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51.
Bakhanashvili M Gedelovich R Grinberg S Rahav G 《Journal of molecular medicine (Berlin, Germany)》2008,86(1):75-88
p53 in cytoplasm displays an intrinsic 3'-->5' exonuclease activity. To understand the significance of p53 exonuclease activity in cytoplasm, cytoplasmic extracts of various cell lines were examined for exonuclease activity with different single-stranded RNA (ssRNA) substrates. Using an in vitro RNA degradation assay, we observed in cytoplasmic extracts of LCC2 cells, expressing high levels of endogenous wtp53, an efficient 3'-->5' exonuclease activity with RNA substrates, removing the 3'-terminal nucleotides. Interestingly, RNA containing AU-rich sequences (ARE) is the permissive substrate for exonucleolytic degradation. Evidence that exonuclease function with RNA detected in cytoplasmic extracts is attributed to the p53 is supported by several facts: (1) this activity closely parallels with status and levels of endogenous cytoplasmic p53; (2) the endogenous exonuclease exerts identical RNA substrate specificity and excision profile characteristic for purified baculovirus-or bacterially-expressed wtp53s; (3) the exonuclease activity with ARE RNA is competed out by the presence of ss or double-stranded DNA substrate utilized by p53 protein in cytoplasm; (4) immunoprecipitation by specific anti-p53 antibodies markedly reduced the exonuclease activity with both RNA and DNA substrates; and (5) transfection of the wtp53, but not exonuclease-deficient mutant p53-R175H, into p53-null H1299 or HCT116 cells induced high levels of exonuclease activity with ARE RNA substrate in cytoplasm with characteristic excision profile. The efficient ARE RNA degradation correlates with the efficient binding of p53 to ARE RNA in cytoplasm. The possible role of p53 exonuclease activity in ARE-mRNA destabilization in cytoplasm, which may be important for expression of proteins that control cell growth and/or apoptosis is discussed. 相似文献
52.
Hindiyeh M Smollen G Grossman Z Ram D Davidson Y Mileguir F Vax M Ben David D Tal I Rahav G Shamiss A Mendelson E Keller N 《Journal of clinical microbiology》2008,46(9):2879-2883
Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (blaKPC) enzymes are among the most common β-lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of blaKPC genes using TaqMan chemistry. The q-PCR amplification of blaKPC DNA was linear over 7 log dilutions (r2 = 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n = 187) collected in duplicate from 128 patients admitted to Sheba Medical Center surgical intensive care units were evaluated for the presence of carbapenem-resistant bacteria by culturing on MacConkey agar-plus-carbapenem disks and for blaKPC genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were isolated from 47 (25.1%) of the 187 samples collected, while blaKPC genes were detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG system. Of these, seven samples were positive for blaKPC genes by q-PCR but negative for carbapenem resistance by culture, while all samples in which no carbapenem-resistant bacteria were detected by culture also tested negative by q-PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9% sensitivity and 96.4% specificity. Overall, the blaKPC q-PCR assay appears to be highly sensitive and specific. The utilization of q-PCR will shorten the time to blaKPC detection from 24 h to 4 h and will help in rapidly isolating colonized or infected patients and assigning them to cohorts. 相似文献
53.
Debby BD Ganor O Yasmin M David L Nathan K Ilana T Dalit S Smollan G Galia R 《European journal of clinical microbiology & infectious diseases》2012,31(8):1811-1817
Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged during recent years in several intensive care units. The objective of our study was to determine the incidence of CRKP and the risk factors associated with acquisition during intensive care unit (ICU) stay. This prospective cohort study was conducted between May 2007 and April 2008 in a medical-surgical ICU at a tertiary medical center. Rectal surveillance cultures were obtained from patients on admission and twice weekly. Of screened patients, 7.0% (21/299) were CRKP colonized on admission to the ICU. One hundred eighty (81%) patients were screened at least twice. Of these, 48 (27%) patients acquired CRKP during ICU stay. Of the 69 CRKP colonized patients (both imported and ICU acquired), 29% (20/69) were first identified by microbiologic cultures, while screening cultures identified 49 patients (71%). Of these, 23 (47%) subsequently developed clinical microbiological cultures. Independent risk factors for CRKP acquisition included recent surgery (OR 7.74; CI 3.42-17.45) and SOFA score on admission (OR 1.17; CI 1-1.22). In conclusion, active surveillance cultures detected a sizable proportion of CRKP colonized patients that were not identified by clinical cultures. Recent surgical procedures and patient severity were independently associated with CRKP acquisition. 相似文献
54.
