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Thirty 15-month-old ewes were randomly allocated to three groups of 10 sheep each. One group was given a single infection of 60,000 T. colubriformis 3rd stage larvae (L3). The second group 2 was infected orally with 20,000, 40,000 and 60,000 L3 T. colubriformis at 21 day intervals and 21 days after the third dose the sheep were treated with Oxfendazole. Seven days later Groups 1 and 2 sheep were challenged with 60,000 L3 T. colubriformis. The third group was left as uninfected controls. All sheep were bled at weekly intervals and the blastogenic responses to Con A, PHA, PWM and LPS of peripheral blood lymphocytes were evaluated using tritiated thymidine incorporation into DNA. When lymphocytes were cultured with Con A, PHA, PWM or LPS, a progressive decrease of blastogenic activity was observed up to 35 days after a single infection of sheep. In multiple infected sheep, the blastogenic responses to the mitogens were generally depressed from the second infection or shortly thereafter with a return to control levels observed only with LPS. Non-mitogen stimulated lymphocytes from single and multiple infected sheep showed significantly increased blastogenic activity on 35 day after each infection. The data indicate that this type of infection with T. colubriformis may have led to activation of peripheral lymphocytes, coinciding with diminished T-cell responsiveness to the mitogens.
An active form of p38 protein kinase, belonging to the mitogen-activated protein kinases subfamily, has been designed based on crystallographically known structures of two other kinases, an active form of protein kinase A (PKA) and an inactive form of extracellular signal-regulated kinase 2 (ERK2). The modelling procedure is described. Its general scheme can also be applied to other kinases. The structure of the active forms of p38 and PKA is very similar in the region which binds the substrate. The ATP-binding mode is very similar in the active forms of all the three studied kinases. Models of the active forms allow for further studies on transphosphorylation processes at the molecular level, and modelling of inhibitors competitive with ATP and/or substrates.
Lymphocyte blastogenesis was determined by ³H-thymidine incorporation assay after stimulation of the cell cultures with mitogens: Concanavalin A, phytohaemagglutitin, and pokeweed mitogen. BIV and/or BLV infection were associated with significant changes in lymphocyte blastogenesis to mitogens. The highest responses to all three mitogens were shown by 3 to 4.5 months after infection when compared to control animals, and thereafter were depressed at the end of the experiment Stimulated lymphocytes revealed in 20 - 50 fold increase in blastogenesis over background based on the unstimulated cells. These results demonstrated that a function impairement of lymphocytes can be observed in the course of BLV and/or BIV infection.
The application of immunostimulators in dogs offers a novel approach to induce or modulate the mechanisms of protection against infectious diseases. In the present studies we evaluated in vitro influence of different concentrations of synthetic product - methisoprinol on the proliferative response of blood lymphocytes stimulated by pokeweed mitogen (PWM), concanavaline A and lipopolisaccharide (LPS) in dogs. The concentrations of methisoprinol between 1 to 50 μg/ml increased the mitogen-induced proliferation rate of canine T and B lymphocytes. Enhanced response to mitogens was observed both in 1-2 and 6-8 years old dogs, but the best results were observed in older animals. The results suggested that methisoprinol demonstrated a stronger effect on the lymphocytes isolated from older animals with the lower proliferative responses.
Endogenous peptide antibiotics are known as evolutionarily old components of in­nate immunity. Due to interaction with cell membrane these peptides cause permeabilization of the membrane and lysis of invading microbes. However, some studies proved that antimicrobial peptides are universal multifunctional molecules and their functions extend far beyond simple antibiotics. In this review we present an overview of the general mechanism of action of antimicrobial peptides and discuss some of their additional properties, like antitumour activity, mitogenic activity, role in signal transduction pathways and adaptive immune response.
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