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排序方式: 共有249条查询结果,搜索用时 31 毫秒
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Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
3.
Kristensen Birte Thomsen Preben Dybdahl Palludan Birthe Wegger Inger 《Acta veterinaria Scandinavica》1986,27(4):486-496
Recently an inherited vitamin G deficiency in the pigs presumably based on an autosomal recessive gene was decribed* Homozygotes are in contrast to heterozygotes and normal pigs unable to synthesize ascorbic acid. In an experiment comprising 3 littermate pigs, 2 homozygous and 1 heterozygous for the vitamin C deficiency gene, the influence of ascorbic acid depletion, and repletion on mitogen stimulation of peripheral blood lymphocytes was studied. Ascorbic acid depletion of the vitamin C dependent pigs resulted in a rapid decline in plasma ascorbic acid. Response of lymphocytes to stimular tion with Concanavalin A (Con A) and phytohemagglutinin M (PHA) decreased more slowly reaching a minimum, which coincidedi with the occurrence of the first clinical symptoms of scurvy. Following resupplementation with vitamin C the plasma content of ascorbic acid rapidly returned to normal, while the lymphocyte response to Con A and PHA stimulation only gradually approached the initial values. The repletion with ascorbic acid caused a transitory increase in the response to pokeweed mitogen (PWM) stimulation. The significance of these findings in relation to the cellular immune system in normal pigs is discussed. 相似文献
4.
Kinetic differences between Ca(2+)-dependent K+ channels in smooth muscle cells isolated from normal and atherosclerotic human aorta. 总被引:1,自引:0,他引:1
V Bolotina M Gericke P Bregestovski 《Proceedings. Biological sciences / The Royal Society》1991,244(1309):51-55
The properties of large conductance Ca(2+)-dependent K+ channels in smooth muscle cells (SMC) isolated from normal and atherosclerotic human aorta were studied using the patch-clamp technique. It was shown that SMC from normal human aorta possess a homogeneous population of normal Ca(2+)-dependent K+ channels. In atherosclerotic aorta two kinetically different types of these channels could be distinguished: along with normal 'long' (L)-type channels there appeared channels of 'short' (s)-type. Under similar conditions s-type channels had about a four times shorter mean open time. About five times higher [Ca2+]in was necessary for s-type channels to reach the probability of the channels being open equal to L-type channels. No differences in conductance and voltage dependency were found between the two channel types. Channels of the s-type resembled those previously described in SMC isolated from foetal human aorta. Thus, it can be suggested that during the development of atherosclerosis a population of SMC with s-type Ca(2+)-dependent K+ channels appears in human aorta. 相似文献
5.
Birthe Tegtmeyer Gabrielle Vieyres Daniel Todt Chris Lauber Corinne Ginkel Michael Engelmann Maike Herrmann Christian K. Pfaller Florian W. R. Vondran Ruth Broering Ehsan Vafadarnejad Antoine-Emmanuel Saliba Christina Puff Wolfgang Baumgrtner Csaba Miskey Zoltn Ivics Eike Steinmann Thomas Pietschmann Richard J. P. Brown 《Journal of virology》2021,95(10)
6.
Norbert Pfeiffer Julia Lamparter Adrian Gericke Franz H. Grus Esther M. Hoffmann Jochen Wahl 《Cell and tissue research》2013,353(2):245-251
Intraocular pressure (IOP)-lowering therapy has been shown to arrest or retard the progression of optic neuropathy typical for glaucoma and can, thus, be described as neuroprotective. At present, six classes of medical therapy are employed, namely parasympathomimetics, alpha/beta-sympathomimetics, β-blockers, carbonic anhydrase inhibitors, α2-adrenergic receptor agonists and prostaglandin analogues. For several of these substances, some experimental evidence exists of a possible neuroprotective mechanism, beyond their IOP-lowering activity. β-Blockers are involved in the up-regulation of brain-derived neurotrophic factor (BDNF) and can decrease glutamate-mediated NMDA receptor activation. Not only systemic but also topical carbonic anhydrase inhibitors are able to increase retinal blood flow. α2-Adrenergic receptor agonists can up-regulate the formation of BDNF and anti-apoptotic factors. Prostaglandin analogues increase blood flow to the eye, possibly including the retina. To date, evidence for a neuroprotective effect independent of IOP regulation in human glaucoma is scarce and has only been shown to be likely for the α2-adrenergic receptor agonist, brimonidine. 相似文献
7.
