18F]-Dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism.

There are few reports of positron emission tomography (PET) in juvenile parkinsonism (JP). We report on the results of (18)F-6-fluoro-L-dopa (FD) PET in a 14-year-old patient with JP of 5 years duration associated with atypical features. This is the youngest subject to be investigated to date. There was a severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient in the putamen similar to that seen in adult-onset idiopathic parkinsonism. Extensive DNA analysis in this patient did not show mutations in the parkin gene.     

Dementia in Parkinson's disease: a post-mortem study in a population of brain donors

OBJECTIVE: To identify factors associated with dementia in a cohort of Parkinson's disease (PD) brain donors and determine whether its presence may influence the clinical phenotype of the disease. METHODS: We included 67 consecutive patients with a clinical and pathological diagnosis of PD, who while alive, consented to donate their brains to the University of Miami Brain Endowment Bank(TM). Dementia and psychiatric complications of PD were diagnosed according to established criteria. Case histories were abstracted and reviewed and comparisons between PD patients with (PD-D, n = 34) and without (PD, n = 33) dementia were made. RESULTS: Age at death, age at disease onset and disease duration did not differ significantly between PD-D and PD patients. Other symptoms were similar in both groups. Visual hallucinations and bilateral symptoms at diagnosis were significantly higher in PD-D patients. No association between dementia and overall survival duration was found. Although the frequency of depression and psychosis was higher in the PD patients with dementia no statistical significance was reached. The overall lifetime prevalence of dementia in our group was 50.7%. CONCLUSIONS: Visual hallucinations and bilateral symptoms were associated with dementia in our cohort of PD brain donors. No association between dementia and survival duration was found. Understanding the influence of dementia on the clinical phenotype of the disease and predicting its development is essential for the successful management of PD.     

Watching social interactions produces dorsomedial prefrontal and medial parietal BOLD fMRI signal increases compared to a resting baseline

Some human brain areas are tonically active in a resting state when subjects are not engaged in any overt task. The activity of these areas decreases when subjects are engaged in a wide variety of laboratory tasks designed to study cognitive operations. It has been suggested that these areas, among them the medial parietal (precyneus) and the dorsomedial prefrontal cortices, may support a "default state" of the human brain. Passive visual observation of laboratory stimuli typically yields no change in activity in these default areas compared to rest. Here we report functional magnetic resonance imaging (fMRI) data on normal subjects watching realistic movie clips depicting everyday social interactions. In contrast with previous findings on default state brain areas, the observation of the relational segment of the movie clip, during which two persons interact, yielded increased activity in the medial parietal (precuneus) and dorsomedial prefrontal cortices, compared to rest and to observation of the segment of the movie clip depicting a single individual engaged in everyday activities. To the best of our knowledge, this is the first report of joint increased activity in medial parietal and dorsomedial prefrontal cortices. We suggest that the default state areas may participate in the processing of social relations in concert with regions previously identified as critical for social cognition that were also activated by our stimuli, including the inferior frontal cortex, the superior temporal cortex, and the fusiform gyrus.     

胃肠胰胰岛淀粉样多肽的定位和表达

胰岛淀粉样多肽(islet armyloid polypeptide,IAPP)是1986年瑞典学者Westermarket al[1,2 ]从胰岛素瘤患者的瘤组织,糖尿病猫及Ⅱ型糖尿病患者胰岛淀粉样沉积物中分离出来的一种多肽,几乎在同时,英国生物化学家Cooper et al[3,4]也从Ⅱ型糖尿病患者的胰岛淀粉样沉积物中分离出该肽.IAPP又称为amylin.对IAPP的分子结构、基因表达和生理作用等已有许多报道[5].近年来,在IAPP定位、表达及胃肠胰IAPP免疫反应(immunoreactive,IR)细胞定位、发生、发育方面的研究报道,为探讨IAPP的生理作用及疾病状态下的改变,提供了形态学依据,现综述如下.     

Ameliorating effect of microdoses of a potentized homeopathic drug,Arsenicum Album,on arsenic-induced toxicity in mice

Background  

Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols.     

