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991.
Determination of the substrate-docking site of protein tyrosine kinase C-terminal Src kinase
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Lee S Lin X Nam NH Parang K Sun G 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(25):14707-14712
Protein tyrosine kinases (PTK) are key enzymes of mammalian signal transduction. For the fidelity of signal transduction, each PTK phosphorylates only one or a few proteins on specific Tyr residues. Substrate specificity is thought to be mediated by PTK-substrate docking interactions and recognition of the phosphorylation site sequence by the kinase active site. However, a substrate-docking site has not been determined on any PTK. C-terminal Src kinase (Csk) is a PTK that specifically phosphorylates Src family kinases on a C-terminal Tyr. In this study, by sequence alignment and site-specific mutagenesis, we located a substrate-docking site on Csk. Mutations in the docking site disabled Csk to phosphorylate, regulate, and complex with Src but only moderately affected its general kinase activity. A peptide mimicking the docking site potently inhibited (IC50 = 21 microM) Csk phosphorylation of Src but only moderately inhibited (IC50 = 422 microM) its general kinase activity. Determination of the substrate-docking site provides the structural basis of substrate specificity in Csk and a model for understanding substrate specificity in other PTKs. 相似文献
992.
Park JY Kim DY Suh DS Kim JH Kim YM Kim YT Nam JH 《Journal of cancer research and clinical oncology》2008,134(12):1277-1287
Purpose Uterine sarcoma is a rare malignancy with the worst prognosis of all uterine cancers. This study evaluated the prognostic
factors and treatment outcomes of patients with this disease.
Methods A retrospective analysis was performed on 127 patients with histologically verified uterine sarcoma who were treated and followed
at the Asan Medical Center (Seoul, Korea) from 1989 to 2007.
Results Histological analyses revealed that 37 patients had endometrial stromal sarcoma, 44 had malignant mixed mullerian tumors and
46 had leiomyosarcoma. Surgical stages, as defined by the International Federation of Gynecology and Obstetrics (FIGO) system,
were I in 82 patients, II in 6 patients, III in 18 patients and IV in 19 patients. All patients underwent surgical treatment
and 72 patients received adjuvant therapy. The 10-year disease-free survival (DFS) rate was 30% and the 10-year overall survival
(OS) rate was 48%, with a mean follow-up time of 38 months (ranging from 1 to 212 months). Adjuvant radiation and chemotherapy
had limited impact on the outcome of early-stage disease. However, patients with advanced-stage disease who received adjuvant
chemotherapy had significantly longer OS times. A multivariate analysis revealed that FIGO stage (P = 0.025), depth of myometrial invasion (P = 0.004), and complete cytoreduction (P = 0.030) were significantly associated with DFS, while menopausal status (P = 0.044), FIGO stage (P = 0.016), depth of myometrial invasion (P = 0.029), and lymph-vascular space invasion (LVSI) (P = 0.020) were significantly associated with OS.
Conclusions This study suggests that complete cytoreduction is important and adjuvant chemotherapy can help achieve favorable prognoses
in patients with advanced stage disease. However, postmenopausal status, advanced FIGO stage, deep myometrial invasion, and
positive LVSI were associated with poor prognosis. 相似文献
993.
Kyeong Ho Yun Myung Ho Jeong Seok Kyu Oh Jun-Ho Choi Sang Jae Rhee Eun Mi Park Nam Jin Yoo Nam-Ho Kim Young Keun Ahn Jin-Won Jeong 《Circulation journal》2008,72(2):195-199
BACKGROUND: The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery. METHODS AND RESULTS: The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index > or =2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications. CONCLUSIONS: Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations. 相似文献
994.
995.
Park YS Jun DW Kim SH Lee HH Jo YJ Song MH Kim NI Lee JS 《World journal of gastroenterology : WJG》2008,14(32):5051-5058
AIM: TO evaluate the efficacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS: We prospectively analyzed the colonoscopic findings before and after short term anti- tuberculosis treatment in 18 patients with nonspecific ulcers on the ileocecal area and compared them with 7 patients of confirmed tuberculous colitis by acid-fast bacilli or caseating granuloma on colonic biopsy. RESULTS: Mean duration for short-term follow- up was 107.3 d with combined chemotherapy containing isoniazid, rifampicin, ethambutol and pyrazinamide. Seven patients with tuberculous colitis showed complete healing of active ulcers after short-term medication. After short-term anti-tuberculosis treatment, follow-up colonoscopy findings devided 18 patients with nonspecific ulcers into two groups by ulcer state. One is the "suspicious tuberculous colitis group" showing healing of ulcers and erosions and another is the "suspicious inflammatory bowel disease group" showing active ulcers with or without aggravation of the lesion. Finally, all 9 of the "suspicious tuberculous colitis group" were diagnosed as tuberculous colitis showing no recurrence of ulcers after termination of 9 mo of anti-tuberculosis medication. Patients of the "suspicious inflammatory bowel disease group" were finally diagnosed as Crohn' s disease or nonspecific colonic ulcers during long-term follow up, CONCLUSION: Follow-up colonoscopy shows a healing stage ulcer or scarring change without an active ulcer with just 2 mo to 3 mo of medication in patients with tuberculous colitis. Colonoscopy follow-up after short term anti-tuberculosis trial in patients with nonspecific ulcers on the ileocecal area is valuable in making early differential diagnosis of tuberculous colitis. 相似文献
996.
