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['The inflammatory milieu decreases in the placenta and amniotic fluid (AF) with gestational age (GA). However, there is no information about whether the inflammatory milieu of AF in the setting of the same placental inflammatory condition decreases with GA. We hypothesized that the inflammatory milieu of AF in acute chorioamnionitis would decrease with increasing GA.', 'The inflammatory milieu of AF was examined in 617 singleton preterm pregnancies (<36 weeks) delivered within 5 days of amniocentesis. Study population was divided into GA at delivery ≤30 weeks (n = 148), 30-34 weeks (n = 226), and 34-36 weeks (n = 226). Acute-chorioamnionitis was classified according to the severity (i.e., mild, total grade 1; moderate, total grade 2; and severe, total grade 3-6) or involved compartment (i.e., chorionic plate, amnion and chorio-decidua). The inflammatory milieu of AF was determined by matrix metalloproteinase-8 (MMP-8) concentration.', '1) AF MMP-8 concentrations decreased in patients with acute-chorioamnionitis (P < 0.001), but not inflammation-free placenta, with increasing GA; 2) AF MMP-8 concentrations were less intense at higher GA in patients with moderate and severe (each-for P < 0.005), but not mild, acute-chorioamnionitis; 3) AF MMP-8 concentrations decreased in the context of the same involved compartment (i.e., chorionic plate inflammation, amnionitis, or chorio-deciduitis) of acute-chorioamnionitis (each-for P < 0.001) with increasing GA; 4) Moreover, there was a significant inverse relationship between GA and AF MMP-8 concentrations in patients with acute-chorioamnionitis (r = -0.453, P < 0.0000001), but not inflammation-free placenta (r = -0.071, P = 0.170).'] |
['Our aim was to examine whether serial blood lactate levels could be used as predictors of outcome.', 'We prospectively studied 44 high-risk, hemodynamically stable, surgical patients. Blood lactate values, mean arterial pressure, heart rate and urine output were obtained at patient admission to the study, at 12, 24 and 48 hours.', 'The nonsurvivors (n = 7) had similar blood lactate levels initially (3.1 +/- 2.3 mmol/l versus 2.2 +/- 1.0 mmol/l, P = not significant [NS]), but had higher levels after 12 hours (2.9 +/- 1.7 mmol/l versus 1.6 +/- 0.9 mmol/l, P = 0.012), after 24 hours (2.1 +/- 0.6 mmol/l versus 1.5 +/- 0.7 mmol/l, P = NS) and after 48 hours (2.7 +/- 1.8 mmol/l versus 1.9 +/- 1.4 mmol/l, P = NS) as compared with the survivors (n = 37). Arterial bicarbonate concentrations increased significantly in survivors and were higher than in nonsurvivors after 24 hours (22.9 +/- 5.2 mEq/l versus 16.7 +/- 3.9 mEq/l, P = 0.01) and after 48 hours (23.1 +/- 4.1 mEq/l versus 17.6 +/- 7.1 mEq/l, P = NS). The PaO2/FiO2 ratio was higher in survivors initially (334 +/- 121 mmHg versus 241 +/- 133 mmHg, P = 0.03) and remained elevated for 48 hours. There were no significant differences in mean arterial pressure, heart rate, and arterial blood oxygenation at any time between survivors and nonsurvivors. The intensive care unit stay (40 +/- 42 hours versus 142 +/- 143 hours, P < 0.001) and the hospital stay (12 +/- 11 days versus 24 +/- 17 days, P = 0.022) were longer for nonsurvivors than for survivors. The Simplified Acute Physiology Score II score was higher for nonsurvivors than for survivors (34 +/- 9 versus 25 +/- 14, P = NS). The urine output was slightly lower in the nonsurvivor group (P = NS). The areas under the receiving operating characteristic curves were larger for initial values of Simplified Acute Physiology Score II and blood lactate for predicting death.'] |
['Baseline carbohydrate antigen 19-9 (CA 19-9) is a useful prognostic marker in pancreatic ductal adenocarcinoma (PDA); however, data on the significance of a change in CA 19-9 following neoadjuvant therapy are lacking.', "All patients receiving neoadjuvant therapy for PDA from July 2010 to February 2013 were retrospectively reviewed. Resection rate, R0 resection rate, need for venous resection, and overall survival were correlated to CA 19-9 response. Fisher's exact test, Kaplan-Meier survival analysis, and multivariate analysis using Cox regression were used.", 'A total of 78 patients were studied (21 patients with resectable disease, 40 borderline resectable, and 17 with locally advanced disease). A variety of chemotherapies ± radiation were utilized during the study period. Overall, 56 patients (72 %) had a decrease in CA 19-9 of >50 % with neoadjuvant treatment. In borderline resectable patients, CA 19-9 response of >50 % predicted R0 resection (odds ratio 4.2; p = 0.05). In borderline resectable patients who had an increase in CA 19-9, none of five (0 %) underwent R0 resection compared with 80 % of the remaining cohort (p = 0.001). The complete pathologic response rate was 29 % in patients who had a CA 19-9 response of >90 % versus 0 % in the remaining patients (p < 0.001). A CA 19-9 response of >50 % resulted in improved overall survival (28.0 vs. 11.1 months; p < 0.0001) and was an independent predictor of survival (hazard ratio 0.26; 95 % CI 0.13-0.55; p < 0.0001).'] |
['Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers.', 'Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with "acceptable" pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of > or =90% of baseline) was calculated using a linear regression model.', 'At peak blockade (TOF ratio 0.5 +/- 0.16), forced inspiratory flow was impaired (53 +/- 19%) to a greater degree than forced expiratory flow (75 +/- 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 +/- 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22-0.71) predicts "acceptable" recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82-1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively.'] |
['To compare plasma and milk lycopene concentrations and the changes in lycopene isomer patterns in lactating women before and after a 3-day dietary intervention with fresh or processed tomato products.', 'Randomized prospective trial.', '24 lactating women, 4 to 12 weeks postpartum, aged 22 to 39 years.', 'Subjects initially consumed a low-lycopene diet for 7 days (washout period) and then were randomly assigned to one of 3 dietary groups (n=8 per group) without any other sources of lycopene: control (low-lycopene), fresh tomatoes, or processed tomato sauce. Subjects in each of the tomato groups consumed approximately 50 mg total lycopene over 3 days.', 'Before and after dietary intervention, plasma and breast milk samples were obtained for high-performance liquid chromotography analysis of lycopene and its geometric isomers (all-trans, 5-cis, all other cis, and total lycopene).', "Descriptive statistics, analysis of variance to test for differences among intervention groups, and Spearman's correlation coefficients to test for blood-milk relationships.", 'Plasma total lycopene and lycopene isomer concentrations increased in the fresh and processed tomato group but not in the low-lycopene control group during the study. Milk total and cis- and trans-lycopene concentrations (unadjusted for fat) increased in the processed tomato group but did not change in the fresh tomato group. In the control group, milk total and trans-lycopene decreased. Milk total lycopene concentrations were not significantly different from baseline in any group when adjusted for fat content of milk.'] |
["The pathological hallmarks of Parkinson's disease are intracellular inclusions composed mainly of misfolded α-synuclein (αSYN). Under physiological conditions αSYN is mostly localized in synapses. In addition, a portion of αSYN is secreted to the extracellular space, where it may be sequestered by neighboring cells and could induce inflammatory responses. The mechanisms of αSYN internalization and signal transduction are not unequivocally clarified. In this work we investigated in primary mouse astrocytes the involvement of toll-like receptor 4 (TLR4) in the induction of inflammatory responses upon exposure to purified human αSYN produced in bacteria.", 'The mRNA induction of pro-inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase-2 was significantly reduced in TLR4 knockout astrocytes. The αSYN-mediated activation of c-Jun N-terminal kinases and p38 mitogen-activated protein kinase tended to be diminished, and nuclear translocation of the p65 subunit of nuclear factor κB was abolished in TLR4 knockout astrocytes. In contrast, the uptake of exogenous αSYN was unaffected by TLR4 knockout.'] |
['To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells.', 'To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step "pop-in/pop-out" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation.'] |
['Emergency department (ED) crowding increases ambulance diversion. Ambulance diversion disproportionately affects individuals who rely on ambulance transport. The purpose of this study is to determine which populations rely most on ambulance transport.', 'We queried the National Hospital Ambulatory Medical Care Survey database for 1997 to 2000 and 2003 to 2005 for patients who arrived by ambulance or personal transport. We performed bivariate analysis to assess the extent to which all patients and a subset of critically ill patients use ambulance transport relative to self-transport.', 'In our sample, 30,455 (15%; 95% confidence interval [CI] 15% to 16%) patients arrived by ambulance and 162,091 (85%; 95% CI 84% to 85%) arrived by walk-in/self-transport. Overall, patients with Medicare insurance were more likely to rely on ambulance transport, at 34% (95% CI 33% to 35%), than the privately insured, at 11% (95% CI 10% to 11%). Among the critically ill, privately insured patients were less likely to rely on ambulance transport, at 47% (95% CI 42% to 52%), than those with Medicare insurance (61%; 95% CI 58% to 65%), the publicly insured (60%; 95% CI 52% to 67%), or the uninsured (57%; 95% CI 49% to 64%). Among the critically ill, patients aged 15 to 24 years and those older than 74 years were most likely to rely on ambulance transport, at 63% (95% CI 53% to 72%) and 67% (95% CI 62% to 71%), respectively. Fifty-seven percent (95% CI 54% to 59%) of the critically ill used ambulance versus 15% (95% CI 14% to 15%) of noncritical patients.'] |
['We have successfully generated an IgE-associated (extrinsic/allergic) mouse model of atopic dermatitis in K14-IL-4-Tg/CByB6 mice. The newly described subset of non-IgE-associated (intrinsic/non-allergic) atopic dermatitis in human patients raises the question on the role of IgE in the pathogenesis.', 'The aim of this study was to develop a non-IgE-associated atopic dermatitis model in K14-IL-4-Tg/SKH1 mice.', 'K14-IL-4-Tg/CByB6 mice were crossed with SKH1 mice to produce K14-IL-4-Tg/SKH1 mice. Phenotypes of clinical and histological, cytokine expression in the skin lesions, and total serum IgE in K14-IL-4-Tg/CByB6 and K14-IL-4-Tg/SKH1 mice were compared. The CD40 and CD40L on T and B cells were also studied to differentiate their roles in IgE production.', 'K14-IL-4-Tg/SKH1mice had a normal total serum IgE level and manifested a chronic inflammatory skin phenotype identical to that of K14-IL-4-Tg/CByB6 IgE-mediated mice in clinical morphology, histology, infiltration of mononuclear cells/eosinophils/mast cells, mast cell degranulation, and up-regulation of chronic lesional cytokine mRNA expression of IL-1 beta, IL-3, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-gamma, TNF-alpha, and TNF-beta. We also found that the inability of CD4(+) T cells of the K14-IL-4-Tg/SKH1mice to up-regulate CD40L expression upon stimulation might account for their inability to up-regulate the IgE level. B cell abnormality was ruled out as CD19(+) B cells of K14-IL-4-Tg/SKH1 mice synthesized the same amount of IgE in vitro compared with K14-IL-4-Tg/CByB6 mice in the presence of IL-4 and soluble CD40L. Our studies further suggested that the defect of early growth response-1 in T cells might be responsible for the impaired CD40L up-regulation in K14-IL-4-Tg/SKH1 mice.'] |
['Autopsy studies have shown that hypertrophic hearts of uremic patients have peculiar characteristics. Changes in tissue structure are detectable by ultrasound as changes in echo reflectivity.', 'We studied 96 dialysis patients, 18 hypertensive subjects with normal renal function and 52 healthy subjects. The echo pattern of interventricular septum was assessed by videodensitometry (VDT) (i.e., a computer-assisted quantitative analysis of gray levels). For each pixel a numerical value from 0 (black) to 255 (white) was assigned. From the resulting histogram of gray level frequency distribution, we obtained indexes of central tendency (reflectivity) and of homogeneity of distribution (uniformity).', 'For the same septum thickness, dialysis patients showed a significantly greater reflectivity (87 +/- 19 and 70 +/- 17) (P < 0.001) and lower uniformity (137 +/- 32 and 184 +/- 71) (P < 0.007) compared with hypertensives. Hypertensive patients showed VDT parameters similar to control subjects in spite of significantly higher septum thickness (P < 0.003). Followed up after 5 years, dialysis patients with a reduced homogeneity of distribution of gray levels (lower uniformity) showed a significantly shorter survival (HR by Cox 2.5, 95% CI 1.21-5.27).'] |
['Although the fundamental role of the E2F transcription factor family in cell proliferation is well established, the specific function of E2F4 is unclear. On the basis of findings from cell culture experiments, E2F4 is generally considered as an inhibitor of cell proliferation. Accumulating evidence suggests, however, that E2F4 acts as an activator of cell proliferation in certain contexts. Here, we have investigated the role of E2F4 during heart development and in proliferating cardiomyocytes.', 'Nuclear E2F4 expression in cardiomyocytes declined during mouse heart development, which correlates with the loss of proliferative capacity of cardiomyocytes. Re-induction of proliferation in postnatal cardiomyocytes increased nuclear E2F4 expression. E2F4 accumulated in the nucleus at the end of the S phase, remained nuclear during mitosis, and disappeared at the end of cytokinesis. siRNA-mediated inhibition of E2F4 in proliferating postnatal cardiomyocytes resulted in a significant reduction in mitosis, but not in DNA synthesis. Co-staining of E2F4 and Crest revealed that E2F4 co-localizes with kinetochores. Moreover, chromatin immunoprecipitation showed that E2F4 binds to centromeric alpha-satellite DNA during mitosis.'] |
['Human obesity is associated with elevated leptin levels and a high risk of death from cardiovascular disease. In the present study, we investigated the effects of leptin on vascular wound healing and arterial lesion growth in mice.', 'Wild-type mice placed on an atherogenic, high-fat diet had elevated (9-fold) leptin levels compared with their counterparts maintained on normal chow, and the former demonstrated significantly enhanced neointimal thickening after carotid artery injury with ferric chloride. The lesions forming in response to injury strongly expressed leptin receptor mRNA and protein. Unexpectedly, the atherogenic diet had no effect on injured vessels from leptin-deficient ob/ob mice despite aggravating obesity, diabetes, and hyperlipidemia in these animals. Daily administration of leptin to ob/ob mice during the 3-week period after injury reversed this phenotype, dramatically increasing neointimal thickness and the severity of luminal stenosis. Exogenous leptin also enhanced lesion growth and increased cellular proliferation in injured arteries from wild-type mice but had no effect on vessels from leptin receptor-deficient db/db mice.'] |
