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排序方式: 共有180条查询结果,搜索用时 31 毫秒
1.
Ignacio Prieto Charles Tease Nieves Pezzi José M. Buesa Sagrario Ortega Leonor Kremer Alicia Martínez Carlos Martínez-A Maj A. Hultén José L. Barbero 《Chromosome research》2004,12(3):197-213
Cohesins are chromosomal proteins that form complexes involved in the maintenance of sister chromatid cohesion during division of somatic and germ cells. Three meiosis-specific cohesin subunits have been reported in mammals, REC8, STAG3 and SMC1 beta; their expression in mouse spermatocytes has also been described. Here we studied the localization of different meiotic and mitotic cohesin components during prophase I in human and murine female germ cells. In normal and atretic human fetal oocytes, from leptotene to diplotene stages, REC8 and STAG3 colocalize in fibers. In murine oocytes, SMC1beta, SMC3 and STAG3 are localized along fibers that correspond first to the chromosome axis and then to the synaptonemal complex in pachytene. Mitotic cohesin subunit RAD21 is also found in fibers that decorate the SC during prophase I in mouse oocytes, suggesting a role for this cohesin in mammalian sister chromatid cohesion in female meiosis. We observed that, unlike human oocytes, murine synaptonemal complex protein SYCP3 localizes to nucleoli throughout prophase I stages, and centromeres cluster in discrete locations from leptotene to dictyate. At difference from meiosis in male mice, the cohesin axis is progressively lost during the first week after birth in females with a parallel destruction of the axial elements at dictyate arrest, demonstrating sexual dimorphism in sister chromatid cohesion in meiosis. 相似文献
2.
3.
Julia Carracedo Paula Buendía Ana Merino Sagrario Soriano Elvira Esquivias Alejandro Martín-Malo Pedro Aljama Rafael Ramírez 《Experimental gerontology》2013
Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway. We examined whether senescence-associated to oxidative stress determines the injury induced by the uremia in endothelial cells. 相似文献
4.
Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth 总被引:1,自引:0,他引:1
Abéngozar MA de Frutos S Ferreiro S Soriano J Perez-Martinez M Olmeda D Marenchino M Cañamero M Ortega S Megias D Rodriguez A Martínez-Torrecuadrada JL 《Blood》2012,119(19):4565-4576
Membrane-anchored ephrinB2 and its receptor EphB4 are involved in the formation of blood and lymphatic vessels in normal and pathologic conditions. Eph/ephrin activation requires cell-cell interactions and leads to bidirectional signaling pathways in both ligand- and receptor-expressing cells. To investigate the functional consequences of blocking ephrinB2 activity, 2 highly specific human single-chain Fv (scFv) Ab fragments against ephrinB2 were generated and characterized. Both Ab fragments suppressed endothelial cell migration and tube formation in vitro in response to VEGF and provoked abnormal cell motility and actin cytoskeleton alterations in isolated endothelial cells. As only one of them (B11) competed for binding of ephrinB2 to EphB4, these data suggest an EphB-receptor-independent blocking mechanism. Anti-ephrinB2 therapy reduced VEGF-induced neovascularization in a mouse Matrigel plug assay. Moreover, systemic administration of ephrinB2-blocking Abs caused a drastic reduction in the number of blood and lymphatic vessels in xenografted mice and a concomitant reduction in tumor growth. Our results show for the first time that specific Ab-based ephrinB2 targeting may represent an effective therapeutic strategy to be used as an alternative or in combination with existing antiangiogenic drugs for treating patients with cancer and other angiogenesis-related diseases. 相似文献
5.
