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排序方式: 共有453条查询结果,搜索用时 15 毫秒
1.
Kyoung-Ah Kim Min-Jung Kim Ji-Young Park Ji-Hong Shon Young-Ran Yoon Sang-Seop Lee Kwang-Hyeon Liu Jin-Ho Chun Myung-Ho Hyun Jae-Gook Shin 《Drug metabolism and disposition》2003,31(10):1227-1234
The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNA-expressed cytochrome p450 (p450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Clint) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9- and 2.4-fold higher than those from the R-form, respectively. The sums of formation Clint of both metabolites were 13.5 and 57.3 microl/min/mg protein for R- and S-lansoprazole, respectively, suggesting that S-lansoprazole would be cleared more rapidly than the R-form. The p450 isoform selective inhibition study in liver microsomes, and the incubation study of cDNA-expressed enzymes, demonstrated that the stereoselective sulfoxidation is mediated by CYP3A4 and that the hydroxylation is mediated by CYP2C9 and CYP3A4 as well as by CYP2C19. Total Clint values of hydroxy and sulfone metabolite formation catalyzed by all these p450 enzymes were consistently higher for S-lansoprazole than for the R-form. The CYP3A4 produced the greatest difference of Clint between S- and R-enantiomers, mainly due to a difference of sulfoxidation metabolism (Clint 76.5 versus 10.8 microl/min/nmol of p450, respectively), whereas CYP2C19-catalyzed hydroxylation resulted in a minor difference of Clint between S- and R-enantiomers (179.6 versus 143.3 microl/min/nmol of p450, respectively). However, the affinity of CYP2C19 on hydroxylation was 5.7-fold higher for S-enantiomer than for the R-form (Km 2.3 versus 13.1 microM), suggesting that the role of CYP2C19 on stereoselective hydroxylation would be more prominent at concentrations around the usual therapeutic level. These findings suggest that both CYP2C19 and CYP3A4 are major enzymes contributing to the stereoselective disposition of lansoprazole, but stereoselective hydroxylation of lansoprazole enantiomers is mainly influenced by CYP2C19, especially at the usual therapeutic doses. 相似文献
2.
Steenbergen EJ; Verhagen OJ; van Leeuwen EF; van den Berg H; von dem Borne AE; van der Schoot CE 《Blood》1995,86(2):692-702
Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL. 相似文献
3.
The focus of our research is to understand the immune response to foreign tissue. We believe that adichotomy exists within
the immune response to an allograft such that part of the response is dedicated to the protection of the graft. Nevertheless,
in a dominantly graft-aggressive environment, rejection typically ensues. In this article, we describe models that have been
set up to test directly the ability of potentially protective aspects of the immune response to prevent allograft rejection.
We discussour data in the context of a growing body of exciting and often controversial literature. 相似文献
4.
Transition metal complexes containing vanadium IV have been shown to
modulate the cellular redox potential and catalyse the generation of
reactive oxygen intermediates (ROI). Since sperm function is exquisitely
susceptible to ROI, we examined the effects of stable chelate complexes of
vanadocenes on human sperm motility. We synthesized seven structurally
distinct chelate complexes of bis(cyclopentadienyl)vanadium(IV) with
bidentate ligands [i.e. vanadocene acetylacetonato monotriflate (VDacac),
vanadocene hexafluoro acetylacetonato monotriflate (VDHfacac), vanadocene
N-phenyl benzohydroxamato monotriflate (VDPH), vanadocene acethydroxamato
monotriflate (VDH), vanadocene catecholate (VDCAT), vanadocene bipyridino
ditriflate (VDBPY), and vanadocene dithiocarbamate monotriflate (VDDTC)],
and evaluated their spermicidal activity using computer-assisted sperm
analysis (CASA; Hamilton-Thorne). All seven chelate complexes of vanadocene
elicited potent spermicidal activity at micromolar concentrations (EC50
values: 3.9-106 microM) without affecting the sperm acrosome integrity. The
catecholate and acetylacetonate complexes of vanadocene were the most
active and the bipyridyl complex the least active with an order of efficacy
VDCAT > VDacac > VDDTC > VDPH > VDH > VDHfacac > VDBPY.
The spermicidal activity of chelate complexes of vanadocenes was rapid and
irreversible since the treated spermatozoa underwent apoptosis, as
determined by the flow cytometric analysis of mitochondrial membrane
potential, surface annexin V binding assay, in-situ nick-end labelling of
sperm nuclei, and confocal laser scanning microscopy. These results provide
unprecedented evidence that chelate complexes of vanadocene with bidentate
ligands have spermicidal and apoptosis inducing properties. These
vanadocene complexes, especially VDacac, may be useful as contraceptive
agents.
