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151.
GL Grunewald VH Dahanukar RK Jalluri KR Criscione 《Canadian Metallurgical Quarterly》1999,42(1):118-134
7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599pi - 0.0725MR + 1. 55sigmam + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2-adrenoceptor (alpha2 pKi = 0.599pi - 0. 0542MR - 0.951sigmam + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT. 相似文献
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153.
G He J Hart OS Kim GL Szot CT Siegel JR Thistlethwaite KA Newell 《Canadian Metallurgical Quarterly》1999,67(1):131-137
Studies were performed to determine the effects of PTH and related compounds on phosphatidylcholine (PC) hydrolysis in UMR-106 cells and the pathway by which the PTH effects occurred. The responses were compared with those of phorbol 12,13-dibutyrate (PDBu). Both bovine PTH-(1-34) [bPTH-(1-34)] and PDBu stimulated PC hydrolysis within 10 min. Significant effects were elicited by concentrations of 0.3-1 nM bPTH-(1-34) and 5 nM PDBu. Dose-dependent increases were seen at higher concentrations of both compounds, however, the response to bPTH-(1-34) was reduced at 30 nM. Bovine or human PTH-(1-34) and human PTH-related peptide-(1-34) [hPTHrP-(1-34)] were equipotent in their effects, whereas bovine [Nle(8,18)Tyr34]PTH-(3-34) amide [bPTH-(3-34)] and hPTH-(1-31) amide [hPTH-(1-31)] were less potent than bPTH-(1-34). bPTH-(3-34) did not antagonize the effects of bPTH-(1-34). Down-regulation of protein kinase C isozymes by 24-h treatment with PDBu completely prevented the stimulatory effect of PDBu on PC hydrolysis, but did not significantly affect the stimulatory effect of bPTH-(1-34). Both bPTH-(1-34) and PDBu stimulated transphosphatidylation of PC, indicating a phospholipase D-stimulated mechanism. The results suggest that in the UMR-106 cell line PTH can stimulate activation of PLD by a mechanism other than through protein kinase C. 相似文献
154.
May Davis Hill 《History of Photography》2013,37(4):310-312
Abstract The photographic work of Ella Fuller was unknown until 1970, when more than 225 anonymous glass negatives came to the University of Michigan as the gift of H. Mark Hildebrandt, who bought them at an auction in rural Michigan in 1968. The plates turned out to be the work of Ella Grace Frisbee Fuller, a woman of Quaker origin. Born in 1872 in Belleville, near Detroit, she took up photography soon after her marriage in 1894 to Ira Fuller, a farmer from Ypsilanti Township. At about the same time she was reporting the events of her small community to a local newspaper. The plates span a period from around 1900 to just before the First World War. From later years only run-of-the-mill snapshots survive. Fuller took much interest in the temperance movement and at the age of 86 made her first air trip to attend an international Women's Christian Temperance Union conference in Mexico City in 1959. She died in 1968 at the age of 94. 相似文献
155.
Mehrdad Rafat May Griffith Malik Hakim Lea Muzakare Frank Li K.C. Khulbe Takeshi Matsuura 《应用聚合物科学杂志》2007,106(3):2056-2064
Argon plasma treatment enhanced the attachment of epithelial cells to a collagen‐based artificial cornea crosslinked using glutaraldehyde (GA) and glutaraldehyde‐polyethylene oxide dialdehyde (GA‐PEODA) systems. The epithelialization of untreated and treated surfaces was evaluated by the seeding and growth of human corneal epithelial cells. Characterization of polymer surface properties such as surface hydrophilicity and roughness was also made by contact angle measurement and atomic force microscopy, respectively. Contact angle analysis revealed that the surface hydrophilicity significantly increased after the treatment. In addition, AFM characterization showed an increase in surface roughness through argon plasma treatment. Based on the biological and surface analysis, argon plasma treatment displays promising potential for biocompatibility enhancement of collagen‐based artificial corneas. It was also found that the cell attachment to artificial cornea surfaces was influenced by the combined effects of surface chemistry (i.e., surface energy), polymer surface morphology (i.e., surface roughness), and polar interactions between functional groups at the polymer surface and cell membrane proteins. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007 相似文献
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Do clinic-referred children and their parents agree on the problems for which treatment is undertaken? The authors asked 381 outpatient-clinic-referred children and their parents to list, independently, the child's target problems. Of the parent-child pairs, 63 % failed to agree on even a single problem. When problems were grouped into broad categories (e.g., delinquent, withdrawn), more than a third of the pairs still failed to agree on a single broad problem area. Parent-child agreement was higher for externalizing than for internalizing problem categories (though poor for both). Low parent-child agreement may help explain the poor outcomes often reported for clinic-based child therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
158.