Claudio Erratico Noelia Negreira Helia Norouzizadeh Adrian Covaci Hugo Neels Kristof Maudens Alexander L.N. van Nuijs 《Drug testing and analysis》2015,7(10):866-876
N‐[(1S)‐1‐(aminocarbonyl)‐2‐methylpropyl]‐1‐(cyclohexylmethyl)‐1H‐indazole‐3‐carboxamide (AB‐CHMINACA) is a recently introduced synthetic cannabinoid. At present, no information is available about in vitro or in vivo human metabolism of AB‐CHMINACA. Therefore, biomonitoring studies to screen AB‐CHMINACA consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated the in vitro metabolism of AB‐CHMINACA using human liver microsomes (HLMs). Formation of AB‐CHMINACA metabolites was monitored using liquid chromatography coupled to time‐of‐flight mass spectrometry. Twenty‐six metabolites of AB‐CHMINACA were detected including seven mono‐hydroxylated and six di‐hydroxylated metabolites and a metabolite resulting from N‐dealkylation of AB‐CHMINACA, all produced by cytochrome P450 (CYP) enzymes. Two carboxylated metabolites, likely produced by amidase enzymes, and five glucuronidated metabolites were also formed. Five mono‐hydroxylated and one carboxylated metabolite were likely the major metabolites detected. The involvement of individual CYPs in the formation of AB‐CHMINACA metabolites was tested using a panel of seven human recombinant CYPs (rCYPs). All the hydroxylated AB‐CHMINACA metabolites produced by HLMs were also produced by the rCYPs tested, among which rCYP3A4 was the most active enzyme. Most of the in vitro metabolites of AB‐CHMINACA were also present in urine obtained from an AB‐CHMINACA user, therefore showing the reliability of the results obtained using the in vitro metabolism experiments conducted to predict AB‐CHMINACA in vivo metabolism. The AB‐CHMINACA metabolites to target in biomonitoring studies using urine samples are now reliably identified and can be used for routine analysis. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
6.
Laura Caneda-Martínez Manuel Monasterio Jaime Moreno-Juez Sagrario Martínez-Ramírez Rosario García Moiss Frías 《Materials》2021,14(5)
This work analyses the influence of fine concrete fractions (<5 mm) of different natures —calcareous (HcG) and siliceous (HsT)—obtained from construction and demolition waste (C&DW) on the behaviour of blended cement pastes with partial replacements between 5 and 10%. The two C&DW fractions were characterised by different instrumental techniques. Subsequently, their lime-fixing capacity and the physico-mechanical properties of the blended cement pastes were analysed. Lastly, the environmental benefits of reusing these fine wastes in the manufacture of future eco-efficient cement pastes were examined. The results show that HsT and HcG exhibit weak pozzolanic activity, owing to their low reactive silica and alumina content. Despite this, the new cement pastes meet the physical and mechanical requirements of the existing regulations for common cements. It should be highlighted that the blended cement pastes initially showed a coarser pore network, but then they underwent a refinement process between 2 and 28 days, along with a gain in compressive strength, possibly due to the double pozzolanic and filler effect of the wastes. The environmental viability of the blended cements was evaluated in a Life Cycle Assessment (LCA) concluding that the overall environmental impact could be reduced in the same proportion of the replacement rate. This is in line with the Circular Economy goals and the 2030 Agenda for Sustainable Development. 相似文献
7.
Sambuelli A Boerr L Negreira S Gil A Camartino G Huernos S Kogan Z Cabanne A Graziano A Peredo H Doldán I Gonzalez O Sugai E Lumi M Bai JC 《Alimentary pharmacology & therapeutics》2002,16(1):27-34
BACKGROUND: Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon-like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis. AIM: To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole. MATERIALS AND METHODS: Twenty-six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score >or= 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double-blind, double-dummy, 6-week, controlled trial. RESULTS: Based on the intention-to-treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P < 0.01). After that, improvement was moderated until stabilization at 4 weeks in both treatments. The per protocol analysis showed that both drugs had similar efficacy in terms of disease activity, clinical and endoscopic findings. Fifty-eight per cent and 50% of patients improved (decrease in pouchitis disease activity index >or= 3) with budesonide enema and metronidazole, respectively (odds ratio, 1.4; confidence interval, 0.2-8.9). Adverse effects were observed in 57% of patients given metronidazole and in 25% of patients given budesonide. CONCLUSIONS: Budesonide enemas are an alternative treatment for active pouchitis, with similar efficacy but better tolerability than oral metronidazole. 相似文献
8.
