Background: G-protein activation mediates inhibition of N-type Ca2+ currents. Volatile anesthetics affect G-protein pathways at various levels, and activation of G-proteins has been shown to increase the volatile anesthetic potency for inhibiting the electrical-induced contraction in ileum. The authors investigated whether isoflurane inhibition of N-type Ba2+ currents was mediated by G-protein activation.
Methods: N-type Ba2+ currents were measured in the human neuronal SH-SY5Y cell line by using the whole cell voltage-clamp method.
Results: Isoflurane was found to have two effects on N-type Ba2+ currents. First, isoflurane reduced the magnitude of N-type Ba2+ currents to a similar extent (IC50 ~ 0.28 mm) in the absence and presence of GDP[beta]S (a nonhydrolyzable GDP analog). Interestingly, GTP[gamma]S (a nonhydrolyzable GTP analog and G-protein activator) in a dose-dependent manner reduced the isoflurane block; 120 [mu]m GTP[gamma]S completely eliminated the block of 0.3 mm isoflurane and reduced the apparent isoflurane potency by ~ 2.4 times (IC50 ~ 0.68 mm). Pretreatment with pertussis toxin or cholera toxin did not eliminate the GTP[gamma]S-induced protection against the isoflurane block. Furthermore, isoflurane reduced the magnitude of voltage-dependent G-protein-mediated inhibition of N-type Ba2+ currents, and this effect was eliminated by pretreatment with pertussis toxin or cholera toxin. 相似文献
Many features of the interferon gamma (IFN-gamma) signaling pathway would suggest that it is anti-tumorigenic. The IFN-gamma signaling pathway leads to apoptosis and to the expression of immune function proteins that could cooperate with T cells in the destruction of tumor. Various lines of experimental approach have, in general, supported the hypothesis that the IFN-gamma signaling pathway is anti-tumorigenic. However, data also indicate that the idea that the IFN-gamma signaling pathway is exclusively anti-tumorigenic is too simplistic. Also, to date, very little of the knowledge regarding the anti-tumor effects of the IFN-gamma pathway has been useful in the prognosis or therapy of cancer. This review summarizes the current state of knowledge regarding the IFN-gamma signaling pathway in tumorigenesis, with an emphasis on MHC class II induction in tumor cells and the induction of apoptosis in tumor cells. The review also indicates some future areas of investigation that offer hope for applying this knowledge in reducing cancer mortality. 相似文献
Malignancy in patients with constitutional chromosome abnormality is of interest not only because it permits insights into the relationship between chromosome abnormality and cancer, but also because it provides opportunities to address such questions as the clonality and evolution of tumors. We report Ph1-positive chronic myelogenous leukemia (CML) in a 50-year-old mosaic (45,X/46,XX) Turner syndrome patient whose leukemia was restricted to the monosomic cell line. Our extensive cytogenetic studies of this patient demonstrated that non-leukemic normal cells persisted in the marrow and were able to proliferate during a period of temporary suppression of the leukemic clone following aggressive treatment. 相似文献
Male and female Wistar rats were given an initiating i.p. injectionof diethylnitrosamine (DEN; 200 mg/kg body wt). Two weeks laterthe rats were given a diet containing 0.02% (w/w) 2-acetylaminofluorene(2-AAF) for 2 weeks. In the middle of the 2-AAF treatment a70% partial hepatectomy (PH) was performed. In order to identifythe pituitary hormone responsible for the previously observedsex difference (male > female) in and influence of ectopicpituitary grafts on focal growth during 2-AAF/PH selection ofenzyme-altered foci, male rats were treated with a continuousinfusion of bovine growth hormone (bGH; 6 µg/h) or ovineprolactin (oPrl; 6 µg/h) by way of osmotic minipumps.Hormonal treatment was started 1 week after initiation and wasfinished 1 week after the 2-AAF selection period. All rats werekilled 6 weeks after initiation and liver sections were stainedfor -ghitamyttransferase. The number of foci/cm2 as well asthe area per focus and area ratio (mm2 foci/cm2 liver section)were calculated. Whereas no significant differences in the numberof foci /cm2 were observed between the different groups of rats,bGH treatment of male rats decreased both the area/focus andthe area ratio down to the female level. No significant effectswere seen following oPrl administration when compared with controlmales. In vitro studies of subcellular preparations from theliver lobes obtained at PH showed that the sexually differentiatedN-hydroxy-2-AAF sulfotransferase activity (male > female)in male rats was feminized, i.e. decreased, bybGH administration, but not by infusion of oPrl. The presentinvestigation strengthens the view of growth hormone as an importantdeterminant of sex differences in chemical carcinogenesis inrat liver, possibly via an influence on carcinogen metabolism. 相似文献
