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41.
Martin RS Luong LA Welsh NJ Eglen RM Martin GR MacLennan SJ 《British journal of pharmacology》2000,129(8):1707-1715
This study investigated the cannabinoid receptor, known to inhibit neuronally-evoked contractions of the mouse isolated urinary bladder, in bladder sections isolated from mouse, rat, dog, pig non-human primate or human. The CB(1)-like pharmacology of the cannabinoid receptor in mouse isolated bladder observed previously was confirmed in this study by the rank order of agonist potencies: CP 55940>/=WIN 55212-2>HU 210>JWH 015>anandamide, the high affinity of the CB(1) selective antagonist, SR 141716A (apparent pK(B) 8.7), and the low affinity of the CB(2) antagonist, SR 144528 (apparent pK(B)<6.5). In these studies, SR 141716A (10-100 nM) significantly potentiated electrically-evoked contractions in this tissue by an undetermined mechanism. A similar rank order of agonist potencies was determined in rat isolated bladder sections (CP 55, 940> or =WIN 55212-2>JWH 015). In this tissue, the maximal inhibitory effect of all agonists was lower than in the mouse bladder. Indeed, the effects of both HU 210 and anandamide were too modest to quantify potency accurately. In the rat isolated bladder, SR 141716A (30 nM) or SR 144528 (100 nM), reversed the inhibitory effect of WIN 55212-2 (apparent pK(B) = 8.4 and 8.0, respectively) or JWH 015 (apparent pK(B) = 8.2 and 7.4, respectively). These findings may demonstrate pharmacological differences between the rat and mouse orthologues of the CB(1) receptor. Alternatively, they may be attributed to a mixed population of CB(1) and CB(2) receptors that jointly influence neurogenic contraction of the rat bladder, but cannot be differentiated without more selective ligands. WIN 55212-2 had no effect on electrically-evoked contractions of bladder sections isolated from dog, pig, cynomolgus monkey and human. These findings suggest that the effect of cannabinoid agonists to inhibit neurogenic contraction of the mouse and rat bladder is not conserved across all mammalian species. 相似文献
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Tyrosine phosphorylation in T cells is regulated by phosphatase activity: studies with phenylarsine oxide. 总被引:8,自引:8,他引:0 下载免费PDF全文
P Garcia-Morales Y Minami E Luong R D Klausner L E Samelson 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(23):9255-9259
Activation of T cells induces rapid tyrosine phosphorylation on the T-cell receptor zeta chain and other substrates. These phosphorylations can be regulated by a number of protein-tyrosine kinases (ATP: protein-tyrosine O-phosphotransferase, EC 2.7.1.112) and protein-tyrosine-phosphatases (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48). In this study, we demonstrate that phenylarsine oxide can inhibit tyrosine phosphatases while leaving tyrosine kinase function intact. We use this reagent to investigate the effect of tyrosine phosphatase inhibition in a murine T-cell hybridoma. Increasing concentrations of phenylarsine oxide result in an increase in tyrosine phosphate on a number of intracellular substrates in unstimulated T cells, suggesting that a protein-tyrosine kinase is constitutively active in these cells. The effect of phenylarsine oxide on T cells stimulated with an anti-Thy 1 monoclonal antibody is more complex. At low concentrations of drug, there is a synergistic increase in the level of tyrosine phosphate on certain cellular substrates. At higher concentrations, anti-Thy 1-stimulated tyrosine phosphorylation is inhibited. These results indicate that tyrosine phosphorylation in T cells is tightly regulated by tyrosine phosphatases. Partial inhibition of these enzymes results in enhanced substrate phosphorylation. Inhibition of all stimulated tyrosine phosphorylation by high doses of phenylarsine oxide suggests that tyrosine kinase activity is regulated by tyrosine phosphatases. 相似文献
44.