Synergistic interaction between vinorelbine and gamma-linolenic acid in breast cancer cells 总被引:3,自引:0,他引:3
Menéndez JA Ropero S del Barbacid MM Montero S Solanas M Escrich E Cortés-Funes H Colomer R 《Breast cancer research and treatment》2002,72(3):203-219
It has been suggested that exogenous unsaturated fatty acids (UFAs) may increase the cytotoxic activity of cancer chemotherapeutic
agents. We examined how γ-linolenic acid (GLA; 18 : 3n-6), the most promising UFA in the treatment of human tumors, affects
the effectiveness of the lipophilic drug vinorelbine (VNR) on human breast carcinoma cell lines. Cells were exposed simultaneously
to VNR and GLA or sequentially to GLA followed by VNR. Cell viability was determined by MTT assay. The increase in VNR-induced
cell growth inhibition was measured by dividing the IC50 and IC70 values (50 and 70% inhibitory concentrations, respectively) that were obtained when the cells were exposed to VNR alone with
those with VNR plus GLA. We found that GLA enhanced in a dose-dependent manner the cell growth inhibitory activity of VNR on MCF-7 cells (up
to 9-fold). As GLA by itself showed anti-proliferative effects, possible GLA-VNR interactions at the cellular level were assessed
employing the isobologram analysis and the combination index (CI) method of Chou–Talalay. Both methods showed an overall synergism
between GLA and VNR in MCF-7 cells. At a high level of cell kill, the synergism was greater when a 24 h GLA pre-exposure or
co-exposures were tested. Synergy was likewise observed with the GLA-VNR combination in MDA-MB-231, T47D, and SK-Br3 breast
cancer cells. In all cell lines, the synergism was independent of the treatment schedule and the exposure time. Under conditions
inhibiting lipid peroxidation using Vitamin E (dl-α-tocopherol), the enhancing effect of GLA (an easily oxidizable UFA) on
VNR activity was partially abolished. However, when Vitamin E was used in combination, a similar synergistic increase in growth
inhibition was obtained. These latter observations strongly implies that the synergistic effects of GLA with VNR are not mediated
through a mechanism involving a generation of lipoperoxides. For comparison, the effects of other UFAs were examined on VNR
chemosensitivity: GLA was the most potent at enhancing VNR activity, followed by docosahexaenoic acid (22 : 6n-3), eicosapentaenoic
acid (20 : 5n-3) and α-linolenic acid (18 : 3n-3), whereas linoleic acid (18 : 2n-6) and arachidonic acid (20 : 4n-6) did
not increase VNR chemosensitivity. Very high concentrations of oleic acid (OA; 18 : 1n-9), an UFA inversely correlated with
breast cancer risk, also enhanced VNR effectiveness. Thus, various types of UFAs were not equivalent with respect to their
actions on VNR effectiveness. In conclusion, our results give experimental support to the hypothesis that some UFAs can be
used as modulators of tumor cell chemosensitivity and provide the rationale for in vivo preclinical investigation. 相似文献
9.
Díaz-Lobato S Gómez Mendieta MA Moreno García MS Mayoralas-Alises S Arpa Gutierrez FJ 《Respiration; international review of thoracic diseases》2005,72(6):654-656
Mitochondrial myopathies are a group of diseases characterized by metabolic defects at the mitochondrial respiratory chain level which result in impaired oxidative phosphorylation and ATP synthesis. As with other neuromuscular diseases, respiratory muscles can be affected and ventilatory failure may occur. There have been isolated case reports of pregnant patients with ventilatory failure due to neuromuscular diseases such as polio and spinal muscular atrophy. We describe the case of a 34-year-old patient with mitochondrial myopathy and ventilatory failure requiring non-invasive ventilation who carried two pregnancies to term with no complications. We have not found a similar case in the literature. 相似文献
10.
Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation 总被引:6,自引:0,他引:6
Torres A García S Gómez A González A Barrios Y Concepción MT Hernández D García JJ Checa MD Lorenzo V Salido E 《Kidney international》2004,65(2):705-712
BACKGROUND: Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia. METHODS: This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL). RESULTS: Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03). CONCLUSION: Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype. 相似文献