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11.
F I Carroll Y Gao P Abraham A H Lewin R Lew A Patel J W Boja M J Kuhar 《Journal of medicinal chemistry》1992,35(10):1813-1817
Several potentially irreversible ligands (i.e., wash-resistant binding inhibitors) for the cocaine receptor site on the dopamine transporter, derived from (-)-cocaine or 3 beta-phenyltropan-2 beta-carboxylic acid methyl ester (WIN 35,065-2), were prepared and shown to produce wash-resistant inhibition of [3H]-3 beta-(p-fluorophenyl)tropan-2 beta-carboxylic acid methyl ester ([3H]WIN 35,428) binding. All the compounds prepared had the same absolute configuration as cocaine; they include analogues possessing chemically reactive groups such as the isothiocyanato and bromoacetamido as well as photoactive azido groups. The potentially irreversible ligands, as well as all the intermediates prepared in this study, were evaluated for their ability to inhibit the binding of [3H]WIN 35,428 in coincubation experiments. Of the potentially irreversible ligands, 3 beta-(p-chlorophenyl)tropan-2 beta-carboxylic acid 2-[p-(bromoacetamido)phenyl]ethyl ester (6c) had the highest apparent potency. The potentially irreversible ligands were also preincubated, and inhibition of [3H]WIN 35,428 binding was determined both before and after washing the ligand-exposed tissues. The most effective ligands in this regard were 3 beta-(3-iodo-4-azidophenyl)tropan-2 beta-carboxylic acid methyl ester (5) and 3 beta-(p-chlorophenyl)tropan-2 beta-carboxylic acid 2-(3-iodo-4-azidophenyl)ethyl ester (6d). The structure-activity relationships of these data are discussed. 相似文献
12.
Roald Bahr Fernando Pena Joe Shine William D. Lew Conrad Lindquist Stein Tyrdal Lars Engebretsen 《Acta orthopaedica》1997,68(5):435-441
We analyzed the changes in lateral ligament forces during anterior drawer and talar tilt testing and examined ankle joint motion during testing, following an isolated lesion of the anterior talofibular ligament (ATFL) or a combined lesion of the ATFL and calcaneofibular ligament (CFL). 8 cadaver specimens were held in a specially designed testing apparatus in which the ankle position (dorsiflexion-plantarflexion and supination-pronation) could be varied in a controlled manner. Ligament forces were measured with buckle transducers, and joint motion was measured with an instrumented spatial linkage. An anterior drawer test was performed using an 80 N anterior translating force, and a talar tilt test was performed using a 5.7 Nm supination torque with intact ligaments, after sectioning of the ATFL, and again after sectioning of the CFL. The tests were repeated at 10° dorsiflexion, neutral, and 10° and 20° plantarflexion. In the intact ankle, the largest increases in ATFL force were observed during testing in plantarflexion, whereas the largest increases in CFL force were observed in dorsiflexion. Isolated ATFL injury caused only small laxity changes, but a pronounced increase in laxity was observed after a combined CFL and ATFL injury. 相似文献
13.
D Ing R I Glass C W LeBaron J F Lew 《Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)》1992,41(3):47-56
Geographic and temporal trends of rotavirus detections in the United States for the period January 1989-May 1991 were determined by analyzing data reported monthly by 47 virology laboratories participating in the North American Rotavirus Surveillance System. Reports included complete information on the number of specimens tested, the number of test results positive for rotavirus, and the method used to detect rotavirus. Consistent trends in regional and geographic area were identified, with distinctly different peaks of rotavirus activity in the western and eastern states. Each year in the western states, rotavirus activity began in November and peaked in December-January, whereas in the eastern states activity began in January and peaked in February-March. These differences do not correlate with obvious trends in strain variation of rotavirus and remain unexplained. Unexpected reporting of summer rotavirus activity by some laboratories in 1989 was traced to the use of a single diagnostic kit and to two questionable laboratory practices: having more than six medical technologists perform the test and failure to use controls with the test. Laboratory-based surveillance of rotavirus activity has proven to be useful in identifying and correcting problems in laboratory methods for detecting rotavirus and will be a sensitive means for monitoring coverage of the rotavirus vaccine now being developed. 相似文献
14.
