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Eleven cases of newborns with acrania and macroscopically diagnosed anencephaly were neuropathologically examined. They presented changes in which 1 group corresponded to the diagnosis of aprosencephaly. In the second group, the development of prosencephalic structures was more advanced. The pathomechanism of the observed anomalies was analyzed in relation to data provided by molecular-genetic classification of nervous system malformations, but that did not exclude the influence of eventual extrinsic factors.  相似文献   
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Summary To verify our hypothesis of defective protease inhibitor domains that are encoded by abnormal processing of amyloid precursor protein (APP) in brains of patients with neuronal ceroid lipofuscinoses (NCL), immunohistochemical and cytochemical studies were performed with monoclonal antibodies (mAbs) directed against various domains of APP. For the studies, 22 autopsy brains were used: 12 with different forms of NCL, and 10 control brains. The staining procedure for the avidin-biotin complex (ABC) technique and the postembedding gold-labelled procedure for electron microscopy (EM) were employed. Of all mAbs used for the study, only mAbs generated against amyloid B-protein bound to neural tissue were affected with NCL. The strongest immunostaining of neurons and of some reactive glial cells was found in brains with the juvenile form of NCL. Only in the infantile form of the disease were some neurons overloaded with storage material weakly immunoreactive. In brains of patients with the adult form of NCL, immunoreactivity was found in affected neurons and in extracellularly deposited material of senile plaques. The results of EM study showed that the immunoreactivity was restricted to lysosomal cytosomes in neural tissue with any form of NCL selectively localized on the curvilinear and fingerprint proteinaceous component of ceroid lipofuscin. Studies performed on control aging brains and Alzheimer's disease (AD) brains confirmed previous observations of immunoreactivity being found diffusely in the protein component of some neurons containing lipopigment. The defective processing of APP in brains with NCL and AD and in ageing brains is discussed. Our present results support the notion of heterogeneity of ceroid lipofuscin storage material in various forms of NCL and underline the hypothesis that abnormalities found in the protease inhibitors or APP in the proteinaceous composition of storage lipopigment could be a key to the unknown etiology of NCL.Supported by NIH grant NS23717  相似文献   
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Summary The ultrastructural demonstration of acid phosphatase activity in neuronal and glial lipofuscin of the aged human brain indicates lysosomal activity. Contrary to the constantly high enzyme activity of astroglial lipofuscin and low activity of oligodendroglial lipofuscin, the enzyme activity of neuronal pigment differs in different locations, i.e., in different neuronal populations. The activity is probably based on the importation of lysosomal enzymes into the pigment component of lipofuscin. These facts indicate the possibility of a continuous autophagosomal function of lipofuscin in neuronal and glial cell physiology. Therefore, the findings are arguments against the view that lipofuscin is a wear-and-tear material only and claim for it an active role in cell metabolism.Supported by the Deutsche Forschungsgemeinschaft (grant Schl. 141/6)  相似文献   
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