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61.
Hamdheydari L Christov A Ottman T Hensley K Grammas P 《Biochemical and biophysical research communications》2003,311(2):486-490
There is an increase in the generation of reactive oxygen species and nitric oxide in the cerebral microcirculation in Alzheimer's disease. The factors that cause this increase in oxidative stress have not been identified. Increasing evidence suggests that there are common mechanisms in atherosclerosis and Alzheimer's disease. The objective of this study was to determine the effects of oxidized low density lipoproteins (LDLs) on brain endothelial cells. Cultured rat brain endothelial cells were treated with either native LDL (10 microg/ml) or LDL oxidized in vitro using 4-hydroxy-2-nonenal (HNE-LDL) (10 microg/ml), for 24h. The results showed that HNE-LDL significantly increased production of nitric oxide (p<0.01), decreased membrane fluidity (p<0.05), and increased reactive oxygen species generation (p<0.01). These data demonstrate that oxidized LDLs affect nitric oxide and radical generation in brain endothelial cells and could contribute to cerebrovascular dysfunction in Alzheimer's disease. 相似文献
62.
Laskin DL Fakhrzadeh L Heck DE Gerecke D Laskin JD 《Molecular and cellular biochemistry》2002,(1-2):91-98
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The antibacterial activity of hemin onStaphylococcus aureus is described. Hemin binding to bacteria was a rapid process, and each cell accumulated 5×105 to 1×106 molecules within 5 min. Bacterial growth was stopped completely after 30 min from addition of low concentration of hemin (3–10 g/ml). Cell viability was reduced by 99.9% in 1 h of exposure, and the effect was consistent at any stage of the growth curve whenever hemin was added. Glucose utilization was arrested immediately after hemin addition, and no CO2 was produced. The survivors of hemin treatment regrow in a time-related kinetics depending on the dose of hemin to which the cells were exposed. The recovered bacteria were again sensitive to hemin, similar to an untreated culture. We suggested that the recovery phenomenon is a result of an on-off mechanism regulating sensitivity to hemin, rather than a selection mechanism giving rise to hemin-resistant mutants. 相似文献
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Wolfgang J?ger Igor Moskalev Claudia Janssen Tetsutaro Hayashi Shannon Awrey Kilian M. Gust Alan I. So Kaixin Zhang Ladan Fazli Estelle Li Joachim W. Thüroff Dirk Lange Peter C. Black 《PloS one》2013,8(3)
Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice. 相似文献
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Ommati Mohammad Mehdi Heidari Reza Zamiri Mohammad Javad Sabouri Samira Zaker Ladan Farshad Omid Jamshidzadeh Akram Mousapour Saeed 《Biological trace element research》2020,195(1):125-134
Biological Trace Element Research - Exposure to arsenic (AS) causes abnormalities in the reproductive system; however, the precise cellular pathway of AS toxicity on steroidogenesis in developing... 相似文献
67.
