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41.
Hantaviruses predominantly infect human endothelial cells and, in the absence of cell lysis, cause two diseases resulting from increased vascular permeability. Andes virus (ANDV) causes a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). ANDV infection enhances the permeability of endothelial cells in response to vascular endothelial growth factor (VEGF) by increasing signaling responses directed by the VEGFR2-Src-VE-cadherin pathway, which directs adherens junction (AJ) disassembly. Here we demonstrate that inhibiting pathway-specific VEGFR2 and Src family kinases (SFKs) blocks ANDV-induced endothelial cell permeability. Small interfering RNA (siRNA) knockdown of Src within ANDV-infected endothelial cells resulted in an ~70% decrease in endothelial cell permeability compared to that for siRNA controls. This finding suggested that existing FDA-approved small-molecule kinase inhibitors might similarly block ANDV-induced permeability. The VEGFR2 kinase inhibitor pazopanib as well as SFK inhibitors dasatinib, PP1, bosutinib, and Src inhibitor 1 dramatically inhibited ANDV-induced endothelial cell permeability. Consistent with their kinase-inhibitory concentrations, dasatinib, PP1, and pazopanib inhibited ANDV-induced permeability at 1, 10, and 100 nanomolar 50% inhibitory concentrations (IC(50)s), respectively. We further demonstrated that dasatinib and pazopanib blocked VE-cadherin dissociation from the AJs of ANDV-infected endothelial cells by >90%. These findings indicate that VEGFR2 and Src kinases are potential targets for therapeutically reducing ANDV-induced endothelial cell permeability and, as a result, capillary permeability during HPS. Since the functions of VEGFR2 and SFK inhibitors are already well defined and FDA approved for clinical use, these findings rationalize their therapeutic evaluation for efficacy in reducing HPS disease. Endothelial cell barrier functions are disrupted by a number of viruses that cause hemorrhagic, edematous, or neurologic disease, and as a result, our findings suggest that VEGFR2 and SFK inhibitors should be considered for regulating endothelial cell barrier functions altered by additional viral pathogens. 相似文献
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43.
Mapping of ceruloplasmin gene in human and mouse chromosomes was carried out using the cloned fragments of rat chromosomal ceruloplasmin gene and of ceruloplasmin cDNA as specific hybridization probes. DNA probes were nick-translated with 125I-dCTP up to the high specific capacity. The number of silver grains as well as their distribution along the differentially stained chromosomes were analyzed in 120 metaphase plates from bone marrow cells of laboratory mice and in 181 plates from human lymphocyte cultures. The most probable localization of human ceruloplasmin gene is centromeric region q11-13 of chromosome 15(14?). In laboratory mice ceruloplasmin gene is assigned to the euchromatic part of D-disc of chromosome 9. The possible causes for gene synteny in laboratory mouse and in man as well as its evolutionary implication are discussed. 相似文献
44.
The content was studied of biogenic amines and their metabolites (by the method of high-effective fluid chromatography electrochemical detection) in the reticular formation of the midbrain, locus coeruleus and sensorimotor cortex in the rats of Wistar and August lines, differing in the behaviour in the open field, in conditions of immobilization stress. The dependence was revealed of the biogenic amines level on the animals genotype and individual characteristics. Most probably, the level of biogenic amines metabolism in central brain structures determines the stability of the animals against emotional stress. 相似文献
45.
V A Gorbunova 《Antibiotiki i khimioterapii͡a》1992,37(3):35-39
Carminomycin is an original antitumor antibiotic from the anthracycline group isolated at the Institute of New Antibiotics (USSR) in 1973. Pharmacological investigation of carminomycin revealed its satisfactory absorption from the gastrointestinal tract which proved to be a distinguishing property of the antibiotic as compared to other anthracyclines such as adriamycin and rubomycin. The clinical trials of carminomycin showed that it was mainly active against soft tissue sarcoma and breast cancer, lymphosarcoma, neuroblastoma, Wilms' tumor and Ewing's sarcoma in children, as well as acute leukemia. Various regimens for the antibiotic administration were applied: short-term, single and long-term. Suppression of hemopoiesis was considered as a limiting toxic effect. By the data available carminomycin had lower cardiotoxicity as compared with rubomycin and adriamycin. Development of oral carminomycin is believed promising. 相似文献
46.
