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51.
JB Thomas SW Mascarella RB Rothman JS Partilla H Xu KB McCullough CM Dersch BE Cantrell DM Zimmerman FI Carroll 《Canadian Metallurgical Quarterly》1998,41(11):1980-1990
A study of the binding site requirements associated with the N-substituent of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken using a set of rigid vs flexible N-substituents. The study showed that compounds 7-9 bearing the trans-cinnamyl N-substituent most closely reproduced the potency at the opioid receptor of the flexible N-propylphenyl or N-propylcyclohexyl analogues previously reported. Neither the N-substituted cis-cinnamyl nor the cis-phenylcyclopropylmethyl compounds 10 and 11, respectively, showed high affinity for the opioid receptor. However, the N-trans-phenylcyclopropylmethyl compound 12 closely approximated the affinity of compounds 7-9. Additionally, we found that free rotation of the phenyl ring is necessary for high affinity binding and mu receptor subtype selectivity as the planar N-substituted thianaphthylmethyl and benzofuranylmethyl compounds 13 and 14 had significantly lower binding affinities. Altogether, these findings suggest that the high binding affinity, selectivity, and antagonist potency of N-propylphenyl or N-propylcyclohexyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) are achieved via a conformation wherein the connecting chain of the N-substituents is extended away from piperidine nitrogen with the appended ring system rotated out-of-plane relative to the connecting chain atoms. This conformation is quite similar to that observed in the solid state for 5, as determined by single crystal X-ray analysis. Additionally, it was found that, unlike naltrexone, N-substituents bearing secondary carbons attached directly to the piperidine nitrogen of 4 suffer dramatic losses of potency vs analogues not substituted in this manner. Using a functional assay which measured stimulation or inhibition of [35S]GTP-gamma-S binding, we show that the trans-cinnamyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) retain opioid pure antagonist activity and possess picomolar antagonist potency at the mu receptor. 相似文献
52.
KB Thomas 《Canadian Metallurgical Quarterly》1994,344(8929):1066-1067
53.
H Kovacs ID Campbell P Strong S Johnson FJ Ward KB Reid P Eggleton 《Canadian Metallurgical Quarterly》1998,37(51):17865-17874
Calreticulin (CRT) is located predominantly in the endoplasmic reticulum (ER) of cells, where it functions as a quality control controller of protein folding. However, CRT is also a prevalent autoantigen in patients with systemic lupus erythematosus (SLE), where its release from the cell may arise as a results of dysfunctional apoptosis and inefficient removal of ER vesicles, which are an abundant source of CRT and other autoantigens. Indicative of this is the presence of autoantibodies against CRT in the sera of 40-60% of all SLE patients. Once released into the circulation, CRT might bind directly to C1q and we have suggested that this association may result in a defect in C1q-mediated clearance of antigen-antibody complexes. It has been previously shown that CRT under physiological salt conditions binds to the globular head of C1q. It is known that the globular head region of C1q binds to the CH2 domain in the Fc portion of immunoglobulin gamma (IgG). The N-terminal half of CRT contains a number of short regions of 7-10 amino acids that show sequence similarity to the putative C1q binding region in the CH2 domain of IgG. By use of a series of 92 overlapping CRT synthetic peptides, a number of C1q binding sites on the CRT molecule have been identified, including several containing a CH2-like motif similar to the ExKxKx C1q binding motif found in the CH2 domain of IgG. A number of these peptides were shown to inhibit binding of C1q to IgG and reduce binding of native CRT to C1q. Moreover, several of the peptides were capable of inhibiting the classical pathway of complement activation. These studies have identified specific binding sites on the CRT molecule for C1q and lend support to the hypothesis that interaction of CRT with C1q may interfere with the ability of C1q to associate with immune complexes in autoimmune-related disorders. 相似文献
54.
J Werner C Fernández-del Castillo JA Rivera N Kollias KB Lewandrowski DW Rattner AL Warshaw 《Canadian Metallurgical Quarterly》1998,43(3):401-407
Nucleosome dimers from chicken erythrocytes show an ionic strength dependence of sedimentation coefficient similar to that of trimers, and indicative of a degree of compaction over a range of low ionic strengths. This is not easily reconciled with straight linkers but is consistent with bending or kinking of the linker DNA. 相似文献
55.
