用非线性成长率理论分析人眼视力发展规律。方法使用高斯光学及成像方程推导出两个参数：屈光状态改变率（M）及眼轴成长率（N），用以预测MOS（初始近视）、年龄（A^＊）及其后视力的发展情况。结果当有效焦距F=（21-22）、密码M=（2．67—2．9）（D／mm）时，此计算值符合实验平均值（2．7）。当年龄A^＊=（3，6）岁的屈光度变化已知时，我们计算其MOS预测年龄为A^＊=（7．3，21．8）岁（在不同条件下）。此值反比于M值在A=6及A=3的比值或N=N—N^＊，即非正视态及正视态的眼轴成长率之差。本理论也可用来预测在年龄A=25时的近视度，分别为D=-14及-0．49的上述两例情况，同时也能分析Lain等人的测量值（由出生到青年期的视力发展情况）。结论本理论可预测MOS、其后发展情况及其符合实验值（M）。使用成长率差值（dN）比使用L/rl比值能更准确地预测MOS。     

运用模糊聚类方法分析中药微量元素含量与药效的关系

目的:不同中药中各种微量元素的含量数据离散,从含量数据上很难说明不同药物的药物相似性,故运用模糊分类方法研究药物微量元素含量与药物疗效的关系,验证其在药物功效的相似性及不同种类中药定量指标评价方面的作用。方法:实验于2005-10/2006-11在吉林省中医药管理局中药微量元素分析实验室完成。用原子吸收分光光度法检测合欢花、黄芪、石菖蒲、远志、山楂、银杏叶、人参、元肉、蒲黄、酸枣仁、苏木11种中药中钾、钠、钙、镁、铁、铬、镍、锰、铜、锌元素的含量,结合锌/铜比值、镁/钙比值,以数据极差法进行统计指标的标准化处理,以数量积法算出衡量被分类对象之间的相关系数,确定论域上的模糊矩阵。结果:相关系数r=0.50时,合欢花,石菖蒲,远志,人参,元肉,蒲黄,酸枣仁7种药物聚类相似;相关系数r=0.65时,合欢花,石菖蒲,元肉,蒲黄,酸枣仁5种药物聚类相似;r=0.75时,合欢花,石菖蒲,蒲黄3种药物聚类相似。研究还发现:药物中金属元素含量丰富,而且相关系数较大的药物,其药物疗效相似。结论:运用数学与化学计量学方法建立模糊聚类分析模型,可以把离散的数据标准化处理,确定论域上的模糊矩阵可以研究不同药物间的药效相似性,可以对不同种类的中药进行定量指标的明确评价。     

糖尿病大鼠视网膜细胞间黏附分子1表达与羟苯磺酸钙的干预效应

目的:观察糖尿病大鼠视网膜细胞间黏附分子1表达及羟苯磺酸钙对细胞间黏附分子1表达的影响。方法:实验于2004-09/2005-02在山东医学高等专科学校实验室完成。①实验分组:雄性SD大鼠55只,随机选择10只为正常对照组,其余大鼠均腹腔注射链脲佐菌素,72h后断尾取血测空腹血糖≥16.7mmol/L者为造模成功,成模大鼠随机分为糖尿病模型组20只和羟苯磺酸钙治疗组20只。②实验方法:羟苯磺酸钙组大鼠给予羟苯磺酸钙120mg/(kg·d)灌胃。其他两组大鼠灌胃等量生理盐水。③实验评估:12周后麻醉下处死动物,检测血糖、糖化血红蛋白水平;光镜下观察大鼠视网膜病理变化;以RT-PCR法检测细胞间黏附分子1mRNA表达;Westernblot法检测细胞间黏附分子1蛋白表达。结果:5只造模未成功弃之不用,余50只大鼠进入结果分析。①血糖:糖尿病模型组及羟苯磺酸钙治疗组血糖均高于正常组(P<0.01)。羟苯磺酸钙治疗后血糖有下降趋势但差异无统计学意义(P>0.05)。②糖化血红蛋白水平:糖尿病模型组高于正常组(P<0.01)。羟苯磺酸钙治疗组与正常组相比差异无显著性(P>0.05)。③细胞间黏附分子1mRNA表达:细胞间黏附分子1mRNA在糖尿病组表达最强,羟苯磺酸钙组表达低于糖尿病组(P<0.01)。④细胞间黏附分子1蛋白表达:各组均有细胞间黏附分子1表达,糖尿病大鼠较正常大鼠表达增强,羟苯磺酸钙治疗后呈下降趋势。结论:糖尿病大鼠视网膜细胞间黏附分子1表达增强,羟苯磺酸钙对糖尿病大鼠视网膜具有保护作用,其保护作用机制可能与降低细胞间黏附分子1表达有关。     

肾移植术后肺部感染特征97例分析

回顾性分析解放军总医院第二附属医院1992-05/2007-07收治的97例肾移植术后肺部感染患者的临床资料,患者对治疗方案均知情同意。①肺部感染多发生于术后1￣12个月,尤以术后2￣6个月多见,大剂量激素冲击多为诱因;重症肺部感染多为混合性感染,多为巨细胞病毒、真菌、耐药菌群和条件致病菌感染为主。②97例患者中肺部感染致急性呼吸窘迫综合征25例,13例死亡,死亡率达47.3%;在2007年,4例急性呼吸窘迫综合征中仅1例死亡,死亡率下降为20%,其中,1例最长呼吸机辅助呼吸达33d,患者痊愈出院;2个或2个以上器官障碍者死亡24例,最多见于上消化道出血和肾功能衰竭。③从2006-06开始,对于急性呼吸窘迫综合征患者早期T淋巴细胞亚群CD4 /CD8 <1%,即刻完全停用钙调神经磷酸酶抑制剂和抗细胞代谢免疫抑制剂,仅给小剂量的糖皮质激素,且血肌酐平均下降100mmol/L,其中1例完全停用达25d,血肌酐完全正常。④肾移植术后肺部感染发生率高,早期依据T淋巴细胞亚群和血肌酐的变化及时有效的减少或停用抗排斥药物及抗生素经验性用药是救治成功的前提。病情危重者(特别是急性呼吸窘迫综合征)及早呼吸末正压通气,充分保护其他脏器的正常功能,合理应用糖皮质激素和纤维支气管镜,密切加强各专业学科间协作等是救治成功的关键。