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排序方式: 共有645条查询结果,搜索用时 15 毫秒
11.
Louis SN Nero TL Iakovidis D Jackman GP Louis WJ 《European journal of pharmacology》1999,367(2-3):431-435
LK 204-545 ((+/-)-1-(2-(3-(2-cyano-4-(2-cyclopropyl-methoxy-ethoxy)phenoxy)-2-hydro xy-propyl-amino)-ethyl)-3-(4-hydrxy-phenyl) urea), an antagonist that possesses high beta1-/beta2-selectivity in the rat, and a range of cardio-selective and non-selective beta-adrenoceptor antagonists were examined to compare their radioligand binding affinities for human beta1-, beta2- and beta3-adrenoceptors transfected into CHO cells. LK 204-545 and CGP 20712A displayed the highest beta1-/beta2- (approximately 1800 and approximately 650, respectively) and beta1-/beta3-selectivity (approximately 17000 and approximately 2200, respectively) at human beta-adrenoceptors with LK 204-545 being approximately 2.75-fold more beta1-/beta2-selective and approximately 8-fold beta1-/beta3-selective than CGP 20712A. The high potency of LK 204-545 at transfected human beta1-adrenoceptors and in functional models of rat beta1-adrenoceptors together with its high selectivity, identify it as a useful ligand for studying beta1-adrenoceptors and suggest that it may be the preferred ligand for human beta-adrenoceptor studies. 相似文献
12.
John F. Smyth Rosanne M. Paine Ann L. Jackman Kenneth R. Harrap Marvin M. Chassin Richard H. Adamson David G. Johns 《Cancer chemotherapy and pharmacology》1980,5(2):93-101
Summary 2-deoxycoformycin (2-dCF; Pentostatin), a stoichiometric inhibitor of mammalian adenosine deaminase (ado deaminase), exhibits immunosuppressive and antilymphocytic activity in animal test systems. A clinical pharmacology/phase I study of 2-dCF administered as a single agent has been completed (18 patients). Dose levels ranged from 0.1 mg/kgx1 to 0.25 mg/kg/dayx5; ado deaminase and 2-dCF were measured spectrophotometrically. Plasma decay curves were bi-exponential ( and t1/2 values about 1 and 10 h respectively). Recovery of unchanged 2-dCF from urine (48 h) was 32%–48% of the administered drug. Major toxic manifestations were lymphocytopenia (all patients) and urate nephropathy (1 patient, with subsequent patients in the series receiving allopurinol, 300 mg/day). Three partial responses were seen in seven patients with acute lymphocytic leukaemia receiving 0.25 mg 2-dCF/kg/dayx5. 相似文献
13.
Ruth Plummer Charlotte Rees Andrew Hughes Philip Beale Martin Highley Jose Trigo Sathyarathnarn Gokul Ian Judson Hilary Calvert Ann Jackman Fraser Mitchell Robert Smith Edwin Douglass 《Clinical cancer research》2003,9(4):1313-1322
PURPOSE: ZD9331 is a novel, direct-acting antifolate cytotoxic that does not require polyglutamation for activity, and is a specific thymidylate synthase inhibitor. This Phase I trial aimed to determine the maximum tolerated dose of ZD9331, given as a 30-min i.v. infusion on days 1 and 8 of a 21-day cycle. Pharmacokinetic parameters and tumor response were also assessed. EXPERIMENTAL DESIGN: A total of 71 patients, with a range of solid malignancies and refractory to standard therapies (44% had received > or =3 prior chemotherapy regimens), were treated. The most common malignancies were colorectal cancer (35% of patients) and ovarian cancer (31%). ZD9331 was escalated from 4.8 mg/m(2)/day. RESULTS: Dose-limiting toxicity occurred at 162.5 mg/m(2) ZD9331, with grade 4 thrombocytopenia, grade 4 neutropenia lasting > or =7 days, and grade 3 nonhematologic toxicity. Plasma clearance of ZD9331 was slow and dose-dependent; however, ZD9331 pharmacokinetics were nonlinear. Pharmacodynamics of ZD9331 were determined by measurement of plasma deoxyuridine, which increased at all of the dose levels; dose-related increases in plasma deoxyuridine were significant (P = 0.003) on day 5. Stable disease was observed in 37% of patients; 23% of ovarian cancer patients had a > or =50% reduction in CA125 levels. CONCLUSIONS: The maximum tolerated dose of this schedule was 130 mg/m(2). The toxicity profile at this dose was acceptable, with 7 of 28 patients treated developing grade 3/4 neutropenia and thrombocytopenia, 2 grade 4 diarrhea, and 2 grade 3/4 rash. This schedule was convenient and demonstrated activity in extensively pretreated patients; therefore, this is the recommended dose for study in Phase II trials. 相似文献
14.
Mammographic abnormalities caused by percutaneous stereotactic biopsy of histologically benign lesions evident on follow-up mammograms 总被引:3,自引:0,他引:3
OBJECTIVE: The purpose of our study was to evaluate how often a mammographic abnormality thought to be produced by the biopsy procedure was evident on the initial follow-up mammogram after percutaneous biopsy of impalpable histologically benign lesions. We compared three stereotactic percutaneous biopsy methods. CONCLUSION: A mammographic density seen well only in the projection parallel to the biopsy needle tract was evident in 2% (5/226) of the lesions for which 11-gauge directional vacuum-assisted biopsy was used, 0% (0/96) of the lesions for which 14-gauge directional vacuum-assisted biopsy was used, and 0% (0/422) of the lesions for which 14-gauge automated large-core biopsy was used. No mammographic abnormalities assessed as BI-RADS categories 3, 4, or 5 (according to the American College of Radiology's Breast Imaging Reporting and Data System) and thought to be produced by the biopsy procedure were evident after any of the biopsy methods. 相似文献
15.
