A paradigm for single nucleotide polymorphism analysis: the case of the acetylcholinesterase gene

Acetylcholinesterase (AChE) plays a crucial physiological role in termination of impulse transmission at cholinergic synapses through rapid hydrolysis of acetylcholine. It is a highly conserved molecule, and only a few naturally occurring genetic polymorphisms have been reported in the human gene. The goal of the present study was to make a systematic effort to identify natural single nucleotide polymorphisms (SNPs) in the human ACHE gene. To this end, the genomic coding sequences for acetylcholinesterase of 96 unrelated control individuals from three distinct ethnic groups were analyzed. A total of 13 ACHE SNPs were identified, 10 of which are newly described, and five that should produce amino acid substitutions [c.101G>A (p.Arg34Gln), c.169G>A (p.Gly57Arg), c.1031A>G (p.Glu344Gly), c.1057C>A (p.His353Asn), and c.1775C>G (p.Pro592Arg)]. Population frequencies of 11 of the 13 SNPs were established in four different populations: African Americans, Ashkenazi Jews, Sephardic Jews, and Israeli Arabs; 15 haplotypes and five ethnospecific alleles were identified. The low number of SNPs identified until now in the ACHE gene is ascribed to technical hurdles arising from the high GC content and the presence of numerous repeat sequences, and does not reflect its intrinsic heterozygosity. Among the SNPs resulting in an amino acid substitution, three are within the mature protein, mapping on its external surface: they are thus unlikely to affect its catalytic properties, yet could have antigenic consequences or affect putative protein-protein interactions. Furthermore, the newly identified SNPs open the door to a study of the possible association of AChE with deleterious phenotypes-such as adverse drug responses to AChE inhibitors employed in treatment of Alzheimer patients and hypersensitivity to pesticides.     

脾虚模型脑内一氧化氮与乙酰胆碱酯酶表达变化及归脾汤的影响

目的:研究脾虚模型脑内一氧化氮(NOS)与乙酰胆碱酯酶(ACHE)表达变化及归脾汤的影响作用。方法:采用苦降泻下、饮食失节加劳倦过度法建立脾虚大鼠模型,免疫组化法检测下丘脑腹侧核、海马CA1区、前额叶皮层NOS与ACHE变化及归脾汤治疗的影响作用。结果:模型组NOS和ACHE免疫阳性反应物在下丘脑腹侧核、海马CA1区、前额叶皮层明显降低;治疗组上述脑区的NOS和ACHE免疫阳性反应物明显增加。结论:脾虚模型脑内NOS和ACHE表达有变化,提示归脾汤通过影响NOS与ACHE而调节学习记忆功能。     

A Case Report of Paroxysmal Nocturnal Hemoglobinuria in a Child

A ten-year-old boy with paroxysmal nocturnal hemogulobinuria (PNH) is described. Although hemolytic anemia was evident, Ham's test was negative and the erythorocyte acetylcholinesterase (ACHE) activity was normal at the first admission. The diagnosis of hemolytic anemia of unknown etiology was made. Methylprednisolone pulse therapy was started, but could not prevent the hemolytic crises associated with infections. Twelve months later Ham's test turned positive and ACHE activity decreased. The diagnosis of PNH was confirmed. As the disease is insidious in onset, we emphasize that a high index of suspicion and Ham's test and sucrose water test repeated at regular intervals are required to avoid missing the diagnosis.     

大鼠苍白球乙酰胆碱酯酶阳性神经元的衰老变化——形态计量学研究

本研究结合组织化学和形态计量学方法,观察幼龄(3月龄)和老龄(24月龄)雄性大鼠苍白球内乙酰胆碱酯酶阳性(AChE-P)神经元的衰老变化。老龄苍白球AChE-P神经元的数量,比幼龄组减少约11.8％;幼龄阳性神经元的突起总长度是老龄组的1.4倍;但在老龄组中,约有8.6％阳性神经元的突起总长度,大于幼龄的平均突起总长度(232.1μm);老龄苍白球AChE-P神经元的灰度值,明显高于幼龄组,但约有6.8％老龄阳性神经元的灰度值低于幼龄的平均灰度值(117.8);老龄苍白球AChE-P神经元的截面积,比幼龄增大约9.2％。形态学观察发现,大部分老龄AChE-P神经元呈退行性改变,但有一部分老龄AChE-P神经元胞体增大,染色加深,突起茂密,分支增多。上述结果表明,苍白球内AChE活性的增龄性下降及其神经元的退行性改变,并不是在所有的AChE-P神经元中同步发生。从而提示,在衰老过程中,苍白球AChE-P神经元可能存在着一种与衰老机制密切相关的代偿机制。     

