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451.
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Jacek J. Slon-Usakiewicz Andrew Pasternak Neil Reid Leticia M. Toledo-Sherman 《Clinical proteomics》2004,1(3-4):227-234
Methotrexate has been a clinical agent used in cancer, immunosuppression, rheumatoid arthritis, and other highly proliferative
diseases for many years, yet its underlying molecular mechanism of action in these therapeutic areas is still unclear. We
have previously reported using a chemical proteomics technique on several other potential pharmacodynamic targets of methotrexate.
Here, using a frontal affinity chromatography with mass spectrometry detection, we confirm one of these targets, hypoxanthine-guanine
amidophosphoribosyltransferase, as a true binder of methotrexate with a Kd of 4.2 μM. These results complement and confirm our recent study, but more importantly, shed light into the mechanism of action of
methotrexate in oncology and other highly proliferative diseases and may help explain some unaccounted for effects of this
drug. For example, despite the fact that DNA salvage pathway enzymes are highly active, methotrexate can be effective if it
only targets enzymes of the de novo pathway. 相似文献
454.
Mr2034 has been proposed as a kappa opiate. While Mr2034 inhibited the binding of the kappa opiate 3H-ethylketocyclazocine better than unlabeled ethylketocyclazocine, it also displaced the binding of 3H-dihydromorphine and 3H-SKF 10047 more potently than morphine and SKF 10047, respectively. 3H-D-ala2-D-leu5-enkephalin was displaced equally well by Mr2034 and D-ala2-D-leu5-enkephalin. Saturation studies of 3H-Mr2034 binding demonstrated curvilinear Scatchard plots which could be dissected into two components by computer: KD1 0.06 nM, Bmax1 2.49 fmoles/mg tissue; and KD2 2.4 nM, Bmax2 6.57 fmoles/mg tissue. A portion of the higher affinity (KD 0.06 nM) component was inhibited by naloxonazine treatment in vitro (50 nM), suggesting that 3H-Mr2034 bound with very high affinity to mu1 sites. Displacement of 3H-Mr2034 binding by opioids was multiphasic, again implying that 3H-Mr2034 was binding to more than one class, of site. In view of its similar potency in inhibiting mu (3H-dihydromorphine), kappa (3H-ethylketocycla-zocine), sigma (3H-SKF 10047) and delta (3H-D-ala2-D-leu5-enkephalin) opioids Mr2034 might be considered a universal opiate. 相似文献
455.
Differential genic activity in Paramecium aurelia 总被引:4,自引:0,他引:4
J Pasternak 《The Journal of experimental zoology》1967,165(3):395-417
456.
The effect of stress (heat shock, arsenite, or Semliki Forest virus [SFV] infection) on the induction of increased hexose transport has been compared with that of insulin. All four treatments increase the Vmax for transport by BHK cells three- to five-fold, with little effect (less than 40% decrease) on Km. Hydrogen peroxide and phenylarsine oxide (PAO) prevent the increase in hexose transport induced by stress treatments as effectively as they do that induced by insulin. Pinocytosis is not affected by any of the four treatments. On the other hand, the induction by insulin is sensitive to amiloride, whereas that by arsenite is not. Rat embryo fibroblasts, which respond poorly to insulin, respond well to arsenite, heat shock, or SFV infection. It is concluded that the stress response is mediated by certain compounds that may be common to those required for the action of insulin, but that those compounds act at a stage subsequent to the function of the insulin receptor. 相似文献
457.
Monoclonal antibodies that were raised against cuticular components from the free-living nematode Panagrellus silusiae were found to react with a cuticular collagenous domain from Ascaris lumbricoides. One of these monoclonal antibodies was used to localize the collagenous epitope within sectioned Ascaris cuticles. By indirect immunofluorescence, accessible binding sites were observed in the basal zone of the cuticle. Immunological staining occurred in the innermost lamella of the basal zone, i.e., basal lamella, in which the fibrillar palisade gave a strong response. The three layers of the spiral fiber system of the basal zone exhibited a distinctive immunofluorescence pattern. In each of these layers, irregular shaped blocks, often quadrangular, were immunostained; whereas, adjacent blocks were immunonegative. Immunostaining was, for the most part, absent from the cortical and medial zones of the cuticle as well as from other tissues within the worm. 相似文献
458.
T.K. Rostovtseva C.L. Bashford G.M. Alder G.N. Hill C. McGiffert P.Y. Apel G. Lowe C.A. Pasternak 《The Journal of membrane biology》1996,151(1):29-43
The rates at which ions (86Rb+, [3H]-choline, 36Cl), 3H2O and nonelectrolytes ([14C]-urea, [14C]-glycerol, and [14C]-sugars) equilibrate across track-etched polyethyleneterephthalate (PETP) membranes (isotopic diffusion) have been measured
by a `static' and a `dynamic' technique under conditions where no net flow takes place; the two techniques give essentially
the same results. All tracers diffuse faster the longer the membranes are etched, consistent with an increase in pore size.
Water and neutral solutes diffuse at rates that are relatively independent of ionic strength, pH or the presence of divalent
cations. Diffusion of cations is decreased by high ionic strength, by reducing pH or by addition of divalent catons; diffusion
of chloride is increased by these procedures. Treatment of the membrane with diazomethane to reduce the negative fixed charge
decreases diffusion of cations and increases that of anions; diffusion of water and neutral solutes is unaffected by methylation
except in the membranes with the narrowest pores (i.e., those etched for the shortest time), in which case diffusion is reduced.
We conclude (1) that the special features of flow near a charged surface apply to ions but not to water or nonelectrolytes
and (2) that calculation of absolute rates of diffusion leads to values for the radii of pores through track-etched PETP membranes
that are in remarkably good agreement with measured values.
Received: 14 August 1995/27 November 1995 相似文献
459.
460.