159.
L Struillou C Rabaud N Bischoff MA Preiss T May P Canton 《Canadian Metallurgical Quarterly》1997,26(25):1192-1194
BACKGROUND: Cardiac localization of hydatiosis is uncommon, involving 0.5 to 2% of all cases. CASE REPORTS: The first patient was a 15 year old adolescent whose cardiac hydatidosis was revealed by tamponade. The second case was discovered in a 28-year-old woman without cardiac signs who was explored for allergy manifestations with fever, urticaria and joint point. Both patients underwent surgery. Eighteen months after the operation, the second patient developed hemiplegia leading to the discovery of multi-organ localizations (brain, spleen, kidney) which were not evidenced at the initial work-up. The neurological deficit and brain cysts regress with albendazole treatment. DISCUSSION: The risk of rupture of the cardiac hydatic cyst requires rapid surgical cure. Medical treatments are discussed. Anti-hydatic drugs can be used alone in case of a contraindication for surgery. In other patients they are given during the perioperatie period and for a prolonged period after surgery. 相似文献
160.
Although positron emission tomography (PET) assesses myocardial viability (V) accurately, a rapid, inexpensive substitute is needed. Therefore, the authors developed a low-dose (1 mCi) Iodine-123-Iodophenylpentadecanoic Acid (IPPA) myocardial viability scan requiring analysis of only the first three minutes of data acquired at rest with a standard multicrystal gamma camera. Twenty-one patients > 2 weeks after myocardial infarction (MI) (24 MIs, 10 anterior, 14 inferoposterior, 21 akinetic or dyskinetic) had cardiac catheterization and resting IPPA imaging. V was determined by either transmural myocardial biopsy during coronary bypass surgery (12 patients, 14 MIs) or reinjection tomographic thallium scan (9 patients, 10 MIs), and 50% of MIs were viable. The IPPA variables analyzed were: time to initial left ventricular (LV) uptake in the region of interest (ROI), the ratio of three-minute uptake in the ROI to three-minute LV uptake, three-minute clearing (counts/pixel) in the ROI (decrease in IPPA after initial uptake), and three-minute accumulation (increase in IPPA after initial uptake) in the ROI. Rules for detecting V were generated and applied to 10 healthy volunteers to determine normalcy. While three-minute uptake in nonviable MIs was only 67% of volunteers (P < 0.0001) and 75% of viable MIs, uptake alone identified only 50% of viable MIs and 75% of nonviable MIs. IPPA clearing, however, was > or = 13.5 counts/pixel in 10/12 (83%) of viable MIs, and IPPA accumulation > or = 6.75 counts/pixel identified one more viable MI, for a sensitivity for V of 11/12 (92%), with a specificity of 11/12 (92%), and a 100% normalcy rate. The authors conclude low-dose IPPA (five-minute acquisition with analysis of the first three minutes of data) has potential for providing rapid, inexpensive V data after MI. Since newer multicrystal cameras are mobile, IPPA scans can be done in emergency rooms or coronary care units generating information that might be useful in decisions regarding thrombolysis, angioplasty, or bypass surgery. 相似文献