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161.
162.
A newly developed comparative molecular field analysis (CoMFA) technique, the cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used to build a quantitative structure-activity relationship (3D-QSAR) for nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose affinities for the mouse ER (mER) have been determined in our laboratory. The final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA, with a standard error of prediction of 0.594 at 3 principal components. This model was used to visualize steric and electrostatic features of the ligands that correspond with ER binding affinity. Results obtained from the CoMFA steric and electrostatic plots of this model have also been compared to information from the ER binding affinities of substituted estradiol analogues. This is in an effort to determine structural features of compounds in the CoMFA analysis that may correspond to those of the estradiol analogues and to further clarify the mode of binding of nonsteroidal ER ligands. 相似文献
163.
MK Hong SW Park CW Lee DH Kang JK Song JJ Kim SJ Park MK Hong GS Mintz MB Leon 《Canadian Metallurgical Quarterly》1998,82(5):670-3, A8
We evaluated the role of intravascular ultrasound (IVUS) in 16 patients with unprotected left main coronary artery (LMCA) stenting compared with 80 patients with other (non-LMCA) native coronary artery stenting and found that (1) additional high-pressure or larger size balloon dilations were more frequently performed in LMCA stenting than in non-LMCA stenting (p <0.05) and (2) after IVUS-guided stent implantation, minimum lumen area was > or = 9 mm2 in 88% of patients who underwent LMCA stenting and in 19% of those who underwent non-LMCA stenting (p <0.001). IVUS guidance may be a more important adjunctive imaging modality in the stenting of unprotected LMCA stenoses than in stenting of non-LMCA stenoses. 相似文献
164.
The effect of glucocorticoid(GC) on peak cytosolic free calcium net increment (delta[Ca2+]i) induced by high-K+ was detected with MiraCal Image System. The main results were as follows: (1) Corticosterone(B) could inhibit delta[Ca2+]i in a time-dependent and concentration-dependent manner. (2) The inhibitory effect of B could be mimicked by bovine-serum albumin conjugated corticosterone (B-BSA) also in a dose-dependent manner. (3) G-protein inhibitor, either PTX or GDP beta S significantly reduced the inhibitory effect of B and B-BSA on delta[Ca2+]i (4) PMA, a stimulator for protein kinase C(PKC), could inhibit delta[Ca2+]i. (5) Although the inhibitors of PKC, chelerythrine chloride and bisindolylamide I per se had no influence on delta[Ca2+]i, but they significantly antagonized the inhibitory effect of B and B-BSA on delta[Ca2+]i. It is postulated that GC inhibit delta[Ca2+]i induced by high-K+ through a membrane mechanism and by a pathway involving G-protein and PKC. 相似文献
165.
SP Newman J Brown KP Steed SJ Reader H Kladders 《Canadian Metallurgical Quarterly》1998,113(4):957-963
STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy, nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids. 相似文献
166.
Jimpy is a shortened life-span murine mutant showing recessive sex-linked inheritance. The genetic defect consists of a point mutation in the PLP gene and produces a severe CNS myelin deficiency that is associated with a variety of complex abnormalities affecting all glial populations. The myelin deficiency is primarily due to a failure to produce the normal amount of myelin during development. However, myelin destruction and oligodendrocyte death also account for the drastic myelin deficit observed in jimpy. The oligodendroglial cell line shows complex abnormalities in its differentiation pattern, including the degeneration of oligodendrocytes through an apoptotic mechanism. Oligodendrocytes seem to be the most likely candidate to be primarily altered in a disorder affecting myelination, but disturbances affecting astrocytes and microglia are also remarkable and may have a crucial significance in the development of the jimpy disorder. In fact, the jimpy phenotype may not be attributed to a defect in a single cell but rather to a deficiency in the normal relations between glial cells. Evidences from a variety of sources indicate that the jimpy mutant could be a model for disturbed glial development in the CNS. The accurate knowledge of the significance of PLP and its regulation during development must be of vital importance in order to understand glial abnormalities in jimpy. 相似文献
167.