V S Baranov B Brobohaty N V Tsymbalenko L Tádlicek V N Gorbunova T B Kazakova L Kovác K Bodja 《T?Sitologii?a i genetika》1990,24(2):52-55
Liposomes loaded with FITC-labeled albumin in the presence of PEG-1,500 are actively sorbed on the membranes of mature spermatozoa and remain attached even after thorough washing. Immature sperm cells are able to incorporate alien DNA carried by liposomes. In contrast, the mature spermatozoa could not incorporate plasmid DNA loaded with positively charged liposomes. Chlortetracycline in Ca-P coprecipitate crystals is tightly fixed in the postacrosomal region of mature sperms. Intensity of staining of chlortetracycline is stimulated by DNA load in Ca-P coprecipitate as well as by DMSO or EDTA. The method of Ca-P coprecipitation could not provide for plasmid DNA incorporation into taure sperms. Foreign DNA incorporation in postacrosomal regions of sperm heads seems quite possible in experiments with dimethylsulphoxide (DMSO). 相似文献
47.
Integration of DNA of a temperature-sensitive SV40 mutant (tsA239) into the cell genome was studied. The viral A gene (the oncogene) encodes the tumour T antigen which is ts in the mutant and is devoid of mutagenic and transforming activity under non-permissive conditions (40 degrees C). Clones of Chinese hamster cells infected by tsA239 mutant were analysed. Those infected by wild-type SV40 served as controls. As shown by dot-hybridization, SV40 DNA was detected in cells of 14 out of 18 clones infected by tsA mutant and incubated at 40.5 degrees C, and in all 20 clones infected by tsA mutant and incubated under permissive conditions (33 degrees C), the difference between the two groups being insignificant (p greater than 0.05). By means of blot-hybridization it was established that viral DNA was integrated into the cell genome of all 12 clones analysed, belonging to the three experimental series: infection by tsA mutant, incubation at 40.5 and 33 degrees C, infection by wt SV40, incubation at 40.5 degrees C. The number of integration sites ranged from one to four in different clones. Integration of SV40 DNA in tandems was observed. The data presented allow to conclude that integration per se does not play a crucial role in determining the mutagenic and transforming effect of the virus. Obviously, what matters is the activity of viral oncogene product - the T antigen. 相似文献
48.
M L Gorbunova E I Lobanova T E Drozd S A Turliun V P Maganchuk 《Mikrobiologicheekij zhurnal》1989,51(5):77-81
Representatives of the normal microflora from genus Aerococcus, in particular strain Aerococcus viridans 167 isolated from breast milk are studied for their effect on biological properties of Staphylococcus aureus in vitro and in vivo. It is established that the number of viable cells of the staphylococcus cultivated in the presence of antagonists in the beef-extract agar decreases progressively with each following passage, the population dying after the seventh-eight passage. Electronograms fix deep changes in the cell ultrastructure. A degree of changes in biological properties depends on the duration of the antagonist action. The results obtained reveal one of the mechanisms of the antagonistic action of aerococci-antagonists producing hydrogen peroxide. 相似文献
49.
M. G. Golubeva M. E. Grigroryeva S. A. Gorbunova 《Moscow University Biological Sciences Bulletin》2008,63(2):49-52
In experiments in vitro, the effects of vasopressin and of its analogue DGVAP on aggregation of platelets are compared. Addition of peptides causes aggregation both in plasma rich in platelets both in humans and rats. In the human plasma DGVAP is a much stronger inductor of aggregation than vasopressin, whereas in the plasma of rats the effects are identical. Vasopressin and DGVAP considerably increase thrombin-induced aggregation of washed platelets of rats but do not influence ADP-induced aggregation of platelets. Thus, multifunctional action of these peptides on aggregation of platelets may depend both on their direct interaction with platelets and on a potential synergic action of peptides with other agonists. 相似文献
50.