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排序方式: 共有793条查询结果,搜索用时 15 毫秒
71.
72.
Micheli F Bonanomi G Blaney FE Braggio S Capelli AM Checchia A Curcuruto O Damiani F Fabio RD Donati D Gentile G Gribble A Hamprecht D Tedesco G Terreni S Tarsi L Lightfoot A Stemp G Macdonald G Smith A Pecoraro M Petrone M Perini O Piner J Rossi T Worby A Pilla M Valerio E Griffante C Mugnaini M Wood M Scott C Andreoli M Lacroix L Schwarz A Gozzi A Bifone A Ashby CR Hagan JJ Heidbreder C 《Journal of medicinal chemistry》2007,50(21):5076-5089
The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain. 相似文献
73.
J T Lightfoot M J Turner K A Debate S R Kleeberger 《Medicine and science in sports and exercise》2001,33(12):2053-2057
PURPOSE: The contribution of genetic factors to aerobic capacity is unknown. The purpose of this study was to measure maximal aerobic performance among inbred strains of mice to provide basic heritability estimates. METHODS: Eight female mice, 8 to 10 wk old, in 10 inbred strains (A/J, AKR/J, Balb/cJ, C(3)H/HeJ, C57Bl/6J, C57L/J, C(3)Heb/FeJ, CBA/J, DBA/2J, and SWR/J) were run on a treadmill until exhaustion. The protocol started at 22 m.min(-1) and increased in speed approximately 6 m.min(-1) every 4 min. After 4 min at 42.4 m.min(-1), the grade was increased 2% every 4 min thereafter until the mouse could not run off of the shock grid (150 V; 1.5 mA). RESULTS: There were significant differences between inbred strains in maximal duration of exercise accomplished (P < 0.0001). The order of strain-specific exercise duration was Balb/cJ > SWR/J > CBA/J > C57L/J > C3H/HeJ > C3Heb/FeJ > C57Bl/6J > AKR/J > DBA/2J > A/J. Two measures of heritability in the broad sense, intraclass correlation (0.73), and the coefficient of genetic determination (0.58) were both significant. CONCLUSION: These data indicate that there is a strong genetic contribution to aerobic capacity in mice. 相似文献
74.
HÉLÉNE ELTCHANINOFF M.D. CARLOS GIRON M.D. RAPHAËLLE CARLOT M.D. CATHERINE BIZET M.D. STEPHAN CHASSAING M.D. ALAIN CRIBIER M.D. 《Journal of interventional cardiology》2000,13(4):295-299
Introduced more than 15 years ago, balloon aortic valvuloplasty (BAV) has clearly delineated indications and limitations. Although, aortic valve replacement is undoubtedly the treatment of choice for healthy patients with aortic stenosis, BAV has been demonstrated as a valuable and safe palliative procedure for patients considered too risky or old for current day surgery. Between January 1991 and December 1999, 858 patients (mean age 76 ± 11 years, 479 [57%] women) underwent BAV at our center. Indications for BAV were contraindication to surgery in 16.2% of the patients, high risk in 40.4%, refusal of surgery in 10.7%, personal decision in 18.5%, and other in 14.2%. The mean gradient decreased from 65 ± 23 to 27 ± 12 mmHg and the valve area increased from 0.56 ± 0.19 cm2 to 1.0 ± 0.38 cm2 . Eleven (1.1%) patients died during the procedure. The other severe complications were complete AV block in 18 (1.8%) patients, stroke in 8 (0.8%), tamponade in 6 (0.6%), and massive aortic insufficiency in 4 (0.4%). In conclusion, BAV does not replace valve replacement, even in the elderly. All those who can be operated on, should be. However, if surgical intervention is not considered reasonable, BAV offers good immediate results with an acceptable complication rate. Furthermore, previous published series have demonstrated that BAV is particularly indicated in specific subgroups, such as very old patients with high operative risk, end-stage heart failure, cardiogenic shock, or general anesthesia for noncardiac surgery. 相似文献
75.
