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91.
ME Dolan SK Roy BJ Garbiras P Helft P Paras MY Chae RC Moschel AE Pegg 《Canadian Metallurgical Quarterly》1998,55(10):1701-1709
To modulate the bioavailability and perhaps improve the tumor cell selectivity of O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT inactivators and as substrates for cellular esterases. The potential prodrugs examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7- and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9-esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8-bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at least 75 times less potent than the corresponding benzylated purine against the pure human AGT. In contrast, the activities of esters and their respective benzylated purine were similar in crude cell extracts and in intact cells. The increase in potency of esters in cellular extracts could be explained by a conversion of the respective prodrug to the more potent benzylated purine in the presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor cell hydrolysis of the esters varied considerably as a function of cell type and prodrug structure. These data suggest that these or related prodrugs may be advantageous for selective AGT inactivation in certain tumor types. 相似文献
92.
It is unclear whether the neural algorithm that underlies stereoscopic vision in birds incorporates both low level (camouflage breaking) and high level (depth ordering) comparisons of information available to each of the eyes. Both visual functions were successfully tested by examining transitive inference performance in two barn owls trained to discriminate static Julesz random dot stereograms, thus demonstrating a capacity to detect relative depth using fine retinal disparity as the sole cue for discrimination. Our behavioral tests provide strong evidence that the barn owl possesses global stereopsis comparable to that found in the macaque monkey--the owl's best stereoacuity was 2 min of arc. 相似文献
93.
94.
R Kraus B Reichl SD Kimball M Grabner BJ Murphy WA Catterall J Striessnig 《Canadian Metallurgical Quarterly》1996,271(33):20113-20118
To identify the binding domain for diltiazem-like Ca2+ antagonists on L-type Ca2+ channel alpha1 subunits we synthesized the benzazepine [3H]benziazem as a novel photoaffinity probe. [3H]Benziazem reversibly labeled the benzothiazepine (BTZ)-binding domain of partially purified skeletal muscle Ca2+ channels with high affinity (Kd = 12 nM) and photoincorporated into its binding domain with high yield (>66%). Antibody mapping of proteolytic labeled fragments revealed specific labeling of regions associated with transmembrane segments S6 in repeats III and IV. More than 50% of the labeling was found in the tryptic fragment alanine 1023-lysine 1077 containing IIIS6 together with extracellular and intracellular amino acid residues. The remaining labeling was identified in a second site comprising segment S6 in repeat IV and adjacent residues. Unlike for dihydropyridines, no labeling was observed in the connecting IIIS5-IIIS6 linker. The [3H]benziazem photolabeled regions must be in close contact to the drug molecule when bound to the channel. We propose that the determinants for high affinity BTZ binding are located within or in close proximity to segments IIIS6 and/or IVS6. Therefore the binding domain for BTZs, like for the other main classes of Ca2+ antagonists, must be located in close proximity to pore-forming regions of the channel. 相似文献
95.
A Saunders S Hoibr?ten JJ Kraushaar BJ Kriss RJ Peterson RA Ristinen JT Brack G Hofman EF Gibson CL Morris 《Canadian Metallurgical Quarterly》1996,53(4):1745-1752
We calculated the electrostatic force between a planar interface, such as a planar-supported lipid bilayer membrane, and the tip of a stylus on which another lipid bilayer or some other biomacromolecular system might be deposited. We considered styli with rounded tips as well as conical tips. To take into account the effect of dynamical hydrogen-bonded structures in the aqueous phase, we used a theory of nonlocal electrostatics. We used the Derjaguin approximation and identified the systems for which its use is valid. We pointed out where our approach differs from previous calculations and to what extent the latter are inadequate. We found that 1) the nonlocal interactions have significant effects over distances of 10-15 A from the polar zone and that, at the surface of this zone, the effect on the calculated force can be some orders of magnitude; 2) the lipid dipoles and charges are located a distance L from the hydrophobic layer in the aqueous medium and this can have consequences that may not be appreciated if it is ignored; 3) dipoles, located in the aqueous region, can give rise to forces even though the polar layer is unchanged, and if this is ignored the interpretation of force data can be erroneous if an attempt is made to rationalize an observed force with a knowledge of an uncharged surface; 4) the shape of the stylus tip can be very important, and a failure to take this into account can result in incorrect conclusions, a point made by other workers; and 5) when L is nonzero, the presence of charges and dipoles can yield a force that can be nonmonotonic as a function of ionic concentration. 相似文献
96.
97.
As spinal motor neurons project to their hindlimb targets, their growth cones avoid particular regions along their pathway. T-cadherin is discretely distributed in the avoided caudal sclerotome and on extrasynaptic muscle surfaces (B. J. Fredette and B. Ranscht (1994) J. Neurosci. 14, 7331-7346), and therefore, the ability of T-cadherin to inhibit neurite growth was tested in vitro. T-cadherin inhibited neurite extension from select neuron populations both as a substratum, and as a soluble recombinant protein. Anti-T-cadherin antibodies neutralized the inhibition. Spinal motor neurons were inhibited only during the stages of axon growth across the sclerotome and muscle innervation. Inhibitory responses corresponded to neuronal T-cadherin expression, suggesting a homophilic binding mechanism. These results suggest that T-cadherin is a negative guidance cue for motor axon projections. 相似文献
98.
99.
Twenty patients who had chronic lymphocytic leukemia underwent 25 elective primary total hip arthroplasties at the Mayo Clinic. No patient had a postoperative prosthetic infection. No patient had an intraoperative or postoperative hemorrhagic complication. One patient had a revision for aseptic loosening. After an average follow-up period of 4.6 years, there were 84% good and excellent results. It is concluded that patients who have early-stage chronic lymphocytic leukemia may not be at increased risk for major perioperative or postoperative complications in total hip arthroplasty. The surgeon must remain vigilant for postoperative complications, but satisfactory clinical results can be obtained in this patient population. 相似文献
100.
BJ Conway OH Suleiman FG Rueter RG Antonsen RJ Slayton 《Canadian Metallurgical Quarterly》1994,191(2):323-330
PURPOSE: To determine trends in mammography in the United States. MATERIALS AND METHODS: A sample of mammographic facilities was selected for each year of the Nationwide Evaluation of X-ray Trends. The same protocol was followed for the 1985, 1988, and 1992 surveys. Data were collected with use of the same imaging phantom for all three surveys and also with a different phantom in the 1988 and 1992 surveys. RESULTS: Of the 356 facilities surveyed in 1992, 59% claimed to be in compliance with the Health Care Financing Administration (HCFA) mammography requirements, 42% were accredited by the American College of Radiology (ACR), and 23% did not hold credentials from either the HCFA or the ACR. Since 1985, there has been a 34% improvement in acceptable phantom image quality score and a 20% decrease in the mean glandular dose. CONCLUSION: Mammography as practiced today is essentially a screen-film technique. Mammographic phantom image quality has improved considerably. The overall mean glandular dose has decreased primarily because of the elimination of xeroradiography. 相似文献