Goldenhar 综合征家系的临床表型和遗传学分析

目的分析1组Goldenhar综合征家系的临床表现及遗传学特征。方法我们随访到1组4代33人的Goldenhar综合征家系，对目前存活的29人进行了临床表型和遗传学的初步分析。结果家系内有Goldenhaar综合征患者5人．临床表现具高度多样性，累及眼、耳、脊柱、颜面、口腔等多个器官和系统的发育不良，在遗传方式上属于常染色体显性遗传。从细胞遗传学水平对家系中成员进行染色体检查，未发现核型异常。结论该Goldenhar综合征家系属常染色体显性遗传，染色体检查未发现核型异常。     

氯丙嗪和氯氮平对小鼠生殖细胞和人淋巴细胞的诱变效应

为探讨氯丙嗪和氯氮平在使用临床治疗剂量时的遗传毒理效应，研究了两药对小鼠生殖细胞和小鼠子代体细胞的影响，以及对人体淋巴细胞姊妹染色单体互换（ＳＣＥ）频率及微核率的影响。结果显示：（１）连续给药５天后第１周两药高、中、低三个剂量组均能引起小鼠精子头部畸形率明显增高，但停药４周后对精子的致畸作用基本消失；（２）两药对小鼠睾丸细胞及子代体细胞的染色体结构畸变率均无明显影响；（３）两药在治疗剂量时对人淋巴细胞的ＳＣＥ频率及微核率无明显影响，治疗前后的自身对照研究亦未见两频率有明显改变；（４）两药的血药浓度与ＳＣＥ频率及微核率之间无量效关系。研究结果提示，两药在临床治疗剂量时对小鼠生殖细胞染色体结构以及对人体遗传物质均无明显损伤作用。     

Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine

Abstract: A prospective, randomized study was conducted to evaluate the role of vitamin B₁₂ and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4 + cell counts < 500/mm³ were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B₁₂ (1000 μg monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B₁₂ and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm³ and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B₁₂ or folate levels and development of myelosuppression. Vitamin B₁₂ and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.     

Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

健康人血清叶酸和维生素B_(12)水平的测定

本文对14岁以下健康小儿171名,成人30名及初生儿脐带血30份进行了血清叶酸和维生素B_(12)含量测定,171名小儿于采血前均经补足叶酸和维生素B_(12)。结果:血清叶酸(nmol/L)的正常值低限,<4岁者为6.1,4～14岁为8.4,成人为5.0;血清维生素B_(12)(pmol/L)的正常值低限,<1岁为459,1岁～成人为107。     

A highly variable STR at the D12S391 locus

A total of 103 fragments in the STR D12S391 locus were sequenced. 24 different alleles were found which can be grouped into 12 allelic classes based on the total number of repeats. The structure of this compund STR consists of blocks of (AGAT) and (AGAC) repeats with a consensus structure (AGAT)_8–l7 (AGAC)_6–10 (AGAT)_0–1. Whereas shorter alleles only have (AGAT) repeats, > 225 bp alleles are more complex, having two motifs (AGAT) and (AGAC). Population data showed that this to be a highly polymorphic STR with a heterozygosity of 0.9. This fact together with its simple structure make this STR very suitable for forensic and genetic purposes.     

慢性肾功能衰竭病人高同型半胱氨酸血症及其影响因素

目的 :研究慢性肾衰 (CRF)病人血浆同型半胱氨酸 (Hcy)水平及其影响因素。方法 :采用荧光偏振免疫分析法测定 16 0例CRF病人血浆总同型半胱氨酸 (tHcy)水平 ,同时用离子夺获分析法和微离子酶免疫分析法分别检测血浆叶酸(FA)和维生素B12 (VB12 )浓度。结果 :CRF病人血浆tHcy水平 (2 2 6 9± 12 16 ) μmol/ )明显高于正常对照组 (7 97±2 6 5 ) μmol/L ,CRF病人高同型半胱氨酸血症的发生率为 82 5 0 % ,其中血液透析组血浆tHcy水平 (2 4 13± 12 6 8μmol/L ,n =73)明显高于持续性非卧床腹膜透析 (CAPD)组 (16 4 3± 5 5 8μmol/L ,n =19)和非透析治疗组 (19 79± 10 5 7)μmol/L ,(n =6 8) ,但血浆FA和VB12 与正常对照组均无明显差别 (P >0 0 5 )。CRF病人血浆tHcy水平与血浆FA浓度均呈负相关关系 ,未经透析的CRF病人血浆tHcy水平与内生肌酐清除率和血浆FA水平呈负相关 ;透析治疗组血浆tHcy水平与血浆FA浓度呈负相关。血透 4h使血浆tHcy下降约 4 0 0 % ,透析后 2 0h回复到透析前水平的 76 0 %～86 0 % ,但在采用血仿膜和聚砜膜透析的病人之间 ,血浆tHcy水平无明显差异。结论 :CRF病人普遍存在高同型半胱氨酸血症 ,但没有明显的FA和VB12 缺乏 ,CRF时肾脏损害削弱了对Hcy的代谢或清除能力 ,     

PC12细胞化学缺氧复氧损伤与缺氧诱导因子1表达的关系

目的 研究缺氧诱导因子1(HIF1)在PC12细胞化学缺氧复氧损伤中的作用。方法 在培养液中加入和去除氯化钴模拟化学缺氧和复氧，以乳酸脱氢酶(LDH)漏出和细胞超微结构改变作为细胞损伤指标，观察化学缺氧和复氧后不同时间细胞损伤和HIF1 α蛋白变化。结果 在氯化钴模拟化学缺氧实验中，LDH漏出明显增加，8h达高峰，随后逐渐下降，电镜结果与LDH改变相一致，HIF1 α蛋白表达在化学缺氧后2，4，8和12h均明显增加，8h达高峰，提示化学缺氧8h后细胞损伤逐渐减轻可能与HIF1 α蛋白水平升高有关。在模拟复氧实验中，LDH和细胞形态学改变都显示化学复氧8h细胞损伤最为严重，而HIF1 α蛋白表达在化学复氧4和8h均明显下降，提示细胞化学复氧损伤可能与HIF1 α蛋白水平下降有关。结论 HIF1对神经细胞化学缺氧复氧损伤具有保护作用。     

刺梨酸的分离与结构研究

从刺梨中分离出一种新的五环三萜酸,命名为刺梨酸。通过光谱分析和衍生物的制备,确定其化学结构为2β,3α,7β,19α-四羟基乌苏-12-烯-28-羧酸。     

维生素B_(12)注射液稳定性的研究

作者用恒温加速试验法研究了维生素B_(12)注射液的稳定性。结果表明:该注射液的稳定性在pH值4.80左右较好,加络合剂可增加其稳定性,有效期为5年。