Mohammad Hojjat-Farsangi Abdul Salam Khan Amir Hossein Daneshmanesh Ali Moshfegh ?sa Sandin Ladan Mansouri Marzia Palma Jeanette Lundin Anders ?sterborg H?kan Mellstedt 《PloS one》2013,8(10)
Phosphorylation of receptor tyrosine kinases (RTKs) has a key role in cellular functions contributing to the malignant phenotype of tumor cells. We and others have previously demonstrated that RTK ROR1 is overexpressed in chronic lymphocytic leukemia (CLL). Silencing siRNA downregulated ROR1 and induced apoptosis of CLL cells. In the present study we analysed ROR1 isoforms and the phosphorylation pattern in CLL cells (n=38) applying western blot and flow-cytometry using anti-ROR1 antibodies and an anti-phospho-ROR1 antibody against the TK domain. Two major ROR1 bands with the size of 105 and 130 kDa respectively were identified, presumably representing unglycosylated (immature) and glycosylated (mature) ROR1 respectively as well as a 260 kDa band which may represent dimerized ROR1. A ROR1 band of 64 kDa that may correspond to a C-terminal fragment was also noted, present only in the nucleus. The 105 kDa ROR1 isoform was more frequently expressed in non-progressive as compared to progressive CLL patients (p=0.03). The 64, 105, 130 and 260 kDa bands were constitutively phosphorylated both at tyrosine and serine residues. Phosphorylation intensity of the mature (130 kDa) isoform was significantly higher in progressive than in non-progressive disease (p<0.001). Incubation of CLL cells with a mouse anti-ROR1 KNG or an anti-ROR1 CRD mAb respectively induced dephosphorylation of ROR1 before entering apoptosis. In conclusion CLL cells expressed different isoforms of ROR1 which were constitutively phosphorylated. The mature, phosphorylated ROR1 isoform was associated with a progressive disease stage. Targeting ROR1 by mAbs induced specific dephosphorylation and leukemic cell death. ROR1 might be an interesting therapeutic target. 相似文献
68.
Ladan Mansouri Josefin M. Paulsson Ali Moshfegh Stefan H. Jacobson Joachim Lundahl 《PloS one》2013,8(8)
Introduction
In Chronic Kidney Disease (CKD), immune cells are affected by uremic retention toxins. Given this effect, we analyzed lymphocyte proliferative response and immune modulators production following in vitro stimulation.Methods
Whole blood was drawn from healthy controls, patients with eGFR <20 ml/min/1.73 m2 (Pre-dialysis, CKD stages 4 and 5) and hemodialysis patients (stage 5D). Peripheral cells were incubated for six days with pokeweed mitogen, concanavalin A, Staphylococcus enterotoxin A or influenza A vaccine. Peripheral lymphocyte proliferation was then analyzed by the “Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood” (FASCIA) method, and cytokine profile in the cell supernatants was analyzed by the Milliplex multi-array method.Results
The absolute number of lymphoblasts in response to mitogenic stimulation and the number of cells in each CD4+ and CD8+ subpopulation were similar comparing the three groups, except for a single decline in number of lymphoblasts after stimulation with Staphylococcus enterotoxin A, comparing dialysis patients with healthy controls. Levels of interleukin (IL)-2 (p=0.026), -10 (p=0.019) and -15 (p=0.027) in the Staphylococcus enterotoxin A-stimulated supernatant were lower in hemodialysis patients compared to healthy controls. Levels of IL-15 (p=0.017) from pre-dialysis patients and levels of IL-5 (p=0.019) from hemodialysis patients in influenza A vaccine-stimulated supernatants were also lower compared to controls. In pokeweed mitogen–stimulated supernatant, IL-2 levels (p=0.013) were lower in hemodialysis patients compared to pre-dialysis patients. TNF-α, IL-10, IL-12, IL-15, IL-8, MCP-1, IP-10, IFN-α2, IL-1α and eotaxin levels were all significantly higher in plasma obtained from CKD patients.Conclusion
Our results suggest that T-cells from CKD patients have similar proliferative response to stimulation compared with healthy individuals. Moreover, however the immune cells show inability to produce selected cytokines, most likely due to the uremic milieu or dialysis procedure. 相似文献69.
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Thomas Ibanez Cláudia Baider Chris Birkinshaw Heike Culmsee Susan Cordell F. B. Vincent Florens Janet Franklin Christian P. Giardina Thomas W. Gillespie Melinda Laidlaw Creighton M. Litton Tara G. Martin Rebecca Ostertag Narayanaswamy Parthasarathy Richard Randrianaivo Miramasoandro Randrianjanahary Muthu Rajkumar Ladan Rasingam Fidy Ratovoson Ludovic Reza Lawren Sack Shin‐ichiro Aiba Edward Webb Timothy J. S. Whitfeld Runguo Zang Philippe Birnbaum 《Global Ecology and Biogeography》2018,27(4):474-486