The resistant hepatocyte model was used to investigate the influenceof pituitary factors on the early events of chemical carcinogenesisin rat liver. Diethylnitrosamine (DEN), 200 mg/kg body weight,was used as an initiator of enzyme altered foci. Two weeks afterinitiation the rats were placed on a 0.02% (w/w) 2-acetylaminofluorene(2-AAF) diet for two weeks. Partial hepatectomy (70%) was performedthree weeks after initiation. The rats were killed four to sixweeks after DEN initiation. Sex differences in area/foci aswell as in area ratio (mm2 foci/cm2 liver section) were foundin liver sections from sexually mature male and female rats( > ) of both the Sprague-Dawley and Wistar strains. Ectopicpituitary grafts (PG: s) implanted under the kidney capsuleof male Wistar rats one week before DEN initiation and removedby unilateral nephrectomy one week after initiation did notinfluence the number or area of enzyme altered foci as comparedwith sham operated male rats. On the other hand, PG:s implantedone week before 2-AAF selection in male Wistar rats and allowedto remain until the rats were killed two weeks after the 2-AAFselection period, decreased the area ratio to a level closeto that of sham operated female rats, whereas no effect on thenumber of enzyme altered foci was found. The results suggestthat the hypothalamo-pitu-itary axis may be involved in theregulation of early stages of liver carcinogenesis. 相似文献
OBJECTIVE: This single blind, crossover design, clinical trial provided a comparative assessment of the oral cleaning of two dental devices as demonstrated through the removal of dental plaque when used according to marketed product-use directions. METHODOLOGY: Twenty-six subjects, both male and female between the ages of 19 and 64 years, completed this two-cell crossover study. Subjects were assessed for whole mouth plaque levels, both before and after use of each of the randomly assigned floss devices, by assessing disclosed plaque using the Modified Turesky Plaque Index. The two floss devices were a Mint Floss Pick and a standard rolled floss. Subjects abstained from brushing the night before appearing in the clinic, and based upon meeting the minimum plaque criteria of 1.5 at the first phase of the crossover, used one of the two floss devices according to the directions for use found on the product packaging. Both pre- and post-device use plaque levels were recorded with calculations made of both the actual difference in plaque level, as well as the percent plaque removed. Data were subjected to an analysis of covariance (ANCOVA), and employed a model consistent with crossover design. RESULTS: Overall results from both phases of the crossover showed the Mint Floss Pick product removed 19.4% of the plaque. The standard rolled floss product removed 15% of the plaque. Both products removed statistically significant plaque when assessed versus pre-treatment levels. Although the ANCOVA identified a statistically significant difference between treatments favoring the Floss Pick product, further statistical examination revealed a significant sequence effect, which led to a conservative product comparison of equivalence. This analysis confirmed that the Floss Pick product was "at least as good as" the standard floss product for plaque removal. Additional analyses of various sites in the mouth, i.e., interproximal, anterior, posterior, etc., also confirmed similarity of performance for both products in this test. CONCLUSION: A two-way crossover assessment of the cleaning capability of a Mint Floss Pick product compared to a standard rolled floss product was performed through assessment of the removal of dental plaque. Results of this clinical investigation support the Floss Pick product to be "at least as good as" standard rolled floss in cleaning capability when both products were used according to their product-use directions. 相似文献