抑郁障碍患者人格特征与发病关系的研究

目的探讨抑郁障碍患者的人格特征与其疾病发病间的关系。方法采用自评抑郁量表(SDS)、艾森克人格问卷 (EPQ)、应对方式评定量表 (WCRS)和归因方式问卷 (ASQ)对 76名抑郁障碍患者进行测试 ,同时选取 84名健康被试进行对照研究。结果①抑郁组患者在EPQ中神经质 (N)与精神质 (P)的得分显著高于健康组。②WCRS的结果显示在“宣泄接纳”、“退避调节”两个因子上 ,抑郁组的平均得分低于健康组。③在ASQ的得分中 ,抑郁组在负性事件归因的自身性、持久性和整体性均显著高于健康组。④抑郁障碍患者的“神经质”人格特质与应对方式的“宣泄接纳”和“退避调节”因子呈负相关 (r = 0 .474)。结论抑郁障碍患者的人格特征可表现为较强的神经质及孤僻、交往障碍 ,他们这种人格特征及应对和归因方式在其发病过程中起着重要作用。     

Tau immunoreactivity and SDS solubility of two populations of paired helical filaments that differ in morphology

To further understand the processes that lead to the formation of neurofibrillary tangles from paired helical filaments (PHF) in Alzheimer brains, we studied two morphologically distinct fractions of PHF separated on sucrose density gradient. In a fraction with mostly short and non-aggregated PHF, the majority of filaments could be solubilized in SDS. In a fraction containing primarily PHF aggregated into clusters or bundles, sometimes resembling neurofibrillary tangles, filaments were less soluble in SDS. Immunogold labelling with a panel of tau-immunoreactive antibodies demonstrated that N-terminal epitopes of tau were preserved in the short filaments, but were reduced or absent in aggregated filaments. In contrast, C-terminal epitopes were present in both fractions. Furthermore, the accessibility of the microtubule-binding domain to immunolabelling was markedly impaired in short and non-aggregated filaments compared to aggregated filaments. These results are consistent with proteolytic degradation of the N-terminal epitopes and preservation of the C-terminal epitopes and the microtubule-binding domain of tau in the aggregated filaments. Partial proteolysis may be involved in the generation of aggregated PHF in neurofibrillary tangles.     

Solubility of neurofibrillary tangles and ultrastructure of paired helical filaments in sodium dodecylsulphate

Summary Temporal cortex from 14 cases of Alzheimer-type dementia and 6 cases of Down's syndrome, all selected for severe Alzheimer pathology, was homogenised in distilled water, NaOH, or sodium dodecylsulphate (SDS) containing 0.1% -mercaptoethanol. The homogenates were stained with Congo red, and the neurofibrillary tangles and plaque cores were counted under crossed-polarisation microscopy. The number of tangles and plaque cores in the water-treated extracts was not related to age, sex, postmortem interval or duration of dementia. The number of tangles after extraction in SDS or NaOH, as a percentage of tangles in water-treated extracts, was 57±25 (mean±SD) for 1% SDS, 43±17 for 5% SDS and 37±22 for 0.2 M NaOH. Plaque cores were essentially insoluble in all three agents. The percentage of tangles insoluble in 1% SDS did not correlated with age or post-mortem interval but decreased with increasing duration of dementia. Enhanced tangle solubility with increasing duration of dementia suggests that the nature of tangles changes with time; one possibility is that this reflects transformation of intracellular to extracellular tangles. Paired helical filament (PHF) length and the number of repeats per PHF were measured in electron micrographs of PHF prepared with and without treatment by 1% SDS. There was no significant multimodality of PHF length to suggest that PHF broke at regular intervals. The mean repeat length (PHF length/number of repeats) was greater for PHF isolated in the presence of 1% SDS than in its absence, showing that SDS affects ultrastructure by untwisting PHF. An untwisting process may also occur in vivo producing the straight filaments found, together with PHF, in tangles and neurites.Supported by Miss E. Buchan (to the MRC Brain Metabolism Unit) and the British Foundation for Age Research and the Wellcome Trust (to P. A. M. Eagles). S. Hussey was in receipt of an MRC Partnership Award.     

