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21.
Antifungal activities of posaconazole and granulocyte-macrophage colony-stimulating factor ex vivo and in mice with disseminated infection due to Scedosporium prolificans
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Simitsopoulou M Gil-Lamaignere C Avramidis N Maloukou A Lekkas S Havlova E Kourounaki L Loebenberg D Roilides E 《Antimicrobial agents and chemotherapy》2004,48(10):3801-3805
Invasive infection due to Scedosporium prolificans is characterized by drug resistance and a high rate of mortality. The effects of posaconazole (POS), an investigational antifungal triazole, murine granulocyte-macrophage colony-stimulating factor (GM-CSF), and their combination against S. prolificans were evaluated ex vivo and in a newly developed murine model of disseminated infection due to this organism. When POS was combined with polymorphonuclear leukocytes from untreated or GM-CSF-treated mice (P < 0.01) ex vivo, it had increased activity in terms of the percentage of hyphal damage. Immunocompetent BALB/c mice were infected with 4 x 10(4) conidia of S. prolificans via the lateral tail vein. At 24 h postinfection the mice were treated with GM-CSF (5 microg/kg of body weight/day subcutaneously), POS (50 mg/kg/day by gavage), both agents, or saline only. Half of the brain, lung, liver, and kidney from each animal were cultured; and the other half of each organ was processed for histopathology. The mean survival times were 7.0 +/- 0.3 days for the controls, 7.4 +/- 0.4 days for POS-treated mice, 8.0 +/- 0.3 days for GM-CSF-treated mice (P = 0.08 compared with the results for the controls), and 7.3 +/- 0.3 days for POS-GM-CSF-treated mice. Fungal burdens (determined as the numbers of CFU per gram of tissue) were found in descending orders of magnitude in the kidneys, brains, livers, and lungs. The burdens were significantly reduced in the brains of GM-CSF-treated mice (P < 0.05) and the livers of POS-treated mice (P < 0.05). The numbers of lesions in the organs closely corresponded to the fungal burdens. GM-CSF tended to prolong survival (P = 0.08 compared with the results for the controls). While the combination of POS and GM-CSF showed enhanced activity ex vivo, it did not increase the activities of the two agents against this highly refractory filamentous fungus in mice. 相似文献
22.
Psaridi-Linardaki L Trakas N Mamalaki A Tzartos SJ 《Journal of neuroimmunology》2005,159(1-2):183-191
Antibodies against the acetylcholine receptor (AChR) are the main pathogenic factor in myasthenia gravis (MG). Clinical improvement correlates well with a reduction in levels of circulating anti-AChR antibodies, and plasmapheresis is an efficient short-term MG treatment. The Sepharose-immobilized N-terminal extracellular domain of human muscle AChR alpha-subunit was used to immunoadsorb anti-AChR autoantibodies from 50 MG patients sera. The immunoadsorbents removed 60-94% of the anti-AChR antibodies in 10 sera and a mean of 35% from all samples combined. Immunoadsorption was fast, efficient, and the columns could be used repeatedly without any release or proteolysis of the polypeptide, suggesting the feasibility of antigen-specific MG immunoadsorption therapy. 相似文献
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Winn RM Gil-Lamaignere C Roilides E Simitsopoulou M Lyman CA Maloukou A Walsh TJ 《The Journal of infectious diseases》2003,188(4):585-590
The effects of interleukin (IL)-15 on human polymorphonuclear leukocyte (PMNL) activity against Aspergillus fumigatus and Aspergillus flavus were investigated. Pretreatment with IL-15 for 2 h increased PMNL oxidative burst, as measured by superoxide anion (O(2)(-)) release in response to A. fumigatus (P<.05) but not to A. flavus. However, after 22-h, but not 2-h, treatment with IL-15, there was significant enhancement in PMNL-mediated hyphal damage to A. fumigatus. Furthermore, 22-h exposure to IL-15 mediated an enhanced release of IL-8 from PMNLs challenged with hyphae of A. fumigatus and A. flavus (P<.05). In contrast, IL-15 treatment did not affect the release of tumor necrosis factor-alpha from PMNLs. The selective time- and species-dependent enhancement of O(2)(-) production and hyphal damage, as well as its induction of IL-8 release, suggest that IL-15 may play an important role in the immunomodulation of host response to invasive aspergillosis. 相似文献
24.
