Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease.     

Partial hydatidiform mole and hypertension associated with a live fetus--variable presentation in two cases

Partial hydatidiform mole associated with live births is a rarecondition. There are not enough cases in the literature to allowthe assessment of comprehensive risks to be made and upon whichmanagement policies can be based. Several clinical dilemmasarise following diagnosis of a viable pregnancy associated withmolar tissue. We present two cases demonstrating the problemsand suggest management based on outcome and a review of theliterature.     

狗股动脉拉伸损伤后的顺应性变化

采用成年狗正常股动脉段６例，测定其拉伸后的压力一容积关系，并求出其顺应性。另取狗股狗股动脉段３０例拉伸固定后，观测其形态结构变化。发现狗股动脉段拉伸后的Ｐ－Ｖ曲线可用抛物线来拟合，狗股动脉段拉伸１５％后顺应性明显下降，其形态结构无明显改变，拉伸３０％后才出现明显的结构改变。狗股动脉拉伸后顺应性变化的出现较形态结构变化早。     

Age-dependent cerebral metabolic effects of unilateral nucleus basalis magnocellularis ablation in rats

To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [14C]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalocortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease.     

An Extension of the Regression of Offspring on Mid-Parent to Test for Association and Estimate Locus-Specific Heritability: The Revised ROMP Method

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP_rev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMP_rev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest.
ROMP_rev was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMP_rev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.     

三个常染色体隐性遗传早发型帕金森病家系的PARKIN基因研究

目的 探讨PARKIN基因与中国人常染色体隐性遗传早发型帕金森病（autosomal recessive early-onset Parkinson’s disease，AREP）家系的关系。方法 对3个AREP家系的6例患者和23位成员进行系统的临床检查并进行PARKIN基因PCR扩增，产物通过变性高压液相色谱（denaturing high—performance liquid chmnatogmphy，DHPLC）进行突变检测，阳性结果标本进行基因测序。结果 所有研究对象的PARKIN基因外显子均扩增成功。DHPLC检测和基因测序发现一个家系中存在PARKIN基因杂合Gly284Arg突变，另一个家系中存在PARKIN基因Ser167Asn多态性，且患者均有环境毒物接触史。结论 PARKIN基因杂合Gly284Arg突变在环境因素的协同作用下可能导致发病。PARKIN基因Ser167Asn多态性是帕金森病的易感因素，汞中毒与其共同作用可能导致发病。     

Long-term outcomes using vascular grafts sealed with fragmented autologous adipose tissue for aortoiliac occlusive disease

The aim of this study was to test the safety and efficacy of fragmented autologous adipose tissue (FAT) grafts for revascularization in aortoiliac occlusive disease. Twenty-seven patients with atherosclerotic aortoiliac occlusive disease underwent surgical treatment using FAT grafts. A piece of adipose connective tissue was obtained from the operative wound, cut into small pieces, and pressed into the wall of a fabric vascular prosthesis. Cumulative primary patency rates were 92% at 1 year, 92% at 3 years, and 86% at 6 years. Cumulative secondary patency rates were 96%, 96%, and 90% for the same intervals. In this clinical study, the FAT grafts demonstrated good long-term patency rates and no particular problems. This is the first clinical report of long-term outcomes using FAT grafts for aortofemoral or aortoiliac bypasses. FAT grafts are thus safe for revascularization in aortoiliac occlusive disease.     

Spontaneous coronary artery dissection mimicking aortic dissection

A 51-year-old woman suffered rapidly irreversible cardiogenic shock with left hemiparesis. Transesophageal echocardiography, which represents an essential imaging tool in the emergency room, ruled out aortic dissection involving branch vessels but did not allow an in vivo diagnosis of spontaneous coronary dissection. The in vivo diagnosis of spontaneous coronary dissection is rather difficult because of the dramatic clinical presentation and selective coronary angiography requirement.