E H Gerstin T Luong F J Ehlert 《The Journal of pharmacology and experimental therapeutics》1992,263(3):910-917
The influences of heparin, dextran and trypan blue on muscarinic receptor binding properties and inhibition of adenylate cyclase were investigated in homogenates of the rat heart. These compounds caused a concentration-dependent enhancement in the specific binding of the muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) when measured at a radioligand concentration of approximately 0.5 nM in magnesium-containing, low ionic strength buffer. The maximal enhancements of [3H]NMS binding were 2.89-, 1.68- and 1.43-fold increases for heparin, dextran and trypan blue, respectively; the EC50 values for this effect were 0.12, 0.033 and 4.6 microM, respectively. The effects of heparin, dextran and trypan blue on [3H]NMS binding were attributed mainly to an increase in the overall affinity of muscarinic receptors for [3H]NMS, and were greatly attenuated by 100 mM NaCl. These effects were qualitatively similar to those produced by GTP. Heparin, dextran and trypan blue also affected the binding of the muscarinic agonist oxotremorine-M in a manner similar to that of GTP; that is, in the presence of these compounds, agonist affinity was decreased. Our experiments also showed that heparin and dextran attenuate the inhibition of adenylate cyclase activity caused by oxotremorine-M in myocardial homogenates without influencing basal adenylate cyclase activity. We conclude that heparin and dextran interfere with the muscarinic receptor-G protein coupling in the rat heart. 相似文献
45.
Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy 下载免费PDF全文
46.
Krakauer EL Ngoc NT Green K Van Kham L Khue LN 《Journal of pain and symptom management》2007,33(5):578-583
Vietnam is struggling to meet the growing need for both disease-modifying and palliative care for people with life-threatening chronic diseases such as HIV/AIDS and cancer. Recently, Vietnam initiated rapid development of a national palliative care program for HIV/AIDS and cancer patients that builds on existing palliative care programs and experience and integrates palliative care into standard HIV/AIDS and cancer care. National palliative care guidelines have been issued by the Ministry of Health based on a rapid situation analysis. Plans now call for review and revision of opioid laws and regulations to increase availability of opioids for medical use, training in palliative care for clinicians throughout the country, and development of palliative care programs both in the community and in inpatient referral centers. 相似文献
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Nguyen Thi Lan Anh Nguyen Thi Phuong K. Darwin Murrell Maria Vang Johansen Anders Dalsgaard Luong To Thu Tran Thi Kim Chi Stig Milan Thamsborg 《Emerging infectious diseases》2009,15(4):540-546
Fish-borne zoonotic trematodes (FZT) pose a risk to human food safety and health and may cause substantial economic losses in the aquaculture industry. In Nghe An Province, Vietnam, low prevalence of FZT for fish farmers but high prevalence for fish indicate that reservoir hosts other than humans may play a role in sustaining transmission. To determine whether domestic animals may be reservoir hosts, we assessed prevalence and species composition of FZT infections in dogs, cats, and pigs in a fish-farming community in Vietnam. Feces from 35 cats, 80 dogs, and 114 pigs contained small trematode eggs at 48.6%, 35.0%, and 14.4%, respectively; 7 species of adult FZT were recovered from these hosts. These results, combined with data from previous investigations in this community, imply that domestic animals serve as reservoir hosts for FZT and therefore must be included in any control programs to prevent FZT infection in humans. 相似文献
50.
In this article, we propose a new generalization of the Weibull distribution, which incorporates the exponentiated Weibull distribution introduced by Mudholkar and Srivastava (IEEE Trans. Reliab. 1993; 42 :299–302) as a special case. We refer to the new family of distributions as the beta‐Weibull distribution. We investigate the potential usefulness of the beta‐Weibull distribution for modeling censored survival data from biomedical studies. Several other generalizations of the standard two‐parameter Weibull distribution are compared with regards to maximum likelihood inference of the cumulative incidence function, under the setting of competing risks. These Weibull‐based parametric models are fit to a breast cancer data set from the National Surgical Adjuvant Breast and Bowel Project. In terms of statistical significance of the treatment effect and model adequacy, all generalized models lead to similar conclusions, suggesting that the beta‐Weibull family is a reasonable candidate for modeling survival data. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献