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排序方式: 共有185条查询结果,搜索用时 15 毫秒
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1,1-Dichloro-2, 2-bis(4-chlorophenyl)ethene (DDE), amajor lipophilic metabolite of 1,1,1-trichloro-2, 2-bis(4'-chloro-phenyDethane(DDT), is a hepatic carcinogen in both the mouse and hamsterupon chronic exposure. DDT is tumori-genic only in the formerspecies. The metabolism in the mouse of [14C-UL-phenyl]DDE withand without 5-month DDE pretreatment, is reported. The urine,feces and liver were analyzed and in all cases most of the radioactivityobserved was identified as unchanged DDE. The only metaboliteidentified was the phenolic derivative l, l-dichloro-2-(4-chloro-phenyl)-2-(3"-hydroxy-4"-chlorophenyI)ethene,which was found in significant amounts only in the feces. Noother potential metabolites derived from the oxidation of DDEwere observed. The effect that pretreatment with DDE had onits own metabolism was to decrease the urinary excretion ofDDE and to increase the hepatic levels. It appears from theseresults that any oxidative metabolism of DDE constitutes a veryinsignificant pathway in the mouse. It is also concluded thatthere is no significant change in the metabolism of DDE afterprolonged exposure to the pesticide, and there is no indicationfor the metabolism of DDE to a reactive electrophilic species. 相似文献
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Minggu Zhu Haifeng Yuan Wen Guo Xinyan Li Lin Jin Ulf T. Brunk 《Nutrition and cancer》2013,65(3):464-472
In a Wistar rat model, prolonged supplementation of mustard seed (MS) to the diet significantly ameliorates the induction of colorectal carcinomas by 1,2-dimethylhydrazine (DMH). The expression of the splenocyte major histocompatibility complex class I (MHCI) was found significantly enhanced, whereas that of the major histocompatibility complex class II (MHCII) was significantly decreased. Compared to that of control animals, the proportion of spleenic B- and dendritic cells (DC) was amplified in the MS group. The expressions of MHCI, as well as that of MHCII, were increased in DC cells; whereas in B cells, MHCI expression was augmented but that of MHCII moderately decreased. The percentages of CD8+CD28+ and CD4+CD28+ cells were increased in the MS group, while the CD4+CD25+Foxp3+ subset was depressed. Plasma analysis showed that DMH-exposure induced amplified amounts of interleukin (IL)-4, IL-5, IL-10, and transforming growth factor-beta, whereas MS feeding counteracted this effect but enhanced IL-2, IL12p70, IL21, TNF-alpha, and interferon-gamma. In the SW480 colon adenocarcinoma cell-line, the cytotoxicity of spleenic T-cells from MS-fed animals was significantly increased. In the DMH-exposed rats, the expression of perforin in the spleenic T-cells was dramatically decreased, whereas MS abolished this depression. In summary, dietary MS suppresses DMH-induced immuno-imbalance as well as colon carcinogenesis in rats. 相似文献
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Fabian Brunk Andreas Moritz Annika Nelde Tatjana Bilich Nicolas Casadei Sabine A. K. Fraschka Jonas S. Heitmann Sebastian Hörber Andreas Peter Hans-Georg Rammensee Harpreet Singh Juliane Walz Dominik Maurer Claudia Wagner 《European journal of immunology》2021,51(11):2651-2664
Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells—with the indispensable help of CD4+ T cells—are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8+ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2. 相似文献
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Yuan XM Li W Dalen H Lotem J Kama R Sachs L Brunk UT 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(9):6286-6291
The tumor suppressor wild-type p53 can induce apoptosis. M1-t-p53 myeloid leukemic cells have a temperature-sensitive p53 protein that changes its conformation to wild-type p53 after transfer from 37 degrees C to 32 degrees C. We have now found that these cells showed an early lysosomal rupture after transfer to 32 degrees C. Mitochondrial damage, including decreased membrane potential and release of cytochrome c, and the appearance of apoptotic cells occurred later. Lysosomal rupture, mitochondrial damage, and apoptosis were all inhibited by the cytokine IL-6. Some other compounds can also inhibit apoptosis induced by p53. The protease inhibitor N-tosyl-l-phenylalanine chloromethyl ketone inhibited the decrease in mitochondrial membrane potential and cytochrome c release, the Ca(2+)-ATPase inhibitor thapsigargin inhibited only cytochrome c release, and the antioxidant butylated hydroxyanisole inhibited only the decrease in mitochondrial membrane potential. In contrast to IL-6, these other compounds that inhibited some of the later occurring mitochondrial damage did not inhibit the earlier p53-induced lysosomal damage. The results indicate that apoptosis is induced by p53 through a lysosomal-mitochondrial pathway that is initiated by lysosomal destabilization, and that this pathway can be dissected by using different apoptosis inhibitors. These findings on the induction of p53-induced lysosomal destabilization can also help to formulate new therapies for diseases with apoptotic disorders. 相似文献
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Arif Asif Hector Castro Ahmed Ameen Waheed Vishesh Kumar Syed S Haqqie Gary Siskin Roy O Mathew Darius Mason Tushar Vachharajani Ali Nayer Donna Merrill Muhammad UT Akmal Loay Salman 《Seminars in dialysis》2013,26(4):E30-E32
A retrospective study evaluating the pattern of blood pressure and its related complications before, during, and after percutaneous hemodialysis interventions was performed in patients presenting with asymptomatic hypertension. Hemodialysis patients undergoing percutaneous interventions including tunneled hemodialysis catheter insertion, percutaneous balloon angioplasty and thrombectomy procedure, and stage II hypertension (systolic blood pressure ≥160 mmHg) were included in this analysis. Blood pressure medications were not used while midazolam and fentanyl were routinely administered. Patients were followed for up to 4 weeks to monitor any complications. The mean blood pressure before, during, and after the procedures were 185 ± 18/96 ± 14, 172 ± 22/92 ± 15, and 153 ± 25/87 ± 14, respectively. There was a statistically significant difference between the blood pressure readings before and after the procedure (before = 185 ± 18/96 ± 14, after = 153 ± 25/87 ± 14; p = 0.001). None of the patients had a stroke, myocardial infarction, or acute pulmonary edema before, during, or after the procedure or during the 4‐week follow‐up period. A significant reduction in blood pressure was observed after the procedure without the administration of any antihypertensive medication. These results suggest that the reduction in blood pressure observed after percutaneous dialysis access interventions (particularly in the presence of midazolam and fentanyl) may make it unnecessary to treat asymptomatic hypertension prior to these procedures. 相似文献
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As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological 'garbage' ('waste' materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death. 相似文献
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