Spectre G Zhu L Ersoy M Hjemdahl P Savion N Varon D Li N 《Thrombosis and haemostasis》2012,107(2):328-337
Developing novel anti-platelet therapies is an important clinical strategy for the prevention of arterial thromboses which cause heart attacks and most strokes. Thrombin activates platelets via protease-activated receptors (PARs), and PAR antagonists are currently under investigation as antithrombotics. Yet despite these clinical advances, the importance of PARs to platelet activation during thromboses formed under pathological conditions has not been investigated. To this end, we examined the role of PAR-dependent platelet activation in thrombus formation in the presence of elevated blood shear rates. We used two in vivo thrombosis models and an ex vivo whole blood flow approach in PAR4(-/-) mice, whose platelets are unresponsive to thrombin, to show that the contribution of PAR-mediated platelet activation to thrombosis is diminished at pathological blood shear rates as a direct result of decreased incorporation of thrombin-activated platelets into growing thrombi. Our ex vivo observations were replicated in human whole blood treated with a PAR1 antagonist. These results define a novel, shear-regulated role for thrombin/PAR-dependent platelet activation during thrombosis and provide important insights into the conditions under which PAR antagonists may best be used for the prevention of acute coronary syndromes. 相似文献
55.
La Grutta L Runza G Galia M Maffei E Lo Re G Grassedonio E Tedeschi C Cademartiri F Midiri M 《The international journal of cardiovascular imaging》2012,28(2):405-414
The aim of our study was to evaluate the atherosclerotic pattern of patients with coronary myocardial bridging (MB) by means
of CT Coronary Angiography (CT-CA). 254 consecutive patients (166 male, mean age 58.6 ± 10.3) who underwent 64-slice CT-CA
according to current clinical indications were reviewed for the presence of MB and concomitant segmental atherosclerotic pattern.
Coronary plaques were assessed in all patients enrolled. 73 patients (29%) presented single (90%) or multiple (10%) MB, frequently
(93%) localized in the mid-distal left anterior descending artery. The MB segment was always free of atherosclerosis. Segments
proximal to the MB presented: no atherosclerotic disease (n = 37), positive remodeling (n = 23), <50% (n = 14), or >50% stenoses (n = 7). Distal segments presented a different atherosclerosis pattern (P < 0.0001): absence of disease (n = 73), no significant lesions (n = 8). No significant differences were found between segments proximal to MB and proximal coronary segments apart from left
main trunk. Pattern of atherosclerotic lesions located in segments 6 and 7 significantly differs between patients with MB
and patients without MB (P < 0.05). CT-CA is a reliable method to non-invasively demonstrate MB and related atherosclerotic pattern. CT-CA provides
new insight regarding atherosclerosis distribution in segments close to MB. 相似文献
56.
Andrea González Carolina Valck Gittith Sánchez Steffen H?rtel Jorge Mansilla Galia Ramírez María Soledad Fernández José Luis Arias Norbel Galanti Arturo Ferreira 《The American journal of tropical medicine and hygiene》2015,92(5):887-897
Trypanosoma cruzi calreticulin (TcCRT), a 47-kDa chaperone, translocates from the endoplasmic reticulum to the area of flagellum emergence. There, it binds to complement components C1 and mannan-binding lectin (MBL), thus acting as a main virulence factor, and inhibits the classical and lectin pathways. The localization and functions of TcCRT, once the parasite is inside the host cell, are unknown. In parasites infecting murine macrophages, polyclonal anti-TcCRT antibodies detected TcCRT mainly in the parasite nucleus and kinetoplast. However, with a monoclonal antibody (E2G7), the resolution and specificity of the label markedly improved, and TcCRT was detected mainly in the parasite kinetoplast. Gold particles, bound to the respective antibodies, were used as probes in electron microscopy. This organelle may represent a stopover and accumulation site for TcCRT, previous its translocation to the area of flagellum emergence. Finally, early during T. cruzi infection and by unknown mechanisms, an important decrease in the number of MHC-I positive host cells was observed. 相似文献
57.
58.
Cancer Control in Central and Eastern Europe: Current Situation and Recommendations for Improvement
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59.
Cammà C Di Marco V Cabibbo G Latteri F Sandonato L Parisi P Enea M Attanasio M Galia M Alessi N Licata A Latteri MA Craxì A 《Alimentary pharmacology & therapeutics》2008,28(1):62-75
Background A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately.
Aim To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC.
Methods We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model.
Results One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha-fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients.
Conclusions Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients. 相似文献
Aim To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC.
Methods We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model.
Results One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha-fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients.
Conclusions Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients. 相似文献