Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    In: Transplantation, 1996, Vol.61(12), pp.1763-1770
    Description: Transplantation-related pathogenic factors such as ischemia or allograft-directed inflammation are associated with oxidative changes that might lead to cellular oxidative stress. The aim of this study was to investigate the impact of oxidative stress on: (1) CMV replication in cultured human endothelial cells and (2) the stimulation of endothelial cells by proinflammatory cytokines. Both pathomechanisms are known to contribute to graft rejection crises in vivo. Oxidative stress was induced in endothelial cell cultures with 10-200 μM buthionine sulfoximine. Western blotting showed a significant increase in the production of CMV-specific immediate early and late proteins in buthionine sulfoximine-treated cultures. Immunocytochemical staining suggested that this effect was caused by increased numbers of CMV antigen expressing cells (66% immediate early; 78%, late). Quantitative polymerase chain reaction for CMV-specific DNA and virus titration revealed that enhanced viral replication levels correlated with increased virion production. As a measure for the endothelial cell activation status, the surface expression of HLA-ABC and HLA-DR and adhesion molecules(ICAM-1, ELAM-1, VCAM-1) was quantified by fluorometric methods. Whereas oxidative stress alone did not modulate any surface molecule expression, the IFN-γ-mediated expression of HLA-ABC and HLA-DR and the IL-1-mediated expression of ICAM-1, but not of ELAM-1 and VCAM-1 (IL-1+TNF-α), was amplified. Interestingly, the amplification of HLA molecule expression was even higher in CMV-infected endothelial cells. This study provides evidence that oxidative stress contributes to the regulation of CMV replication, virus shedding, and the activation of endothelial cells by proinflammatory cytokines as it is observed in transplant recipients.
    Keywords: Human Cytomegalovirus ; Human Cytomegalovirus ; Endothelium ; Replication ; Oxidation ; Stress ; Man ; Endothelium ; Replication ; Oxidation ; Stress ; Man ; Viruses ; Immune Response & Immune Mechanisms ; Cytokines ; Cytokines ; Cytokines;
    ISSN: 0041-1337
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Trends in Molecular Medicine, 2011, Vol.17(8), pp.433-441
    Description: Malignant gliomas (MGs) are deadly brain tumors with a median survival after resection, radiotherapy and chemotherapy of only 12 months. The natural immunosuppressive state of MG patients and the locally restricted growth of MGs render this neoplasm an excellent target for immunotherapy. Consequently, several failed attempts were made to treat MGs with immune cells. Recent preclinical experimental studies, however, demonstrate that natural killer (NK) cells can kill MGs and therefore hold promise in immunotherapy of MGs. This review describes the experimental and clinical evidence that support the potential of NK cells in therapy of MGs as well as the limitations to NK therapy. Finally, we propose strategies that could circumvent mitigating factors and enhance NK cell therapy for MG patients.
    Keywords: Medicine ; Biology
    ISSN: 1471-4914
    E-ISSN: 1471-499X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Transplantation, 2000, Vol.69(9), pp.1977-1981
    Description: BACKGROUND.: Prostaglandin E2 (PGE2) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE2-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE2 release. METHODS.: Endothelial cells (HUVEC) were activated by either allogeneic CD4 or CD8 T cells, or by the cytokines interleukin-1 or γ-interferon. Using an enzyme-linked immunosorbent assay, we analyzed PGE2 release of the activated HUVEC in the presence of MMF, cyclosporine, or tacrolimus. As verapamil and mibefradil also possess immunosuppressive properties, they were included in the study as well. RESULTS.: Activation of HUVEC with interleukin-1 or T cells resulted in a drastic accumulation of PGE2 in the supernatant. Cyclosporine or tacrolimus had no effect on PGE2 release. However, Ca channel blockers, when applied at higher dosages, caused a significant increase in PGE2. Interestingly, MMF strongly diminished the PGE2 level in the cell culture supernatant in a concentration-dependent manner. CONCLUSION.: The results demonstrate an inhibitory effect of MMF on PGE2 production, which may lower the benefits of the PGE2-triggered immune response after organ transplantation.
