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1.
Talayev VY Zaichenko IY Babaykina ON Lomunova MA Talayeva EB Nikonova MF 《Clinical and experimental immunology》2005,141(3):440-448
The effects of dexamethasone phosphate and interleukin‐7 upon the proliferation of T‐cells and the production of interferon‐γ in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T‐cell proliferation induced by anti‐CD3 with interleukin‐7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon‐γ in 68‐h cell cultures stimulated with anti‐CD3 both in the presence of interleukin‐7 and without it. However, a 68‐h cultivation of newborn blood cells with dexamethasone, anti‐CD3 and interleukin‐7 resulted in the accumulation of T‐lymphocytes capable of producing interferon‐γ after restimulation. As a result of it the amount of interferon‐γ producing CD7+ T‐cells and the concentration of interferon‐γ in cultural supernatants were maximal in the cell cultures incubated with anti‐CD3, interleukin‐7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12‐myristate 13‐acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti‐CD3 and interleukine‐7 also causes a decrease in the number of naïve T‐cells and central memory cells and an increase in the number of effector memory CD7+CD45RA+CD62L– cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL‐7 receptor expression: it is known that IL‐7 receptor alpha‐chain gene is a glucocorticoid‐inducible gene. 相似文献
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Stephen E. Jones Yuji Kasamaki Toshitsugu Ogura Lesya M. Shuba John R. McCullough Terence F. McDonald 《European journal of pharmacology》1999,370(3):863-327
The antispasmodic agent terodiline has cardiotoxic effects that include QT lengthening. To determine whether inhibition of inwardly-rectifying K+ current (IK1) might be a factor in the cardiotoxicity, we measured IK1 in guinea pig ventricular myocytes. Terodiline reduced outward IK1 with an IC50 of 7 μM; maximal reduction was 60% with 100–300 μM concentration. Inhibition was independent of current direction, and persisted after removal of the drug. Terodiline (3–5 μM) lengthened action potentials in guinea pig papillary muscles by ca. 10%, primarily by slowing phase 3 repolarization; higher concentrations abbreviated the plateau and markedly slowed late repolarization. Terodiline washout provoked an extra lengthening, consistent with persistent inhibition of IK1 and rapid recovery of net inward plateau current. The results suggest that inhibition of IK1 is a likely factor in the cardiotoxicity of the drug. 相似文献
4.
Nikolay M Filipov Lesya M Pinchuk Bobbie L Boyd Patrick L Crittenden 《Toxicological sciences》2005,86(2):324-332
The herbicide atrazine (ATR) is a very widely used pesticide; yet the immunotoxicological potential of ATR has not been studied extensively. Our objective was to examine the effect of ATR on selected immune parameters in juvenile mice. ATR (up to 250 mg/kg) was administered by oral gavage for 14 days to one-month-old male C57BL/6 mice. One day, one week, and seven weeks after the last ATR dose, mice were sacrificed, and blood, spleens, and thymuses were collected and processed for cell counting and flow cytometry. Thymus and spleen weights were decreased by ATR, with the thymus being more sensitive than the spleen; this effect was still present at seven days, but not at seven weeks after the last ATR dose. Similarly, organ cellularity was persistently decreased in the thymus and in the spleen, with the splenic, but not thymic cellularity still being depressed at seven weeks post ATR. Peripheral blood leukocyte counts were not affected by ATR. There were also alterations in the cell phenotypes in that ATR exposure decreased all phenotypes in the thymus, with the number of CD4(+)/CD8(+) being affected the least. At the higher doses, the decreases in the thymic T-cell populations were still present one week after the last ATR dose. In the spleen, the CD8(+) were increased and MHC-II(+) and CD19(+) cells were decreased one day after the last ATR dose. Also, ATR treatment decreased the number of splenic na?ve T helper and T cytotoxic cells, whereas it increased the percentage of highly activated cytotoxic/memory T cells. Interestingly, the proportion of mature splenic dendritic cells (DC; CD11c(high)), was also decreased and it persisted for at least one week, suggesting that ATR inhibited DC maturation. In the circulation, ATR exposure decreased CD4(+) lymphocytes at one day, whereas at seven days after the last ATR dose, in addition to the decrease in CD4(+) lymphocytes, the MHC-II(+) cells were also decreased at the 250 mg/kg dose. Thus, ATR exposure appears to be detrimental to the immune system of juvenile mice by decreasing cellularity and affecting lymphocyte distribution, with certain effects persisting long after exposure has been terminated. 相似文献
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Broshevitskaya N. D. Pavlova I. V. Zaichenko M. I. Gruzdeva V. A. Grigoryan G. A. 《Neuroscience and behavioral physiology》2021,51(3):390-401
Neuroscience and Behavioral Physiology - Early proinflammatory stress created by administration of lipopolysaccharide (LPS) (50 μg/kg s.c.) on days 3 and 5 of postnatal life led to decreases... 相似文献
7.
Expression of the diabetes (db/db) mutation (i.e., leptin receptor defect) in C57BL/KsJ mice results in the functional suppression of the female pituitary-gonadal axis accompanied by premature utero-ovarian lipocytoatrophy. The current studies define the cytostructural, metabolic and endocrine disturbances associated with hypercytolipidemia and coincident nuclear lipoapoptosis following expression of the db/db-mutation. Adult, female C57BL/KsJ control (+/+ and +/? genotypes) and db/db mutant littermates were monitored for systemic alterations in blood glucose, insulin, luteinizing hormone (LH) and 17-B-estradiol (E2) concentrations associated with db/db-enhanced cytolipid depositions and TUNEL-labeled 3'-DNA fragmentation indexed nuclear lipoapoptosis. Obesity, hyperglycemia and hyperinsulinemia, in addition to depressed LH and E2 concentrations, characterized all db/db-mutants relative to control indices. Structural and cytochemical analysis of basophilic gonadotroph cells, ovarian follicular granulosa cells and uterine endometrial epithelial layers indicated that db/db mutants demonstrated prominent hypercytolipidemia relative to control cytoarchitecture profiles. Vasolipidemia and interstitial cytoadiposity were prominent in all db/db tissue compartments. In each affected cell type within the db/db pituitary-reproductive tract axis, hypercytolipidemia was localized with pronounced nuclear lipo-infiltration and 3'-DNA TUNEL-labeled fragmentation. These data indicate that coincident cytostructural, endocrine and metabolic disturbances associated with hypogonadal pituitary-reproductive tract hypercytolipidemia are functional manifestations of the expressed diabetes-obesity syndrome in db/db-mutants. The progressive vaso-, interstitial-, and cyto-lipidemic alterations in cytoarchitecture correlated with the coincident nuclear lipoapoptotic dissolution and pronounced organo-involution, alterations which contributed to the functional disruption of the pituitary-hypogonadal axis in C57BL/KsJ-db/db mice. 相似文献
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M. I. Zaichenko G. Kh. Merzhanova A. V. Demina 《Neuroscience and behavioral physiology》2011,41(6):606-612
Rats divided on the basis of a test in which they were presented with the “right” to choose a more valuable but delayed or
a less valuable but immediate reinforcement into “impulsive” and “self-controlled” groups were studied using the “emotional
resonance” method. These experiments showed that none of the rats of the “self-controlled” group, selecting the more valuable
but delayed reinforcement, avoided defensive arousal signals from another individual of the same species, preferring to spend
a large proportion of time in the dark “house.” Most (80%) of the animals of the “impulsive” group spent more than half the
experimental period in the light sector, thus saving the partner from electrical stimulation. It is suggested that there are
several common mechanisms underlying these two types of behavior. 相似文献
10.
Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 microM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion. 相似文献