L. L. Williams H. M. Lew F. H. Davidorf S. G. Pelok C. T. Singley J. S. Wolinsky 《Archives of virology》1994,134(3-4):379-392
Summary Persistent infection with rubella virus (RV) can alter secondary functions of host cells. Previously we had documented defective phagocytosis of latex beads by cultured human retinal pigment epithelial cells (RPE), persistently infected with M-33 RV (RPE/RV). Here, examining possible mechanisms for altered function, we reported significant differences between the total esterified fatty acids (FA) of RPE and RPE/RV membranes, measured by gas liquid chromatography. RPE/RV contained an increased proportion of saturated FA, particularly palmitic acid, with a presence of unusual chromatographic FA peaks co-eluting with odd-numbered long-chain carbon atom FA not normally found in human cells. Apical membrane microvilli, structures essential to phagocytic activity of RPE and RPE/RV, observed by scanning and transmission electron microscopy, were similar in number and appearance between uninfected RPE and RPE/RV cells before and after latex bead addition. However, RPE/RV microvilli, possibly reflecting altered membrane FA composition, engaged latex beads less effectively than uninfected RPE microvilli. In addition, microvilli remained abnormally distributed on RPE/RV cell surfaces at 48 h after latex addition. Thus, RV persistent infection may affect the cellular membrane fluidity and functional activity of human cells with increased saturated FA proportions and altered FA components of membrane phospholipids. These changes may participate in the defective phagocytosis of RPE/RV. 相似文献
15.
A Patel J W Boja J Lever R Lew R Simantov F I Carroll A H Lewin A Philip Y Gao M J Kuhar 《Brain research》1992,576(1):173-174
Because some evidence suggests that cocaine and GBR12935 bind to different sites, we utilized photoaffinity probes from both classes of compounds to see if they label the same protein. [125I]RTI-82 a cocaine analog, and [125I]DEEP, a GBR analog, labeled protein(s) showing the same molecular weight, a similar pharmacological profile and a similar sensitivity to neuraminidase. 相似文献
16.
Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. 总被引:21,自引:0,他引:21
Heike A Bischoff Hannes B St?helin Walter Dick Regula Akos Margrith Knecht Christian Salis Matthias Nebiker Robert Theiler Michael Pfeifer Bettina Begerow Robert A Lew Martin Conzelmann 《Journal of bone and mineral research》2003,18(2):343-351
Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function. 相似文献
17.
B F O'Donnell D A Drachman H J Barnes K E Peterson J M Swearer R A Lew 《Journal of geriatric psychiatry and neurology》1992,5(1):45-52
Factors predicting the early institutionalization of demented patients were studied in 143 outpatients using univariate and multivariate life-table methods. Four types of factors were evaluated for prognostic value: severity of functional impairment, behavioral disorders, individual patient characteristics, and type of caregiver. After follow-up of 19 +/- 12 months, 51 patients had been institutionalized. Increased global severity of dementia, the presence of troublesome and disruptive behaviors, and incontinence increased the likelihood of institutionalization. The best predictors of institutionalization were paranoia, aggressive behavior, and incontinence. Neither individual patient characteristics (age, education, and gender) nor caregiver relationship to the patient (male spouse, female spouse, and male or female child) influenced institutionalization. Since troublesome behavioral disorders are potentially treatable aspects of dementia leading to institutionalization, their management should be a major focus of therapy in dementia. 相似文献
18.
J Ansell V Klassen R Lew S Ball M Weinstein T VanderSalm N Okike I Gratz J Leslie A Roberts 《The Journal of thoracic and cardiovascular surgery》1992,104(1):117-123
The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively. 相似文献
19.
Jennifer C. Chen Katrina L. Schmid Brian Brown Marion H. Edwards Bibianna SY Yu John KF Lew 《Clinical & experimental optometry》2003,86(5):323-330
Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14A) but not in the emmetropes (0.69 ± 0.9P) or progressing myopes (0.16 ± 0.43A) and this difference between refractive groups was statistically s ignificant (F2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia. 相似文献
20.