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

Summary Immunocytochemical staining with monoclonal antibodies to the -protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the -protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word plaques does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.Supported in part by grants 5-AGO-4220-05 and 5-HD-22634-02 from the National Institutes of Heath     

Altered structural proteins in plaques and tangles: What do they tell us about the biology of Alzheimer''s disease?

The progressive dysfunction and loss of neurons in Alzheimer's disease (AD) is accompanied by marked structural changes in innumerable neuronal cell bodies and neurites, particularly in limbic and association cortices. Qualitatively indistinguishable neuronal lesions occur in much smaller numbers during normal aging. Highly insoluble paired helical filaments (PHF) and antigenically related straight filaments accumulate in perikaryal tangles and the neurites of neuritic plaques. In addition, PHF antibodies reveal the presence of PHF antigens in many individual cortical neurites not clustered into discrete plaques. Recent studies in several laboratories indicate that altered forms of the microtubule-associated phosphoprotein, tau, are important constituents of PHF. Other neuronal cytoskeletal proteins, particularly microtuble-associated protein 2 and neurofilament, have also been associated with PHF. In contrast, the extracellular amyloid filaments found in the centers of many neuritic plaques and in cortical and meningeal vessels appear to be composed of hydrophobic low molecular weight protein(s) distinct from PHF. A major question for further study regards the cellular origin and role of microvascular amyloid in the degeneration of neurites of multiple neurotransmitter specificities in AD cortex. The widespread neuritic and perikaryal alterations in brain tissue are likely to represent, at least in part, the morphological substrate of cortical dysfunction in AD.     

End-plate currents evoked by paired stimuli in frog muscle fibres

Using voltage-clamp techniques spontaneously occuring miniature end-plate currents (mepc) and nerve-evoked end-plate currents (epc) were recorded in frog glycerol-treated or cut muscle preparations. Epcs were induced by pairs of stimuli (the delay of the 2nd stimulus, t being 6 ms–30 s; one pair was delivered every 60–90 s). The decay time constant of the epc (_epc) was longer, the larger its quantal content despite the presence of active acetylcholinesterase (AChE). After treatment with anticholinesterases (prostigmine or armin, an irreversible inhibitor) this increase in _epc became more pronounced. When AChE was fully active the decay of the 1st epc ₁ was slightly faster than the decay of the 2nd epc ₂ only when the interstimulus interval was rather short (t<20 ms). Following treatment with anticholinesterases this difference between ₂ and ₁ could be determined even when t was as long as 30 s. In anticholinesterase-treated preparations was found to be inversely proportional to log t: a 50% increase in the decay time-constant of the 2nd epc occurred with t=120 ms. During continuous stimulation (10 impulses/s) _epc increased from the 1st to the 5–6th responses, but then decreased in parallel with the fall in the epc amplidude. The phenomenon of postsynaptic potentiation we observed could be readily abolished when quantal content was decreased by the presence of magnesium ions, but it was relatively unaffected when the receptor density was decreased by -bungarotoxin (-BuTX).The possible existence is discussed of two kinds of repetitive binding of ACh molecules, first, to free cholinoreceptors (a process which could be inhibited by -BuTX) and, second, to a complex of the cholinoreceptor plus one molecule of ACh (a process which is less sensitive to -BuTX blocking action).     

Characterization of a shared epitope in cortical Lewy body fibrils and Alzheimer paired helical filaments

