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71.
72.
Han W Li H Villar VA Pascua AM Dajani MI Wang X Natarajan A Quinn MT Felder RA Jose PA Yu P 《Hypertension》2008,51(2):481-487
Recent studies have indicated the importance of cholesterol-rich membrane lipid rafts (LRs) in oxidative stress-induced signal transduction. Reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases, the major sources of reactive oxygen species, are implicated in cardiovascular diseases, including hypertension. We tested the hypothesis that NADPH oxidase subunits and activity are regulated by LRs in human renal proximal tubule cells. We report that a high proportion of p22(phox) and the small GTPase Rac1 are expressed in LRs in human renal proximal tubule cells. The D(1)-like receptor agonist, fenoldopam (1 micromol/L per 20 minutes) dispersed Nox subunits within LRs and non-LRs and decreased oxidase activity (30.7+/-3.3%). In contrast, cholesterol depletion (2% methyl-beta-cyclodextrin [beta CD]) translocated NADPH oxidase subunits out of LRs and increased oxidase activity (154.0+/-10.5% versus control, 103.1+/-3.4%), which was reversed by cholesterol repletion (118.9+/-9.9%). Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%). Furthermore, beta CD-induced reactive oxygen species production was reversed by knocking down either Nox2 (81.0+/-5.1% versus beta CD: 162.0+/-2.0%) or Nox4 (108.0+/-10.8% versus beta CD: 152.0+/-9.8%). We have demonstrated for the first time that disruption of LRs results in NADPH oxidase activation that is abolished by antioxidants and silencing of Nox2 or Nox4. Therefore, in human renal proximal tubule cells, LRs maintain NADPH oxidase in an inactive state. 相似文献
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Sanne de Haas Paul Delmar Aruna T. Bansal Matthieu Moisse David W. Miles Natasha Leighl Bernard Escudier Eric Van Cutsem Peter Carmeliet Stefan J. Scherer Celine Pallaud Diether Lambrechts 《Angiogenesis》2014,17(4):909-920
Background
Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified.Methods
We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome.Results
The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene.Conclusions
This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy. 相似文献75.
Jackye Peretz Lisa Vrooman William A. Ricke Patricia A. Hunt Shelley Ehrlich Russ Hauser Vasantha Padmanabhan Hugh S. Taylor Shanna H. Swan Catherine A. VandeVoort Jodi A. Flaws 《Environmental health perspectives》2014,122(8):775-786
Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction.Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action.Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction.Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development.Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant.Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786; http://dx.doi.org/10.1289/ehp.1307728 相似文献
76.
Aruna V. Vanikar Hargovind L. Trivedi Saroj Chooramani Gopal Ashutosh Kumar Shruti D. Dave 《Renal failure》2014,36(3):457-460
Transplantation tolerance is still a Utopian dream for many transplanters. Mesenchymal stem cells (MSC) have shown immuno-modulatory and tolerogenic effects in experimental models. We present a 29-year-old male with end stage renal disease (ESRD) who was transplanted with HLA 4/6 matched kidney from 51-year-old father in June 2010 preceded by co-infusion of donor-adipose tissue derived mesenchymal stem cells (AD-MSC) and bone marrow derived hematopoietic stem cells (BM-HSC) under non-myeloablative conditioning for deleting rejecting T and B-cells. He has maintained fairly stable graft function with serum creatinine (SCr) between 1.5 and 1.8?mg/dL at 3 years post-transplant with absence of donor specific antibodies (DSA), normal protocol graft biopsy, and peripheral T-regulatory cell levels (pTregs) (CD127low/?CD25highCD4+) of 4.57% on zero immunosuppression since 6 months. 相似文献
77.
Vivek B. Kute Priyadarshini S. Shah Aruna V. Vanikar Manoj R. Gumber Himanshu V. Patel Divyesh P. Engineer Pankaj R. Shah Pranjal R. Modi Veena R Shah Syed Jamal Rizvi Hargovind L. Trivedi 《Transplant international》2014,27(10):1015-1021
Because access to transplantation with HLA‐desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end‐stage renal disease (ESRD) patient in India. We present a government and institutional ethical review board approved study of 56 ESRD patients [25 two‐way and 2 three‐way pairs] who consented to participate in KPD transplantation at our center in 2013, performed to avoid blood group incompatibility (n = 52) or positive cross‐match (n = 4). All patients had anatomic, functional, and immunologically comparable donors. The waiting time in KPD was short as compared to deceased donor transplantation. Laparoscopic donor nephrectomy was performed in 54 donors. Donor relationships were spousal (n = 40), parental (n = 13), others (n = 3), with median HLA match of 1. Graft survival was 97.5%. Three patients died with functioning graft. 16% had biopsy‐proven acute rejection. Mean serum creatinine was 1.2 mg/dl at 0.73 ± 0.32 months follow‐up. KPD is a viable, legal, and rapidly growing modality for facilitating LDRT for patients who are incompatible with their healthy, willing living donor. To our knowledge, this is the largest single‐center report from India. 相似文献
78.
BackgroundLeft ventricular hypertrophy (LVH) has been proved as one among the cardiovascular complications and predominant in patients with CKD. In CKD patients, Glycated albumin (GA) express a superior marker of glycemic control than HbA1c. Nevertheless, the precision of GA for the prediction of cardiovascular diseases among the CKD population has been ineffectively reported. The present study looks at the part of GA, HbA1c in CKD to envisage vascular complications.Materials and methodsOne hundred and ninety-four patients were selected in the present study. The study has a control group (Group I, N: 52) and participants were divided into two groups based on vein diseases (Group II, N: 42; two vessels and group III, N: 100; triple vessel disease). Serum glycated albumin, hsCRP and other routine parameters were estimated in all the three groups. 2-dimensional echocardiography (2D Echo) has been done by a cardiologist to all the study patients for assessing ejection fraction and distinguish the sort of vessel diseases.ResultsGroup I compared with group II and III shown there was a significant association among blood glucose, serum creatinine, HbA1c, mean blood glucose, GA, ejection fraction and hsCRP. Additionally, observed that increased levels of HbA1c, GA and creatinine inversely related to the left ventricle ejection fraction. Notwithstanding, GA and hsCRP predict precisely the left ventricle ejection fraction than different parameters.ConclusionGA alongside hsCRP might be appropriate markers for anticipating cardiovascular diseases particularly left ventricle hypertrophy in diabetic CKD population. 相似文献
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K. A. Jeevan Kumar Aruna Kishore Masrom Kapil Patil Ramesh Kunusoth Farzana Begum Veerareddy Venkatesh 《Journal of maxillofacial and oral surgery》2014,13(4):539-545