['Pregnancy-associated malaria (PAM) constitutes one of the most severe forms of malaria infection leading to fetal growth restriction and high risk of infant death. The severity of the pathology is largely attributed to the recruitment of monocytes and macrophages in the placenta which is evidenced by dysregulated inflammation found in placental blood. Importantly, CD36(+) monocytes/macrophages are also thought to participate in the tight control of the pro- and anti-inflammatory responses following Plasmodium detection through elimination of apoptotic cells and malaria-infected erythrocytes, internalization and recycling of oxidized forms of low-density lipoprotein and collaboration with TLR2 in pro-inflammatory response. Interestingly, previous work demonstrated that CD36 expression was upregulated on inflammatory macrophages following stimulation of the Nrf2 transcription factor, whilst the PPARγ pathway was inhibited and non-functional in the same inflammatory conditions. This current study examined the possible role of Nrf2-driven gene expression, CD36 and Haem-Oxygenase-1 (HO-1), in PAM clinical outcomes.', 'Clinical data and biological samples including peripheral blood mononuclear cells were collected from 27 women presenting PAM. Polychromatic flow cytometry was used to characterize innate immune cell subpopulations and quantify CD36 protein expression level on monocytes. mRNA levels of CD36, PPARγ, Nrf2 and HO-1 were determined by qPCR and related to clinical outcomes. Finally, the capacity of monocytes to modulate CD36 expression upon rosiglitazone or sulforaphane treatment, two respective PPARγ or Nrf2 activators, was also investigated.', 'The CD36 receptor, mostly expressed by CD14(+) circulating monocytes, statistically correlated with increased infant birth weights. Interestingly, mRNA levels of the transcription factor Nrf2 and the enzyme HO-1 also correlated with lower parasitaemia and increased infant birth weight, while PPARγ mRNA levels did not. Finally, monocytes isolated from low infant birth weight pregnant women were capable of up-regulating CD36 via the Nrf2 pathway ex vivo.'] |
['Unlike Resuscitation Guidelines (GL) 2000, GL2005 advise resuming cardiopulmonary resuscitation (CPR) immediately after defibrillation. We hypothesized that immediate CPR resumption promotes earlier recurrence of ventricular fibrillation (VF).', 'This study used data of a prospective per-patient randomized controlled trial. Automated external defibrillators used by first responders were randomized to either (1) perform postshock analysis and prompt rescuers to a pulse check (GL2000), or (2) resume CPR immediately after defibrillation (GL2005). Continuous recordings of ECG and impedance signals were collected from all patients with an out-of-hospital cardiac arrest to whom a randomized automated external defibrillator was applied. We included patients with VF as their initial rhythm in whom CPR onset could be determined from the ECG and impedance signals. Time intervals are presented as median (Q1-to-Q3). Of 361 patients, 136 met the inclusion criteria: 68 were randomly assigned to GL2000 and 68 to GL2005. Rescuers resumed CPR 30 (21-to-39) and 8 (7-to-9) seconds, respectively, after the first shock that successfully terminated VF (P<0.001); VF recurred after 40 (21-to-76) and 21 (10-to-80) seconds, respectively (P=0.001). The time interval between start of CPR and VF recurrence was 6 (0-to-67) and 8 (3-to-61) seconds, respectively (P=0.88). The hazard ratio for VF recurrence in the first 2 seconds of CPR was 15.5 (95% confidence interval, 5.63 to 57.7) compared with before CPR resumption. After more than 8 seconds of CPR, the hazard of VF recurrence was similar to before CPR resumption.'] |
['Cardiocirculatory arrest (CCA) activates procoagulant pathways. It has also been reported to inhibit fibrinolysis, resulting in fibrin deposition and further impairment of blood flow. Until now, no studies have used whole-blood viscoelastic tests to characterize coagulation and the impact of fibrinolysis in out-of-hospital cardiac arrest (OHCA).', 'Patient with established OHCA who underwent cardiopulmonary resuscitation (CPR) were enrolled. Blood samples were obtained immediately after placement of an intravenous line at the scene, for full blood cell count, standard coagulation tests and rotational thromboelastometric (ROTEM(®)) analyses. Patients with return of spontaneous circulation (ROSC) were compared to non-ROSC patients.', 'Fifty-three patients (median age 67 years, interquartile range: 56-73 years) were included in the study. ROSC was established in 25 patients. Prothrombin time index (PTI) was significantly lower and activated partial thromboplastin time (aPTT) was significantly prolonged in non-ROSC patients compared to ROSC patients. Clotting time (CT) in the extrinsically activated ROTEM test (EXTEM) was significantly longer in non-ROSC versus ROSC patients. For the remaining EXTEM parameters, there were no significant differences between ROSC and non-ROSC patients. Hyperfibrinolysis (maximum lysis>15% according to ROTEM test results) was observed in 19 patients (35.8%). There was no difference between ROSC and non-ROSC patients in the incidence of hyperfibrinolysis.'] |
['Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CR-Kp)-mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains.', 'Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage-mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by co-immunization with 2 CPSs, and cross-reactivity was investigated.', 'MLST assigned 80% of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying blaKPC-3 were less virulent than those with blaKPC-2. MAb 1C9 cross-reacted with 58% of CR-Kp CPSs.'] |
['The role of atherosclerosis-related processes in aortic root dilatation (ARD) has not been fully determined. The present study was to assess the relationship between carotid IMT, carotid plaque, and ARD.', 'Hypertensive men with ARD (n = 30) were compared with hypertensive men without ARD (n = 52) and normal control subjects (n = 29). Two-dimensional echocardiography was used to measure the aortic root at the aortic annulus, the sinus of Valsalva, the sinotubular junction and the proximal part of the ascending aorta. Carotid IMT and carotid plaque were also assessed by ultrasound.', 'The measured mean carotid IMT was significantly increased in patients with ARD (1.37 +/- 0.80 mm) compared to the subjects without ARD (1.06 +/- 0.54 mm) and healthy control subjects (0.84 +/- 0.44 mm) (P < 0.05). However, no significant differences of the prevalence of carotid plaque were found in the three groups (P > 0.05). Aortic diameters at all levels except for the diameter of the supra-aortic ridge were significantly related to carotid IMT when the hypertensive population was considered (P < 0.05). No significant correlation was found between carotid plaque and aortic root dimension (P > 0.05).'] |
['An induction of gastro-oesophageal reflux has been reported after ingestion of alcoholic beverages in healthy volunteers. However, it is unknown whether reflux in gastro-oesophageal reflux disease patients will be enhanced by the ingestion of alcoholic beverages.', 'To investigate the effects of wine and beer on postprandial reflux in reflux patients.', 'Twenty-five patients (reflux oesophagitis 15, non-erosive reflux disease 10; 18 men and seven women) drank 300-mL white wine (n = 17), 500-mL beer (n = 8), or identical amounts of tap water (controls) together with a standardized meal in a randomized order. pH-measurement was carried out during three postprandial hours by pH-metry and the percentage of time pH < 4 was calculated.', 'Both alcoholic beverages increased reflux compared with water [wine 23% (median), water 12%, P < 0.01; beer 25%, water 11%, P < 0.05]. Between wine and beer, no difference in reflux induction was obtained. The reflux induction was seen in patients with (23%, P < 0.01) and without reflux oesophagitis (22%, P < 0.05) and in both sexes (women 23%, men 25%, P < 0.05 each).'] |
["Patients with Parkinson's disease (PD) are more likely to suffer from cognitive impairment and dementia than healthy older adults. The aim of this study was to investigate smoking history as a risk factor for cognitive decline in PD.", "One hundred thirty-nine PD patients aged 50\xa0years and older (Hoehn and Yahr = 1-3) were recruited from a clinical database. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE) and smoking history was investigated as part of a standard clinical interview. A multiple linear regression analysis was used to develop a model for predicting participants' MMSE scores from age, education, Hoehn and Yahr stage, disease duration, the number of vascular risk factors and the number of smoking pack-years.", 'The regression model significantly accounted for 22.9% of the variance in MMSE scores. Significant predictors were education (β = .312, p < .001), age (β = -.215, p = .013) and total smoking pack-years (β = -.180, p = .029). In former smokers, the number of years since quitting had no effect on global cognition and there were no significant difference between patients who had quit smoking more than 10\xa0years ago and those who had quit less than 10\xa0years ago, F(1, 63) = 1.72, p = .195.'] |
["Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities.", 'We analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score.', 'Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development.'] |
['To analyze predictive factors of cochlear implant outcomes and postoperative complications in the elderly.', 'Prospective, longitudinal study performed in 10 tertiary referral centers.', 'Ninety-four patients aged 65-85 years with a profound, postlingual hearing loss were evaluated before implantation, at time of activation, and 6 and 12 months after cochlear implantation. Speech perception and lipreading were measured using disyllabic word recognition in quiet and noise, and lipreading using disyllabic words and sentences. The influence of preoperative factors on speech perception in quiet and noise at 12 months was tested in a multivariate analysis. Complications, presence of tinnitus and of vestibular symptoms were collected at each evaluation.', 'The effect of age was observed only in difficult noisy conditions at SNR 0 dB. Lipreading ability for words and sentences was negatively correlated with speech perception in quiet and noise. Better speech perception scores were observed in patients with shorter duration of hearing deprivation, persistence of residual hearing for the low frequencies, the use of a hearing aid before implantation, the absence of cardiovascular risk factors, and in those with implantation in the right ear. General and surgical complications were very rare, and the percentage of vestibular symptoms remained stable over time.'] |
['The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses.', 'The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus.'] |
['Besides excessive daytime sleepiness, disturbed nocturnal sleep is a major complaint of patients with narcolepsy. Previously, alterations in skin temperature regulation in narcoleptic patients have been shown to be related to increased sleepiness. This study tests the hypothesis that direct control of nocturnal skin temperature might be applied to improve the disturbed sleep of narcoleptic patients.', 'Participants were eight patients (five males) diagnosed as having narcolepsy with cataplexy according to the ICSD-2 criteria, mean (SD) age 28.6 (6.4) years, range 18-35 years. During two nights, sleep was recorded polysomnographically while proximal and distal skin temperature were manipulated using a comfortable thermosuit that induced skin temperature to cycle slowly with an amplitude of only 0.4 degrees C within the comfortable range normally observed during sleep. Logistic regression was used to evaluate the effect of skin temperature manipulation on the probability of occurrence of different sleep stages and nocturnal wakefulness.', 'Proximal skin warming significantly suppressed wakefulness and enhanced slow wave sleep (SWS). In contrast, distal skin warming enhanced wakefulness and stage 1 sleep at the cost of SWS and REM sleep. The optimal combination of proximal skin warming and distal skin cooling led to a 160% increase in SWS, a 50% increase in REM sleep and a 68% decrease in wakefulness, compared with the least beneficial combination of proximal skin cooling and distal skin warming.'] |
['To understand the relationship between lower urinary tract symptoms (LUTS) and renal function by prostate volume (PV) in Korean men. LUTS can be related to early renal dysfunction, irrespective of bladder outlet obstructive lesions, few studies have been conducted.', 'We conducted a cross-sectional survey of 3713 men, aged≥40 years, who received routine comprehensive health evaluations, including transrectal ultrasonography and the International Prostate Symptom Score questionnaire. We used the estimated glomerular filtration rate (GFR) for the assessment of renal function and the IPSS for LUTS severity. We compared LUTS and GFR using multivariate regression analysis after adjusting for age and/or PV.', 'An increasing severity of LUTS, especially voiding LUTS, was associated with a decreasing GFR in the older age group (≥55 years). In a stratified analysis by PV of 30 cm3, voiding LUTS showed a negative association with GFR, irrespective of the PV (P for trend<.01 and P for trend<.02), but total LUTS did so only in the small PV group.'] |
['To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI.', 'Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC.', 'A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction.'] |
['Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis.', 'We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood.', 'Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model.', 'Children with cystic fibrosis (n\u2009=\u200956) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P\u2009=\u20090.04) lower FEV0.75 compared with healthy subjects (n\u2009=\u200918). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%).'] |
['Matrix metalloproteinase-26 (MMP-26), one of the main mediators of extracellular matrix (ECM) degradation, has been shown to exist in trophoblasts of human placenta and to play a role in trophoblast cell invasion. However, little is known about the regulation of MMP-26 expression in human trophoblasts. Recently, gonadotropin-releasing hormone I (GnRH I) and GnRH II have been shown to regulate the expression of MMP-2, MMP-9/tissue inhibitor of metalloproteinases 1 (TIMP-1), and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor (PAI) in human trophoblasts, suggesting that these two hormones may work as paracrine and/or autocrine regulators in modulating the activities of various protease systems at the feto-maternal interface. In this study, we determined the regulatory effects of GnRH I and GnRH II on the expression of MMP-26 in human immortalized cytotrophoblast-like cell line, B6Tert-1.', 'Real-time PCR was used to quantify mRNA levels of MMP-26 in human trophoblast-like cell line, B6Tert-1 and primary cultured cytotrophoblasts. Western blotting was used to characterize the expression of MMP-26 and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) in B6Tert-1 cells after treatment with GnRH I and GnRH II.', 'We found that GnRH I increased MMP-26 expression in B6Tert-1 cells after 12 h of treatment at both the mRNA and protein level, while GnRH II increased MMP-26 expression beginning at 3 h of treatment. Treatment of GnRH I at 1 nM resulted in maximal increase of MMP-26 mRNA and protein levels, whereas GnRH II treatment at a concentration of 100 nM was required to induce maximal increase in MMP-26 expression. In addition, we demonstrated that the activation of JNK, but not ERK1/2, was required for GnRH I and II-stimulated MMP-26 production in B6Tert-1 cells and primary cytotrophoblasts.'] |
['Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes.', 'We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n\u2009=\u200958), weight stable patients with cancer (C-WS, n\u2009=\u200972), and non-cancer controls (Co, n\u2009=\u200959) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores.', 'GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon-gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P\u2009<\u20090.001 for both).'] |