Young Joon Hong Myung Ho Jeong Sun Ho Hwang Nam Sik Yun Sang Rok Lee Seo Na Hong Kye Hun Kim Hyung Wook Park Ju Han Kim Youngkeun Ahn Jeong Gwan Cho Jong Chun Park Jung Chaee Kang 《Circulation journal》2006,70(10):1269-1274
BACKGROUND: This study assessed the effects of combination therapy with simvastatin and carvedilol on clinical outcome in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). METHODS AND RESULTS: The study retrospectively analyzed the data from 672 patients with LV dysfunction [LV ejection fraction (LVEF) <40%] complicated with AMI who underwent percutaneous coronary intervention (PCI). The patients were divided into 4 treatment groups: combination group (n=160), simvastatin only group (n=216), carvedilol only group (n=242), neither treatment group (n=54). At 6 months after PCI, the LVEF had improved most significantly in the combination group. During 1-year follow-up, cardiac death occurred most frequently in the neither treatment group compared with the other 3 groups (combination: 4%, simvastatin alone: 7%, carvedilol alone: 8%, neither: 17%, p<0.001 between neither treatment and other 3 groups). The results on major adverse cardiovascular events (MACE) showed that the combination of simvastatin and carvedilol was associated with a relative risk reduction of 53% (p<0.001), treatment with simvastatin alone with a relative risk reduction of 44% (p=0.001), and carvedilol alone with a relative risk reduction of 40% (p=0.003) compared with neither treatment. The independent predictors of 1-year MACE were neither treatment, elevated high sensitivity C-reactive protein (> or =0.5 mg/dl), and old age (>70 years). CONCLUSION: Combination therapy with simvastatin and carvedilol had a positive impact on the endpoints of cardiovascular death and MACE and seems to have an additive beneficial effect on these endpoints in patients with LV dysfunction complicated with AMI who underwent PCI. 相似文献
997.
Overexpression of S100A4 is closely associated with progression of colorectal cancer 总被引:27,自引:0,他引:27
Cho YG Kim CJ Nam SW Yoon SH Lee SH Yoo NJ Lee JY Park WS 《World journal of gastroenterology : WJG》2005,11(31):4852-4856
AIM: To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS: A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS: Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 (55.6%) of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 (69.4%) of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes' stage and lymph node metastasis. Nuclear staining was also observed in 24 (19.4%) of 124 samples and dosely associated with Dukes' stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION: Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma. 相似文献
998.
Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation 总被引:3,自引:0,他引:3
CD26 is a T-cell activation antigen that contains dipeptidyl peptidase IV activity and binds adenosine deaminase. Recent work showed that specialized membrane microdomains, also known as lipid rafts, play a key role in T-cell signaling. In this study, we investigate the role of CD26 in cord blood T-cell activation and signal transduction. We demonstrated that different expression levels of CD26 were observed between cord blood T cells (CBTCs) and peripheral blood T cells (PBTCs) and that CD26(+)CD45RA(+) CBTCs were different compared with CD26(+)CD45RA(+) PBTCs. Moreover, the comitogenic effect of CD26 was not as pronounced in CBTCs as in PBTCs. We also showed that CD26 cross-linking induced less phosphorylation of T-cell receptor-signaling molecules, lymphoid T-cell protein tyrosine kinase (Lck), zeta-associated protein 70 (ZAP-70), T-cell receptor zeta (TCRzeta), and linker for activator of T cells (LAT) in CBTCs than in PBTCs. Furthermore, CD26 molecules associated with CD45RA molecules outside lipid rafts in CBTCs. Our results suggest that strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible for the attenuation of T-cell activation signaling through CD26, which may be responsible for immature immune response and the low incidence of severe graft-versus-host disease in cord blood transplantation. 相似文献
999.
Lee NK Kim S Kim GH Heo J Seo HI Kim TU Kang DH 《Journal of magnetic resonance imaging : JMRI》2012,35(3):678-685
Purpose:
To identify MRI biomarkers that could be used to follow disease progression and therapeutic efficacy in one individual muscle in patients with myotonic dystrophy type 1 (DM1).Materials and Methods:
Lower limb MRI and maximal ankle dorsiflexor strength assessment, using a hand‐held dynamometer, were performed in 19 DM1 patients and 6 control subjects. The volume of residual muscle tissue of Tibialis Anterior (TA) muscle was chosen as an index for muscle atrophy, and the T2‐relaxation‐time of the residual muscle tissue was measured to evaluate edema‐like lesions. The fat‐to‐water ratio was assessed using three‐point Dixon images to quantify fat infiltration in the entire muscle.Results:
The intra‐observer variability of MRI indices (~5.2% for the residual muscle tissue volume and 2.5% for the fat‐to‐water ratio) was lower than that of the dorsiflexor torque measurement (~11.5%). A high correlation (r = 0.91) was found between maximal ankle dorsiflexor strength and residual TA muscle tissue volume in DM1 patients. Increases in the fat‐to‐water ratio and T2‐relaxation‐time were associated with a decrease in maximal ankle dorsiflexor strength.Conclusion:
MRI appears as a noninvasive method which can be used to follow disease progression and therapeutic efficacy. J. Magn. Reson. Imaging 2012;35:678‐685. © 2011 Wiley Periodicals, Inc. 相似文献1000.
Kyung Hee Lee Jin Mo Goo Chang Min Park Hyun Ju Lee Kwang Nam Jin 《Korean journal of radiology》2012,13(5):564-571