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Denileukin Diftitox (ONTAK®, DAB389 IL-2) is a recombinant DNA-derived fusion protein depleting cells that express high-affinity IL-2 receptor. Important cell targets are CD4+CD25+Foxp3+ regulatory T cells (Treg). Elimination of immunosuppressive Treg by Denileukin Diftitox may provide a way to modulate immune tolerance following stem cell transplantation. Here, we combined Treg depletion with a vaccination approach to induce donor-specific immune reactions. To investigate this approach we chose the mixed chimerism canine stem cell transplantation model which represents a high state of tolerance between two hematopoietic systems. The aim was therefore to induce a graft versus hematopoiesis effect thereby converting mixed to full donor chimerism. Dog leukocyte antigen identical siblings that had developed a stable mixed chimerism after non-myeloablative stem cell transplantation received a single dose of Denileukin Diftitox (18 μg/kg, i.v.) followed by several cell-lysate vaccinations. Host peripheral blood mononuclear cell lysates combined with CpG-ODN, and Montanide® ISA 51 were locally applied. In vitro studies demonstrated that canine Treg are a target of Denileukin Diftitox. The suppression of T-cell proliferation by Treg was abolished by addition of Denileukin Diftitox (10 nM). An increase of proliferation of median 300% (range: 200%–425%) was observed. No change in donor chimerism was observed after administration of Denileukin Diftitox and vaccination. This study highlights that application of Denileukin Diftitox resulted in a depletion of Treg followed by an increase of immune response in vitro. This effect could not be confirmed in vivo even if the immune system was stimulated by vaccinations.  相似文献   
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In a herd of 1400 dairy goats with an average milk yield of 840 kg/year, 40 "Weisse Deutsche Edelziegen" (October-January: n = 19; April-July: n = 21) were examined. Venous blood samples were collected 6-8, 3-4 and < 2 weeks (wks) ante partum (a. p.) and 2-4 days (d), 3-4 and 6-8 wks post partum (p. p.). Antioxidative Capacity of Water soluble substances (ACW) and Trolox Equivalent Antioxidative Capacity (TEAC) were measured in serum; activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in an erythrocyte pellet and in whole blood. ACW and TEAC increased significantly 3-4 wks p. p. In summer these two parameters showed significantly higher concentrations than in winter. The SOD had a significantly higher activitiy < 2 wks a. p. and 6-8 wks p. p. GPX-activity showed a constant increase from the beginning of investigations and from 3-4 wks p. p. up to the end of investigations activities were significantly higher than 6-8 wks a. p. The samples ante partum and the first sample taken post partum showed significantly higher activities in summer than in winter. The present study shows, that the metabolic challenge associated to the periparturient period in combination with changing capacity of food intake, influences the antioxidative metabolism in dairy goats. Seasonal depending changes on feeding quality and climate (barn temperature, quality of feeding components) also influence this system.  相似文献   
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Fish gills are heavily exposed to the external milieu and may react against irritants with different cellular responses. We describe variations in mucous cell counts in gills from healthy Atlantic salmon (Salmo salar) presmolts in five recirculating aquaculture system (RAS) farms and one flow‐through farm. Based on certain criteria, mucous cells were histologically quantified in a defined lamellar region of the gills and the counts were analysed. Immunohistochemistry (IHC) was used to investigate epithelial responses. The median number of total mucous cells in the defined region was 59 per fish. Between the farms, the medians varied from 31 to 101 with the lowest in the flow‐through farm. A regression model was fitted with “total mucous cells” as the dependent variable and with “fish length” and “fish farm” as independent variables. The proportion of variation in mucous cell counts explained by the model was twice as high when “fish farm” was included compared to only “fish length.” IHC revealed proliferative responses in coherence with high mucous cell numbers. Conclusively, the variation in mucous cell counts depends on combined farm‐related factors. Establishing a baseline for mucous cell counts is fundamental in the development of high‐throughput monitoring programmes of gill health in farmed fish.  相似文献   
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Saltmarshes, functionally important habitats in the marine–terrestrial ecotone that are regularly affected by tidal inundation, are mainly detritus-based in terms of fluxes of nutrients and energy. With respect to the mediating influence of saltmarsh detritivores on microbial colonisation of detritus and on decomposition processes, we tested whether the “intermediate disturbance hypothesis” (IDH) is also applicable to the effects of stress in this stressful environment. Decomposition experiments with litter of the cordgrass, Spartina anglica, and with terrestrial [Porcellio scaber (Isopoda)] and marine/semi-terrestrial [Orchestia gammarellus (Amphipoda)] detritivores as well as animal-free controls were carried out in an artificial saltmarsh system. Different daily flooding regimes served as experimental levels of stress. Both litter mass loss and microbial respiration were mostly higher under aquatic than under terrestrial conditions, no matter whether detritivores were present or not. Considering the intertidal zone, low to intermediate daily inundation rates resulted in increased microbial respiration and an increased influence of detritivores on litter mass loss in early stages of cordgrass decomposition with high rates of detritus mass loss, and intermediate tidal stress led to higher microbial cell counts throughout the entire experiment. Summarised over 3 months, regression analyses suggested that microbial activity and detritus mass loss show a trend towards highest values at low inundation rates and under permanent inundation, although microbial density was higher under longer daily inundation. Access to detritus by detritivores enhanced both litter mass loss and microbial respiration, especially in later decomposition stages, whereas microbial density was reduced by detritivores. In conclusion, we predict that overall the decomposition of cordgrass detritus in saltmarshes is promoted in the intermediate to high area of the intertidal zone with daily inundation of ca. 4–10 hours where both marine and terrestrial detritivores have access to promote decomposition processes through feeding and mediating microbial activity.  相似文献   
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A two-week-old budgerigar (Melopsittacus undulatus) of an outdoor aviary died suddenly and was submitted for determination the cause of illness and death. Macroscopically, the sparsely feathered animal was in a poor body condition. Histopathological examination revealed in various mesenchymal and epithelial tissues, numerous up to 15 microm in diameter large intranuclear, amphophilic to basophilic inclusion bodies with a clearing of the centre. Additionally, a feather dysplasia and retention hyperkeratosis of feather follicles was found. Ultrastructurally, viral particles of approximately 35 nm in diameter were detected in the feather follicle epithelium. A PCR for Avian Polyomavirus on fresh skin samples was negative whereas on formalin-fixed kidney samples with a high amount of viral inclusion bodies yielded a positive result. In addition, viral inclusion body diseases, like Avian Poxvirus, Psittacine Beak and Feather disease virus, Avian Adenovirus, Psittacine Herpesvirus and papillomavirus of psittacines are summarized and compared in the present article.  相似文献   
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