Genetic variation in a haplotype block spanning IDE influences Alzheimer disease

Linkage studies have identified a large (>60-Mb) region on chromosome 10q that segregates with Alzheimer Disease (AD). Within the region, the gene for insulin degrading enzyme (IDE) represents a notable biological candidate given that it degrades amyloid beta-protein (one of the major constituents of senile plaques) and the intracellular amyloid precursor protein (APP) domain released by gamma-secretase processing. We have used a single nucleotide polymorphism (SNP) genetic association strategy to investigate AD in relation to a 480-kb region encompassing IDE. A 276-kb linkage disequilibrium block was revealed that spans three genes (IDE, KNSL1, and HHEX). Assessing this block in several independent sets of case-control materials (early- and late-onset AD) and focusing also upon quantitative measures that are pertinent to AD diagnosis and severity (MMSE scores, microtubule-associated protein Tau [MAPT] levels in CSF, degree of brain pathology, and age-at-onset) produced extensive evidence for significant AD association. Signals (p-values ranging from 0.05 to <1x10(-9)) were generally stronger when examining haplotypes rather than individual SNPs, and quantitative trait tests most uniformly revealed the detected associations. Consistent risk alleles and haplotypes were apparent across the study, with effects in some cases as large as that of the epsilon4 allele of APOE. A subsequent mutation screen of exons in all three suspect genes provided no evidence for common causative mutations. These results provide substantial evidence that genetic variation within or extremely close to IDE impacts both disease risk and traits related to the severity of AD.     

The effects of single oral doses of 17β-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud's phenomenon

The effects of sex, the menstrual cycle, oral contraceptives, pregnancy, and the menopause on skin perfusion in healthy women and in patients with Raynaud's phenomenon suggest a role of female sex hormones. However, no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found. The aim of this study was to investigate the effect of orally administered 17-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud's phenomenon.In each subject standardized finger heating (45°;C water bath, 10 min) and cooling tests (15°;C water bath, 5 min and 20 min recovery) were performed twice on the second (or third) day of two consecutive menstrual cycles. 17-Oestradiol (9 mg) or progesterone (300 mg) were given before the second test, after a first test with placebo. Both hormonal doses resulted in (high) physiological concentrations. Fingertip skin temperature and laser Doppler flux were measured.There were no significant differences in the test results after placebo and after progesterone. Although values of fingertip skin temperature and laser Doppler flux after 17-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance: fingertip skin temperature respectively with placebo and with oestradiol (mean (SD)): 32.7 (1.0) and 33.1 (0.8)°;C; laser Doppler flux with placebo and with oestradiol: 33.6 (11.7) and 42.2 (9.5) perfusion units; both P<0.05). In this study, single oral doses of female sex hormones had only minor effects on finger skin circulation, both in control subjects and in women with Raynaud's phenomenon.     

The vibratory innocent heart murmur in schoolchildren: A case-control Doppler echocardiographic study

Summary In 810 schoolchildren (aged 5–14 years) the prevalence of a grade 1–3/6 vibratory innocent heart murmur (VIHM) is 41%. Restricted to a grade 2 or 3 VIHM, the prevalence is 14%, decreasing from 21% in the age-class 5–6 years to 8% for children 13–14 years of age. The prevalence of a grade 3 VIHM is 1%. Together with a matched control, 84 children with a grade 2 or 3 VIHM underwent further cardiologic examination including electrocardiography, phonocardiography, and Doppler echocardiography. A positive correlation was found between the presence of a VIHM and higher left ventricular voltages on the ECG, but within the normal range; lower heart rate; smaller diameter of the ascending aorta (AAO); and higher blood flow velocity and higher maximal acceleration of the blood flow in the LVOT and the AAO. In 40% of the children with a VIHM, a systolic aortic valve vibration was seen with a frequency 100 Hz and an amplitude 1 mm, whereas this type of vibration was present in only one case control. No significant difference was found concerning the prevalence of false tendons in the left ventricle, systolic and diastolic diameter of the left ventricle, systolic time intervals, and shortening fraction of the left ventricle. The VIHM is strongly associated with a smaller AAO, with higher velocity and acceleration of the blood flow in the LVOT and AAO, and with a vibratory phenomenon of the aortic valve, pointing towards the LVOT-aortic valve region as the site of origin of the VIHM.     

Memory and learning are not impaired in presymptomatic individuals with an increased risk of Huntington's disease

Retrieval from long-term memory in patients with brain injuries was investigated with a memory scanning paradigm (Conway & Engle, 1994), that allows dissociation of scanning processes within short-term memory and memory retrieval processes from long-term memory. The study focused on the influence of brain injury on memory retrieval processes that are assumed to be automatic. Thirteen patients with memory impairment and 13 healthy matched control subjects were tested. In general, patients showed increased reaction times, but they showed set size independent retrieval from long-term memory indicating preserved automatic retrieval processes. In a subgroup of patients with more severe memory deficits, however, automatic retrieval processes appeared not to be intact. Learning profiles of the patients were characterized by smaller item chunks, indicating differences in the process of information acquisition.     