Development of peripheral hindlimb and central spinal cord innervation by subpopulations of dorsal root ganglion cells in the embryonic rat 总被引:7,自引:0,他引:7
The development of rat peripheral hindlimb and lumbar dorsal horn innervation by different subpopulations of dorsal root ganglion cells was investigated from embryonic day (E)13 to birth by using immunostaining. Antibodies to protein gene product (PGP) 9.5, growth associated protein (GAP) 43, and peripherin were used as pan-neuronal markers, RT97 for A fibres; calcitonin gene-related peptide (CGRP), trkA, and the lectin IB4 for small A and C fibres. Size frequency analysis showed that RT97 is a selective marker for large A cells at E18. Although both A and C fibres enter the hindlimb at E13-14, A fibres are the first to innervate the skin and dominate over small fibre innervation until later fetal life. CGRP expression in sensory axons appears at E19 and in all regions simultaneously, suggesting expression in existing fibres. All sensory terminals grow transiently to the skin surface before retracting subepidermally at late embryonic stages. The development of peripheral and central innervation by the same subpopulations of sensory neurons was compared. The entry of A fibre terminals into the lumbar dorsal horn at E14 coincided with hindlimb skin innervation. In contrast, C fibres were not detected in the dorsal horn until E18, 4 days after peripheral innervation. CGRP expression appears in both spinal cord and hindlimb targets at E19. IB4 binding in the central terminals began at E18 but was never observed in embryonic peripheral axons.These results demonstrate that in fetal skin, A fibre innervation dominates over C fibres. In addition, alathough peripheral and central innervation by A fibres coincide, this is not true for C fibres, suggesting that central target factors may control C fibre terminal growth within the dorsal horn. 相似文献
16.
Pohoey Fan M.D. Stavros Stavrakis M.D. Ph.D George Madden M.D Dipesh Pokharel M.D. Sunny S. Po M.D. Ph.D Hiroshi Makagawa M.D. Ph.D. Warren M. Jackman M.D. Chittur A. Sivaram M.D. 《Echocardiography (Mount Kisco, N.Y.)》2011,28(7):774-774
Article Title: Transesophageal Echocardiographic Assessment of Pulmonary Veins and Left Atrium in Patients Undergoing Atrial Fibrillation Ablation (Echocardiography 2011;28:774) 相似文献
17.
Hedgehog signaling regulates dental papilla formation and tooth size during zebrafish odontogenesis
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Jeffrey C. Yu Zachary D. Fox James L. Crimp Hana E. Littleford Andrea L. Jowdry William R. Jackman 《Developmental dynamics》2015,244(4):1-6
Background : Intercellular communication by the hedgehog cell signaling pathway is necessary for tooth development throughout the vertebrates, but it remains unclear which specific developmental signals control cell behavior at different stages of odontogenesis. To address this issue, we have manipulated hedgehog activity during zebrafish tooth development and visualized the results using confocal microscopy. Results : We first established that reporter lines for dlx2b, fli1, NF‐κB, and prdm1a are markers for specific subsets of tooth germ tissues. We then blocked hedgehog signaling with cyclopamine and observed a reduction or elimination of the cranial neural crest derived dental papilla, which normally contains the cells that later give rise to dentin‐producing odontoblasts. Upon further investigation, we observed that the dental papilla begins to form and then regresses in the absence of hedgehog signaling, through a mechanism unrelated to cell proliferation or apoptosis. We also found evidence of an isometric reduction in tooth size that correlates with the time of earliest hedgehog inhibition. Conclusions : We hypothesize that these results reveal a previously uncharacterized function of hedgehog signaling during tooth morphogenesis, regulating the number of cells in the dental papilla and thereby controlling tooth size. Developmental Dynamics 244:577–590, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
18.
19.
Transvenous parasympathetic nerve stimulation in the inferior vena cava and atrioventricular conduction 总被引:1,自引:0,他引:1
Schauerte P Scherlag BJ Scherlag MA Jackman WM Lazzara R 《Journal of cardiovascular electrophysiology》2000,11(1):64-69
INTRODUCTION: In previous reports, we demonstrated a technique for parasympathetic nerve stimulation (PNS) within the superior vena cava, pulmonary artery, and coronary sinus to control rapid ventricular rates during atrial fibrillation (AF). In this report, we describe another vascular site, the inferior vena cava (IVC), at which negative dromotropic effects during AF could consistently be obtained. Moreover, stimulation at this site also induced dual AV nodal electrophysiology. METHODS AND RESULTS: PNS was performed in ten dogs using rectangular stimuli (0.1 msec/20 Hz) delivered through a catheter with an expandable electrode basket at its tip. Within 3 minutes and without using fluoroscopy, the catheter was positioned at an effective PNS site in the IVC at the junction of the right atrium. AF was induced and maintained by rapid atrial pacing. During stepwise increase of the PNS voltage from 2 to 34 V, a graded response of ventricular rate slowing during AF was observed (266 +/- 79 msec without PNS vs 1,539 +/- 2,460 msec with PNS at 34 V; P = 0.005 by analysis of variance), which was abolished by atropine and blunted by hexamethonium. In three animals, PNS was performed during sinus rhythm. Dual AV nodal electrophysiology was present in 1 of 3 dogs in control, whereas with PNS, dual AV nodal electrophysiology was observed in all three dogs. PNS did not significantly change sinus rate or arterial blood pressure during ventricular pacing. CONCLUSION: Stable and consistent transvenous electrical stimulation of parasympathetic nerves innervating the AV node can be achieved in the IVC, a transvenous site that is rapidly and readily accessible. The proposed catheter approach for PNS can be used to control ventricular rate during AF in this animal model. 相似文献
20.