相似文献
5.
Late allograft rejection due to transplant vasculopathy continues to be a major clinical problem. Increasing the ratio of donor transplant size to recipient weight has been shown to reduce the incidence of late allograft failure. Using a murine pancreas transplant model we have tested the hypothesis that increasing the donor transplant size in a recipient can promote long-term allograft survival by promoting recovery from transplant vasculopathy. Recipients of an allograft that showed extensive vasculopathy were transplanted with a second donor transplant. The effect of the second allograft on the vasculopathy present in the first graft was measured. Transplanting a second allograft reversed all signs of ongoing rejection, including transplant vasculopathy, resulting in long-term survival of the first graft. Vasculopathy was only reversed if the first and second grafts were from the same mouse strain, suggesting an antigen-specific mechanism. However, the recovery of the first graft was not associated with antigen-specific peripheral tolerance. 相似文献
6.
Kang BS Chung TW Moon JY Lim JK Shon YH Nam KS Kim DS Jeon BH Kim CH 《Immunopharmacology and immunotoxicology》2004,26(3):355-372
Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27, 2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular weights, corresponding to about 330 kDa as a monomer and 660 kDa as a dimer, were reduced to smaller molecular weight forms by Endo F and trifluoromethanesulfonic acid (TMSF). Deglycosylated porcine Tg (dgpTg) and native pTg were injected i.v. into CBA/J mice, without the aid of adjuvants. Both lymphocytic infiltrations of the thyroid glands and levels of Tg-specific CTL were similar to those found in conventional EAT induced by Tg and adjuvants. In contrast, proliferative responses in native pTg and dgpTg-injected mice could not be detected, and titers of antibodies to pTg and dgpTg were 20 times and 30 times lower than that of pTg and adjuvants, respectively. The EAT-inducer CTL belonged to the CD8+ cell subset and exerted their thyroiditogenic potential through release of IFN-gamma. It was concluded that dgpTg-induced EAT is mediated by type 1 cytotoxic T cells (Tcl). Also, results that EAT induction of the glycosylated pTg (gpTg) was much lower than that of dgpTg, suggested that the abberant and incomplete glycosylation of the thyroglobulin is responsible for the induction of autoimmune thyroiditis. 相似文献
7.
8.
YongSung Kwon Shivshankar Chaudhari ChaEun Kim DaHae Son JiHwan Park MyungJun Moon MinYoung Shon YouIn Park SeungEun Nam 《RSC advances》2018,8(37):20669
Ag-exchanged NaY zeolite (Ag-NaZ) particles were prepared by ion exchange and introduced to a polyvinyl alcohol (PVA) membrane cross-linked with polyacrylic acid (PAA) for the pervaporation dehydration of an isopropanol (IPA) aqueous mixture. The Ag-exchanged NaY zeolite particles were characterized by FE-SEM, EDS, BET, and XRD studies. The prepared Ag-NaZ-loaded PVA/PAA composite membrane was characterized by FE-SEM, XRD, a swelling study, and contact angle measurements. Pervaporation characteristics were investigated in terms of Ag-NaZ concentrations within PVA/PAA membranes using diverse feed solution conditions. The preferential sorption of IPA/water mixtures for Ag-NaZ-introduced membranes were also determined by calculating the apparent activation energies of IPA and water permeation, respectively. As a result, flux and selectivity increased with the Ag-NaZ concentration to 5 wt% in the membrane. Optimum pervaporation performance was observed in a 5 wt% Ag-NaZ-incorporated membrane with a flux equal to 0.084 kg m−2 h−1 and a separation factor of 2717.9 at 40 °C from an 80 wt% IPA aqueous feed solution.Ag-exchanged NaY zeolite (Ag-NaZ) particles were prepared by ion exchange and introduced to a polyvinyl alcohol (PVA) membrane cross-linked with polyacrylic acid (PAA) for the pervaporation dehydration of an isopropanol (IPA) aqueous mixture. 相似文献
9.
10.
Production of immuno and biologically active erythropoietin was documented to occur in the human hepatoblastoma cell line HepG-2. The expression of the erythropoietin gene was further verified by Northern blot analysis using a single stranded RNA probe. In vitro studies showed that erythropoietin production by these cells was not stimulated by hypoxia or cobalt chloride, but was related to the proliferative activity of the cells in culture. In addition it was found that the secretion of erythropoietin was almost completely abrogated by tunicamycin, an inhibitor of N-linked glycosylation. This effect of tunicamycin was also observed in a permanently transfected cell line that secretes erythropoietin in large quantities. 相似文献