Surfactant protein A and stable microbubble formation in tracheal aspirates

This study aimed to determine the role of surfactant protein A (SP-A) in the formation of stable microbubble in tracheal aspirates. Our results showed that as the concentration of anti SP-A antibodies added to tracheal aspirate specimens increased, the number of stable microbubble formed in the specimen decreased. The correlation between stable microbubble counts and the SP-A levels in the tracheal aspirates was good, r = 0.85, p < 0.05. This study suggests that SP-A plays an important role in stable microbubble formation. Measurement of small stable microbubbles is thus a useful bedside test for predicting the SP-A activity in the tracheal aspirates and in indirect measurement of lung maturity.     

Radiocontrast-induced nephropathy in a pair of xiphaomphalopagus conjoined twins during the neonatal period

One of the babies in a pair of xiphaomphalopagus conjoined twins developed oliguria, transient rise in serum creatinine and persistent nephrogram on the sixth day of life following injection of radiocontrast medium for computerised axial tomography scanning of the urinary system. The other twin was spared but developed hypertension and "dialysed" the oliguric twin. The renal profiles of both neonates subsequently remained normal until they reached adequate weight for surgical separation at a later date.     

抗补体蛋白对大鼠局灶脑缺血损伤的作用

0　引言　近年来脑缺血损伤的早期炎症受到重视 .有学者观察到在人脑梗塞部位白细胞集聚 ,临床预后与梗塞部位的白细胞数量有关 ,白细胞多者预后差 [1 ] .还有文献描述了大鼠持续性脑缺血损伤中的多形核中性细胞反应的时间过程 ,收稿日期 :1999-0 3 -2 6;　修回日期 :1999-0 5 -13基金项目 :国家自然科学基金资助项目 ( 3 9170 3 15 ) ;全军医药卫生科研基金资助项目 ( 92 5 0 5 2 )作者简介 :刘　立 ( 195 8-) ,男 (汉族 ) ,江苏省无锡市人 .副教授 ,博士 .Tel.( 0 2 9) 3 3 74819缺血 30 min就可以观察到多形核中性细胞于缺血部位的微血…     

Expression and characterization of Gag protein of HIV-1（CN） in Pichia pastoris

To express the core protein of HIV-1 of Chinese prevalent strain （HIV-1 （CN）） in Pichia pastoris, the fulllength gag gene was inserted into the secretory expression vector pHILS1. Linearized recombinant plasmid pHILGAG by Sail was electrotransformed into the yeast strain GS115, and the yeast transformants were identified by PCR. To induce the interest protein to be expressed, the PCR positive transformants were inoculated in the medium of BMGY and BMMY, mRNA of the strain was detected by RT-PCR, and the expressed protein was analyzed by SDS-PAGE, Western blotting and thin layer scanning. mRNA （1.3 kb） was amplified by RT-PCR. SDS-PAGE and Western blotting analysis showed that the molecular mass of the expressed protein was 55 kD, which was similar to the expected value, and the expressed protein could react with McAb to HIV-1 p24. Thin layer scanning analysis demonstrated that the whole amount of the expressed protein was approximately 13 % of the soluble protein in the supernatant. The recombinant yeast had good genetic stability. The optimal expression conditions of the engineering yeast were as follows： BMMY medium, 80-90% of dissolved oxygen, 1% methanol, and 3-day-cultivation course. Gag proteins were expressed under the optimal expression condition and purified via gel filtration chromatography. The purity of the interest protein was up to 85 %. After the purified proteins were inoculated into BALB/c mice, the anti-HIV-1 antibodies in the immunized mice could be detected by Western blotting.     

DNA vaccination using bacillus Calmette-Guerin-DNA as an adjuvant to enhance immune response to three kinds of swine diseases

In order to enhance the immune efficacy of DNA vaccination, experiments were conducted to investigate the regulating effects of Bacillus Calmette-Guerin （BCG）-DNA as an adjuvant on immune responses of mice against foot-and-mouth disease （FMD）, Aujeszky＇s disease （AID） and classical swine fever （CSF）. BCG-DNA was purified from BCG by ion-exchange chromatography. Three DNA vaccines （pVSG, pVgD and pVE2） against the respective infection were constructed, and BCGDNA was coimmunized to mice by muscle injection. The results showed that titres of specific immunoglobulin （Ig）G to the vaccines mounted remarkably in the sera of the adjuvant covaccinated mice （P〈0.01）. Antibody isotype IgG2a and IgG1 also increased, respectively, in mice coimmunized with BCG-DNA compared with those of the control groups （P〈0.01）. Cellular immune cytokine interferon-gamma and cytotoxic T lymphocytes were detected in coimmunized BCG-DNA groups （P〈0. 05）. Whereas interleukin-4, humoral immune cytokine, was not significant （P〉 0. 05）. These results suggest that codelivery of BCG-DNA with DNA vaccines against FMD, AjD and CSF can enhance the induction of antigen-specific, especially, cell-mediated immunity.