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111.
The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function.  相似文献   
112.
The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.  相似文献   
113.
Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12–q21 region is very common in the intestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)‐specific and ERBB2‐specific probes on ten specimens of gastric carcinoma that, by using comparative genomic hybridization, showed 1) DNA copy number gain or amplification at 17q12–q21, a region known to harbor the GAS and ERBB2 genes (four cases); 2) gain of the entire chromosome 17 (three cases); or 3) normal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric cancer cell lines with or without gain at 17q12–q21 as well as a breast cancer cell line with ERBB2 amplification. Our results showed that simultaneous amplification of both GAS and ERBB2 was four‐ to ninefold in the tumors with the 17q12–q21 amplification. Both genes were amplified in the same nuclei, and the hybridization signals were localized to the same region of the nucleus. Overexpression of GAS and ERBB2 was observed by Western immunoblotting only in the gastric cancer cell line with gain at 17q12–q21. The ERBB2 amplification is also a recurrent change in breast cancer. To investigate whether the GAS amplification is unique in gastric cancer, fluorescence in situ hybridization analysis was performed on 40 breast cancer cell lines. The ERBB2 amplification was observed in 11 cell lines, but none of the lines showed the GAS amplification. This indicates that the formation of an amplicon, in which both the GAS and the ERBB2 genes are amplified, might be unique in gastric cancer, especially in its intestinal type, and that simultaneous amplification of both genes is important to the tumorigenesis of intestinal gastric cancer. We demonstrate here for the first time that a gene of a physiological hormone is amplified in tumors that originate from cells that normally secrete the hormone. Genes Chromosomes Cancer 24:24–29, 1999. © 1999 Wiley‐Liss, Inc.  相似文献   
114.
Synaptic loss is the best pathological correlate of the cognitive decline in Alzheimer's disease; however, the molecular mechanisms underlying synaptic failure are unknown. We found a non-apoptotic baseline caspase-3 activity in hippocampal dendritic spines and an enhancement of this activity at the onset of memory decline in the Tg2576-APPswe mouse model of Alzheimer's disease. In spines, caspase-3 activated calcineurin, which in turn triggered dephosphorylation and removal of the GluR1 subunit of AMPA-type receptor from postsynaptic sites. These molecular modifications led to alterations of glutamatergic synaptic transmission and plasticity and correlated with spine degeneration and a deficit in hippocampal-dependent memory. Notably, pharmacological inhibition of caspase-3 activity in Tg2576 mice rescued the observed Alzheimer-like phenotypes. Our results identify a previously unknown caspase-3-dependent mechanism that drives synaptic failure and contributes to cognitive dysfunction in Alzheimer's disease. These findings indicate that caspase-3 is a potential target for pharmacological therapy during early disease stages.  相似文献   
115.
Merkel cell carcinoma (MCC) is a rare and aggressive primary neuroendocrine carcinoma of the skin. Large tumours, in particular, show rapid progression and metastatic dissemination, while smaller tumours show less aggressive behaviour. Cyclin A is considered to play a central role in cell cycle control. Its overexpression has been found to correlate with prognosis in many types of carcinomas and sarcomas. Twenty-six MCC patients with complete clinical data were selected. Formalin-fixed paraffin-embedded primary tumour samples were immunohistochemically stained for cyclin A. Correlation between expression of cyclin A and primary tumour size, invasion of subcutaneous tissue, local recurrence, metastasis and survival was statistically analysed. Twenty-five samples expressed cyclin A, and the mean value of positive cells was 25%. Our findings demonstrate that even small and superficial MCC show overexpression of cyclin A. There was no statistical correlation between cyclin A expression and the above-mentioned variables. Cyclin A does not seem to be useful as a prognostic tool. Consequently, size of the primary tumour (>/=2 cm) remains the primary prognostic tool. As a result every tumour, even those small in size, should be considered aggressive and treated radically and rapidly.  相似文献   
116.