['To compare early postoperative outcomes of patients undergoing different types of emergency procedures for bleeding or perforated gastroduodenal ulcers.', 'Although definitive acid-reducing procedures are being used less frequently during emergency ulcer surgery, there is little published data to support this change in practice.', 'A retrospective analysis of data for patients from the 2005-2011 American College of Surgeons National Surgical Quality Improvement Program database who underwent emergency operation for bleeding or perforated peptic ulcer disease was performed to determine the association between surgical approach (local procedure alone, vagotomy/drainage, or vagotomy/gastric resection) and 30-day postoperative outcomes. Multivariable regression analysis was used to adjust for a number of patient-related factors.', 'A total of 3611 patients undergoing emergency ulcer surgery (775 for bleeding, 2374 for perforation) were included for data analysis. Compared with patients undergoing local procedures alone, vagotomy/gastric resection was associated with significantly greater postoperative morbidity when performed for either ulcer perforation or bleeding. For patients with perforated ulcers, vagotomy/drainage produced similar outcomes as local procedures but required a significantly greater length of postoperative hospitalization. Conversely, vagotomy/drainage was associated with a significantly lower postoperative mortality rate than local ulcer oversew when performed for bleeding ulcers.'] |
['To study prognosis and prognostic predictors of sporadic non-lesional temporal lobe epilepsy (TLE).', "474 patients with TLE were consecutively seen from April 1987 to April 2004. 190 had a sporadic non-lesional TLE and a follow-up longer than 2 years. 284 patients were excluded because of family history for TLE, incomplete history, poor compliance with treatment, psychogenic seizures, no brain MRI study, presence of intracranial lesions except for scattered T2 hyperintense spots on hemispheric white matter or mesial temporal sclerosis (MTS). The following prognostic predictors were considered: age at onset of epilepsy, gender, family history of non-TLE or febrile seizures, perinatal factors, history of febrile seizures, ictal phenomena, MTS and interictal EEG. The end point was time to 24 month seizure freedom after treatment onset. The χ(2) test, Student's t test, Kaplan-Meier survival curves with log rank test (univariate analysis) and Cox proportional hazards regression models (multivariate analysis) were used to assess seizure prognosis and prognostic predictors.", 'At univariate analysis, patients achieving 24 month seizure freedom had a significantly older age at onset of epilepsy (33.5 ± 19.9 vs 17.2 ± 14.4 years), and lower occurrence of febrile seizures (11.0% vs 24.4%) and MTS (19.0% vs 35.6%). The chance of remission was directly correlated to age at onset of seizures and inversely correlated to a history of febrile seizures and to the presence of MTS. At multivariate analysis, age at onset of epilepsy was the only significant prognostic predictor.'] |
['To clarify the role of vascular NAD(P)H oxidase in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), both the activity and/or activation mechanisms of NAD(P)H oxidase in the cerebral vasculature and the effect of oxidase inhibition on SAH-induced cerebral vasospasm were assessed.', 'The changes in the luminal perimeter of the middle cerebral artery were measured histologically after SAH was induced according to a 2-hemorrhage model in rats. The NAD(P)H oxidase activity in the cerebral vasculature was measured with a lucigenin assay at different time intervals from 12 hours to 14 days after injection of autologous blood into cisterna magna. The membrane translocation of p47phox and the protein expression of membrane subunits (gp91phox and p22phox) of NAD(P)H oxidase were analyzed using Western blot analysis.', 'The luminal perimeter of the middle cerebral artery started to decrease on day 1 and peaked on day 5 after a second injection of blood, and these changes were significantly ameliorated by treatment with an NAD(P)H oxidase inhibitor, diphenyleneiodonium. At 24 hours after the second injection of blood, both vascular production of superoxide anion and NAD(P)H oxidase activity were markedly increased with enhanced membrane translocation of p47phox, but by 48 hours the enzyme activity had regained normal values. However, no significant changes in the expression of gp91phox and p22phox were observed throughout the experiments.'] |
['Cerebral ischemia upregulates aquaporin-4 expression, increases blood-brain barrier (BBB) permeability, and induces brain edema. Mesenchymal stem cells (MSCs) can repress inflammatory cytokines and show great potential for ischemic stroke therapy. However, the effect of MSCs regarding the protection of ischemia-induced BBB break down is unknown.', 'We test whether MSCs therapy protects BBB integrity and explore the molecular mechanisms of aquaporin-4 on BBB integrity.', 'Two hundred and twenty-eight adult CD1 male mice underwent 90 minutes transient middle cerebral artery occlusion and received 2 × 10(5) MSCs intracranial transplantation. The neurological severity score was improved and both ischemia-induced brain edema and BBB leakage were reduced in MSC-treated mice. MSCs therapy reduced astrocyte apoptosis and inhibited ischemia-induced aquaporin-4 upregulation. In addition, small-interfering RNA knockdown of aquaporin-4 after cerebral ischemia effectively reduced aquaporin-4 expression, brain edema, BBB leakage, and astrocyte apoptosis. Conditional medium from lipopolysaccharide (LPS)-activated microglia enhanced aquaporin-4 expression, p38 and JNK phosphorylation, and apoptosis of cultured astrocytes. MSC treatment reduced the expression of inflammatory cytokines in LPS-activated microglia, and subsequently reduced aquaporin-4 expression and apoptosis of astrocytes. Knockdown of aquaporin-4 in cultured astrocytes also reduced apoptosis. Treatment with p38 and JNK inhibitors showed that p38, but not the JNK signaling pathway, was responsible for the aquaporin-4 upregulation.'] |
['Two recent independent studies showed that patients with familial combined hyperlipidemia (FCHL) have elevated plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) and markers of cholesterol synthesis. Both PCSK9 expression and cholesterol synthesis are downstream effects of hepatic activation of sterol regulatory element binding protein 2 (SREBP2). The present study was conducted to study the relationship between plasma PCSK9 and markers of cholesterol synthesis in FCHL.', 'Markers of cholesterol synthesis (squalene, desmosterol, lathosterol), cholesterol absorption (campesterol, sitosterol, cholestanol) and PCSK9 were measured in plasma of FCHL patients (n = 103) and their normolipidemic relatives (NLR; n = 240). Plasma PCSK9, lathosterol and desmosterol levels were higher in FCHL patients than their NLR (p < 0.001, age and sex adjusted). Heritability calculations demonstrated that 35% of the variance in PCSK9 levels could be explained by additive genetic effects (p < 0.001). Significant age- and sex-adjusted correlations were observed for the relationship between PCSK9 and lathosterol, both unadjusted and adjusted for cholesterol, in the overall FCHL population (both p < 0.001). Multivariate regression analyses, with PCSK9 as the dependent variable, showed that the regression coefficient for FCHL status decreased by 25% (from 0.8 to 0.6) when lathosterol was included. Nevertheless, FCHL status remained an independent contributor to plasma PCSK9 (p < 0.001).'] |
['Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood.', "Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E' ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction."] |
['Ursodeoxycholic acid (UDCA) has been found to inhibit the development of colon carcinoma induced by chemical carcinogens with unidentified mechanisms. Sphingomyelin metabolism has emerged as a novel signal transduction pathway closely related to cell proliferation and apoptosis. We recently found that alkaline sphingomyelinase (SMase) activity was decreased in human colon cancer. The present study is to investigate whether UDCA has effect on the levels of SMase and whether the activity of caspase-3, a key regulatory protease in apoptosis that can be activated by sphingomyelin breakdown products, is also influenced by UDCA.', 'Rats were fed UDCA in amounts ranging from 37.5 to 300 mg/kg/day for 10 days by gavage. The colonic mucosa was scraped, homogenized, and sonicated. The activities of acid, neutral and alkaline SMases, and caspase-3 were determined.', 'UDCA dose-dependently increased alkaline SMase activity in colonic mucosa and faeces, slightly increased acid SMase activity in the mucosa, and had no effect on neutral SMase. UDCA also dose-dependently increased caspase-3 activity in the colonic mucosa, and the increase correlated significantly with the changes in alkaline but not that in acid or neutral SMase activity.'] |
['Retrobulbar injection can be associated with significant pain, due to both needle insertion and deposition of the local anaesthetic solution. The local anaesthetic cream EMLA (eutectic mixture of local anaesthetics) which contains a mixture of lignocaine and prilocaine has been shown to reduce the pain associated with skin puncture. The efficacy of EMLA in alleviating the pain of retrobulbar injection for cataract surgery was assessed in this study.', 'In this, randomised double-blind study, EMLA (n = 53) or lignocaine 5% ointment (n = 50) was administered to the inferior orbital margin at least 45 min before retrobulbar block in 103 patients. Pain assessed during retrobulbar block was marked subjectively by the patient on a 10-point numerical rating scale.', 'Median verbal pain scores were 3.0 with an interquartile range of 1.5-6.5 in the control group and 3.50 with an interquartile range of 2.0-6.0 in the EMLA(R) group (P = 0.67). There was no significant difference between the EMLA group and the lignocaine ointment group according to this pain assessment.'] |
['This study aims to investigate the in vitro effects of Ulinastatin (UTI) and Taxotere (TXT) on cell proliferation; cell apoptosis; xenografted tumor growth; and expression of insulin-like growth factor receptor 1 (IGF-1R), platelet-derived growth factor A (PDGFA), nerve growth factor (NGF), c-Jun N-terminal kinase 2 (JNk-2), and NF-κB in a human primary breast cancer cells and breast cancer cell line MDA-MB-231.', 'The cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT group, and 4) UTI+TXT group. The method of MTT essay, flow cytometry, and RT-PCR were used to detect cell proliferation, cell apoptosis, and expression of IGF-1R, PDGFA, NGF, NF-κB, JNk-2, respectively. The growth of xenografted tumor in nude mice was used to calculate the anti-tumor rate. Immunohistochemistry staining (SP) was used to detect the expression of IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-κB.', 'Proliferation of human breast cancer cells and MDA-MB-231 cell lines, and growth rate of xenografted tumor decreased in order of UTI+TXT > TXT > UTI > control, apoptosis increased in the order control < UTI < TXT < UTI+TXT. The gene expression and protein expression of IGF-1R, PDGFA, NGF, NF-κB and JNk-2 in breast cancer cells was inhibited by UTI and TXT.'] |
['Integrin-mediated cell migration is essential for wound repair. Previous studies have shown that the interaction between integrins and the extracellular matrix (ECM) can initiate intracellular signaling pathways to regulate cell movement. Both the focal adhesion kinase (FAK) and the extracellular signal-regulated kinase/activated mitogen-activated protein kinase (ERK/MAPK) signaling pathways are required for efficient cell migration. Our previous work has shown that co-expression of the integrin alpha5beta1 inhibits alphavbeta3-mediated cell migration. We hypothesized that alpha5beta1 may regulate cell migration by modulating these alphavbeta3-mediated intracellular signaling events.', 'CHO B3 (alphavbeta3+) and B3C5 (alphavbeta3+/alpha5beta1+) cells were monitored by flow cytometry to determine integrin expression. Cells were allowed to migrate on fibrinogen (FBG)-coated transwells, with or without PD98059, an inhibitor of the ERK activator, mitogen-activated protein kinase kinase (MEK). Fixation, staining, and cell counting were used to quantify cell migration. Cells adherent to FBG were lysed and analyzed for FAK and ERK/MAPK activation by immunoblotting followed by image analysis densitometry. All experiments were repeated in triplicate.', 'Treatment with PD98059 significantly decreased alphavbeta3-mediated cell migration on FBG (P = 0.0001) to a level comparable to untreated B3C5 cells. Following adhesion to FBG, B3 cells demonstrated a marked increase in ERK/MAPK activation compared to B3C5 cells. However, no significant difference was detected in FAK activation.'] |
['The disturbances of haemostasis and enhanced oxidative stress (SOX) appear to contribute to the cardiovascular disease (CVD) in hemodialysis (HD) patients. The aim of the present study was to investigate if the disorders of coagulation/fibrinolysis system are associated with the presence of CVD in these patients.', 'We compared pre-dialysis levels of uPA, suPAR, tissue factor (TF) and its inhibitor (TFPI), prothrombin fragment F1+2 (F1+2); a marker of SOX-Cu/Zn superoxide dismutase (Cu/Zn SOD) and a surrogate of inflammation-high sensitivity C-reactive protein (hs CRP) in HD patients with and without CVD.', 'The uPA/suPAR system and hs CRP values were significantly greater in patients with CVD than in those without CVD; whereas TF, TFPI, F1+2 and Cu/Zn SOD levels were comparable in both patient groups. TF was positively correlated with both uPA (p<0.001) and suPAR levels (p<0.05). Logistic regression analysis showed that elevated levels of suPAR, TF and uPA were independently associated with the presence of CVD in HD patients.'] |
['Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs.', 'The IL-4/GM-CSF (granulocyte-macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells.', 'Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-gamma production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid.'] |
['The purpose of this study was to evaluate the effect of obesity on the success of the tension-free vaginal tape (TVT) procedure for stress urinary incontinence. Specifically, do patients with a body mass index (BMI) of 35 kg/m(2) or greater have a lower cure rate of stress urinary incontinence?', 'This retrospective cohort study identified 35 patient pairs who had undergone TVT in Winnipeg, Manitoba, Canada, for stress urinary incontinence from November 1999 to July 2001. Obese patients (defined as BMI greater than or equal to 35 kg/m(2)) were paired with nonobese patients (defined as BMI less than or equal to 30 kg/m(2)). The subjects were matched for age (within 5 years) and prior continence surgeries. Patients with a maximum urethral closure pressure of less than or equal to 20 cm H(2)O were excluded. Follow-up was either by objective cough stress test or subjective cure assessed by telephone interview. Cure was defined as no postoperative stress incontinence. Statistical analysis was performed by conditional logistic regression for matched controls.', 'The follow-up range was 6 to 24 months. There were seven failures in all, four in obese and three in nonobese patients, giving cure rates of 88.6% and 91.4%, respectively. This difference was not statistically significant (P>.05). There were five bladder perforations (identified at the time of the procedure), all occurring in nonobese patients (P< .05).'] |