Chrissa Kioussi Avgi Mamalaki Kristjan Jesse Rhona Mirsky Louis B. Hersh Rebecca Matsas 《The European journal of neuroscience》1995,7(5):951-961
Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukaemia antigen CD1O (CALLA), is a cell surface Zn2+ metalloprotease that regulates peptide-induced responses in different tissues, including the nervous and immune systems. In the peripheral nervous system, high levels of the enzyme are present in all neonatal and early postnatal Schwann cells, while as myelination proceeds it is gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. In the present study we have investigated the effects of transection, crush and regeneration of the adult rat sciatic nerve on the expression of the endopeptidase by Schwann cells in situ. Endopeptidase-24.11 was monitored by immunocytochemistry using the monoclonal anti-endopeptidase antibody 23811. For comparison, a parallel study was carried out with a monoclonal antibody directed against the rat nerve growth factor receptor. We found that (i) all Schwann cells of the distal segment re-expressed endopeptidase-24.11 as early as 4 days after axotomy, the level of immunostaining reaching a maximum after 2 weeks, (ii) axonal regeneration repressed Schwann cell expression of endopeptidase-24.11, and (iii) the induction of the nerve growth factor receptor followed a similar pattern to that of endopeptidase-24.11 in the transected and crushed nerve. Enzymatic amplification of endopeptidase-24.11 cDNA from normal and axotomized adult rat sciatic nerve confirmed the expression of endopeptidase-24.11 in these tissues. Our results show that the expression of endopeptidase-24.11 in Schwann cells, as is the case with the nerve growth factor receptor, is induced by the loss of the normal axon-Schwann cell contact. The significant increase in the expression of endopeptidase-24.11 by Schwann cells after axonal damage suggests that the enzyme could play a role in axonal regeneration. 相似文献
25.
Socrates J. Tzartos Tom Barkas M. Thong Cung Avgi Mamalaki Michel Marraud Piotr Orlewski Danai Papanastasiou Constantinos Sakarellos Maria Sakarellos-Daitsiotis Panayota Tsantili Vassilios Tsikaris 《Immunological reviews》1998,163(1):89-120
Summary: The neuromuscular junction nicotinic acetylcholine receptor (AChR), a pentameric membrane glycoprotein, is the autoantigen involved in the autoimmune disease myasthenia gravis (MG). In animals immunized with intact AChR and in human MG, the anti-AChR antibody response is polyclonal. However, a small extracellular region of the AChR a-subunit, the main immunogenic region (MIR), seems to be a major target for anti-AChR antibodies. A major loop containing overlapping epitopes for several anti-MIR monoclonal antibodies (mAbs) lies within residues α67–76 at the extreme synaptic end of each a-subunit; however, anti-MIR mAbs are functionally and structurally quite heterogeneous. Anti-MIR mAbs do not affect channel gating, but are very effective in the passive transfer of MG to animals; in contrast, their Fab or Fv fragments protect the AChR from the pathogenic effects of the intact antibodies. Antibodies against the cytoplas-mic region of the AChR can be elicited by immunization with denatured AChR and the precise epitopes of many such mAbs have been identified; however, it is unlikely that such antibodies are present in significant amounts in human MG. Antibodies to other extracellular epitopes on all AChR subunits are present in both experimental and human MG; these include antibodies to the acetylcholine-binding site which affect AChR function in various ways and also induce acute experimental MG. Finally, anti-AChR antibodies cross-reactive with noti-AChR antigens exist, suggesting that MG may result from molecular mimicry. Despite extensive studies, many gaps remain in our understanding of the antigenic structure of the AChR, especially in relation to human MG. A thorough understanding of the antigenic structure of the AChR is required for an in-depth understanding, and for possible specific immunotherapy, of MG. 相似文献
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Gil-Lamaignere C Simitsopoulou M Roilides E Maloukou A Winn RM Walsh TJ 《The Journal of infectious diseases》2005,191(7):1180-1187
Zygomycetes cause serious invasive infections, predominantly in immunocompromised and diabetic patients with poor prognoses and limited therapeutic options. We compared the antifungal function of human polymorphonuclear leukocytes (PMNLs) against hyphae of Rhizopus oryzae and R. microsporus, the most frequently isolated zygomycetes, with that against the less frequently isolated Absidia corymbifera. We then evaluated the effects of interferon (IFN)- gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF), alone or combined, on PMNL antifungal function against these zygomycetes. Both PMNL oxidative burst in response to hyphae and PMNL-induced hyphal damage were significantly lower in response to Rhizopus species than in response to A. corymbifera. Incubation of PMNLs with IFN- gamma and GM-CSF alone or combined for 22 h increased the PMNL-induced hyphal damage of all 3 species. The treatment of PMNLs with the combination of IFN- gamma and GM-CSF significantly increased the release of tumor necrosis factor- alpha in response to R. microsporus and A. corymbifera hyphae. IFN- gamma significantly reduced interleukin-8 release in response to all zygomycetes. Although Rhizopus species demonstrate a decreased susceptibility to the antifungal activity of human PMNLs, in comparison with A. corymbifera, IFN- gamma and GM-CSF augment the hyphal damage of all 3 zygomycetes, suggesting a role for IFN- gamma and GM-CSF in the management of invasive zygomycosis. 相似文献
28.
Yiting Wang Jia Liu Avgi Loizidou Luc A Bugeja Ross Warner Bethan R Hawley Zhiwei Cai Ashley M Toye David N Sheppard Hongyu Li 《British journal of pharmacology》2014,171(19):4490-4503