The purpose of this study is to review the management and running of the Helsinki Skin Bank between the years 2001 and 2008. Further aims were to assess the microbiological safety of the glycerol‐preserved allograft skin and analyse its clinical use. The files of the Helsinki Skin Bank were reviewed for allograft skin harvested from organ donors between 2001 and 2008. Data on harvested skin area and microbiological culture results were collected. The patients receiving allograft were also identified and operation indications analysed. Allograft skin was collected from 115 donors, with a mean of 44 335 cm2 per year. No skin batches were discarded. Microbiological cultures of the allograft skin batches were negative in 86 (75%) cases. Thirty‐five donor skin batches were used in 69 operations. The most common indication was ‘Biological dressing on partial‐thickness burns', comprising 52% of cases. The cost per cm2 was 0.81. The use of allograft skin in the Helsinki Skin Bank is microbiologically safe and continues to provide a versatile and useful treatment modality in many major burn cases with few observed complications. As compared with synthetically produced temporary dressings currently available, our allograft skin is also more economical.  相似文献   
117.
Phytosterols (PS) are the analogues of animal cholesterol in various plants. beta-Sitosterol is a PS used in margarines and natural remedies to lower elevated serum cholesterol levels. PS enter the ecosystem via pulp mill effluents. The study investigated the endocrine and metabolic effects of PS on the female raccoon dog (Nyctereutes procyonoides), a canid omnivore. Eight female animals were exposed perorally to 8 mg PS/kg/d for 4 wk with 8 animals in the control group. In the PS-treated females, there was a transitory decrease in the plasma estradiol concentrations with an increase in the plasma follicle-stimulating hormone levels. The plasma triiodothyronine concentrations were higher in the PS group. Serum lipid concentrations decreased in PS-treated and control animals. This probably represents a seasonal adaptation. Most of the cholesterol in raccoon dog serum was high-density lipoprotein cholesterol, unlike that in humans but similar to some other carnivores. Liver and kidney ethoxyresorufin O-deethylase activities were lower in the PS treated females. Data indicate that raccoon dogs may not be a sentinel species for PS effects.  相似文献   
118.
119.
BACKGROUND: Estramustine is an anti-mitotic cytostatic drug that also enhances the effect of radiotherapy. The mechanism of radiosensitization is not thoroughly known. Since both radiotherapy and estramustine induce apoptosis in prostate cancer cells, we conducted an experiment to show whether radiosensitization is mediated by apoptosis. MATERIALS AND METHODS: DU-145 human prostate cancer cells were xenografted to nude mice and treated with estramustine for 2 weeks and external radiation for 3 to 6 days (18 to 36 Gy). Tumor regression was measured mechanically and the rate of apoptosis defined by the amount of low molecular weight DNA fragmentation. Follow-up time was 1 to 18 days. RESULTS: The tumor size regressed in the group of mice receiving both radiotherapy and estramustine. Four weeks after the treatment, apoptosis was accentuated in the tumors treated with estramustine or radiation but not with their combination. CONCLUSION: Estramustine potentiates radiotherapy, but not by enhancing radiation-induced apoptosis.  相似文献   
120.
Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a poor prognosis and an unknown cell of origin. Proffered cells of origin include epithelial stem cells of the hair follicle or interfollicular epidermis, dermal stem cells and pro/pre- or pre-B cells. MCC has also been proposed to have more than one cell of origin and indeed to represent more than one type of carcinoma, currently grouped together due to phenotypic similarities. We explored the heterogeneous nature of MCC by studying the most variably expressed genes with the goal of identifying gene expression patterns that are either clinically relevant or have implications regarding the cell(s) of origin. We performed RNA sequencing on primary tumor samples from 102 patients and identified the top 200 most variably expressed genes. These genes and the tumor samples were hierarchically clustered based on their expression. The functions of three gene clusters exhibiting clearly divergent expression between samples were studied by cross-referencing the lists of genes with online databases. High expression of a gene cluster related to embryonic developmental processes and low expression of a gene cluster related to neuroendocrine processes distinguished Merkel cell polyomavirus (MCPyV)-negative tumors from MCPyV-positive tumors. Furthermore, two prognostically relevant subgroups of MCPyV-positive MCC were identified based on dichotomic expression of genes related to epidermal structures and processes. We identified three distinct molecular subgroups of MCC with prognostic relevance. We propose that the dichotomic expression of epidermis-related genes might reflect both an epidermal and a nonepidermal origin for MCPyV-positive MCC.  相似文献   
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