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11.
Effect of essential fatty acids on circulating T cell subsets in patients with colorectal cancer 总被引:2,自引:0,他引:2
P. Purasiri J. Ashby S. D. Heys O. Eremin 《Cancer immunology, immunotherapy : CII》1994,39(4):217-222
The effect of essential fatty acids (EFA), given orally as dietary supplements, on the responsiveness in vitro of peripheral blood lymphocytes (PBL), to the mitogen concanavalin A have been studied in 10 patients with localized and 14 patients with advanced colorectal cancer. The degree of lymphocyte activation was assessed by measuring the amount of tritiated [3H]thymidine incorporated into newly synthesised lymphocyte DNA. The results were expressed as stimulation indices. T cell responses to concanavalin A stimulation showed a significant reduction of stimulation indices following EFA supplementation, in both the localized (P=0.026) and advanced (P=0.016) tumour groups, when compared with pretreatment activity in vitro. Mixing experiments, using EFA-supplemented and non-EFA-supplemented lymphocytes with concanavalin A, suggest no enhancement of T suppressor cell activity. Cell surface marker analysis (fluorescence-activated cell sorting for CD phenotyping) revealed a reduction of absolute numbers of CD4+ and CD8+ lymphocytes following EFA supplementation. The stimulation indices returned to presupplementation values 3 months following cessation of EFA intake. There was no significant change of these indices in the control (no EFA supplementation) advanced tumour group tested. This study suggests that EFA supplementation in patients with colorectal cancer selectively reduces circulating PBL. and T cell subset (including suppressor cells) numbers and/or activity. Such effects may have an important outcome in patients with malignant disease.This work was supported by grants from the Grampian Health Broad, the Royal College of Surgeons of Edinburgh, and Scottish Hospital Endownment Research Trust 相似文献
12.
Effects of glucose and insulin on the activation of lipoprotin lipase and on protein-synthesis in rat adipose tissue. 总被引:4,自引:1,他引:3 下载免费PDF全文
Glucose, and certain sugars that can readily be converted to glucose 6-phosphate, bring about an activation of adipose-tissue lipoprotein lipase when epididymal fat-bodies from starved rats are incubated in the presence of cycloheximide. Other substrates do not support the activation. If the tissue is preincubated in the presence of cycloheximide for longer than 2h, the ability of added glucose to activate the enzyme is lost. On the other hand, the addition of glucose still brings about an increase in lipoprotein lipase activity after preincubation in the absence of cycloheximide for as long as 4h. The magnitude of the increase in enzyme activity brought about by the addition of glucose is increased when protein synthesis is stimulated during the preincubation period by insulin. The results are interpreted in terms of the existence in adipose tissue of a proenzyme pool of lipoprotein lipase that is normally maintained by protein synthesis and that is converted to complete enzyme of higher specific activity by a process that specifically requires glucose. 相似文献
13.
D J Brusick J Ashby F J de Serres P H Lohman T Matsushima B E Matter M L Mendelsohn D H Moore S Nesnow M D Waters 《Mutation research》1992,266(1):1-6
The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive', AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined. Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes displayed a high constant level throughout the animals' lifetime, the O6-methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA normalisation of results): the O6-MT activity significantly increased within the first month of animal life and enhanced again after 6 months reaching a maximum plateau in the 12-18-month-old animals. Thereafter a net significant decrease of O6-MT enzyme was detected in the 24-month-old group. While the repair of the widely formed AP sites appeared uniformly efficient like 'house keeping' functions, the removal of the rare precancerous O6-methylguanine is age-dependent indicating a decreased protection of the youngest and oldest animals against this 'mis-instructive' damage. However, any extrapolation of the age-associated cancer risk needs further assessment. 相似文献
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Terezie Mandkov Kaylynn Ashby Bo J. Price Michael D. Windham John G. Carman Martin A. Lysak 《植物分类学报:英文版》2021,59(1):83-92
Apomixis in crucifer (Brassicaceae) species is rare, reported in just four genera (Boechera, Draba, Erysimum, and Parrya), and one intergeneric hybrid (Raphanobrassica). It is well studied only in Boechera, where it is widespread among 100+ recognized species. However, its occurrence in related genera of the tribe Boechereae has not been documented previously. Here we analyzed genome evolution, mode of reproduction, and fertility of the monospecific Boechereae genus Phoenicaulis (P. cheiranthoides), endemic to the northwestern United States. We discovered that the species encompasses diploid (2n = 2x = 14), triploid (2n = 3x = 21), and tetraploid (2n = 4x = 28) populations. Comparative chromosome painting analyses revealed that the three karyotypes are essentially structurally identical, differing only in the presence of a largely heterochromatic chromosome (Het) in the triploid and tetraploid cytotypes. The genome structure of Phoenicaulis appeared identical to that of Boechera species previously analyzed, suggesting genomic stasis despite the morphological and molecular divergence of the two genera. This genome colinearity extended to the presence and structure of the Het chromosomes, which are closely associated with apomictic reproduction in Boechera. Interestingly, all three cytotypes of Phoenicaulis proved to be apomictic, regardless of the presence or absence of a Het chromosome, and sexual populations have yet to be identified. 相似文献
