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排序方式: 共有230条查询结果,搜索用时 15 毫秒
81.
Shen W Fakhoury S Donner G Henry K Lee J Zhang H Cohen J Warner R Saeed B Cherian S Tahir S Kovar P Bauch J Ng SC Marsh K Sham H Rosenberg S 《Bioorganic & medicinal chemistry letters》1999,9(5):703-708
Synthesis and biological evaluation of heteroarenes as reduced cysteine replacements are described. Of the heteroaryl groups examined with respect to FT inhibitor FTI-276 (1), pyridyl was the replacement found to be most effective. Substitutions at C4 of the pyridyl moiety did not affect the in vitro activity. Compound 9a was found to have moderate in vivo bioavailability. 相似文献
82.
Intermittent administration stimulates bone formation, whereas sustained elevation of parathyroid hormone (PTH) as in hyperparathyroidism stimulates bone resorption. Even though PTH(1-34) is the only anabolic agent clinically approved for the treatment of osteoporosis, the molecular mechanism whereby PTH mediates these opposing effects depending on timing of administration is not well understood. In this study, we sought to determine the involvement of gap junctions and hemichannels, and the protein that forms them, connexin 43 (Cx43), in the effect of PTH(1-34) on osteoblast mineralization. The osteoblast-like cell line MLO-A5 that rapidly mineralizes in culture was used. Intermittent PTH enhances mineralization, whereas continuous PTH inhibits this process. The mineralization was significantly inhibited by 18 beta-glycyrrhetinic acid, an inhibitor known to block gap junctions and hemichannels. When the cells were treated with PTH(1-34), gap junctional coupling was increased; however, the degree of stimulation was similar between intermittent and continuous treatment. The permeabilization to dye was not detected under various intermittent or continuous PTH treatments. On the other hand, the overall level of Cx43 protein increased in response to continuous PTH treatment. In contrast, when the cells were subjected to intermittent treatment overall level of Cx43 was unchanged, but there was an increase of connexons associated with an increase in Cx43 expression on the cell surface. Our results suggest that Cx43 overall expression, connexon formation and cell surface expression are differentially regulated by intermittent and continuous PTH(1-34), implying the involvement of Cx43 and Cx43-forming channels in mediating the effects of PTH on bone formation. 相似文献
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85.
Antigenic drift and shift involving the surface proteins of Influenza virus gave rise to new strains that caused epidemics affecting millions of people worldwide over the last hundred years. Variations in the membrane proteins like Hemagglutinin (HA) and Neuraminidase (NA) necessitates new vaccine strains to be updated frequently and poses challenge to effective vaccine design. Though the HA protein, the primary target of the human immune system, has been well studied, reports on the antigenic variability in the other membrane protein NA are sparse. In this paper we investigate the molecular basis of antigenic drift in the NA protein of the Influenza A/H3N2 vaccine strains between 1968 and 2009 and proceed to establish correlation between antigenic drift and antigen-antibody interactions. Sequence alignments and phylogenetic analyses were carried out and the antigenic variability was evaluated in terms of antigenic distance. To study the effects of antigenic drift on the protein structures, 3D structure of NA from various strains were predicted. Also, rigid body docking protocol has been used to study the interactions between these NA proteins and antibody Mem5, a 1998 antibody. 相似文献
86.
Contusion injury is produced experimentally in anaesthetised monkeys by weight drop method. A group of animals having laminectomy alone served as sham controls. Drugs were administered 30 min after injury initially. Naloxone and nifedipine were administered as single dose administration immediately after injury. Dipyridamole and DMSO were administered daily for a period of 1 week. Acetylcholinesterase (AchE) was estimated in 2 spinal tissue segments, S1-at the site of injury and S2-the segment above the site of injury, at the end of 1 week after sacrificing the animals. Contusion injury produced significant decrease in specific activity of AchE in the traumatised segment of the experimental animals. The non-traumatised adjacent segment did not show any significant change. Nifedipine, naloxone and DMSO produced a decrease in AchE activity in S1 and S2 segments. Monkeys developed paraplegia after contusion injury. A score 2+ was observed after 1 week as compared to the score of 4+ of sham controls. Single dose administration of naloxone seemed to reverse the motor deficit by getting a score of 3+; other drugs did not produce any beneficial effect on motor deficit. 相似文献
87.
Joyce Nikolakopoulos Cherian Zachariah Duarte Mota de Freitas †Evan B. Stubbs Jr. ‡Ravichandran Ramasamy §M. Margarida C. A. Castro §Carlos F. G. C. Geraldes 《Journal of neurochemistry》1998,71(4):1676-1684
Abstract: Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel 7 Li NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane- N,N ', N ", N ‴-tetramethylene phosphonate (HTmDOTP4− ). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 m M HTmDOTP4− were 0.055 ± 0.006 (n = 4) and −0.025 ± 0.006 min−1 (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 m M veratridine indicated the presence of Na+ channel-mediated Li+ transport in SH-SY5Y cells. 7 Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs. 相似文献
88.
A. S. Balasubramanian T. Alam R. Mathur S. Lakshmi R. Cherian K. Alvares 《Journal of biosciences》1983,5(1):61-64
Concanavalin A bound to Sepharose has been used for the purification of brain β-galactosidase, α-L-fucosidase, α-D-mannosidase, arylsulphatase and β-glucuronidase.0 Several factorsviz pH, temperature and concentration of α-methyl glucoside influenced the binding and elution of these enzymes. A lysosomal acid α-mannosidase and a cytosolic neutral mannosidase were separable by concanavalin A-Sepharose chromatography. Similarly lysosomal and microsomal β-glucuronidases were separable using gradient elution with α-methyl glucoside. The results indicate the usefulness of this lectin for the isolation of wide variety of enzymes under specified experimental conditions. 相似文献
89.
Martha E. I. Leibbrandt James Koropatnick John F. Harris M. George Cherian 《Biological trace element research》1991,30(3):245-256
We describe a competitive, solid-phase radioimmunoassay for metallothionein, which employs a rabbit antiserum directed against rat MT-2 to detect metallothionein (MT) from several different species (rabbit, mouse, rat, Chinese hamster, and human). The lower limit of detection of the assay for rat MT-2 was 0.7 ng; for rabbit MT-2 it was 2 ng. The method is capable of measuring both isoforms of MT (MT-1 and MT-2). When MT levels in rat and mouse tissues were estimated with this RIA and the silver-saturation method, both assays gave the same pattern of MT induction in control and cadmium-treated animals. Both methods measured high levels of MT in human liver samples. Chinese hamster ovary cells induced with cadmium also showed elevated MT expression. The detectability of MTs from a broad range of species is facilitated by the use of solid-phase MT, which has an avidity for the antiserum similar to that of the MT in the tested sample. 相似文献
90.