抗血管生成因子Angiostatin与Endostatin作用下肿瘤血管生成的二维数值模拟

目的数值模拟抗血管生成因子Angiostatin和Endostatin对肿瘤血管生成的影响。方法建立肿瘤内外血管生成的二维离散数学模型。模型耦合两种抗血管生成因子Angiostatin和Endostatin的抑制效应,数值模拟在促血管生成因子诱导下肿瘤微血管网生成,讨论血管生成抑制因子的影响。结果抗血管生成因子Angiostatin对肿瘤内外血管网络生成的速度和成熟度有抑制作用。抗血管生成因子Angiostatin和Endostatin耦合作用时,在肿瘤血管生成的早期有明显的抑制效应;在肿瘤血管生成的中后期,它们可以降低肿瘤血管化程度。结论本文模型能够较好的模拟抗血管生成因子Angiostatin和Endostatin对内皮细胞迁移和增殖的抑制作用。     

Pharmacologic and genetic inhibition of hsp90-dependent trafficking reduces aggregation and promotes degradation of the expanded glutamine androgen receptor without stress protein induction

The molecular chaperone hsp90 has emerged as an important therapeutic target in cancer and neurodegenerative diseases, including the polyglutamine expansion disorders, because of its ability to regulate the activity, turnover and trafficking of many proteins. For neurodegenerative disorders associated with protein aggregation, the rationale has been that inhibition of hsp90 by geldanamycin and related compounds activates heat shock factor 1 (HSF1) to induce the production of the chaperones hsp70 and hsp40 that promote disaggregation and protein degradation. However, we show here that geldanamycin blocks the development of aggregates of the expanded glutamine androgen receptor (AR112Q) of Kennedy disease in Hsf1(-/-) mouse embryonic fibroblasts where these chaperones are not induced. Geldanamycin is additionally known to inhibit hsp90-dependent protein trafficking and to promote proteasomal degradation of client proteins. Overexpression of the hsp90 cochaperone p23 also promotes AR112Q degradation, and inhibits both AR trafficking and AR112Q aggregation without altering levels of hsp70 or hsp40. The hsp90-dependent trafficking mechanism has been defined, and it is shown that key immunophilin (IMM) components of the trafficking machinery are present in polyglutamine aggregates in cell and mouse models of Kennedy disease. Our results indicate that inhibition of the hsp90-dependent trafficking mechanism prevents aggregation of the expanded glutamine androgen receptor, thereby opening a variety of novel therapeutic approaches to these neurodegenerative disorders.     

Serological Evidence of Acute Infection with the Chlamydia-Like Microorganism Simkania negevensis (Z) in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

The aims of this study were twofold: (i) to test for possible associations between serological evidence of acute Simkania negevensis (Sn) infection and acute exacerbation of chronic obstructive pulmonary disease and (ii) to examine the prevalence of past infections with Sn in patients with chronic obstructive pulmonary disease. In 120 patients (63%) there was serological evidence of past infection with Sn, which was not significantly different from the rate in a control population. In five hospitalizations serological evidence existed of acute infection with Sn around the time of the exacerbation of chronic obstructive pulmonary disease. In four of these cases, there was serological evidence of acute infection with at least one other respiratory pathogen. It is concluded that Sn can be associated serologically with exacerbation of chronic obstructive pulmonary disease, in most cases together with other respiratory pathogens. The implications of these findings should be investigated further. Electronic Publication     

Pneumococcal community-acquired pneumonia in 148 hospitalized adult patients

In a previous prospective study,Streptococcus pneumoniae was identified as the causative agent in 148 (42.8%) of 346 adult patients hospitalized over the course of one year with community-acquired pneumonia (CAP) in the Soroka Medical Center, Beer-Sheva, Israel. The present study characterizes those cases in whichStreptococcus pneumoniae was the only pathogen and those in which additional etiological agents were identified. Pneumococcal CAP was diagnosed by standard blood cultures or positive serological tests by one of two laboratory methods. In 100 (67.6%) patients, at least one other etiological agent of CAP was identified in addition toStreptococcus pneumoniae. Compared with patients who were not infected byStreptococcus pneumoniae, patients withStreptococcus pneumoniae CAP were older and had a higher rate of comorbidity (39.5% vs. 29.8%).Streptococcus pneumoniae CAP had a more severe clinical course and a higher mortality rate, especially whenStreptococcus pneumoniae was the only pathogen. Community-acquired pneumonia due toStreptococcus pneumoniae only was more similar in its clinical manifestations to classic typical pneumococcal pneumonia. When an additional etiological agent was identified, the clinical characteristics could not be distinguished from those of atypical pneumonia. It is concluded thatStreptococcus pneumoniae remains the principal cause of CAP in this region. The frequency of additional etiological agents of CAP and the difficulty in differentiating clinically between cases due toStreptococcus pneumoniae only and those due toStreptococcus pneumoniae plus other organisms necessitates initial empirical treatment that coversStreptococcus pneumoniae as well as other causative agents of atypical pneumonia.