Disinfectant surveys from responding members of the American Society of Postanesthesia Nurses were divided into two groups based on whether or not they considered themselves to be exposed to disinfectants in their work environment. Their survey responses were then compared with those obtained previously from members of the Society of Gastroenterology Nurses and Associates, Inc., who were regularly exposed to 2% alkaline glutaraldehyde in the work setting. There were significant differences among the groups in the percentage of respondents who reported having headaches, eye irritations, respiratory problems, shortness of breath, rashes, memory loss, mood swings, and fatigue. These findings support the association of these complaints with 2% alkaline glutaraldehyde exposure. In contrast, there were no significant differences among the groups in the percentage of respondents who reported having asthma, rhinitis, chest pain, nausea, diarrhea, muscle/joint pain, visual disturbances, or dermatitis. 相似文献
56.
Hereditary inclusion body myopathies comprise autosomal recessive and autosomal dominant muscle disorders that have a variable clinical phenotype but share similar morphological features. These include rimmed vacuoles within muscle fibres and collections of intrasarcoplasmic and intranuclear tubulofilamentous inclusions, 16-18 nm in external diameter. The resemblances and the differences between the sporadic and the hereditary inclusion body myopathies are discussed. Recent advances in the identification of various proteins involved in these diseases are mentioned because they have provided better insight into their underlying pathophysiological mechanisms. Linkage studies have allowed the localization of the genetic defect of some hereditary inclusion body myopathies and related disorders, contributing to their individualization. 相似文献
57.
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59.
The effect of an enriched inspired oxygen concentration on perceived exertion (RPE) was investigated while running at two submaximal treadmill loads. Twelve males (VO2 max = 49.3 ml/kg-min) worked at 50% and 80% VO2 max, breathing either air or 80% O2-20% N2 in random order using a single blind technique. Subjects were evaluated while running for 10 min and during a 20 min recovery. Heart rate (HR), ventilation (VE), respiration rate (RR), tidal volume (VT) and RPE were measured before, during and after work. Blood lactate was measured 1 min after work. Oxygen concentration did not statistically affect HR, VE, RR or VT during exercise or recovery. At both loads, RPE at the end of exercise was significantly reduced breathing the hyperoxic mixture. At 50% VO2 max, mean RPE decreased from 11.2 breathing room air to 9.6 breathing 80% O2 and, 80% VO2 max, from 13.8 to 11.7 (P less than 0.01). Blood lactates were significantly reduced breathing 80% O2; from 23.4 mg to 13.3 at 50% VO2 max and from 55.5 to 36.5 at 80% VO2 max (P less than 0.01). The RPE correlated with lactate (r=0.64) at the end of work. Results indicate that during moderate and heavy work RPE is significantly affected by the inspired O2 concentration and there is a significant relationship between RPE and blood lactate. 相似文献
60.
The commercial separation of zirconium and hafniumvia aqueous/organic extraction procedures is both difficult and expensive. The principal objective of the present work was to
study an alternative procedure involving the oxidation-reduction equilibria of zir-conium and hafnium between a molten salt
phase and molten zincvia the displacement reaction: Zr(IV)molten salt + Hfmolten zink ⇌ Hf(IV)molten salt + Zrmolten zink The reaction goes strongly to the right with an equilibrium constant: logK =0.432 ×104/T - 1.565 for Na2Zr(Hf)F6 dissolved in NaKCl2 solvent, thus showing promise as the basis for an anhydrous process for separating zirconium and hafnium. The rate of approach
to chemi-cal equilibrium was studied in a baffled stirred reactor. The equilibration rate was found to be controlled by the
hafnium mass transfer rate from the molten zinc to the metal-salt interface. The mass transfer rate could be estimated from
the physical properties of the molten metal and the salt phases, using the Mayer correlation.
Formerly with the Teledyne Wah Chang Cor-poration, Albany, OR. 相似文献