['Neuroblastoma is the most common extracranial solid cancer type in childhood, and high-risk patients have poor prognosis despite aggressive multimodal treatment. Neuroblastoma-driven inflammation contributes to the induction of suppressive myeloid cells that hamper efficient antitumor immune responses. Therefore, we sought to enhance antitumor immunity by removing immunosuppression mediated by myeloid cells.', 'The prognostic values of myeloid cells are demonstrated by analyzing genomic datasets of neuroblastoma patients. The impact of tumor-derived factors on myelopoiesis and local induction of suppressive myeloid cells is dissected by in vitro culture models using freshly isolated human CD34(+) hematopoietic stem cells, primary human monocytes, and murine bone marrow cells. To test the therapeutic efficacy of BLZ945 as a monotherapy or in combination with checkpoint inhibitors, we used a transgenic murine model (TH-MYCN) that develops aggressive spontaneous neuroblastoma.', 'We report that infiltrating CSF-1R(+) myeloid cells predict poor clinical outcome in patients with neuroblastoma. In vitro, neuroblastoma-derived factors interfere with early development of myeloid cells and enable suppressive functions on human monocytes through M-CSF/CSF-1R interaction. In a transgenic mouse model (TH-MYCN) resembling high-risk human neuroblastoma, antagonizing CSF-1R with a selective inhibitor (BLZ945) modulates the induction of human and murine suppressive myeloid cells and efficiently limit tumor progression. While checkpoint inhibitors are insufficient in controlling tumor growth, combining BLZ945 with PD-1/PD-L1 blocking antibodies results in superior tumor control.'] |
['We sought to elucidate whether minocycline, a broad-spectrum tetracycline antibiotic with potent anti-inflammation capacity, could mitigate inflammatory response and organ dysfunction in the lungs and liver induced by hemorrhagic shock/resuscitation (HS) plus abdominal compartment syndrome (ACS).', 'Adult male rats were randomized to receive HS plus ACS or HS plus ACS plus minocycline (denoted as the HS/A and HS/A-M group, respectively; n = 12). Sham-instrumentation groups were employed to serve as the controls. Hemorrhagic shock/resuscitation was induced by blood drawing (mean arterial pressure: 40-45 mm Hg for 60 min) followed by shed blood/saline mixture reinfusion. Subsequently, intra-abdominal pressure (IAP) was increased to 25 mm Hg by injecting air into the preplaced intraperitoneal latex balloon to induce ACS. Minocycline (20 mg/kg) was intravenously administered immediately after resuscitation. IAP was maintained at 25 mm Hg for 6 h. Then, all rats were euthanized.', 'The levels of polymorphonuclear leukocyte infiltration, the wet/dry weight ratio, and the concentrations of inflammatory molecules (e.g., chemokine, cytokine, and prostaglandin E2) in lung and liver tissues of the HS/A group were significantly higher than those of the HS/A-M groups (all P < 0.05). Moreover, the levels of lung dysfunction (assayed by arterial blood gas) and liver dysfunction (assayed by plasma concentrations of bilirubin, aspartate aminotransferase, and alaninine aminotransferase) of the HS/A group were significantly higher than those of the HS/A-M group (all P < 0.05).'] |
['The aim of this study was to determine whether TWIST and androgen receptor (AR) expression can predict the outcome in radical prostatectomy (RP) patients.', 'Samples from different tumour areas of 181 prostate cancer patients were analysed for TWIST and AR expression, and the results were correlated with known clinicopathological data and biochemical recurrence-free survival (BFS).', 'TWIST overexpression in the margin area of the tumour (M-TWIST) was related to positive surgical margin (p = 0.047), capsule invasion (p = 0.006) and biochemical recurrence (BCR) (p = 0.004). AR expression in the margin area of the tumour (M-AR) was associated with high Gleason score (p = 0.004), positive surgical margin (p = 0.004) and BCR (p = 0.05). M-TWIST overexpression was clearly associated with M-AR expression (p < 0.0001). Four parameters, i.e. M-TWIST overexpression (p < 0.0001), positive surgical margin (p = 0.003), high Gleason score (p < 0.0001) and M-AR expression (p = 0.008), predicted BFS. In the multivariate analysis, M-TWIST overexpression (p = 0.011) and Gleason score (p = 0.002) were the only independent predictors of BFS.'] |
["Nicotine is the main addictive component of tobacco and modifies brain function via its action on neuronal acetylcholine nicotinic receptors (nAChRs). The mesolimbic dopamine (DA) system, where neurons of the ventral tegmental area (VTA) project to the nucleus accumbens (ACb), is considered a core site for the processing of nicotine's reinforcing properties. However, the precise subtypes of nAChRs that mediate the rewarding properties of nicotine and that contribute to the development of addiction remain to be identified.", 'We investigated the role of the nAChRs containing the α7 nicotinic subunit (α7 nAChRs) in the reinforcing properties of nicotine within the VTA and in the nicotine-induced changes in ACb DA outflow in vivo.', 'We performed intra-VTA self-administration and microdialysis experiments in genetically modified mice lacking the α7 nicotinic subunit or after pharmacological blockade of α7 nAChRs in wild-type mice.', 'We show that the reinforcing properties of nicotine within the VTA are lower in the absence or after pharmacological blockade of α7 nAChRs. We also report that nicotine-induced increases in ACb DA extracellular levels last longer in the absence of these receptors, suggesting that α7 nAChRs regulate the action of nicotine on DA levels over time.'] |
['To evaluate the effects of missense mutations within the skeletal muscle sodium (Na) channel on slow inactivation (SI) in periodic paralysis and related myotonic disorders.', 'Na channel mutations in hyperkalemic periodic paralysis and the nondystrophic myotonias interfere with the normally rapid inactivation of muscle Na currents following an action potential. This defect causes persistent inward Na currents that produce muscle depolarization, myotonia, or onset of weakness. Distinct from fast inactivation is the process called SI, which limits availability of Na channels on a time scale of seconds to minutes, thereby influencing muscle excitability.', 'Human Na channel cDNAs containing mutations associated with paralytic and nonparalytic phenotypes were transiently expressed in human embryonic kidney cells for whole-cell Na current recording. Extent of SI over a range of conditioning voltages (-120 to +20 mV) was defined as the fraction of Na current that failed to recover within 20 ms at - 100 mV. The time course of entry to SI at -30 mV was measured using a conditioning pulse duration of 20 ms to 60 seconds. Recovery from SI at -100 mV was assessed over 20 ms to 10 seconds.', 'The two most common hyperkalemic periodic paralysis (HyperPP) mutations responsible for episodic attacks of weakness or paralysis, T704M and M1592V, showed clearly impaired SI, as we and others have observed previously for the rat homologs of these mutations. In addition, a new paralysis-associated mutant, I693T, with cold-induced weakness, exhibited a comparable defect in SI. However, SI remained intact for both the HyperPP/paramyotonia congenita (PMC) mutant, A1156T, and the nonparalytic potassium-aggravated myotonia (PAM) mutant, V1589M.'] |
['We sought to determine if human papillomavirus (HPV) infection of extravillous trophoblast cells reduces cell invasion and if placental infection is associated with adverse reproductive outcomes attributed to placental dysfunction.', 'We conducted apoptosis and invasion assays using extravillous trophoblast (HTR-8/SVneo) cells that were transfected with a plasmid (pAT-HPV-16) containing the entire HPV-16 genome. In order to associate HPV infection with reproductive outcomes, we conducted a case-control study to detect HPV DNA in the extravillous trophoblast region of placentas from cases of spontaneous preterm delivery, severe pre-eclampsia requiring delivery at <37 weeks and controls who delivered at term.', 'Rates of apoptosis were 3- to 6-fold greater in transfected cells than in non-transfected cells or cells transfected with an empty plasmid. Invasion of transfected cells through extracellular matrices was 25-58% lower than that of the controls. HPV was detected more frequently in placentas from spontaneous preterm deliveries than in placentas from controls (P = 0.03). Identification of HPV in placentas from cases of pre-eclampsia was not significantly different to controls.'] |
['Quality of life (QoL) in head and neck cancer patients has been of increasing interest for some years. Unfortunately, only poor data exist regarding the impact of professional psychological support on QoL.', 'The purpose of this study was to investigate psychological aspects of QoL as well as the potential need for additional psychological treatment.', "A total collective of 1761 patients from 38 hospitals yielding 1652 patients' questionnaires containing 147 items was evaluated. QoL, impairments and psychological and surgical treatment were evaluated.", 'Most patients had no psychological interview, and the majority of those who had an interview did not even want one. However, 17% of those patients who did not receive an interview wished to have one. When a psychological interview was performed, most patients (77.5%) evaluated this as helpful. Patients who wished to have a psychological interview but did not receive one showed a significantly worse QoL than those patients without a wish for such an interview. Moreover, having an interview, which does not meet the needs of the patients, diminishes QoL compared with not having an interview.'] |
['Bacterial infections continue to pose a threat to health in many institutional and communal settings, and epidemics are frequent. Current control measures are clearly inadequate; thus, there is a need for a simple, effective, and safe way to decontaminate surfaces.', 'We evaluated the efficacy of a portable ozone-generating machine, equipped with a catalytic converter and an accessory humidifier, to inactivate 15 different species of medically important bacteria.', 'An ozone dosage of 25 ppm for 20 minutes, with a short burst of humidity in excess of 90% relative humidity, was able to inactivate more than 3 log(10) colony-forming units of most of the bacteria, including Acinetobacter baumannii, Clostridium difficile, and methicillin-resistant Staphylococcus aureus, in both in a laboratory test system and simulated field conditions. In many cases, complete eradication was achieved. Dried and wet samples were equally vulnerable to the ozone. Inactivation of bacterial samples dried onto soft surfaces (eg, fabric, cotton, filter paper) were comparable with that observed for samples on plastic.'] |
['Epidermal growth factor (EGF) might be a suitable immunotherapeutic target in non-small-cell lung cancer (NSCLC). Our approach consists of active immunotherapy with EGF. The aim of the study is to characterize the humoral response and its effects on signal transduction in relation with the clinical outcome.', 'Eighty NSCLC patients treated with first-line chemotherapy were randomized to receive the EGF vaccine or supportive care. EGF concentration in sera, anti-EGF antibodies and their capacity to inhibit the binding between EGF/EGF receptor (EGFR), and the EGFR phosphorylation were measured.', 'Seventy-three percent of vaccinated patients developed a good antibody response, whereas none of the controls did. In good antibody-responder patients, self EGF in sera was significantly reduced. In 58% of vaccinated patients, the post-immune sera inhibited EGF/EGFR binding; in the control group, no inhibition occurred. Post-immune sera inhibited the EGFR phosphorylation whereas sera from control patients did not have this capacity. Good antibody-responder patients younger than 60 years had a significantly better survival. A high correlation between anti-EGF antibody titers, EGFR phosphorylation inhibition, and EGF/EGFR binding inhibition was found. There was a significantly better survival for vaccinated patients that showed the higher capacity to inhibit EGF/EGFR binding and for those who showed an immunodominance by the central region of EGF molecule.'] |
['Tumor-initiating cells are resistant to chemotherapy, but how microRNAs play a role in regulating drug resistance of breast tumor-initiating cells (BT-IC) needs to be clarified.', 'Lentivirus-mediated miR-128 transduction was done in BT-ICs, enriched by mammosphere cultures or CD44(+)CD24(-) fluorescence-activated cell sorting. Apoptosis and DNA damage were determined upon treatment with doxorubicin. Expression of miR-128 in breast cancer tissues was examined by in situ hybridization and correlated with breast tumor response to neoadjuvant chemotherapy and patient survival.', 'MiR-128 was significantly reduced in chemoresistant BT-ICs enriched from breast cancer cell lines and primary breast tumors (P < 0.01), accompanied by an overexpression of Bmi-1 and ABCC5, which were identified as targets of miR-128. Ectopic expression of miR-128 reduced the protein levels of Bmi-1 and ABCC5 in BT-ICs, along with decreased cell viability (P < 0.001) and increased apoptosis (P < 0.001) and DNA damage (P < 0.001) in the presence of doxorubicin. Reduced miR-128 expression in breast tumor tissues was associated with chemotherapeutic resistance (P < 0.001) and poor survival of breast cancer patients (P < 0.05; n = 57).'] |
['Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity.', 'Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided.', 'In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively).'] |
['Mucosa-associated lymphoid tissue (MALT) lymphoma comprises approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in the gastro-intestinal tract. It is caused by genetic abnormalities or bacterial infections/chronic inflammation. B-cell lymphoma/leukemia 10 (BCL10) overexpression and nuclear expression have been associated with high-grade MALT lymphomas with genetic abnormalities that are unresponsive to Helicobacter pylori eradication treatment. To explore the molecular mechanism of BCL10 overexpression on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EµSR-BCL10 transgenic mice.', 'By generation of heterozygous and homozygous EuSR-BCL10 mice and showing BCL10 expression levels in these mice, we quantitatively examined relation of MZ B cell expansion and inhibition of caspase-8 activity with BCL10 protein level. We also investigated API2 and caspase-8 expression by Western blot and their interaction with BCL10 by co-immunoprecipitation.', 'MZ B-cell expansion is directly related to BCL10 protein level in a dose-dependent manner. The activity of caspases-8 and -3, but not caspase-9, was inhibited with increasing of BCL10 protein level. Expanded MZ B cells showed selective survival under stimulation of anti-immunoglobulin M, but not dexamethasone, γ-irradiation, or anti-CD95, implying that overexpressed BCL10 exerts anti-apoptotic effects through B-cell antigen receptor (BCR) pathway. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and API2 protein, suggesting an in vivo interaction of them.'] |
['In search of safer treatments for inflammatory bowel disease in subjects not responding to, or showing adverse effects to TNF-α antagonists, we tested three novel indoline carbamates in the 2,4-dinitrobenzene sulfonic acid (DNBS) model of colitis in rats. The compounds have anti-inflammatory activity in other disease models in mice.', 'AN827 (3-(2-(methoxy carbonyl) ethyl) indolin-4-ylethyl methyl) carbamate (0.1 or 1mg/kg), AN680 (3-(2-(methoxy carbonyl) ethyl) indolin-6-ylethyl methyl) carbamate (1.25 or 2.5mg/kg) and AN917 (3-(3-amino propyl) indolin-4-ylethyl methyl) carbamate (1 or 2mg/kg), 5-aminosalycilic acid (5-ASA) (1 or 100mg/kg) or saline (1ml/kg) were administered rectally 1h after intracolonic administration of DNBS, (35mg/kg in 30% alcohol). Disease severity was assessed four days after DNBS administration by change in body weight, colon weight, area of ulceration, myeloid peroxidase (MPO) activity, colonic TNF-α, IL-6 and IL-1β levels. Histopathological scoring was performed after staining colon sections with hematoxylin and eosin and with antibodies to CD68 and CD11b.', 'AN827 (0.1 and 1mg/kg), AN680 (2.5mg/kg) and AN917 (2.0mg/kg) significantly reduced all macroscopic and microscopic parameters of colitis, colonic pro-inflammatory cytokines, TNF-α, IL-1β and IL-6 and MPO activity by about 80%.'] |