Einar Osland Vik-Mo Marta Nyakas Birthe Viftrup Mikkelsen Morten Carstens Moe Paulina Due-Tønnesen Else Marit Inderberg Suso Stein Sæbøe-Larssen Cecilie Sandberg Jan E. Brinchmann Eirik Helseth Anne-Marie Rasmussen Knut Lote Steinar Aamdal Gustav Gaudernack Gunnar Kvalheim Iver A. Langmoen 《Cancer immunology, immunotherapy : CII》2013,62(9):1499-1509
Background
The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting.Methods
We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor. Brain tumor biopsies were dissociated into single-cell suspensions, and autologous CSCs were expanded in vitro as tumorspheres. From these, CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs. The DCs were aliquoted to 9–18 vaccines containing 107 cells each. These vaccines were injected intradermally at specified intervals after the patients had received a standard 6-week course of post-operative radio-chemotherapy. The study was registered with the ClinicalTrials.gov identifier NCT00846456.Results
Autologous CSC cultures were established from ten out of eleven tumors. High-quality RNA was isolated, and mRNA was amplified in all cases. Seven patients were able to be weaned from corticosteroids to receive DC immunotherapy. An immune response induced by vaccination was identified in all seven patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test).Conclusion
These findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival. 相似文献8.
John J. Milledge Birthe V. Nielsen David Bailey 《Reviews in Environmental Science and Biotechnology》2016,15(1):67-88
Marine seaweeds represent an abundant source of natural products and may harbour valuable chemicals. The brown seaweed Sargassum muticum is an invasive species to the coasts of the British Isles, mainland Europe and North America. Attempts at its eradication and control have generally not been successful, although time-consuming and costly. Commercial exploration of this biomass for food, fuel and pharmaceutical products could encourage its harvesting and control. Though S. muticum might be unsuitable as a source of biofuel due to high ash and water content, this rapidly growing macroalga has a naturally high content of antioxidants, carotenoids and phenols, including the well-known anti-cancer compound fucoxanthin, making this species a potential source of a range of pharmaceutically relevant materials. 相似文献
9.
Birthe Thormann Dirk Ahrens Diego Marín Armijos Marcell K. Peters Thomas Wagner Johann W. W?gele 《PloS one》2016,11(2)
Background
Tropical mountain forests are hotspots of biodiversity hosting a huge but little known diversity of insects that is endangered by habitat destruction and climate change. Therefore, rapid assessment approaches of insect diversity are urgently needed to complement slower traditional taxonomic approaches. We empirically compare different DNA-based species delimitation approaches for a rapid biodiversity assessment of hyperdiverse leaf beetle assemblages along an elevational gradient in southern Ecuador and explore their effect on species richness estimates.Methodology/Principal Findings
Based on a COI barcode data set of 674 leaf beetle specimens (Coleoptera: Chrysomelidae) of 266 morphospecies from three sample sites in the Podocarpus National Park, we employed statistical parsimony analysis, distance-based clustering, GMYC- and PTP-modelling to delimit species-like units and compared them to morphology-based (parataxonomic) species identifications. The four different approaches for DNA-based species delimitation revealed highly similar numbers of molecular operational taxonomic units (MOTUs) (n = 284–289). Estimated total species richness was considerably higher than the sampled amount, 414 for morphospecies (Chao2) and 469–481 for the different MOTU types. Assemblages at different elevational levels (1000 vs. 2000 m) had similar species numbers but a very distinct species composition for all delimitation methods. Most species were found only at one elevation while this turnover pattern was even more pronounced for DNA-based delimitation.Conclusions/Significance
Given the high congruence of DNA-based delimitation results, probably due to the sampling structure, our study suggests that when applied to species communities on a regionally limited level with high amount of rare species (i.e. ~50% singletons), the choice of species delimitation method can be of minor relevance for assessing species numbers and turnover in tropical insect communities. Therefore, DNA-based species delimitation is confirmed as a valuable tool for evaluating biodiversity of hyperdiverse insect communities, especially when exact taxonomic identifications are missing. 相似文献10.