银杏内酯对大鼠基底前脑神经元生长发育的影响

目的：观察银杏内酯对培养的胚胎大鼠基底前脑胆碱能神经元和NADPH-d阳性神经元生长发育的作用。方法：取E17Wistar大鼠胚胎基底前脑进行体外细胞培养，并给予银杏内酯。进行乙酰胆碱酯酶(acetyl cholinesterase，AChE)和NADPH-d酶组织化学染色，并在光镜下进行阳性细胞计数和显微测量胞体及突起发育状况。结果：给予银杏内酯处理后，培养物中乙酰胆碱酯酶阳性神经元和NADPH-d阳性神经元数量均较对照组显著增加，且神经元发育状况好于对照组，胞体大，突起多且长。结论：银杏内酯可以促进体外培养的基底前脑神经元中乙酰胆碱酯酶和NADPH-d的表达，并能促进表达这两种酶的神经元生长发育。     

树鼩中枢某些神经核乙酰胆碱酯酶阳性神经元的定量研究

本文应用AchE药理组化技术测定树鼩脑干和脊髓前角某些神经核的AchE阳性神经细胞密度、细胞体大小及各类神经绍胞构成比例。结果:神经细胞密度以孤束核最大,迷走神经背核第二,脊髓前角细胞密度最小;神经细胞体平均径以孤束核最小,脊髓前角细胞最大;神经细胞构成比,孤束核以小型细胞为主(60%),中型细胞次之,未见大型细胞。脊髓前角和舌下神经核以大型细胞为主(78%,70%),未见小型细胞。其他如红核、动眼神经核、三叉神经运动核、展神经核等以中型细胞为主,小型细胞很少。     

4th National Conference on the Expanding Importance of Central Service in Infection Control

Set to go into effect on October 1, the new Medicarephysician-reimbursement system attempts to bring Medicare payments ever closer in line with physicians' actual costs. Among other things, the new fee schedule should eventually reduce the disparity between specialty and family-practice physicians' reimbursements and encourage more med students to enter primary care. Hospitals should be aware, however, that some things—like the conflict between their and physicians' financial incentives—will not change.     

实验性冲击波负压暴露后豚鼠耳蜗基底膜AChE和SDH活性的变化

目的 探讨冲击波负压（BUP）暴露对豚鼠耳蜗基底膜乙酰胆碱酯酶（AChE）和琥珀酸脱氢酶（SDH）活性的影响。方法 中等强度BUP重复暴露3次后2h～3d检测豚鼠听性脑干反应（ABR）阈值，然后处死并应用酶组织化学技术观察其耳蜗基底膜两种酶的活性产物的变化。结果 负压峰值为-44．5kPa～-48．8kPa的BUP暴露后2h，耳蜗基底膜外毛细胞下神经末梢区域AChE活性产物明显减少，在负压暴露后24h和3d时有所恢复，但仍低于正常对照组。基底膜SDH活性下降主要发生于外毛细胞，且以第二转第三排最为明显；BUP暴露后2h活性下降幅度最大，至24h和3d时有所恢复。上述两种酶活性产物的变化，与动物的ABR阈移幅度变化是一致的。结论 BUP暴露后豚鼠耳蜗基底膜的AChE和SDH活性有不同程度的下降，这可能是造成BUP暴露后听力损失的一个主要原因。     

Cytosolic protein kinase activity associated with the maturation of the malaria parasite Plasmodium berghei

Seven cytosolic phosphoproteins with relative molecular masses of 110, 58, 52, 46, 38, 36 and 34kDa and isoelectric points between 4.2 and 5.0 are identified from the rodent malaria parasite Plasmodium berghei. Similar patterns of phosphorylated proteins are obtained from parasite cytosol after incubation of intact infected erythrocytes with [32P]orthophosphate, or from parasite cytosol incubated with [gamma-32P]ATP. The characteristics of the phosphorylation reaction are similar to the previously described Plasmodium protein kinase [Wiser, M.F., Eaton, J.W. and Sheppard, J.R. (1983) J. Cell. Biochem. 21, 305-314], suggesting that the same protein kinase is involved. More protein phosphorylation activity is associated with the mature parasites than the immature forms, suggesting that these phosphoproteins may play some role in the parasite's erythrocytic stage cycle.