Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Abeta and RAGE peptides

Plasma samples derived from 33 Alzheimer's disease (AD) and 42 control participants were subjected to several steps to purify specific anti-(amyloid)Abeta IgGs. Affinity-purified IgGs binding the peptide Abeta1-42, a neurotoxic sequence derived from the trans-membrane amyloid precursor protein, exhibited nearly four-fold higher titers in AD patients compared with their control non-AD cohort. Affinity-purified IgGs binding a fragment of the receptor for advanced glycation end products (RAGE) likewise were increased nearly three-fold in AD individuals. Abeta and RAGE IgG titers were negatively correlated with cognitive status, i.e. the more cognitively impaired individuals tended to exhibit higher IgG titers. Abeta IgG titers were negatively correlated with age in the control group, but not with the AD group. Levels of circulating AB- and RAGE-like proteins were not different between AD and control participants, nor was there a relationship between individual IgG titers and the respective Abeta- and RAGE-like proteins. Freshly prepared leukocyte preparations were subjected to flow cytometric analysis. AD individuals exhibited significantly increased populations of cells expressing binding sites for monoclonal antibodies directed against Abeta (5.5-fold), betaAPP (3.5-fold), and RAGE (2.6-fold) relative to the control group. These findings confirm the presence of circulating IgGs specifically directed at proteins implicated in immunological processes linked to AD. The close relationship between titers for Abeta and RAGE IgGs suggests the possibility that the antibodies are being produced in response to a common mechanism or protein complex (with the respective epitopes) linked to the disease.     

The development of resistance in different inbred strains of mice to infection with Nematospiroides dubius

Infection by the intestinal nematode parasite Nematospiroides dubius was studied in seven different inbred mouse strains. Although there was some minor variation in the susceptibility of the different strains to a primary infection there were marked differences in their ability to develop resistance to infection following repeated exposure to infective larvae. The strains of mice which developed the best resistance also expelled adult worms arising from the previous infections. The adult worms resulting from a primary infection were slowly eliminated in two inbred strains studied whereas no loss occurred from outbred LACA mice. Although males and females of two strains, C3H/HeJ and CBA/H were equally susceptible to a primary infection, the females developed better resistance than the male mice following two oral administrations of third stage larvae. Infected mice of every strain and both sexes contained high levels of IgG1 in the serum.     

Association between statin use and Alzheimer's disease

CONTEXT: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been associated with a decreased risk for Alzheimer's disease (AD). OBJECTIVE: To evaluate the association between statin use and AD adjusted for comorbid medical conditions. DESIGN: A nested case-control study. PATIENTS: Patients at the Veterans Affairs Medical Center in Birmingham, Ala., USA with a new diagnosis of AD (cases) between 1997 and 2001 (n = 309) and age-matched non-AD controls (n = 3,088). MAIN OUTCOME MEASURE: Odds ratio for association between AD and statin use. RESULTS: Statin users had a 39% lower risk of AD relative to nonstatin users (odds ratio 0.61, 95% confidence interval 0.42-0.87). This association appeared to be modified by the presence of certain chronic medical conditions (i.e., hypertension, ischemic heart disease and cerebrovascular disease) in that the reduced risk was observed among those with these diseases, whereas no association was observed among those without any of these conditions. CONCLUSIONS: In this study, following adjustment for confounding factors, a statistically significant inverse association between statin use and AD was observed. The results lend support to looking at AD outcomes in trials of statins to further evaluate their possible beneficial effects.     

骨骼肌缺血再灌注损伤及发病机制初探

目的：探讨骨骼肌缺血再灌注损伤过程的微循环变化。组织学改变以及多肽含量变化和意义。方法：42只雄性大鼠随机分为留伴行神经组和去伴行神经组,建立标准骨骼肌缺血再灌注模型,采用激光多谱勒及显微放大分析系统,组织学方法以及凝胶电泳方法等观察缺血再灌注损伤变化。结果：缺血再灌注损伤后的骨骼肌微血管管径在20分钟时恢复率基本达到高峰约60％,此后为平台期：90分钟最高峰,为75％,主干血管流速率亦在20分钟基本达到上限,病理检查显示：缺血的骨骼肌纤维呈空泡状,核形态增大,染色加深,红细胞严重聚集,凝胶蛋白电泳提示：缺血骨骼肌中分子量20KD左右的多肽显著增加。结论：骨骼肌缺血再灌注损伤发生后,骨骼肌的微循环发生不同程度的破坏,及因之导致骨骼结构损伤和异常的20KD多肽含量明显增加,以及红细胞凝聚,白细胞的改变,这些共同构成了缺血再灌注损伤机制。     

Unilateral cerebral inactivation produces differential left/right heart rate responses

We studied heart rate following unilateral hemispheric inactivation by intracarotid amobarbital in 25 patients undergoing preoperative evaluation for epilepsy surgery. Heart rate increased after left hemisphere inactivation, but decreased following right hemisphere inactivation. The results are consistent with differential left/right cerebral hemispheric effects on autonomic function, and appear related to functional and anatomic asymmetries in both the central and peripheral nervous systems.     

Reproducibility of P3.

The P3 event-related potential has been widely employed in both clinical and research investigations. In the present study, P3 latency and amplitude intersession reliability were evaluated in 4 sessions over an average of 33 days in 24 healthy adults using the P3 tonal oddball paradigm. Mean group latencies ranged from 302-305 ms and mean amplitudes ranged from 7.75-8.87 microV. No significant group differences were found across sessions for latency or amplitude. Intrasubject variability was large; the 95% confidence interval for the difference between the means of two combined sessions was +/- 20 ms for latency and +/- 4.63 microV for amplitude. The results suggest that P3 latency and amplitude are reliable and reproducible over weeks for groups, but have greater variability for individuals.