['To evaluate MHC class I expression on papillary thyroid cancer (PTC) and analyze changes in MHC expression and associated immune activation with current and experimental treatments for thyroid cancer using in vitro PTC cell lines.', 'MHC class I expression and assessment of tumor-infiltrating leukocyte populations were evaluated by immunohistochemistry. PTC cell lines were analyzed for HLA-ABC expression by flow cytometry following tyrosine kinase inhibitor, IFNα or IFNγ, or radiation treatment. Functional changes in antigenicity were assessed by coculture of allogeneic donor peripheral blood leukocytes (PBL) with pretreated or untreated PTC cell lines and measurement of T-cell activation and cytokine production.', 'Both MHC class I and β2-microglobulin expression was reduced or absent in 76% of PTC specimens and was associated with reduced tumor-infiltrating immune cells, including effector (CD3(+), CD8(+), CD16(+)) and suppressor (FoxP3(+)) populations. Treatment of PTC cell lines with the MEK1/2 inhibitor selumetinib or IFN increased HLA-ABC expression. This phenotypic change was associated with increased T-cell activation (%CD25(+) of CD3(+)) and IL2 production by PBL cocultured with treated PTC cell lines. Additive effects were seen with combination selumetinib and IFN treatment.'] |
['Altered vascular responses to vasopressor agents contribute to the pathogenesis of the circulatory dysfunction in cirrhosis. This study aims to assess the role of endogenous nitric oxide (NO) in the reduced vascular responsiveness to angiotensin II (ANG-II) in eight patients with preascitic cirrhosis compared with eight age- and sex-matched healthy controls.', "Forearm blood flow (FBF) responses to sub-systemic, locally-active intra-brachial infusions of ANG-II were measured using venous occlusion plethysmography before and during the application of an 'NO-clamp', a balanced co-infusion of L-N(G)-monomethyl-arginine (a selective NO synthase inhibitor) and sodium nitroprusside (an exogenous NO donor) to block endogenous NO production and restore normal NO-mediated basal blood flow, respectively.", "Before applying the 'NO-clamp', ANG-II caused dose-dependent reductions of FBF in both groups (P<0.001) that were significantly attenuated in the cirrhotic patients (P=0.012). In the presence of the 'NO-clamp', the ANG-II-mediated vasoconstriction was enhanced in cirrhotic patients (P<0.01), unchanged in controls, and now similar in both groups."] |
['Anterior knee pain (AKP) is a common complication following intramedullary nailing of tibial shaft fractures. Our aim was, by analysing the postoperative lateral knee X-rays and clinical status (VAS score), to find the best intramedullary tip position of a non protruded nail that will provide the best postoperative outcome avoiding AKP.', 'We evaluated the postoperative outcome of 221 patients, from the last four years, with healed fractures initially treated with intramedullary reamed nails with two or three interlocking screws proximally and distally through a medial paratendinous incision for nail entry portal. Our aim was to analyse a possible relationship between AKP according to the VAS scale, and nail position marked as a distance from tip of nail to tibial plateau (NP) and to tibial tuberosity (NT), measured postoperatively on lateral knee X-rays.', 'Two groups of patients were formed on the basis of presence of pain related to AKP (the level of pain was neglected): group A were patients with pain and group B without pain. The difference between the two groups concerning NP and NT measurements appeared to be statistically significant concerning NT measurement (p < 0.05), with high accuracy according to the classification tree.'] |
['To determine the prevalence of bodily pain measures (pain intensity and interference) in elderly people and their relationship with Perceived Stress Scale (PSS) scores.', 'Cross-sectional.', 'Community.', 'A representative community sample of 578 individuals aged 70 and older (mean age 78.8, 63% female).', 'The prevalence of pain intensity and pain interference and their relationship with PSS scores, demographic factors, past medical history, and neuropsychological testing scores were examined. Pain intensity and pain interference were measured using the Medical Outcomes Study 36-item Short-Form Survey bodily pain questions.', 'Bivariate analysis for pain measures showed that PSS scores, neuropsychological test scores, and medical histories were associated with pain intensity and interference. Logistic regression showed that higher PSS scores were significantly associated with greater odds of having moderate to severe pain intensity and moderate to severe pain interference (with and without the inclusion of pain intensity in the models).'] |
['Fibrates were reported to be effective in reducing recurrent coronary events in coronary heart disease patients with elevated triglycerides. It is not known whether this effect is related to the extent of triglyceride reduction.', 'Participants comprised 3090 coronary heart disease patients enrolled in the Bezafibrate Infarction Prevention study, which showed a nonsignificant reduction (9.4%; P=0.26) in fatal or nonfatal myocardial infarction and sudden death during a mean follow-up time of 6.2 years.', 'Significant reduction in triglyceride serum level was evident only among patients allocated to bezafibrate, ranging between 0.06 mmol/l (5 mg/dl) in the lowest decile of baseline triglycerides level and 0.68 mmol/l (60 mg/dl) in the highest baseline decile. The extent of triglyceride reduction with bezafibrate was significantly associated with the reduction of risk; relative risk reduction of 55% (hazards ratio: 0.45; 95% confidence interval: 0.24-0.84) was observed among patients with baseline triglycerides>or=2.26 mmol/l who reduced triglyceride level to >0.50 mmol/l (>44.3 mg/dl). In contrast, the risk of recurrent events among patients treated with bezafibrate and achieving less triglyceride reduction or failing to reduce triglyceride level was not significantly different from that of patients treated with placebo.'] |
['Nyctanthes arbor-tristis Linn (Oleaceae) is a well-known traditional medicinal plant used throughout the India as an herbal remedy for treating various infectious and non-infectious diseases.', 'To evaluate the antioxidative activity of hydro-alcoholic extract of flower in the lymphocytes exposed to oxidative stress induced by H(2)O(2) .', 'Isolated lymphocytes were treated in vitro with extract or extract+H(2)O(2,) and the level of reduced glutathione (GSH) as well as the activity of glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) were measured.', 'Treatment of lymphocyte with flower extract (50, 100, and 200 μg/ ml) significantly increased the level of GSH and decreased the activity of GST. The LDH activity measured in the cell-free medium decreased significantly. Pre-treatment of lymphocyte with flower extract protects the lymphocyte from the H(2)O(2) induced oxidative stress by significantly increasing the levels of GSH as compared to the cells treated only with H(2)O(2). Pre-treatment also reduced the activity of LDH significantly as compared to the cells treated only with H(2)O(2). The LDH activity in cell-free medium is associated with membrane damage, the decreased levels of LDH activity reflects the reduced level of membrane damage due to H(2)O(2).'] |
['Tannin-rich plant materials are commonly used in the traditional medicine as external anti-inflammatory, antioxidant and antimicrobial agents. Plant extracts containing significant quantities of tannins are often used in the prevention and treatment of oral cavity diseases such as periodontosis or gingivitis. The contribution of pure ellagitannins to the observed anti-inflammatory activity of tannin-rich remedies is still not resolved.', 'The aim of the present study the study was to establish if ellagitannins and their precursor - pentagalloylglucose (1) can modulate the inflammatory response of ex-vivo stimulated neutrophils.', 'Human neutrophils were isolated from the buffy coats obtained from healthy volunteers. Neutrophils were cultivated with or without tested compounds. The influence of ellagitannins and 1 on the production and release of pro-inflammatory factors such as elastase, reactive oxygen species, interleukin-8, tumour necrosis factor alpha (TNF-α) and metalloproteinase-9 was evaluated using ELISA sets or chemical methods. The effect on surface expression of toll like receptor 4 (TLR-4) and apoptosis was also checked using flow cytometry.', 'The results showed that ellgitannins modulate the inflammatory response of human neutrophils by the inhibition of production and release of chosen cytokines and pro-inflammatory enzymes. By the induction of TNF-α ellagitannins enhance neutrophil apoptosis, which is of interest in the case of chronic inflammation within oral cavity. Ellagitannins also decrease the surface expression of TLR-4 in activated neutrophils.'] |
['Chronic pain involves hypervigilance for pain-related stimuli. Selective attention to pain-related stimuli, known as pain attentional bias (AB), can exacerbate chronic pain, prolong suffering, and undermine quality of life. The aim of this study was to determine if a multimodal mindfulness-oriented intervention could significantly reduce pain AB among chronic pain patients receiving opioid analgesics.', 'A total of 67 chronic pain patients were randomized to an 8-week Mindfulness-Oriented Recovery Enhancement (MORE) intervention or a social support group intervention and began treatment. A dot probe task was used to measure pain AB. Primary outcomes were pain AB scores for cues presented for 2,000 and 200 ms.', 'Prior to intervention, participants exhibited a significant bias towards pain-related cues presented for 2,000 ms, but no bias for cues presented for 200 ms. A statistically significant time × intervention condition interaction was observed for 2,000 ms pain AB, such that participants in MORE evidenced significantly reduced posttreatment pain AB relative to pretreatment levels, whereas no significant pre-post treatment changes in pain AB were observed for support group participants. Decreases in pain AB were associated with increased perceived control over pain and attenuated reactivity to distressing thoughts and emotions.'] |
['The objective of this study was to examine the epithelial stem cell proliferation kinetics in a rat model with keratoconjunctivitis sicca (KCS).', 'Wistar rats received a daily injection of 5-bromo-2-deoxyuridine (BrdU) at a dose of 5 mg/100 g of body weight for 2 weeks. Dry eye was induced in 2 groups of rats by subcutaneous injection of scopolamine and placed in a desiccating environment: The first group received dry eye treatment at the beginning of BrdU labeling for 2 weeks; the second group received dry eye treatment after BrdU labeling for 4 weeks. Rats receiving no dry eye treatment were used as controls. Aqueous tear production, tear clearance, and corneal barrier function of dry eye rats were compared with those of control rats. Ocular epithelial morphology and goblet cell density were also evaluated in histologic sections. One month after BrdU injection, epithelial stem cell proliferation kinetics was assessed by BrdU labeling.', 'Significant decreases in tear fluid secretion and tear clearance were noted in rats 5 days after dry eye treatment, with significantly increased corneal carboxy fluorescein uptake. Changes in ocular surface epithelial morphology and significantly reduced density of conjunctival goblet cells were found in dry eye groups. The number of conjunctival BrdU label-retaining cells in the rats with dry eye was significantly decreased compared with control rats (P < 0.01 for both groups). Furthermore, BrdU labeling in the before dry eye induction group showed more label-retaining basal cells in the conjunctiva than labeling in the dry eye state group (P < 0.01).'] |
['Insulin exerts anti-apoptotic effects in both cardiomyocytes and coronary endothelial cells following ischemia/reperfusion (I/R) via the Akt-endothelial nitric oxide synthase survival signal pathway. This important insulin signaling might further contribute to the improvement of cardiac function after reperfusion. In this study, we tested the hypothesis that sarcoplasmic reticulum calcium-ATPase (SERCA2a) is involved in the insulin-induced improvement of cardiac contractile function following I/R.', "Ventricular myocytes were enzymatically isolated from adult SD rats. Simulated I/R was induced by perfusing cells with chemical anoxic solution for 15 min followed by reperfusion with Tyrode's solution with or without insulin for 30 min. Myocyte shortening and intracellular calcium transients were assessed and underlying mechanisms were investigated.", 'Reperfusion with insulin (10(-7) mol/L) significantly improved the recovery of contractile function (n=15-20 myocytes from 6-8 hearts, P<0.05), and increased calcium transients, as evidenced by the increased calcium [Ca2+] fluorescence ratio, shortened time to peak Ca2+ and time to 50% diastolic Ca2+, compared with those in cells reperfused with vehicle (P<0.05). In addition, Akt phosphorylation and SERCA2a activity were both increased in insulin-treated I/R cardiomyocytes, which were markedly inhibited by pretreatment of cells with a specific Akt inhibitor. Moreover, inhibition of Akt activity abolished insulin-induced positive contractile and calcium transients responses in I/R cardiomyocytes.'] |
['Disease severity in viral bronchiolitis is often difficult to predict at onset, and may be related to the host immune response. Recognizing the particular immunologic features of infants who develop severe disease might offer an opportunity for developing diagnostic tools to facilitate early intervention and improve outcomes.', 'We compared cytokine gene expression (by real-time reverse-transcriptase polymerase chain reaction), cytokine concentrations (by enzyme-linked immunosorbent assay) and the activation status of lymphocytes (by flow cytometry) in the peripheral blood of children hospitalized with moderate and severe viral bronchiolitis and a group of age-matched controls.', 'Analysis was undertaken on 57 children with viral bronchiolitis and 33 controls. Interleukin-7 mRNA expression at enrollment in peripheral blood mononuclear cells differed significantly between those with moderate and severe bronchiolitis, and correlated with both the subsequent length of hospital stay and need for supplemental oxygen therapy. Serum interleukin-10 concentration also distinguished moderate from severe disease. Participants with viral bronchiolitis demonstrated a more activated γδ-T cell phenotype (Vδ1+), but a more naive TCR αβ-T cell compartment compared with controls.'] |