The straight fibrils of the Lewy body contain an epitope related to phosphorylation of the KSPV motif common to the C termini of the 200- and 170-kDa neurofilament subunits and . To further characterize this phosphorylated neurofilament/ epitope in Lewy bodies and to analyze the constituents of isolated Lewy bodies we used a combined biochemical and immunochemical approach. In formalin-fixed paraffin-embedded tissue cortical Lewy bodies were labelled by monoclonal antibodies directed to phosphorylation-dependent KSPV epitopes in the sequences of neurofilament and phosphorylation-independent epitopes. Immunoblotting of solubilized Lewy body fibrils with the same antibodies which stained Lewy bodies in tissue sections revealed that the immunoreactive Lewy body proteins were phosphorylated neurofilament subunits. An antibody to the 68-kDa neurofilament subunit labelled Lewy bodies and Lewy body protein at 50–68 kDa. We conclude that the shared phosphorylated epitope in Lewy body fibrils and paired helical filaments is related to the common KSPV sequence in neurofilament and , and that all three neurofilament subunits are present in the Lewy body. This result indicates that although Lewy bodies and neurofibrillary tangles share epitopes they are comprised of distinct structural subunits.Supported by grants from the Parkinson Foundation of Canada and the Alzheimer Society of Canada to C.B. M.S.P. is a recipient of a Medical Research Council of Canada Studentship     

Monitoring pathological assembly of tau and β-amyloid proteins in Alzheimer's disease

This double-labelling confocal microscopy study of the neuropathology of Alzheimer's disease (AD) reports the use of a fluorescent dye, thiazin red, which has staining properties similar to thioflavin-S. Thiazin red fluorescence can be visualised selectively in the red channel, and we have used this property to compare it with the labelling seen using monoclonal antibody (mAb) 423, which detects tau protein C-terminally truncated at Glu-391, and mAb 4G8, which detects -amyloid protein. Thiazin red is shown to recognized the typical histopathological deposits associated with both proteins. However, not all deposits containing these proteins are stained. Specifically, diffuse -amyloid plaques and severely degraded extracellular tangles are unlabelled. Likewise a characteristic mAb 423-reactive granular plaque-like structure, typically present in cases with abundant extracellular tangels, is unlabelled by thiazin red. Such plaques can be shown to be continuous with the basal dendrites of degraded tanglebearing pyramidal cells. These findings suggest that paired helical filaments (PHFs) continue to undergo degradation in the extracellular space, which is associated with loss of thiazin red binding sites, but preservation of mAb 423 immunoreactivity. This epitope appears to be characteristic of a stable core element of the PHF which is highly resistant to proteolysis. Compounds such as thiazin red with high affinity for -pleated protein structures can be used to monitor the state of pathological assembly of amyloidogenic protein species found in AD.Supported in part by CONACyT grant #1624-N9208 (to R.M.), the Medical Research Council (U.K.), Zeneca Pharmaceuticals and the Alzheimer Disease Research Fund and the Leopold Muller Estate     

超声乳化白内障吸除术中对向角膜切口矫正术前角膜散光的临床观察

目的 观察导航系统引导下超声乳化白内障吸除术中在角膜曲率最大子午线上行对向透明角膜切口矫正术前角膜散光的临床疗效.方法 队列研究.选择35例(40眼)术前角膜散光度均大于1.0 D白内障患者为实验组,在表面麻醉下于最大角膜曲率子午线上做2.8 mm对向透明角膜切口;另选27例(30眼)术前角膜散光度均大于1.0 D白内障患者为对照组,在表面麻醉下于最大角膜曲率子午线上做2.8 mm单个透明角膜切口.观察2组术前及术后3个月角膜散光度及平均角膜曲率的变化.根据Jaffe's矢量分析原理计算手术源性角膜散光,采用独立样本t检验与配对t检验进行数据分析.结果 对照组术前及术后3个月角膜散光度分别为(1.84±0.40)D和(1.49±0.36)D,差异有统计学意义(t=7.55,P＜0.05).实验组分别为(1.89±0.74)D和(0.71±0.60)D,差异有统计学意义(t=13.93,P＜0.05).术后3个月2组角膜散光度相比差异有统计学意义(t=-6.31,P＜0.05).2组手术源性散光分别为(0.38±0.18)D和(1.55±0.84)D.对照组术前及术后3个月平均角膜曲率分别为(44.18±1.31)D和(44.14±1.31)D,差异无统计学意义(t=1.21,P＞0.05).实验组分别为(44.33±1.51)D和(44.29±1.52)D,差异无统计学意义(t=0.73,P＞0.05).结论 超声乳化吸除术中行对向透明角膜切口是一种安全、有效的矫正角膜散光的方法.