Henry M. Rosevear Andrew J. Lightfoot Michael A. O’Donnell Thomas S. Griffith 《Cancer metastasis reviews》2009,28(3-4):345-353
Intravesical Mycobacterium bovis bacillus Calmette–Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy’s mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research. 相似文献
76.
R. Freeman P. R. Sisson D. R. Jenkins A. C. Ward N. F. Lightfoot S. J. O'Brien 《Epidemiology and infection》1995,114(3):433-440
Thirty-six encoded isolates of Escherichia coli. 32 of which were of serotype O157, were examined by pyrolysis mass spectrometry (PyMS). Thirty-one of the serotype O157 isolates possessed the flagellar antigen H7 and produced Verocytotoxin (VT), the other isolate serotyped as H45 and was non-toxigenic. Eighteen of the VT-producing E. coli (VTEC) isolates were from sporadic disease in residents of the Northern Region. Standard principal component (PC) and canonical variate (CV) analysis of the data distinguished only the four non-O157 isolates from the remainder which were indistinguishable by this approach. A similarity matrix based on differences between individual CV means distinguished a further ten isolates. The matrix correctly clustered 2 pairs of isolates from siblings and 4 isolates from an affected family. A further 5 clusters of 3 or more isolates and 6 pairs of isolates were defined. These groupings proved to be homogenous for toxin phenotype but occasionally entrained isolates of dissimilar phage type. However, in general, PyMS-derived clustering of apparently sporadic isolates accorded with geographical locations as determined by postcode. PyMS, which is a quick and high volume capacity phenotypic technique, may be a useful addition to existing methods in the investigation of the epidemiology of sporadic VTEC disease. 相似文献
77.
Lightfoot Therese; Lewkonla Raymond M.; Snyder Floyd F. 《Human molecular genetics》1994,3(8):1377-1381
We have sequenced and studied the expressed protein of an HPRTmutation characterized by 512% residual erythrocyte activity,for which affected males exhibit hyperuricemia, arthritis andrenal disease but are without severe neurological Involvement.The HPRTMoose Jaw mutation is due to a single C to G transverslonat nucleotlde 582 relative to Initiation of translation correspondingto substitution of aspartate 194 by glutamate. The mutant andwild type proteins were expressed and purified using the bacterialexpression vector, pMAL-c2. The Km for hypoxanthlne was Increased12-fold from 0.94 ± 0.26 to 11.5 ± 1.3 µMfor control and mutant respectively. The apparent Km for PP-rlbose-Pwas Increased 44-fold from 6.8 ± 0.6 to 295 ±7 µM for control and mutant respectively. Although theKcat of the mutant protein was equivalent to wild type, thecatalytic efficiency, Kcat/Km, of the purified mutant proteinwas only 6 and 3% of wild type with hypoxanthine and PP-rlbose-Prespectively. The mutant protein also exhibited positive cooperativitywith PP-ribose-P, having a Hill coefficient of 2.3. The decreasedsubstrate affinities and PP-ribose-P associated cooperativityof HPRTMoose Jaw provide additional evidence for the influenceof carboxy-terminal residues of HPRT in specific catalytic functions. 相似文献
78.
L A Beauregard R Fabiszewski C H Black B Lightfoot P L Schraeder T Toly H L Waxman 《The American journal of cardiology》1991,68(10):1067-1072
Evaluation of patients with syncope often includes a battery of noninvasive tests. In this study, 45 patients (26 with suspected neurologic and 19 with suspected cardiac syncope) were evaluated with simultaneous 24-hour electroencephalographic (EEG) and 2-channel electrocardiographic (ECG) recordings. Isolated cardiac rhythm abnormalities were noted in 21 patients, but none of these was symptomatic and no definitive arrhythmias occurred. Isolated EEG abnormalities were noted in 11 patients, 5 of whom had EEG abnormalities consistent with seizure disorders. Simultaneous EEG and ECG abnormalities were seen in 4 patients. In 2 cases, a previously unsuspected etiology for syncope was found: seizures in 1 patient with heart disease, and sinus pauses in another thought to have a seizure disorder. Thus, combined ambulatory EEG/ECG monitoring may prove useful in the evaluation of some patients with syncope. 相似文献
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80.