    Keywords: Endothelium ; Cytokines ; Lymphocytes T ; Immunosuppression ; Transplantation ; Interleukin 1 ; ^G-Interferon ; Prostaglandin E2 ; Mycophenolate Mofetil ; Clinical ; Man ; Immunology ; Gamma -Interferon ; Immunology ; Man ; Mycophenolate Mofetil ; Prostaglandin E2;
    ISSN: 0041-1337
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Transplantation, 2000, Vol.69(4), pp.588-597
    Description: BACKGROUND.: Cyclosporine A (CsA) and tacrolimus prevent proliferation but not transendothelial migration of alloreactive lymphocytes into donor organs. As a result, serious adverse effects, such as nephrotoxicity and neurotoxicity, have been observed under CsA/tacrolimus therapy. The incorporation of new drugs with infiltration blocking properties might enhance the efficacy of the current immunosuppressive protocol, allowing lower CsA/tacrolimus dosage. Because Ca plays a critical role in cell-cell interaction, the Ca-channel blocker verapamil might be a good cany.didate for supporting CsA/tacrolimus-based therap METHODS.: A T-cell endothelial cell coculture model or immobilized immunoglobulin G globulin chimeras were employed to investigate how S- and R- verapamil interfere with the lymphocytic infiltration process. The expression and arrangement of membranous adhesion receptors and cytoskeletal F-actin filaments were analyzed by fluorometric method in the presence of. verapamil. RESULTS.: Both verapamil enantiomers strongly inhibited lymphocyte infiltration. CD4 and CD8 T-cells were influenced to a similar extent with regard to horizontal locomotion (CD4=CD8), but to a different extent with regard to adhesion and penetration (CD4 〉 CD8). Moreover, penetration was blocked to a higher extent than was adhesion. ID50-values were 31 μM (CD4-adhesion) and 11 μM (CD4-penetration). Verapamil reduced P-selectin expression on endothelial cells and effectively down-regulated binding of T-cells to immobilized P-selectin immunoglobulin G globulins (ID50=4.4 μM; CD4). A verapamil-induced reduction of intracellular F-actin in T-lymphocytes was proven to be mainly responsible for diminished cell locomotion. CONCLUSIONS.: The prevention of CD4 T-cell penetration by verapamil might argue for its use as an adjunct to CsA/tacrolimus-based immunosuppressive therapy.
    Keywords: Immunosuppression ; Endothelium ; Lymphocytes T ; Immunosuppressive Agents ; Cell Motility ; Verapamil ; Calcium Channel Blockers ; Experimental ; Function ; Immunology ; Calcium Channel Blockers ; Cell Motility ; Immunology ; Verapamil;
    ISSN: 0041-1337
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(9), p.e108758
    Description: Aurora kinase inhibitors displayed activity in pre-clinical neuroblastoma models. Here, we studied the effects of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) and the aurora kinase inhibitor alisertib (MLN8237) that shows some specificity for aurora kinase A over aurora kinase B in a panel of neuroblastoma cell lines with acquired drug resistance. Both compounds displayed anti-neuroblastoma activity in the nanomolar range. The anti-neuroblastoma mechanism included inhibition of aurora kinase signalling as indicated by decreased phosphorylation of the aurora kinase substrate histone H3, cell cycle inhibition in G2/M phase, and induction of apoptosis. The activity of alisertib but not of tozasertib was affected by ABCB1 expression. Aurora kinase inhibitors induced a p53 response and their activity was enhanced in combination with the MDM2 inhibitor and p53 activator nutlin-3 in p53 wild-type cells. In conclusion, aurora kinases are potential drug targets in therapy-refractory neuroblastoma, in particular for the vast majority of p53 wild-type cases.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Clinical Ophthalmology, Annual, 2013, Vol.7, p.1061(7)