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Ben Ashby 《Evolution; international journal of organic evolution》2020,74(1):43-56
Sexually transmitted infections (STIs) are predicted to play an important role in the evolution of host mating strategies, and vice versa, yet our understanding of host-STI coevolution is limited. Previous theoretical work has shown mate choice can evolve to prevent runaway STI virulence evolution in chronic, sterilizing infections. Here, I generalize this theory to examine how a broader range of life-history traits influence coevolution; specifically, how host preferences for healthy mates and STI virulence coevolve when infections are acute and can cause mortality or sterility, and hosts do not form long-term sexual partnerships. I show that mate choice reduces both mortality and sterility virulence, with qualitatively different outcomes depending on the mode of virulence, costs associated with mate choice, recovery rates, and host lifespan. For example, fluctuating selection—a key finding in previous work—is most likely when hosts have moderate lifespans, STIs cause sterility and long infections, and costs of mate choice are low. The results reveal new insights into the coevolution of mate choice and STI virulence as different life-history traits vary, providing increased support for parasite-mediated sexual selection as a potential driver of host mate choice, and mate choice as a constraint on the evolution of virulence. 相似文献
18.
Bhargav A. Patel Charles R. Ashby Diane Hardej Tanaji T. Talele 《Bioorganic & medicinal chemistry letters》2013,23(20):5523-5527
A focused library of rhodanine compounds containing novel substituents at the C5-position was synthesized and tested in vitro against a panel of clinically relevant MRSA strains. The present SAR study was based on our lead compound 1 (MIC = 1.95 μg/mL), with a focus on identifying optimal C5-arylidene substituents. In order to obtain this objective, we condensed several unique aromatic aldehydes with phenylalanine-derived rhodanine intermediates to obtain C5-substituted target rhodanine compounds for evaluation as anti-MRSA compounds. These efforts produced three compounds with significant efficacy: 23, 32 and 44, with MIC values ranging from 0.98 to 1.95 μg/mL against all tested MRSA strains as compared to the reference antibiotics penicillin G (MIC = 15.60–250.0 μg/mL) and ciprofloxacin (MIC = 7.80–62.50 μg/mL) and comparable to that of vancomycin (MIC = 0.48 μg/mL). In addition, compounds 24, 28, 37, 41, 46 and 48 (MIC = 1.95–3.90 μg/mL) were efficacious against all MRSA strains. The majority of the synthesized compounds had bactericidal activity at concentrations only two to fourfold higher than their MIC. Overall, the results suggest that compounds 23, 32 and 44 may be of potential use in the treatment of MRSA infections. 相似文献
19.
Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-kappaB-independent, FoxO1-dependent mechanism 总被引:8,自引:0,他引:8
McFarlane C Plummer E Thomas M Hennebry A Ashby M Ling N Smith H Sharma M Kambadur R 《Journal of cellular physiology》2006,209(2):501-514
Myostatin, a transforming growth factor-beta (TGF-beta) super-family member, has been well characterized as a negative regulator of muscle growth and development. Myostatin has been implicated in several forms of muscle wasting including the severe cachexia observed as a result of conditions such as AIDS and liver cirrhosis. Here we show that Myostatin induces cachexia by a mechanism independent of NF-kappaB. Myostatin treatment resulted in a reduction in both myotube number and size in vitro, as well as a loss in body mass in vivo. Furthermore, the expression of the myogenic genes myoD and pax3 was reduced, while NF-kappaB (the p65 subunit) localization and expression remained unchanged. In addition, promoter analysis has confirmed Myostatin inhibition of myoD and pax3. An increase in the expression of genes involved in ubiquitin-mediated proteolysis is observed during many forms of muscle wasting. Hence we analyzed the effect of Myostatin treatment on proteolytic gene expression. The ubiquitin associated genes atrogin-1, MuRF-1, and E214k were upregulated following Myostatin treatment. We analyzed how Myostatin may be signaling to induce cachexia. Myostatin signaling reversed the IGF-1/PI3K/AKT hypertrophy pathway by inhibiting AKT phosphorylation thereby increasing the levels of active FoxO1, allowing for increased expression of atrophy-related genes. Therefore, our results suggest that Myostatin induces cachexia through an NF-kappaB-independent mechanism. Furthermore, increased Myostatin levels appear to antagonize hypertrophy signaling through regulation of the AKT-FoxO1 pathway. 相似文献
20.