['Symptomatic knee osteoarthritis (OA) is poorly correlated with radiographic severity, but subchondral bone measures may be useful for risk assessment as bone shape is grossly unaffected at early radiographic stages. We sought to determine whether compartment-specific size mismatch in the naturally asymmetric tibiofemoral joint, measured as tibiofemoral subchondral surface ratio (SSR): (1) predicts incident symptoms, (2) predicts incident or progressive OA, (3) is reproducible and time invariant.', 'OA Initiative participants with baseline MRIs and up to 48-month follow-up (n\xa0=\xa01,338) were analyzed. Logistic regression was used to determine the association between SSR and incident symptoms, incident OA, and progression of OA after adjusting for demographic, radiologic, injury-related, and lifestyle-related factors. Reproducibility was assessed as % coefficient of variation (CV) on repeat MRI studies at baseline and 24 months.', 'Increased medial SSR is protective against incident symptoms at 48 months (per 0.1 increase: OR 0.48 CI 0.30, 0.75; P\xa0=\xa00.001). Increased lateral SSR values are protective against lateral OA incidence (OR 0.23 CI 0.06, 0.77; P\xa0=\xa00.016) or progression (OR 0.66 CI 0.43, 0.99; P\xa0=\xa00.049) at 24 months. Both medial and lateral SSR are stable over time (medial: mean change 0.001 SD 0.016; lateral: mean change 0.000 SD 0.017) and are highly reproducible (3.0% CV medial SSR; 2.7% CV lateral SSR).'] |
['Epithelial to mesenchymal transition (EMT), implicated as a mechanism for tumor dissemination, is marked by loss of E-cadherin, disruption of cell adhesion, and induction of cell motility and invasion. In most intraductal breast carcinomas E-cadherin is regulated epigenetically via methylation of the promoter. E-cadherin expression is therefore dynamic and open to modulation by the microenvironment. In addition, it has been observed that metastatic foci commonly appear more differentiated than the primary tumor, suggesting that cancer cells may further undergo a mesenchymal to epithelial reverting transition (MErT) in the secondary organ environment following the EMT that allows for escape.', 'We first examined E-cadherin expression in primary breast tumors and their corresponding metastases to liver, lung and brain and discovered that 62% (10/16) of cases showed increased E-cadherin expression in the metastases compared to the primaries. These observations led to the question of whether the positive metastatic foci arose from expansion of E-cadherin-positive cells or from MErT of originally E-cadherin-negative disseminated cells. Thus, we aimed to determine whether it was possible for the mesenchymal-like MDA-MB-231 breast cancer cells to undergo an MErT through the re-expression of E-cadherin, either through exogenous introduction or induction by the microenvironment. Ectopic expression of full-length E-cadherin in MDA-MB-231 cells resulted in a morphological and functional reversion of the epithelial phenotype, with even just the cytosolic domain of E-cadherin yielding a partial phenotype. Introduction of MDA-MB-231 cells or primary explants into a secondary organ environment simulated by a hepatocyte coculture system induced E-cadherin re-expression through passive loss of methylation of the promoter. Furthermore, detection of E-cadherin-positive metastatic foci following the spontaneous metastasis of MDA-MB-231 cells injected into the mammary fat pad of mice suggests that this re-expression is functional.'] |
["ClC-Kb and ClC-Ka are homologous chloride channels that facilitate chloride homeostasis in the kidney and inner ear. Disruption of ClC-Kb leads to Bartter's Syndrome, a kidney disease. A point mutation in ClC-Kb, R538P, linked to Bartter's Syndrome and located in the C-terminal cytoplasmic domain was hypothesized to alter electrophysiological properties due to its proximity to an important membrane-embedded helix.", 'Two-electrode voltage clamp experiments were used to examine the electrophysiological properties of the mutation R538P in both ClC-Kb and ClC-Ka. R538P selectively abolishes extracellular calcium activation of ClC-Kb but not ClC-Ka. In attempting to determine the reason for this specificity, we hypothesized that the ClC-Kb C-terminal domain had either a different oligomeric status or dimerization interface than that of ClC-Ka, for which a crystal structure has been published. We purified a recombinant protein corresponding to the ClC-Kb C-terminal domain and used multi-angle light scattering together with a cysteine-crosslinking approach to show that the dimerization interface is conserved between the ClC-Kb and ClC-Ka C-terminal domains, despite the fact that there are several differences in the amino acids that occur at this interface.'] |
['Recent studies suggest that ovarian volume and antral follicle numbers may be sensitive, specific, and early indicators of menopausal status. The accuracy of these markers, however, has not been compared directly to more traditional markers [age and follicle-stimulating hormone (FSH) levels]. Thus, the purpose of this study was to test whether ovarian volume and antral follicle counts are more sensitive and specific markers of menopausal status than age or FSH levels.', 'Premenopausal (n = 34) and postmenopausal (n = 25) women between 40 and 54 years old received a transvaginal ultrasound for determination of ovarian volume and antral follicle numbers, provided blood for measurement of FSH levels, and completed a questionnaire. FSH levels, age, ovarian volume, and antral follicle numbers were compared using t tests. Receiver operating characteristic curves were generated to evaluate the sensitivity and specificity of each marker.', 'Postmenopausal women had significantly higher FSH levels (p < or = 0.0001), smaller ovarian volumes (p < or = 0.002), and fewer antral follicles (p < or = 0.002) than premenopausal women. Ovarian volume and antral follicle numbers had similar sensitivity (27.3-100%) and specificity (3.4-92.9%) in indicating postmenopausal status as FSH levels and age.'] |
['Perioperative myocardial ischemia poses a vital threat to surgical patients. Means to protect postischemic myocardium are clinically not available. Lidocaine has been demonstrated to exert antiinflammatory pleiotropic effects. The authors set out to test if lidocaine protects ischemic myocardium from reperfusion injury.', 'A mouse model of transient coronary artery ligation (30 min) and reperfusion (24 h) was used with animal care committee approval. Infarct size and area-at-risk were determined. Leukocyte recruitment was quantified on immunohistochemical stainings. Apoptosis was assessed using enzyme-linked immunosorbent assay to detect histone modifications and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Lidocaine effects on leukocyte-endothelial interactions were assessed in vitro by using a parallel-plate flow chamber or static adhesion assays.', 'Infarct size per area-at-risk was reduced by 27% in mice treated with a lidocaine bolus (1 mg/kg) before a continuous infusion (0.6 mg . kg(-1) . h(-1)) during ischemia (P < 0.005). Neutrophil density in the infarct and periinfarct zone was not reduced by lidocaine, although the size of the infiltrated area was. Terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cardiomyocytes and endothelial cells were significantly reduced in the periinfarct zone by lidocaine. In vitro, no effect on leukocyte rolling or firm adhesion to resting or activated endothelium was demonstrable. In vitro, lidocaine reduced cardiomyocyte apoptosis induced by hypoxia and reoxygenation (3h/1h) significantly. Infarct size and in vitro cardiomyocyte apoptosis were likewise reduced when lidocaine bolus and infusion were administered after the ischemic insult.'] |
['Cardiac allograft vasculopathy (CAV) is the major determinant of long-term survival after heart transplantation. The characteristic diffuse concentric intimal thickening of CAV detected by intravascular ultrasound (IVUS) imaging may not be perceivable on coronary angiogram. Previous studies of hepatocyte growth factor (HGF) in murine models suggested the protective effects on vascular endothelium and allograft survival. However, the possible role of circulating HGF that contributes to the development of CAV in human is unclear.', 'IVUS was used to assess the left anterior descending coronary arteries of 47 patients who had survived cardiac transplantation for more than 1 year and had no angiographically detectable CAV. The IVUS measurements for the extent of intimal hyperplasia, including volume index (calculated as [total plaque volume/total vessel volume] x 100) and maximum area stenosis, were compared with plasma levels of HGF by linear regression analyses.', 'The volume index significantly correlated with maximum area stenosis in the IVUS measurements (r = 0.90, p < 0.0001). Both volume index and maximum area stenosis inversely correlated with plasma HGF levels (r = -0.39, p = 0.007 and r = -0.42, p = 0.003, respectively).'] |
['Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent skeletal muscles. No study has examined this relationship in human tissues.', 'This study investigated the effect of hyperthyroid status on the expression of the alpha- and beta-subunits of the Na+-K+-ATPase.', 'The vastus lateralis muscles from eight hyperthyroid patients were biopsied before and after treatment. Ten age-matched euthyroid subjects served as controls.', 'In hyperthyroid patients, the average T3 level was three times higher in pretreatment compared with posttreatment (262 +/- 75 vs. 86 +/- 21 ng/dl, P = 0.001). The relative mRNA expression of the alpha2, but not alpha1 or alpha3, subunit was increased approximately 3-fold in pretreatment (2.98 +/- 0.52 vs. 0.95 +/- 0.40, P < 0.01), whereas that of beta1, not beta2 or beta3, subunit was increased approximately 2.8-fold in pretreatment (2.83 +/- 0.38 vs. 1.10 +/- 0.27, P < 0.01). The relative mRNA expression of the alpha2 and beta1 subunits was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P = 0.003, respectively). Immunohistochemistry studies revealed an increase in protein abundance of the alpha2 and beta1, but not alpha1 or beta2, subunits in the plasma membrane of muscle fibers of hyperthyroid patients, which decreased after treatment.'] |
['The mechanisms responsible for the accumulation of eosinophils in pleural fluid are not fully understood. The purpose of this study was to evaluate the relationship between eosinophil accumulation and the levels of interleukin (IL)-5, IL-3, and granulocyte/macrophage colony-simulating factor (GM-CSF) in pleural effusions.', 'We evaluated 30 patients with eosinophilic pleural effusions (eosinophil count > 10% nucleated cells in pleural fluid) and 10 patients with noneosinophilic pleural effusions. The patients with eosinophilic pleural effusions included 22 patients with post-coronary artery bypass graft surgery pleural effusions and 8 patients with eosinophilic pleural effusions caused by other causes. IL-5, IL-3, and GM-CSF in all pleural fluids were measured using enzyme-linked immunosorbent assay kits.', 'The mean level of IL-5 in eosinophilic pleural effusions (283.1 +/- 341.6 pg/mL) was significantly (p < 0.025) higher than that in the noneosinophilic effusions (28.2 +/- 19.0 pg/mL). The absolute eosinophil count and percentage correlated significantly with the level of IL-5 in all patients (r = 0.55, p < 0.001, and r = 0.54, p < 0.001, respectively). There was no significant correlation between IL-5 levels and RBC counts in all patients (r = 0.24, p > 0.05). GM-CSF and IL-3 levels were below the detectable range in all pleural fluids.'] |
['The ATP-binding cassette (ABC) transporter B6 (ABCB6) is highly expressed in megakaryocyte progenitors, but its role in platelet production and disease has not been elucidated.', 'Among various ABC transporters, ABCB6 was highly expressed in megakaryocyte progenitors, exhibiting the same pattern of expression of genes involved in heme synthesis pathway. Transplantation of Abcb6 deficient (Abcb6(-/-)) bone marrow into low density lipoprotein receptor deficient recipient mice resulted in expansion and proliferation of megakaryocyte progenitors, attributable to increased reactive oxygen species production in response to porphyrin loading. The enhanced megakaryopoiesis in Abcb6(-/-) bone marrow-transplanted mice was further illustrated by increased platelet counts, mean platelet volume, and platelet activity. Platelets from Abcb6(-/-) bone marrow-transplanted mice had higher levels of chemokine (C-C motif) ligand 5, which was associated with increased plasma chemokine (C-C motif) ligand 5 levels. There were also increased platelet-leukocyte aggregates, which resulted in leukocyte activation. Abcb6(-/-) bone marrow-transplanted mice had accelerated atherosclerosis which was associated with deposition of the chemotactic agent, chemokine (C-C motif) ligand 5 in atherosclerotic plaques, resulting in increased macrophage accumulation.'] |
['Diabetes is associated with nitrosative stress in multiple tissues. Overactivation of the Wnt pathway has been shown to play a pathogenic role in diabetic retinopathy (DR). The purpose of this study was to investigate whether nitrosative stress contributes to aberrant activation of Wnt signaling in diabetes.', 'Nitrosative stress induced by peroxynitrite (PN), 4-hydroxynonenal (HNE), or high glucose (HG) in retinal cells was assessed by a dichlorofluorescein fluorescence assay or by Western blot analysis and enzyme-linked immunosorbent assay of 3-nitrotyrosine (3-NT). These nitrosative stress inducers activated the canonical Wnt pathway, as shown by Western blot analysis of phosphorylated low-density lipoprotein receptor-related protein 6 (pLRP6), total and nuclear β-catenin levels, Luciferase reporter assay, and expression of the Wnt target genes intercellular adhesion molecule 1 (ICAM-1) and vascular endothelial growth factor (VEGF). Uric acid (UA), a PN scavenger, and 5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinato Iron III Chloride (FeTPPS), a PN decomposition catalyst, suppressed Wnt signaling and ICAM-1 and VEGF overexpression induced by PN, HNE, and HG. Furthermore, UA and FeTPPS also inhibited Wnt signaling induced by the Wnt ligand. In streptozotocin-induced diabetic rats, retinal levels of 3-NT, β-catenin, nuclear β-catenin, pLRP6, VEGF, and ICAM-1 were markedly increased. UA treatment for 6 weeks ameliorated diabetes-induced Wnt signaling in the diabetic rat retina. The UA treatment also decreased inflammatory cell infiltration and extraverted serum albumin in the perfused retina of diabetic rats, suggesting decreased retinal inflammation and vascular leakage.'] |
['In this study, the effects of lutein on neuroinflammation in lipopolysaccharide (LPS)-activated BV-2 microglia were investigated.', 'The production of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and nitric oxide was measured in culture medium using enzyme immunoassay and Griess reagent, respectively. The expression of proteins was determined using Western blot. Pretreatment with lutein (50 μM) prior to LPS (1 μg/mL, 12 h) stimulation resulted in a significant inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression, as well as tumor necrosis factor-α, interleukin-1β, and nitric oxide production (p < 0.05). Further experiments demonstrated that lutein suppressed LPS-induced NF-κB activation by inhibiting the phosphorylation of p38 kinase, c-Jun N-terminal kinase (JNK), and Akt kinase (p < 0.05). Moreover, lutein markedly quenched reactive oxygen species and promoted antioxidant protein expression including heme oxygenase-1 and', 'quinone oxidoreductase by enhancing the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mediated NF-E2-related factor 2 (Nrf2) activation (p < 0.05).'] |
