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Ahmadi S Kotalla C Gühring H Takeshima H Pahl A Zeilhofer HU 《Molecular pharmacology》2001,59(3):612-618
Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two neuropeptides derived from the same precursor protein that exhibit opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually identified neurons in spinal cord dorsal horn slices of genetically modified mice to investigate the role of the N/OFQ receptor (N/OFQ-R) in the modulatory action of both peptides on excitatory glutamatergic and inhibitory glycinergic and gamma-aminobutyric acid (GABA)-ergic synaptic transmission. In wild-type mice, N/OFQ selectively suppressed excitatory transmission in a concentration-dependent manner but left inhibitory synaptic transmission unaffected. In contrast, NST reduced only inhibitory but not alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated excitatory synaptic transmission. N/OFQ-mediated inhibition of excitatory transmission was completely absent in N/OFQ-R receptor-deficient (N/OFQ-R(-/-)) mice and significantly reduced in heterozygous (N/OFQ-R(+/-)) mice, whereas the action of NST on inhibitory neurotransmission was completely retained. To test for the relevance of these results for spinal nociception, we investigated the effects of intrathecally injected N/OFQ in the mouse formalin test, an animal model of tonic pain. N/OFQ (3 nmol/mouse) induced significant antinociception in wild-type mice, but had no antinociceptive effects in N/OFQ-R(-/-) mice. These results indicate that the inhibitory action of N/OFQ on excitatory glutamatergic synaptic transmission and its spinal antinociceptive action are mediated via the N/OFQ receptor, whereas the action of NST is independent of this receptor. 相似文献
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Steinhart H Bohlender JE Constantinidis J Urbschat S Fischer U Iro H Pahl S Meese E 《Oncology reports》2001,8(6):1229-1231
Multiple chromosomal aberrations have been reported in head and neck squamous cell carcinoma (HNSCC). But less information is available on specific patterns of chromosomal amplifications which distinguish different areas of head and neck tumors. To elucidate genetic mechanisms causing the aggressive growth and high proliferation of hypopharyngeal squamous cell carcinoma (SCC), we performed reverse chromosome painting (RCP) on a total of eight hypopharyngeal SCC including invasive carcinoma and preinvasive tissue. Five hypopharyngeal invasive carcinomas showed amplifications on chromosome 3q. Furthermore, we detected gains on chromosomes 11q and 6p. Compared to the histologically classified preinvasive tissues, we found amplified alterations on chromosome 6p, 11q and 12q, but none of them showed gains on chromosome 3q. This observed heterogeneity in hypopharyngeal SCC might reflect a specific role of chromosome 3q as a late event in the highly invasive capacity of these SCC. 相似文献
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The midtrimester abortion program at a large community hospital was evaluated. During the 3-year study, 1839 patients aborted in the midtrimester by intraamniotic injection of hypertonic saline, prostaglandin F2alpha or a combination of saline and prostaglandin F2alpha. The method, using a combination of saline and prostaglandin F2alpha together with intracervical laminaria, showed significant reduction in the number of failures (4.3 to 1.0%), reduction in the injection-abortion interval from 33.9 to 14.6 hours, shortening of the hospital stay from 2 1/2 to 1 1/3 days, minimum incidence of live abortions (0.9%), infrequent need for oxytocin to effect delivery (7.7%); and low rates of hemorrhage (1.5%) and fever (2.8%). The main disadvantage was an increased rate of incomplete abortions (32.3%), which could be reduced to 27% by patient selection. 相似文献
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J Li S Yousefi M Sterling G Carandang N Vaziri M Pahl T Cesario 《Journal of clinical & laboratory immunology》1987,22(1):13-17
We have shown that hydrocortisone in physiological concentrations can inhibit the production of leukocyte migration inhibition factor (LMIF), but does not diminish the action of this lymphokine. Other agents tested failed to influence LMIF production. Inhibition of LMIF production by corticosteroids was influenced by the nature of the stimulus used for the production as an effect could be seen with PHA or Con A, but not Staphylococcal enterotoxin A (SEA). Production of LMIF was promptly restored after removal of the steroids. Furthermore, addition of a calcium ionophore to PHA restored the production of LMIF even in the presence of corticosteroids. In contrast, addition of exogenous IL-2 did not correct the defect in lymphokine secretion. We believe that inhibition of the production of LMIF by steroid may lead to defective granulocytic function and thus, predispose to infection. 相似文献
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A comparison of neurological, metabolic, structural, and genetic evaluations in persons at risk for Huntington's disease 总被引:6,自引:0,他引:6
S T Grafton J C Mazziotta J J Pahl P St George-Hyslop J L Haines J Gusella J M Hoffman L R Baxter M E Phelps 《Annals of neurology》1990,28(5):614-621
We compared four diagnostic data sets for the assessment of individuals at risk for Huntington's disease. Fifty-four chorea-free persons were evaluated by neurological examination, positron emission tomography measurement of glucose metabolism, radiographic computerized tomographic measurement of caudate size, and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125. Twelve (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities of motor control, and 7 (13%) had computed tomographic evidence of caudate atrophy, compared with an expected gene frequency of 34% for this population. In 20 persons with unambiguous genetic test results or the subsequent phenotypic expression of Huntington's disease (chorea), there was a greater sensitivity of the positron emission tomographic measurement of caudate metabolism (75%) relative to computed tomography (33%) or the clinical examination (17%) for the determination of a subpopulation of probable Huntington's disease gene carriers. Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the precentral gyrus were also associated with a high probability of carrying the Huntington's disease gene. The findings support the hypothesis that abnormalities of cerebral metabolism precede clinical or structural (computed tomographic) abnormalities in gene-positive individuals at risk for Huntington's disease. 相似文献