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61.
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
62.
Hy De Lee Euy Young Soh Hoon Sang Chi Byong Ro Kim Kyong Sik Lee Kyung Soon Song Hyun Joo Jung 《Surgery today》1990,20(2):180-185
The relationship between primary tumor proliferative activity and clinical and pathologic characteristics was analyzed in
relation to menopausal status in 32 patients with malignant or benign breast disease. The thymidine labeling index (TLI) showed
significantly higher median values in the cancer patients (3.48 per cent) than in the patients with benign diseases (1.02
per cent). TLI was not significantly affected by delayed incubation at room temperature for about 1 hour. In the breast cancer
patients, TLI did not significantly correlate to tumor size, the presence of axillary lymph node metastasis or pathologic
nuclear grading. The only significant difference was limited to the breast cancer patients without axillary lymph node metastasis
in relation to menopausal status; the TLI in the premenopausal patients (5.10 per cent) was significantly higher (p<0.05)
than that in the postmenopausal patients (2.28 per cent). These data thus suggest that among premenopausal patients without
axillary lymph node metastasis, those with a high TLI could be potential candidates for adjuvant chemotherapy. 相似文献
63.
Kyung Cheon Kim Kwang Jin Rhee Hyun Dae Shin Young Mo Kim 《Knee surgery, sports traumatology, arthroscopy》2007,15(12):1478-1481
Calcific tendinitis is a common condition with characteristic clinical and radiological findings. Although we do not know
which condition initiated the pathologic cascade, we present a rare case of calcific tendinitis of the long head of the biceps
brachii at its origin, associated with a SLAP lesion. The calcium deposit was removed and the SLAP lesion was repaired with
a suture anchor arthroscopically. 相似文献
64.
Mark A. Beilke Debra Riding In Rebecca Hamilton Gary A. Stone Elaine K. Jordan Gene Brashears Wayne Nusbaum David Huddleston Clarence J. Gibbs Jr. Maneth Gravell 《Journal of neuroimmunology》1991,33(2):129-143
HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system. 相似文献
65.
Simple measurement of spinal cord evoked potential: a valuable data source in the rat spinal cord injury model. 总被引:1,自引:0,他引:1
Jong-Pil Park Ki-Jeong Kim Ji Hoon Phi Chul-Kee Park Jong-Hoon Kim Hyo Jin Kang Dohun Lee Kyu Hyun Han Kyu-Chang Wang Sun Ha Paek 《Journal of clinical neuroscience》2007,14(11):1099-1105
Measurement of spinal cord evoked potentials (SCEPs) is proposed as a means of predicting locomotion outcome in the rat spinal cord injury (SCI) model. Using 55 rats, three reproducible peak waves (waves I, II and III) were observed during stimulation at the C7 level with recording at the L1 epidural space. Hemisection at the T13 level showed three wave loss patterns: wave III loss only, loss of both wave II and III, and loss of all three waves. Defining an ideal SCI model as establishment of stable monoparesis or paraparesis, all animals in the wave II-III loss group showed favorable results. Histological data and electrophysiological properties allowed reasonable assumptions of wave origin: wave I from extrapyramidal tracts, wave II from the ventral corticospinal tract, and wave III from the dorsal corticospinal tract. Complete destruction of pyramidal tracts in both dorsal and ventral fibers was essential for long-term impairment of locomotion. 相似文献
66.
Seok Hyun Cho Hyun Jung Min Hong Xiu Han Seung Sam Paik Kyung Rae Kim 《Otolaryngology--head and neck surgery》2006,135(3):404-408
OBJECTIVE: To evaluate the findings of computed tomography (CT) and histopathology of the bulla ethmoidalis as objective markers of bone remodeling in chronic rhinosinusitis (CRS). METHODS: Preoperative ostiomeatal unit (OMU) scans and histopathologic findings of the bulla ethmoidalis were performed on 23 patients (39 sides) undergoing endoscopic sinus surgery for CRS. Lund-Mackay scores and Hounsfield units (HU) of the bulla were checked in coronal CT scans. The pathologist graded the severities of the mucosal and bony changes in histopathology. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient (r). RESULTS: The HU values of the bulla were significantly increased with higher Lund-Mackay scores in OMU CT (r = 0.405, P = 0.01). The bony grades in histopathology were significantly increased with higher mucosal grades (r = 0.821, P = 0.0001). These findings in CT scans and histopathology were well correlated with each other (r > 0.3, P < 0.05). CONCLUSION: HU may be a useful objective marker of bone remodeling in chronic rhinosinusitis. 相似文献
67.
The hexane extract from Nutmeg, the seed ofMyristica fragrans significantly inhibited hepatic drug-metabolizing enzyme activity. Through systematic fractionation by SiO2 column and vacuum liquid chromatography monitoring by bioassay, three components, myristicin, (I), licarin-B(II) and dehydrodiisoeugenol(III) were isolated as active principles. Compounds II and III, with a single treatment (200 mg/kg, i.p.) showed not only a significant prolongation of hexobarbital-induced sleeping time but also a significant inhibition of aminopyrine N-demethylase and hexobarbital hydroxylase activities in mice. Compounds I and II provoked a sleep episode at a subhypnotic dose of HB, suggesting that they posses CNS-depressant properties. 相似文献
68.
Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer 总被引:25,自引:0,他引:25
Cho YG Nam SW Kim TY Kim YS Kim CJ Park JY Lee JH Kim HS Lee JW Park CH Song YH Lee SH Yoo NJ Lee JY Park WS 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(5):539-545
Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea. 相似文献
69.
Dina Ruano António Macedo Ana Dourado Maria Jo?o Soares José Valente Isabel Coelho Vítor Santos Maria Helena Azevedo Ann Goodman Mara Helena Hutz Clarissa Gama Maria Inês Lobato Paulo Belmonte-de-Abreu Joana Almeida Palha 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2004,(1):41-45
70.
Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis 总被引:3,自引:0,他引:3
Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated
with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells
stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580)
on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated
phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and
MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion
and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated
cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer
and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献