['RANKL is an essential mediator of bone erosions, but the role of RANKL in systemic bone loss had not been studied in arthritis. RANKL protein was increased in rat joint extracts and serum at the earliest stages of arthritis. Osteoprotegerin (OPG) treatment reversed local and systemic bone loss, suggesting that RANKL is both a marker and mediator of bone loss in arthritis.', 'RANKL is well established as an essential mediator of bone erosions in inflammatory arthritis, but the role of RANKL in systemic bone loss in arthritis had not been studied. We hypothesized that serum RANKL could serve as both a mediator and as a novel biomarker for local and systemic bone loss in arthritis. We challenged this hypothesis in two established rat models of inflammatory arthritis. We sought to determine whether serum RANKL was elevated early in disease progression and whether RANKL suppression could prevent both local and systemic bone loss in these models.', 'Detailed time-course studies were conducted in animals with collagen-induced (CIA) or adjuvant-induced (AIA) arthritis to evaluate the onset and progression of inflammation (paw swelling), bone erosions, osteoclast numbers, and RANKL protein levels in arthritic joints and in serum. Additional CIA and AIA rats (n=8/group) received placebo (PBS) or recombinant OPG (3 mg/kg three times weekly) for 10 days beginning 4 days after disease onset (first macroscopic evidence of hind paw erythema and edema) to assess the role of RANKL in local and systemic bone loss.', 'RANKL protein was significantly elevated in the joints and serum of CIA and AIA rats within 1-2 days of disease onset. Increased RANKL levels were associated with local (hind paw) and systemic (vertebral) osteopenia in both models. The RANKL inhibitor OPG prevented local and systemic osteopenia in both models of established disease.'] |
['Gene promoter hypermethylation is common in colorectal cancer and is associated with transcriptional silencing. However, the clinicopathological significance of p16(INK4a) gene silencing with hypermethylation is unknown. Therefore, the aim of this study was to analyze loss of p16 expression and its relationship to hypermethylation in sporadic colorectal cancer.', 'Tissue from 426 colorectal cancers underwent histological analysis. Immunohistochemistry was performed for p16 expression. Fresh tumor DNA was analyzed for microsatellite instability (MSI) and the presence of K-ras mutations. In addition, DNA was bisulphite-modified and analyzed for p16(INK4a) promoter methylation by methylation-specific PCR.', "There were 25% of tumors with p16(INK4a) promoter hypermethylation. These tumors were associated with older patients, right-sidedness, MSI and were poorly differentiated, mucinous, and had intraepithelial and peritumoral lymphocytes and a Crohn's-type lymphocytic reaction (P < 0.05). However, only right-sidedness was significant on multivariate analysis (P < 0.001). Only 8.1% of tumors did not express p16, and this was associated with hypermethylation (P < 0.05)."] |
['Colorectal cancer (CRC) is the third leading cause of cancer death in Japan. CD10 expression is closely associated with liver metastasis. In the present study, we explored the possibility of serum CD10 as a marker of liver metastasis in CRC.', 'BALB/c mouse with subcutaneous tumor of syngeneic CT26 CRC cells were examined serum CD10. In 84 CRC patients and patients undergoing hemodialysis, serum CD10 was examined. CD10 concentration was measured by enzyme-linked immunosorbent assay.', 'In a mouse subcutaneous tumor model, serum CD10 correlated with the weight of the tumors. Serum CD10 was examined in 84 patients with CRC. The serum levels of CD10 were higher in patients with more advanced cancer stages. Patients with liver metastasis showed the highest levels of serum CD10 among all patients. Importantly, patients with high serum CD10 levels had metachronous liver metastasis. Healthy volunteers showed low levels of CD10; however, serum CD10 levels in patients undergoing hemodialysis showed levels as high as those with stage II and III CRC. A cutoff of serum CD10 set to >1000 pg/mL showed 70% sensitivity and 93% specificity for liver metastasis in CRC. This cutoff included all cases of metachronous liver metastasis.'] |
['To determine the prevalence, associated correlates and impact of oral pain in 12-year-old schoolchildren in Stayroypoli, Greece.', 'Cross-sectional survey of all schoolchildren attending the last year of government primary schools using self-administered questionnaires. Approval was granted by the Greek Ministry of Education and Religion. Cooperation was obtained from the schools. Children whose parents did not refuse their participation were invited to complete a questionnaire. Oral pain prevalence was estimated and association with sociodemographic/economic factors tested. Associations between pain experience and impact on daily activities were examined.', 'Of the 296 children registered, 225 (76.0%) were present on the days data were collected. Usable questionnaires were completed by 187 children (83.1%). Oral pain in the previous 4 weeks, reported by 70 (37.4%), was more likely to affect children living with one parent/other people (OR 3.0, 95% CI = 1.2-7.4, P = 0.013) and those who brushed less than twice a day (OR 2.8, 1.5-5.2, P = 0.001). Impact on daily activities was reported by 64 children (91.4%). The most commonly stated impacts were eating (40.0%), cleaning teeth (25.7%) and sleeping (18.6%).'] |
['The rostral anterior cingulate cortex (rACC) has been implicated as a structural neural correlate of familial major depressive disorder, raising the possibility that the structure of this region may act as a biologic marker of depression vulnerability. The aim of the current study was to determine whether children and adolescents with depressive symptoms have lower rACC volume relative to those without symptoms and examine how a positive family history of depression affects this relationship.', 'One hundred twelve normal healthy children (59 boys, 53 girls), age 7 to 17, without a current diagnosis or history of depression or other psychiatric illness, were recruited from the community. Mood symptoms were collected using the Pediatric Behavior Scale, a parent- and teacher-reported questionnaire. Volumetric measures of the rACC were generated using structural magnetic resonance imaging (MRI). The relationship of depressive symptoms and rACC volume was examined.', '1) The rACC volume was significantly lower in boys with subclinical depressive symptoms compared with boys with no depressive symptoms, particularly on the left side (14.6% reduction; F = 8.90, p = .005). 2) There was a negative correlation of rACC volume and depressive symptoms in boys, a finding that was more robust in subjects with a positive family history of depression. 3) In girls, there was not a significant association of depressive symptoms and rACC volume.'] |
["Chronic cocaine exposure has been associated with progressive brain structural and functional changes. Clarifying mechanisms underlying cocaine's progressive brain effects may help in the development of effective cocaine abuse treatments.", 'We used a controlled squirrel monkey model of chronic cocaine exposure (45\xa0mg/kg/week for 9\xa0months) combined with ultra-high magnetic field (9.4\xa0T) proton magnetic resonance spectroscopy to prospectively measure putamen metabolite changes.', 'Proton metabolites were measured with a STEAM sequence, quantified with LCModel using a simulated basis set, and expressed as metabolite/total creatine (tCr) ratios.', 'We found cocaine-induced time-dependent changes in putamen glutamate/tCr and glutamine/tCr metabolite ratios suggestive of altered glutamate compartmentalization, neurotransmission, and metabolism. By contrast, saline-treated monkeys exhibited no metabolite changes over time. The time course of cocaine-induced metabolite abnormalities we detected is consistent with the apparent time course of glutamate abnormalities identified in a cross-sectional study in human cocaine users, as well as with microdialysis findings in rodent models of repeated cocaine exposure.'] |
['Inflammatory bowel disease (IBD)-associated colorectal carcinogenesis involves dysregulation of multiple cellular pathways, including p53 signaling and cytokine action. The purpose of the current study was to evaluate the effects of tumor necrosis factor alpha (TNF-alpha) on p53 and p53 up-regulated modulator of apoptosis (PUMA), a downstream effector of p53 in the apoptotic pathway in colorectal cancer cells.', 'The cell lines HT29 (which express mutant p53) and HCT116 (which express wild-type p53) were treated with TNF-alpha (0, 50, 100, or 500 ng/mL) for 1, 12, 24, or 48 hours. Protein expression and subcellular localization of p53 and PUMA were determined by immunoblot and immunofluorescence. Changes in p53 and PUMA mRNA expression were determined by quantitative real time polymerase chain reaction.', 'Nuclear p53 expression was increased in TNF-alpha-treated HT29 cells; in contrast, expression was decreased or minimally changed in TNF-alpha-treated HCT116 cells, as determined by immunoblot and immunofluorescence. At 24 hours, p53 mRNA transcript levels were minimally increased in HT29 cells, whereas PUMA increased 34-fold.'] |
['The toll-like receptor 4 (TLR4) and inducible nitric oxide synthase are proteins from the innate immune system that, when activated, can induce insulin resistance. Polymorphisms in these genes, TLR4 and NOS2, respectively, could affect the immune response, as well as the prevalence of Type 2 diabetes (T2DM).', 'The aim of the present study was to investigate the contribution of four polymorphisms (two from TLR4 and two from NOS2) to susceptibility to T2DM in a southeast Brazilian population.', 'A total of 211 patients with T2DM and 200 unrelated controls were genotyped for the Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene and for the insertion (I)/deletion (D) AAAT and (CCTTT)n polymorphisms of the NOS2 promoter gene.', 'With regard to the NOS2 promoter region, the data showed that the I allele of the I/D AAAT polymorphism was more prevalent in the T2DM group and that the L/L genotype of the (CCTTT)n polymorphism was also more frequent in the same group. In contrast, the 299Gly allele and the 399Ile allele from the Asp299Gly and Thr399Ile TLR4 gene polymorphisms, respectively, were associated with protection of T2DM. It is believed that the persistence of these genetic variations in human populations may be indicative of a selective advantage in the face of different environmental pressures.'] |
['The endoscopic management of malignant hilar biliary strictures using multiple metallic stents (MS) is technically demanding, in the initial deployment of MS and the recovery from MS occlusion with deployment of multiple plastic stents (PS). We evaluated the outcomes of the application of a Soehendra stent retriever (SSR) as a dilator of intractable strictures.', 'Fifty-nine patients with malignant hilar biliary strictures had multiple MS inserted using a partial stent-in-stent procedure. When we encountered intractable strictures, we adopted SSR to dilate the stricture and the interstice of the MS. We evaluated the success rate of MS or PS deployment after SSR application and procedural complications.', 'Five of 59 patients (8%) were subjected to SSR application for the initial MS deployment. MS were successfully deployed in all of these patients (100%). MS occlusion was noted in 27 patients. We applied SSR to seven patients (26%) for the deployment of multiple PS after MS occlusion. In five patients (71%), successful PS deployment was achieved after the SSR application. No complications related to dilatation using SSR occurred in any patient.'] |
['Treatment of supraintercondylar (AO/OTA 33-C) and supracondylar (AO/OTA 33-A) femur fractures is generally challenging. Standard treatments include open reduction and internal fixation. However, optimal implants are now being well-defined. This study focus on the comparison between clinical and functional outcomes of fractures treated with condylar buttress plates (CBPs).', 'We treated 87 patients with supraintercondylar or supracondylar femur fracture from 2004 to 2008, including 30 supraintercondylar and 24 supracondylar fractures treated with CBPs. Both knee and function scores (per Knee Society) were given to clinical and functional outcomes, and concomitant knee function was assessed per Mize criteria.', 'Union rate of supraintercondylar fractures was 90\xa0% (27/30) and supracondylar fractures was 91.7\xa0% (22/24) (P\u2009=\u20090.68). In supraintercondylar group, 16.7\xa0% revealed postoperative varus deformity, whereas none in supracondylar group (P\u2009=\u20090.045). Knee Society knee score was 73.6 in supraintercondylar group and 85.5 in supracondylar group (P\u2009=\u20090.009); and function score was 62.5 in supraintercondylar group and 83.1 in supracondylar group (P\u2009=\u20090.023). A satisfactory result based on modified Mize criteria was achieved in 50\xa0% of supraintercondylar fractures and in 79.1\xa0% of supracondylar fractures (P\u2009=\u20090.09).'] |
['Senescence prevents cellular transformation. We investigated whether vascular endothelial growth factor (VEGF) signaling via its receptor, VEGFR2, regulates senescence and proliferation of tumor cells in mice with colitis-associated cancer (CAC).', 'CAC was induced in VEGFR2(ΔIEC) mice, which do not express VEGFR2 in the intestinal epithelium, and VEGFR2(fl/fl) mice (controls) by administration of azoxymethane followed by dextran sodium sulfate. Tumor development and inflammation were determined by endoscopy. Colorectal tissues were collected for immunoblot, immunohistochemical, and quantitative polymerase chain reaction analyses. Findings from mouse tissues were confirmed in human HCT116 colorectal cancer cells. We analyzed colorectal tumor samples from patients before and after treatment with bevacizumab.', 'After colitis induction, VEGFR2(ΔIEC) mice developed significantly fewer tumors than control mice. A greater number of intestinal tumor cells from VEGFR2(ΔIEC) mice were in senescence than tumor cells from control mice. We found VEGFR2 to activate phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT, resulting in inactivation of p21 in HCT116 cells. Inhibitors of VEGFR2 and AKT induced senescence in HCT116 cells. Tumor cell senescence promoted an anti-tumor immune response by CD8(+) T cells in mice. Patients whose tumor samples showed an increase in the proportion of senescent cells after treatment with bevacizumab had longer progression-free survival than patients in which the proportion of senescent tumor cells did not change before and after treatment.'] |
['Fanconi anemia protein, FANCJ, directly interacts with MLH1, a key protein involved in DNA mismatch repair. Deficient mismatch repair, or microsatellite instability, is a potent marker for the ineffectiveness of 5-fluorouracil (5-FU) in colorectal cancer (CRC). We investigated the significance of FANCJ expression in CRC, focusing on the effects of 5-FU-based adjuvant chemotherapy.', 'Clinicopathologic features and immunohistochemical expression of FANCJ and MLH1 were studied in 219 patients with CRC. We also analyzed 5-FU sensitivity in CRC cell lines with varying levels of FANCJ expression.', 'FANCJ expression was elevated in tumor tissues compared with normal epithelial tissue. High expression of FANCJ was significantly associated with 5-FU resistance measured by the SDI test (P < 0.05) and poor recurrence-free survival (RFS) (P < 0.05). Among patients with stage II/III tumors who received 5-FU, patients with tumors exhibiting high FANCJ expression had significantly worse RFS than did patients with tumors exhibiting low FANCJ expression (P < 0.01). Among patients who did not receive adjuvant chemotherapy, FANCJ expression was not correlated with RFS (P = 0.76). High FANCJ expression was correlated with 5-FU resistance in tumors with normal MLH1 expression (P < 0.05) but not in tumors not expressing MLH1 (P = 0.9). In vitro, FANCJ overexpression was correlated with 5-FU resistance in MLH1-proficient HCT116 3-6 cells but not in MLH1-deficient HCT116 cells.'] |