Lipoprotein lipase regulates the hydrolysis of circulating triglyceride and the uptake of fatty acids by most tissues, including the mammary gland and adipose tissue. Thus, lipoprotein lipase is critical for the uptake and secretion of the long-chain fatty acids in milk and for the assimilation of a high-fat milk diet by suckling young. In the lactating female, lipoprotein lipase appears to be regulated such that levels in adipose tissue are almost completely depressed while those in the mammary gland are high. Thus, circulating fatty acids are directed to the mammary gland for milk fat production. Phocid seals serve as excellent models in the study of lipoprotein lipase and fat transfer during lactation because mothers may fast completely while secreting large quantities of high fat milks and pups deposit large amounts of fat as blubber. We measured pup body composition and milk fat intake by isotope (deuterium oxide) dilution and plasma post-heparin lipoprotein lipase activity in six grey seal (Halichoerus grypus) mother-pup pairs at birth and again late in the 16-day lactation period. Maternal post-heparin lipoprotein lipase activity increased by an average of four-fold by late lactation (P = 0.027), which paralleled an increase in milk fat concentration (from 38 to 56%; P = 0.043). Increasing lipoprotein lipase activity was correlated with increasing milk fat output (1.3-2.1 kg fat per day) over lactation (P = 0.019). Maternal plasma triglyceride (during fasting) was inversely correlated to lipoprotein lipase activity (P = 0.027) and may be associated with the direct incorporation of long-chain fatty acids from blubber into milk. In pups, post-heparin lipoprotein lipase activity was already high at birth and increased as total body fat content (P = 0.028) and the ratio of body fat: protein increased (P = 0.036) during lactation. Although pup plasma triglyceride increased with increasing daily milk fat intake (P = 0.023), pups effectively cleared lipid from the circulation and deposited 70% of milk fat consumed throughout lactation. Lipoprotein lipase may play an important role in the mechanisms involved with the extraordinary rates of fat transfer in phocid seals. 相似文献
168.
JC Divino Filho SJ Hazel P Fürst J Bergstr?m K Hall 《Canadian Metallurgical Quarterly》1998,156(3):519-527
A simple, sensitive, and rapid method for simultaneous determination of residues of flumequine and its microbiologically active metabolite 7-hydroxyflumequine in 100 mg sheep edible tissues (muscle, liver, kidney, and fat) by liquid chromatography is reported. After liquid-liquid cleanup with ethyl acetate, tissue extracts were injected onto a Select B column. The 2 compounds were determined by ultraviolet and fluorimetric detection. The method was repeatable and reproducible for flumequine and 7-hydroxyflumequine in muscle, liver, kidney, and fat, with limits of detection below 2 and 3 micrograms/kg for flumequine and 7-hydroxyflumequine, respectively. Mean recoveries for flumequine were 90 +/- 7, 82 +/- 7, 89 +/- 5, and 82 +/- 6% in muscle, liver, kidney, and fat respectively. Mean recoveries for 7-hydroxyflumequine were 91 +/- 2, 90 +/- 4, 86 +/- 3, and 84 +/- 4% in muscle, liver, kidney, and fat, respectively. 相似文献
169.
BR Babu SJ Zhu AV Ramayya JH Hamilton LK Peker MG Wang TN Ginter J Kormicki WC Ma JD Cole R Aryaeinejad K Butler-Moore YX Dardenne MW Drigert GM Ter-Akopian YT Oganessian JO Rasmussen S Asztalos IY Lee AO Macchiavelli SY Chu KE Gregorich MF Mohar S Prussin MA Stoyer RW Lougheed KJ Moody JF Wild 《Canadian Metallurgical Quarterly》1996,54(2):568-571
170.
KN Furuya PR Durie EA Roberts SJ Soldin Z Verjee L Yung-Jato E Giesbrecht L Ellis 《Canadian Metallurgical Quarterly》1995,28(5):531-540
N-Acetyl aspartate (NAA) is the second most abundant amino acid in the human brain. NAA is synthesized by L-aspartate N-acetyl transferase or by cleavage from N-acetyl aspartyl glutamate by N-acylated alpha-linked L-amino dipeptidase (NAALADase); and it is catabolized to acetate and aspartate by N-acetyl aspartate amino hydrolase (amino acylase II). NAA is localized primarily to neurons, where it is concentrated in the cytosol. Although NAA is devoid of neurophysiological effects, it serves as an acetyl donor, an initiator of protein synthesis or a carbon transfer source across the mitochondrial membrane. The concentration of NAA in human brain increases 3-fold between midgestation and adulthood. In Canavan's Disease, an autosomal recessive disorder due to a null mutation in amino acylase II, NAA levels in brain are markedly increased and disrupt myelination. NAA levels have been found to be reduced in neurodegenerative disorders, including Alzheimer's Disease and Huntington's Disease. Since endogenous NAA can be readily detected in human brain by magnetic resonance spectroscopy, it is increasingly being exploited as a marker for functional and structural integrity of neurons in an expanding number of disorders. 相似文献