    Description: Purpose: To assess the levels of inflammatory and angiogenic cytokines in undiluted vitreous from treatment-naive patients with macular edema secondary to nonischemic branch retinal vein occlusion (BRVO), with flow cytometric bead array (CBA) and to correlate the results with subjective and multiple spectral-domain optical coherence tomography (SD-OCT) parameters. Methods: A total of 43 eyes from 43 patients (mean age 69.7 years, 23 male) were divided into groups of new, "fresh" (n = 28; mean duration after onset 4.1 months) and older BRVO (n = 15; 11.6 months). Because of macular edema, these patients underwent an intravitreal therapy combining a single-site 23 g core vitrectomy with bevacizumab and dexamethasone. Undiluted vitreous was then analyzed for interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor isoform A (VEGF-A) levels with CBA and correlated with visual acuity (VA), clinical parameters of BRVO (type and perfusion status), and morphologic parameters, such as central macular thickness, central retinal thickness, thickness of the neurosensory retina, thickness of the serous retinal detachment, and the disruption of the ellipsoid line (photoreceptor inner and outer segments) and the external limiting membrane, as measured with SD-OCT. Twenty-eight undiluted vitreous samples from patients with idiopathic, nonuveitis vitreous floaters served as the controls. Results: The mean IL-6 was 23.2 pg/mL (standard deviation, [+ or -]48.8), MCP-1 was 602.6 ([+ or -]490.3), and VEGF-A was 161.8 ([+ or -]314.3), and this was higher than in the control group, which had a mean IL-6 of 6.2 [+ or -] 3.4 pg/mL (P = 0.17), MCP-1 of 253.2 [+ or -] 73.5 (P 〈 0.0000001), and VEGF-A of 7.0 [+ or -] 4.9 (P 〈 0.003). In all BRVO samples, IL-6 correlated positively with MCP-1 and VEGF-A (correlation coefficient r = 0.79 and r = 0.46, respectively). VEGF-A was the only cytokine to correlate significantly with SD-OCT parameters (thickness of the neurosensory retina r = 0.31; disruption of the ellipsoid line r = 0.33). In the older BRVO group, there was a positive correlation between cytokines (IL-6 with MCP-1, r = 0.77; Il-6 with VEGF-A, r = 0.68; MCP-1 and VEGF-A, r = 0.68), whereas only IL-6 correlated with MCP-1 in the fresh group (r = 0.8). Conclusion: The inflammatory markers and VEGF-A were elevated in the vitreous fluid of patients with BRVO, and these correlated with one another. VEGF-A was more often correlated with the morphologic changes assessed by SD-OCT, whereas the inflammatory markers had no significant influence on SD-OCT changes. Keywords: vitreous samples, BRVO, VEGF, MCP, IL-6, CBA, SD-OCT
    Keywords: Cytokines -- Identification And Classification ; Body Fluids -- Composition ; Retinal Diseases -- Physiological Aspects ; Optical Tomography -- Methods
    ISSN: 1177-5483
    ISSN: 11775467
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Acta Ophthalmologica, March 2012, Vol.90(2), pp.e98-e103
    Description: To compare cytokines in undiluted vitreous of treatment‐naïve patients with macular oedema without vitreomacular traction secondary to branch (BRVO), central (CRVO) and hemi‐central (H‐CRVO) retinal vein occlusion. Ninety‐four patients (median age 72 years, 42 men) underwent an intravitreal combination therapy, including a single‐site 23‐gauge core vitrectomy and the application of bevacizumab and dexamethasone due to vision‐decreasing macular oedema. Among these were 43 patients with BRVO, 35 with CRVO and 16 patients with hemi‐CRVO, which were distributed in a fresh or old retinal vein occlusion type (seven or more months after onset). Undiluted vitreous samples were analysed for interleukin 6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1) and vascular endothelial growth factor (VEGF‐A) with cytometric BEAD assay. Vitreous samples from patients with idiopathic epiretinal membrane served as controls ( = 14). The mean cytokine values were highest in the CRVO group with IL‐6 = 64.7 pg/ml (SD ± 115.8), MCP‐1 = 1015.8 pg/ml (±970.1) and VEGF‐A = 278.4 pg/ml (±512.8), followed by the H‐CRVO group with IL‐6 = 59.9 pg/ml (SD ± 97.5), MCP‐1 = 938.8 pg/ml (±561.1) and VEGF‐A = 211.5 pg/ml (±232.4). The BRVO group had IL‐6 = 23.2 pg/ml (SD ± 48.8), MCP‐1 = 602.6 pg/ml (±490.3) and VEGF‐A = 161.8 pg/ml (±314.4). The values of MCP‐1 and VEGF‐A were significantly different for CRVO or H‐CRVO versus BRVO. All values were significantly higher than in the control samples, which had 6.2 ± 3.4 pg/ml (IL‐6), 253 ± 74 pg/ml (MCP‐1) and 7 ± 4.9 pg/ml (VEGF‐A). Within the old RVO type, only MCP‐1 was significantly different for CRVO or H‐CRVO versus BRVO. Both inflammatory markers and VEGF‐A were higher in CRVO and H‐CRVO than in BRVO undiluted vitreous samples. It seems that monocyte recruitment to the vessel wall, which might underlie the importance of eosinophils in tissue remodelling after RVO, is of special interest owing to the significant difference in MCP‐1 in the older RVO types.