['There are no prior studies assessing the relationship between left atrial volume (LAV) and inappropriate implantable cardioverter-defibrillator (ICD) therapy following treatment with cardiac resynchronization therapy.', 'The purpose of this study was to investigate the hypothesis that patients randomized to cardiac resynchronization therapy with defibrillator (CRT-D) in the Multicenter Automatic Defibrillator Trial-Cardiac Resynchronization Therapy (MADIT-CRT) who had significant LAV reductions would have reduced risks of inappropriate ICD therapy.', 'Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients. Patients were stratified into quartiles based on percent reduction of LAV change. High LAV responders were those in the highest 3 quartiles of LAV reduction (LAV reduction ≥21%). Low LAV responders were those in the lowest quartile of LAV reduction (LAV reduction <21%). Clinical factors associated with ≥21% reduction in LAV were evaluated by linear regression analysis.', 'In Cox proportional hazards regression analyses, high LAV responders had a 39% reduction in the risk of inappropriate therapy (hazard ratio 0.61, P = .04) and left bundle branch block patients exhibited an even greater risk reduction in inappropriate therapy (hazard ratio 0.51, P = .02) compared to low LAV responders during follow-up extending up to 3 years after the 12-month echocardiogram. High LAV responders also had a significantly lower risk of heart failure or death during follow-up than did low LAV responders.'] |
['The prevalence of dyslipidemia and overweight is significantly higher in aircrews than that in general population. The purpose of the study was to examine the distribution of APOE gene polymorphism and the influence of which as well as occupational environment on dyslipidemia and overweight in Chinese civil aircrews.', 'APOE gene polymorphism was investigated using PCR-RFLP, plasma lipid parameters were measured by standard enzymatic kits and personal information of the aircrews was collected through questionnaires.', 'The allele frequencies among aircrews were ε2: 17.0%, ε3: 80.9%, and ε4: 2.1%, APOE gene polymorphism was associated with significant differences in TC and LDL-C. E2 individuals had the lowest TC and LDL-C concentrations, and E4 participants had the highest levels (p<0.001). In addition, the TC and LDL-C concentrations, as well as BMI rose with the increasing cumulative flying hours (p<0.05). The further logistic regression analysis showed the significant associations of BMI and dyslipidemia (p<0.0001, OR=2.093), cumulative flight time and overweight (p<0.0001, OR=1.560).'] |
['BCR-ABL1 mutation analysis is recommended to facilitate selection of appropriate therapy for patients with chronic myeloid leukemia after treatment with imatinib has failed, since some frequently occurring mutations confer clinical resistance to nilotinib and/or dasatinib. However, mutations could be present below the detection limit of conventional direct sequencing. We developed a sensitive, multiplexed mass spectrometry assay (detection limit, 0.05% to 0.5%) to determine the impact of low-level mutations after imatinib treatment has failed.', 'Mutation status was assessed in 220 patients treated with nilotinib or dasatinib after they experienced resistance to imatinib.', 'Mutations were detected by sequencing in 128 patients before commencing nilotinib or dasatinib therapy (switchover). In 64 patients, 132 additional low-level mutations were detected by mass spectrometry alone (50 of 132 mutations were resistant to nilotinib and/or dasatinib). When patients received the inhibitor for which the mutation confers resistance, 84% of the low-level resistant mutations rapidly became dominant clones detectable by sequencing, including 11 of 12 T315I mutations. Subsequent complete cytogenetic response rates were lower for patients with resistant mutations at switchover detected by sequencing (0%) or mass spectrometry alone (16%) compared with patients with other mutations or no mutations (41% and 49%, respectively; P < .001). Failure-free survival among the 100 patients with chronic phase chronic myeloid leukemia when resistant mutations were detected at switchover by sequencing or mass spectrometry alone was 0% and 0% compared with 51% and 45% for patients with other mutations or no mutations (P = .003).'] |
['Degeneration of central nervous system normal appearing white matter (NAWM) underlies disability and progression in multiple sclerosis (MS). Axon loss typifies NAWM degeneration.', 'The objective of this paper is to assess correlation between cortical lesion load and magnetisation transfer ratio (MTR) of the NAWM in MS. This was in order to test the hypothesis that cortical lesions cause NAWM degeneration.', 'Nineteen patients with MS underwent 7 Tesla magnetisation-prepared-rapid-acquisition-gradient-echo (MPRAGE), and magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI). Cortical lesions were identified using MPRAGE and MTR images of cortical ribbons. White matter lesions (WMLs) were segmented using MPRAGE images. WML maps were subtracted from white matter volumes to produce NAWM masks. Pearson correlation was calculated for NAWM MTR vs cortical lesion load, and WML volumes.', 'Cortical lesion volumes and counts all had significant correlation with NAWM mean MTR. The strongest correlation was with cortical lesion volumes obtained using MTR images (r = -0.6874, p = 0.0006). WML volume had no significant correlation with NAWM mean MTR (r = -0.08706, p = 0.3615).'] |
['Nitric oxide (NO.) derived from donor drugs has been shown to be an effective chemosensitizer in vitro. We investigated the combination of inducible nitric oxide synthase (iNOS) gene transfer, driven by a strong constitutive promoter (cytomegalovirus; CMV) with the DNA cross-linking agent cisplatin in mouse and human tumour cell lines.', 'Proof of principal experiments were performed in the radiation-induced fibrosarcoma-1 (RIF-1) murine cell line. Cells were transfected with constitutively expressed CMV/iNOS plasmid DNA using a cationic lipid vector, before exposure to cisplatin. In vivo efficacy was determined in an intradermal RIF-1 tumour model, with intraperitoneal administration of cisplatin. Additionally, treatment potential was investigated in various human tumour cell lines including human prostate (DU145 and PC3) and human colon (HT29 and HCT116) cancer cell lines. Experimental endpoints were established using western blot, Greiss test, clonogenic assay and tumour growth delay.', 'Transfection of RIF-1 tumour cells in vitro with the CMV/iNOS significantly enhanced the cytotoxicity of cisplatin (0.2-1.0 microM). In vivo transfer of CMV/iNOS by direct injection into established RIF-1 tumours caused a significant (p = 0.0027) delay in tumour growth. CMV/iNOS gene transfer in vitro resulted in the strong expression of iNOS DNA in all cell lines, and significantly increased levels of NO. in all cell lines except HCT116.'] |
['To study the effect of lycopene on ameliorating renal function of diabetic nephropathy.', 'Sixty male SD rats were divided into four groups: normal untreated (NC-U), normal treatment (NC-L), diabetes untreated (DM-U) and diabetes treatment (DM-L). DM was prepared by a single injection of STZ (70 mg/kg, intraperitoneally) dissolved in 0.1 M citrate buffer (pH 4.5). DM-U and NC-U rats received control diet; DM-L and NC-L rats received lycopene. After treated with lycopene for 8 weeks, blood was obtained for analyzing plasma lipid profiles, glucose and renal function. The kidneys were used to determine SOD activity, malondialdehyde (MDA) level, processed for histological examination and western blot.', 'Treatment of diabetic rats with lycopene decreased the values of blood urea nitrogen, 24 h urea protein and creatinine. The serum lipids like TC, TG, and LDL were decreased and HDL was increased in DM-L rats when compared with those of diabetic rats. Administration of lycopene decreased the levels of MDA content and expression of CTGF, increased Akt/PKB phosphorylation and SOD activity in diabetic renal tissues.'] |
['An increased basal growth hormone (GH) secretion and a parodoxical GH response to the oral glucose tolerance test (OGTT) have been reported in patients with liver cirrhosis. It has been suggested that the ratio between branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) (BCAA/ AAA ratio) may determine in part the brain concentration of the AAAs, since the BCAAs compete with the AAAs for entry across the blood-brain barrier, leading to the accumulation of false neurotransmitters such as octopamine and phenylethanolamine, which are able to stimulate GH secretion (via alpha 2-adrenergic stimulation). In this study we investigated the role of amino acids, particularly the BCAA/AAA ratio, in the paradoxical response of GH to the OGTT in patients with liver cirrhosis.', 'Twelve non-diabetic patients with biopsy-proven cirrhosis of the liver underwent an OGTT. Three of the five patients with a paradoxical response of GH to the OGTT underwent a second oral glucose administration associated with an infusion of BCAA solution from -30 min until 180 min.', 'During the OGTT, glucose and insulin levels increased from 4.8 +/- 0.2 to 9.6 +/- 0.7 mmol/l (P < 0.001) and from 18.8 +/- 2.6 to 104.4 +/- 13.8 mU/l (P < 0.005), respectively. GH levels increased from 8.6 +/- 2.6 to 22.4 +/- 10.8 mU/l although not significantly. Five patients had a paradoxical GH response to the OGTT. A negative correlation between serum GH values and BCAA/AAA ratio in the plasma at every time point of the OGTT was found. After co-administration of glucose and BCAA in three patients the BCAA/AAAs ratio increased, abolishing the paradoxical GH secretion.'] |
["Proteasome inhibition abrogates donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) in patients posttransplant. However, its effects on protective humoral immunity to vaccine antigens remain unknown. Herein, we report on bortezomib's safety regarding protective immunity in patients who have experienced HLA antibody reduction/removal.", 'Thirteen living donor renal transplant patients were treated with bortezomib one to two cycles (1.3 mg/m² × 4 doses) and plasmapheresis in 2008 to remove HLA antibodies posttransplant. Serial measurements of HLA antibody were conducted weekly before, during, and after treatment by means of single antigen bead on Luminex (One Lambda Inc., Canoga Park, CA). Measles and tetanus toxoid IgGs were measured quantitatively by using ELISA (American Research Products Inc., Belmont, MA).', 'All patients treated with bortezomib/plasmapheresis resulted in a primary DSA reduction of more than 50%. In 10 of 13 patients, complete DSA removal (to below 1000 mean fluorescent intensity) occurred. At 1 year posttreatment, antibody intensity remains significantly depressed in the group as a whole. Despite the significant effect on antibody production, tetanus toxoid and measles IgG levels remained unchanged and above the level of protection at 1 year posttreatment.'] |
['To investigate whether luteal E(2) administration reduces size discrepancies of early antral follicles.', 'Prospective, crossover study.', 'ART unit, Clamart, France.', 'Sixty women and 120 cycles.', 'On cycle day 3 (baseline day 3), all women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. From day 20 until the next cycle day 2, 30 of them received oral 17beta-E(2), whereas the remaining women served as controls. The day after E(2) discontinuation (E(2) day 3) or on subsequent cycle day 3 (control day 3), participants were reevaluated as on baseline day 3.', 'Magnitude of follicular size discrepancies.', 'Follicular size discrepancies and follicular diameters were significantly attenuated on E(2) day 3 (3.7 +/- 0.5 mm) as compared with baseline day 3 (4.9 +/- 1.0 mm), but not in controls (5.0 +/- 0.8 vs. 4.9 +/- 0.8 mm). FSH (4.3 +/- 1.9 vs. 7.3 +/- 3.3 mIU/mL) and inhibin B (34 +/- 28 vs. 71 +/- 32 pg/mL) levels were consistently lower on E(2) day 3 than on baseline day 3 but remained unchanged in controls.'] |
['The urinary CXC chemokine ligand (CXCL)10 detects renal transplant inflammation noninvasively, but has limited sensitivity and specificity. In this study, we performed urinary proteomic analysis to identify novel biomarkers that may improve the diagnostic performance of urinary CXCL10 for detecting alloimmune inflammation in renal transplant patients.', 'In preliminary studies, adult renal transplant patients with normal histology (n = 5), interstitial fibrosis and tubular atrophy (n = 6), subclinical (n = 6) and clinical rejection (n = 6), underwent in-depth urine protein compositional analysis with LC-MS/MS, and matrix metalloproteinase-7 (MMP7) were identified as a potential candidate for the diagnosis of renal allograft inflammation. Urine MMP7 performance was then studied in a larger, prospective adult renal transplant population (n = 148 urines from n = 133 patients) with matched surveillance/indication biopsies. The diagnostic performance of urinary MMP7 and CXCL10 in combination was next evaluated using concordance (C-) statistics, net reclassification improvement and integrated discrimination improvement indices, to determine whether it was better than CXCL10 alone.', 'Urinary MMP7:creatinine (Cr) was lower in normal transplants compared to those with inflammation: glomerulonephritis (P = 0.009), viral nephropathies (P = 0.002), interstitial fibrosis and tubular atrophy and inflammation (P = 0.04), borderline (P = 0.08), subclinical (P = 0.01) and clinical rejection (P = 0.0006), and acute tubular necrosis (P < 0.0001). Urinary MMP7:Cr and CXCL10:Cr significantly distinguished noninflamed from inflamed biopsies (area under the curve, 0.74 and 0.70, respectively). The addition of urinary MMP7:Cr to CXCL10:Cr improved the diagnostic performance for subclinical and clinical inflammation/injury by integrated discrimination improvement (P = 0.002) and net reclassification improvement (P = 0.006) analyses.'] |
['The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.', "Mouse lymphomas induced by 1,3-butadiene or 2',3'-dideoxycytidine were analysed for mutations in the Bcl11b gene using single strand conformation analysis and direct DNA sequencing. Effects on cell proliferation by the detected mutations were studied by expressing wild-type and mutant Bcl11b in the cytokine-dependent hematopoietic progenitor cell line FDC-P1, lacking endogenous Bcl11b expression.", 'Missense and frameshift (FS) mutations were identified in 7 of 47 tumors (15%). Interestingly, all mutations were found between amino acids 778-844 which encode the three C-terminal DNA-binding zinc fingers. In FDC-P1 cells, wild-type Bcl11b suppressed cell proliferation, whereas the mutated versions (S778N, K828T, Y844C and FS823) enhanced proliferation several-fold.'] |
['We describe a method to improve tumor cell detection compared to currently available immunocytochemical methods by using immunomagnetic cell enrichment.', 'Two different methods of immunomagnetic cell enrichment using antibody coated magnetic beads were tested and compared with unenriched immunocytochemistry. One method was positive selection of epithelial cells from mononuclear cells with the antiepithelial antibody BER-EP4 and the other was depletion of mononuclear cells with the antileukocyte antibody CD45. Mononuclear cells were isolated from peripheral blood by density centrifugation and various numbers of tumor cells were added. The 5 different cell lines from urological malignancies used in the study were DU-145, RT-4, CAKI-2, KTCTL-2 and KTCTL-30. Following incubation of cell suspensions with the beads, cell separation was performed in a magnetic field. After centrifugation on glass slides immunocytochemical staining for cytokeratin was performed. A total of 112 experiments were completed and negative controls were obtained.', 'The number of tumor cells detected by positive selection and depletion was significantly higher than by immunocytochemistry (p <0.001). The median enrichment factor and tumor cell recovery rate for positive selection and depletion were 15.3 and 61.2%, and 13.0 and 57.3%, respectively (not significant). With less than 1 tumor cell suspended in 106 mononuclear cells, the probability of tumor cell detection was 23% for immunocytochemistry alone and 93.3% for both enrichment methods (p <0.01). No false-positive results were observed.'] |
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