1,621 research outputs found

    Stimulation by a low-molecular-weight angiogenic factor of capillary endothelial cells in culture.

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    A low-mol.-wt compound isolated from rat Walker 256 carcinoma and found to induce neovascularization in vivo was tested on cultures of cow brain-derived endothelial cells (CBEC) growing on plastic and collagen substrates. This factor had a mitogenic effect on CBEC cultured on native collagen gels and for this reason has been called "endothelial-cell-stimulating angiogenesis factor" (ESAF). CBEC growing on plastic culture dishes or denatured collagen films were not stimulated by ESAF. The mitogenic effect of ESAF was equally apparent when added to cells already attached to the native collagen substrate or when the collagen substrate was pre-incubated with ESAF before plating the cells. A floating collagen gel pre-incubated with ESAF in cultures of CBEC growing on plastic dishes did not stimulate cell growth. Our data indicate that the substrate influences cell behaviour and that CBEC only respond to ESAF when growing on a native collagen substrate

    Relationship between vascularity, age and survival in non-small-cell lung cancer.

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    Lung tumours in the elderly show reduced growth potential; impaired angiogenesis may contribute to this phenomenon. Recent studies have suggested that the angiogenic potential of a tumour may be inferred by the vascularity measured in histological sections. The purpose of this study has been to determine whether vascularity is related to age, survival or other clinical parameters in resected non-small-cell lung cancer (NSCLC). A group of 88 consecutive patients with a follow-up period of at least 5 years was selected. The group exhibited a wide age range (37-78 years) and similar survival characteristics to those of the general NSCLC population. Tumour sections were stained with a pan-endothelial antibody (vWF) and vascularity was quantitated, without knowledge of the clinical details, by three methods: highest microvascular density; average microvascular density; and average microvascular volume. The results were analysed by non-parametric statistical tests. A correlation was found between all three methods of quantitation. Vascularity was not associated with age, sex, tumour type, stage, volume, size (TNM-T) nodal status (TNM-N) or survival. However, survival time was generally longer for patients with higher vascularity, reaching borderline significance (P = 0.06) for the average microvascular density values. Higher tumour volume (P = 0.02) and stage (P = 0.05) were associated with lower survival times. Using multivariate survival analysis, tumour volume was the only factor related to survival. We conclude that vascularity is not associated with age and has no significant prognostic value in NSCLC

    Superconducting crossed correlations in ferromagnets: implications for thermodynamics and quantum transport

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    It is demonstrated that non local Cooper pairs can propagate in ferromagnetic electrodes having an opposite spin orientation. In the presence of such crossed correlations, the superconducting gap is found to depend explicitly on the relative orientation of the ferromagnetic electrodes. Non local Cooper pairs can in principle be probed with dc-transport. With two ferromagnetic electrodes, we propose a ``quantum switch'' that can be used to detect correlated pairs of electrons. With three or more ferromagnetic electrodes, the Cooper pair-like state is a linear superposition of Cooper pairs which could be detected in dc-transport. The effect also induces an enhancement of the ferromagnetic proximity effect on the basis of crossed superconducting correlations propagating along domain walls.Comment: 4 pages, RevTe

    High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

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    Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. the results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of ( pro) renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. the increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. the consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.UNIFESP, Div Renal, BR-04023900 São Paulo, BrazilUNIFESP, Div Renal, BR-04023900 São Paulo, BrazilWeb of Scienc

    Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

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    Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.Univ Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, BrazilUniv Cruzeiro Sul, Programa Interdisciplinar Ciencias Saude, Inst Ciencias Atividade Fis & Esporte, Sao Paulo, SP, BrazilUniv Sao Paulo, LEMA, Escola Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilWeb of Scienc

    Smoke gets in your eyes:what is sociological about cigarettes?

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    Contemporary public health approaches increasingly draw attention to the unequal social distribution of cigarette smoking. In contrast, critical accounts emphasize the importance of smokers’ situated agency, the relevance of embodiment and how public health measures against smoking potentially play upon and exacerbate social divisions and inequality. Nevertheless, if the social context of cigarettes is worthy of such attention, and sociology lays a distinct claim to understanding the social, we need to articulate a distinct, positive and systematic claim for smoking as an object of sociological enquiry. This article attempts to address this by situating smoking across three main dimensions of sociological thinking: history and social change; individual agency and experience; and social structures and power. It locates the emergence and development of cigarettes in everyday life within the project of modernity of the nineteenth and twentieth centuries. It goes on to assess the habituated, temporal and experiential aspects of individual smoking practices in everyday lifeworlds. Finally, it argues that smoking, while distributed in important ways by social class, also works relationally to render and inscribe it

    Laser-UV-microirradiation of interphase nuclei and posttreatment with caffeine: a new approach to establish the arrangement of interphase chromosomes

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    Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small area of the metaphase spread, III) mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus

    Ensemble Analysis of Angiogenic Growth in Three-Dimensional Microfluidic Cell Cultures

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    We demonstrate ensemble three-dimensional cell cultures and quantitative analysis of angiogenic growth from uniform endothelial monolayers. Our approach combines two key elements: a micro-fluidic assay that enables parallelized angiogenic growth instances subject to common extracellular conditions, and an automated image acquisition and processing scheme enabling high-throughput, unbiased quantification of angiogenic growth. Because of the increased throughput of the assay in comparison to existing three-dimensional morphogenic assays, statistical properties of angiogenic growth can be reliably estimated. We used the assay to evaluate the combined effects of vascular endothelial growth factor (VEGF) and the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the importance of S1P in amplifying the angiogenic response in the presence of VEGF gradients. Furthermore, the application of S1P with VEGF gradients resulted in angiogenic sprouts with higher aspect ratio than S1P with background levels of VEGF, despite reduced total migratory activity. This implies a synergistic effect between the growth factors in promoting angiogenic activity. Finally, the variance in the computed angiogenic metrics (as measured by ensemble standard deviation) was found to increase linearly with the ensemble mean. This finding is consistent with stochastic agent-based mathematical models of angiogenesis that represent angiogenic growth as a series of independent stochastic cell-level decisions.National Science Foundation (U.S.). Office of Emerging Frontiers in Research and Innovation (grant #0735997
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