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1.
The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21 000 (p21ras) which are involved in the transduction of stimuli for cell proliferation. There have been conflicting reports about the detection and significance of expression of p21ras protein in human breast disease as determined by immunohistochemistry. The antibody Y13-259, which detects a single protein of Mr 21 000, has been applied immunohistochemically to frozen sections of normal, benign proliferative breast, fibroadenomas, and carcinomas. Uniform staining of normal breast epithelium and myoepithelium was found, with occasional stronger staining in areas of epithelial hyperplasia in benign breast disease. Contrary to previous reports, decreased expression, usually heterogeneous, was found in half of the carcinomas examined. Thirty per cent of the carcinomas exhibited heterogeneous staining stronger than that of normal breast, interpreted as increased expression of p21ras protein. This did not relate to tumour grade or node status but showed a significant correlation with proliferation rate as determined by the monoclonal antibody Ki-67. This study confirms previous reports that p21ras protein expression is a feature of normal cells, and has identified increased expression in 30 per cent of tumours associated with higher proliferation rates, which is a lower incidence than previously claimed when a different antibody was employed. 相似文献
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Warwick JM Carey PD Cassimjee N Lochner C Hemmings S Moolman-Smook H Beetge E Dupont P Stein DJ 《Metabolic brain disease》2012,27(2):151-158
Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed
to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is
however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding
in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised
SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram.
DAT single photon emission computed tomography (SPECT) using 123I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy,
and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The
study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects’ Liebowitz Social Anxiety
Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left
putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup
of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in
DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is
consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration. 相似文献
3.
<正>In the cell,one-carbon metabolism modulates nucleotide synthesis,DNA repair,as well as methylation through the reduction of homocysteine(Figure 1).High levels of plasma homocysteine have been associated with negative health outcomes in humans(Murray et al.,2017).Folates,B-vitamins,are a major component of one-carbon metabolism and play an important role in brain function.Specifically,they are involved in nucleotide synthesis,DNA repair,methylation,second messenger systems,ion channels,protein,and 相似文献
4.
Effect of paternal administration of an antiestrogen, tamoxifen on embryo development in rats 总被引:2,自引:0,他引:2
Balasinor N Gill-Sharma MK Parte P D'Souza S Kedia N Juneja HS 《Molecular and cellular endocrinology》2002,190(1-2):159-166
We have earlier reported that oral administration of tamoxifen causes a dose-dependent reduction in the fertility of adult male rats. The decrease in fertility was mainly due to an increase in pre-implantation loss without an effect on fertilizing ability. During the study, an increased incidence of post-implantation loss of conceptuses sired by tamoxifen-treated male rats was observed. A detailed study was undertaken to investigate dose-related changes in pre- and post-implantation loss and the stage(s) of development at which these losses occurred. The present study demonstrates that tamoxifen treatment produced few normal litters as well as significantly increased pre-implantation loss without affecting the rate of fertilization. Also a significant increase in the number of degenerating embryos at the 2–4-cell stage (days 1–2 of gestation), retrieved from the oviduct/uterus of females mated with tamoxifen-treated males was observed. Histology of the resorbed fetuses, in both control and treated groups, showed presence of trophoblast outgrowth indicative of early placenta formation, which normally occurs on days 8–9 of gestation. The present results suggest that pre-implantation loss occurred at the 2–4-cell stage and the post-implantation loss occurred around days 8–9 of gestation, i.e. around midgestation. The possible effects of paternal tamoxifen treatment on embryogenesis may be due to the reduction of androgens or by the blockage of the estrogen receptor by tamoxifen, thereby affecting germ cell maturation during spermatogenesis. 相似文献
5.
Sperm chromatin packaging is a very complex and highly regulated phenomenon. While most of the sperm chromatin is replaced by protamines, some are retained in nucleosomes. It is recently being recognised that these nucleosomes are intentionally retained and could be contributing to the expression of genes in the very early stages of embryogenesis. Endocrine disruption has been previously shown to affect reproductive outcome and sperm DNA methylation. This study aims to decipher the possibility of changes in nucleosome occupancy in sperm chromatin, induced by tamoxifen (selective oestrogen receptor modulator) and cyproterone acetate (androgen antagonist). We used next‐generation sequencing approach (MNase‐Seq) to identify changes in the nucleosome landscape of the spermatozoa. We demonstrated that endocrine disruption affects nucleosome occupancy at critical regions of the genome and many of them harbour genes relevant for embryogenesis. This study emphasises that environmental factors could affect embryo development by way of modulating male epigenetic factors. 相似文献
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Smith LK Jadavji NM Colwell KL Katrina Perehudoff S Metz GA 《The European journal of neuroscience》2008,27(8):2133-2146
The causes of most cases of Parkinson's disease (PD) are still poorly understood. Here we show that chronic stress and elevated corticosterone levels exaggerate motor deficits and neurodegenerative events in a Parkinson's disease rat model. Animals were tested in skilled and non-skilled movement while being exposed to daily restraint stress or oral corticosterone treatment. Stress and corticosterone compromised normal motor function and exaggerated motor deficits caused by unilateral 6-hydroxydopamine lesion of the nigrostriatal bundle. Moreover, stress and corticosterone treatments diminished the ability to acquire compensatory strategies in limb use during skilled reaching and skilled walking. In contrast, lesion control animals were able to significantly improve in the ability of skilled limb use during the repeated test sessions. The exaggerated motor impairments in stress-treated animals were related to accelerated loss of midbrain dopamine-producing neurons during the first week postlesion. Correlation analysis revealed a significant connection between loss of tyrosine hydroxylase-positive cells and increase in Fluoro-Jade-positive cells only in stress- and corticosterone-treated animals. Furthermore, stress and elevated corticosterone levels caused greater permanent loss of midbrain neurons than found in non-treated lesion animals. These findings demonstrate that stress and elevated corticosterone levels can exaggerate nigral neuronal loss and motor symptoms in a rat analogue of PD. It is therefore possible that stress represents a key factor in the pathogenesis of human PD by impeding functional and structural compensation and exaggerating neurodegenerative processes. 相似文献
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