    Keywords: Cytometric Bead Array ; Interleukin 6 ; Monocyte Chemoattractant Protein ; Retinal Vein Occlusion ; Vascular Endothelial Growth Factor ; Vitreous Samples
    ISSN: 1755-375X
    E-ISSN: 1755-3768
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: PLoS ONE, Sept 30, 2014, Vol.9(9)
    Description: Aurora kinase inhibitors displayed activity in pre-clinical neuroblastoma models. Here, we studied the effects of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) and the aurora kinase inhibitor alisertib (MLN8237) that shows some specificity for aurora kinase A over aurora kinase B in a panel of neuroblastoma cell lines with acquired drug resistance. Both compounds displayed anti-neuroblastoma activity in the nanomolar range. The anti-neuroblastoma mechanism included inhibition of aurora kinase signalling as indicated by decreased phosphorylation of the aurora kinase substrate histone H3, cell cycle inhibition in G2/M phase, and induction of apoptosis. The activity of alisertib but not of tozasertib was affected by ABCB1 expression. Aurora kinase inhibitors induced a p53 response and their activity was enhanced in combination with the MDM2 inhibitor and p53 activator nutlin-3 in p53 wild-type cells. In conclusion, aurora kinases are potential drug targets in therapy-refractory neuroblastoma, in particular for the vast majority of p53 wild-type cases.
    Keywords: Tumor Proteins ; Apoptosis ; Phosphotransferases ; Neuroblastoma
    ISSN: 1932-6203
    Source: Cengage Learning, Inc.
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: PLoS ONE, 2011, Vol.6(5), p.e19705
    Description: Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
    Keywords: Research Article ; Medicine ; Infectious Diseases ; Pharmacology
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e36506
    Description: Oncolytic influenza A viruses with deleted NS1 gene (delNS1) replicate selectively in tumour cells with defective interferon response and/or activated Ras/Raf/MEK/ERK signalling pathway. To develop a delNS1 virus with specific immunostimulatory properties, we used an optimised technology to insert the interleukin-15 (IL-15) coding sequence into the viral NS gene segment (delNS1-IL-15). DelNS1 and delNS1-IL-15 exerted similar oncolytic effects. Both viruses replicated and caused caspase-dependent apoptosis in interferon-defective melanoma cells. Virus replication was required for their oncolytic activity. Cisplatin enhanced the oncolytic activity of delNS1 viruses. The cytotoxic drug increased delNS1 replication and delNS1-induced caspase-dependent apoptosis. Interference with MEK/ERK signalling by RNAi-mediated depletion or the MEK inhibitor U0126 did not affect the oncolytic effects of the delNS1 viruses. In oncolysis sensitive melanoma cells, delNS1-IL-15 (but not delNS1) infection resulted in the production of IL-15 levels ranging from 70 to 1140 pg/mL in the cell culture supernatants. The supernatants of delNS1-IL-15-infected (but not of delNS1-infected) melanoma cells induced primary human natural killer cell-mediated lysis of non-infected tumour cells. In conclusion, we constructed a novel oncolytic influenza virus that combines the oncolytic activity of delNS1 viruses with immunostimulatory properties through production of functional IL-15. Moreover, we showed that the oncolytic activity of delNS1 viruses can be enhanced in combination with cytotoxic anti-cancer drugs.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Infectious Diseases ; Molecular Biology ; Oncology ; Dermatology
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages