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['Diabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90-95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED.', 'Goto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability.', 'Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured.', 'GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein.', 'GK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages.'] Is erectile dysfunction in young non-obese type II diabetic Goto-Kakizaki rats associated with decreased eNOS phosphorylation at Ser1177?
|
qiaojin/PubMedQA
| 2 |
[
-2.316260576248169,
-1.2871675491333008,
2.565574884414673
] |
['Ezrin/radixin/moesin (ERM) proteins are highly homologous proteins that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin are both expressed in mature lymphocytes, where they play overlapping roles in cell signaling and polarity, but their role in lymphoid development has not been explored.', 'We characterized ERM protein expression in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid development. In wildtype mice, we found that most cells in the spleen and thymus express both ezrin and moesin, but little radixin. ERM protein expression in the thymus was differentially regulated, such that ezrin expression was highest in immature thymocytes and diminished during T cell development. In contrast, moesin expression was low in early thymocytes and upregulated during T cell development. Mice bearing a germline deletion of ezrin exhibited profound defects in the size and cellularity of the spleen and thymus, abnormal thymic architecture, diminished hematopoiesis, and increased proportions of granulocytic precursors. Further analysis using fetal liver chimeras and thymic transplants showed that ezrin expression is dispensable in hematopoietic and stromal lineages, and that most of the defects in lymphoid development in ezrin(-/-) mice likely arise as a consequence of nutritional stress.'] Is ezrin highly expressed in early thymocytes , but dispensable for T cell development in mice?
|
qiaojin/PubMedQA
| 2 |
[
-2.4346439838409424,
-1.1188886165618896,
2.5806596279144287
] |
['Small animal model has not been available to study cardiac pathophysiology during hemorrhagic shock. The main purpose of this study, therefore, was to establish earlier differences in left ventricle functional disturbances during hypovolemia comparable in survival and nonsurvival animals. Ventricular pressure-volume relationships have become well established as the most rigorous and comprehensive venue to assess intact heart function.', 'Studies were performed in anesthetized hamsters subjected to a 40% of blood volume hemorrhage to induce the hypovolemic shock. A miniaturized conductance catheter was used to measure left ventricular pressure and volume. Derived from the pressure-volume measurements, cardiac performance was evaluated using systolic and diastolic function indices.', 'Thirteen animals were included; all animals survived the hemorrhage. Survival rate after 30 minutes of hypovolemic shock was 61.5%. End-systolic pressure was improved at the late stage of shock in the survival group, whereas no change of this index was found in the nonsurvival group. No significant differences in end-diastolic pressure and relaxation time constant were found between the nonsurvival and the survival groups. Fifteen minutes after the hemorrhage, the stroke work per stroke volume ratio significantly improved in the survival compared with nonsurvival, which also restored blood pressure.'] Does cardiac systolic function recovery after hemorrhage determine survivability during shock?
|
qiaojin/PubMedQA
| 2 |
[
-2.1188571453094482,
-0.9450963139533997,
2.144394636154175
] |
['Quantitative measures derived from magnetic resonance imaging (MRI) have been widely investigated as non-invasive biomarkers in multiple sclerosis (MS). However, the correlation of single measures with Expanded Disability Status Scale (EDSS) is poor, especially for studies with large population samples.', 'To explore the correlation of MRI-derived measures with EDSS through composite MRI scores.', "Magnetic resonance images of 126 patients with relapsing-remitting MS were segmented into white and gray matter, cerebrospinal fluid, T2-hyperintense lesions, gadolinium contrast-enhancing lesions, T1-hypointense lesions ('black holes': BH). The volumes and average T2 values for each of these tissues and lesions were calculated and converted to a z-score (in units of standard deviation from the mean). These z-scores were combined to construct composite z-scores, and evaluated against individual z-scores for correlation with EDSS.", 'Composite scores including relaxation times of different tissues and/or volumetric measures generally correlated more strongly with EDSS than individual measures. The maximum observed correlation of a composite with EDSS was r = 0.344 (p < 0.0001), which is an improvement over the highest-performing single MRI measure (BH; r = 0.298, p < 0.001).'] Do composite MRI scores improve correlation with EDSS in multiple sclerosis?
|
qiaojin/PubMedQA
| 2 |
[
-1.3963947296142578,
-1.4870922565460205,
1.7764315605163574
] |
['Exercise is associated with a decrease in bone mineral density under certain conditions. One potential mechanism is increased bone resorption due to an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by dermal calcium loss. The purpose of this investigation was to determine whether calcium supplementation either before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of Type I collagen (CTX; a marker of bone resorption).', 'Male endurance athletes (n = 20) completed three 35-km cycling time trials under differing calcium supplementation conditions: 1) 1000 mg of calcium 20 min before exercise and placebo during, 2) placebo before and 250 mg of calcium every 15 min during exercise (1000 mg total), or 3) placebo before and during exercise. Calcium was delivered in a 1000-mg·L(-1) solution. Supplementation was double-blinded, and trials were performed in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of bone formation), and ionized calcium (iCa) were measured before and immediately after exercise.', 'CTX increased and iCa decreased similarly in response to exercise under all test conditions. When compared with placebo, calcium supplementation before exercise attenuated the increase in PTH (mean ± SE: 55.8 ± 15.0 vs 74.0 ± 14.2 pg·mL(-1), P = 0.04); there was a similar trend (58.0 ± 17.4, P = 0.07) for calcium supplementation during exercise. There were no effects of calcium on changes in CTX, BAP, and iCa.'] Does acute calcium ingestion attenuate exercise-induced disruption of calcium homeostasis?
|
qiaojin/PubMedQA
| 2 |
[
-1.3227872848510742,
-1.5969977378845215,
1.8498942852020264
] |
['A previous study has reported that the Ile227 and Ala357 genetic variants of human urea transporter-2 (HUT2) were associated with blood pressure in males in Asian population. In this study, we aimed to investigate five known HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study cohort.', 'Five HUT2 single nucleotide polymorphisms (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study cohort. We first computed allele frequency and performed Hardy-Weinberg equilibrium (HWE) test in controls for each SNP. Next, we tested genotype associations with metabolic syndrome using multiple generalized estimating equations (GEE) models with covariate adjustment. Furthermore, multi-marker and multi-trait association tests were carried out using FBAT program. To account for multiple testing, Bonferroni correction was applied in this study.', 'Among those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the total sample and females, separately (9×10(-4)≤p≤0.04), but only the association between SNP 1 and MetS in females remained statistically significant after Bonferroni correction. When testing 5 SNPs simultaneously, significant associations were found with triglycerides (TG) (p=0.04). Likewise, significant multi-trait association (combining the data of waist circumference, TG, high density lipoprotein (HDL) cholesterol and fasting glucose together) was found with SNP 2 (p=0.04), but both results of multi-maker and multi-trait associations did not remain significant after multiple testing correction.'] Are genetic variants of human urea transporter-2 associated with metabolic syndrome in Asian population?
|
qiaojin/PubMedQA
| 2 |
[
-1.5953410863876343,
-1.4378867149353027,
1.966622233390808
] |
['This study aimed to investigate the role of the neurotensin/neurotensin receptor I (NTSR1) complex in non-small cell lung cancer (NSCLC) progression.', 'The expression of neurotensin and NTSR1 was studied by transcriptome analysis and immunohistochemistry in two series of 74 and 139 consecutive patients with pathologic stage I NSCLC adenocarcinoma. The findings were correlated with clinic-pathologic features. Experimental tumors were generated from the malignant human lung carcinoma cell line A459, and a subclone of LNM35, LNM-R. The role of the neurotensin signaling system on tumor growth and metastasis was investigated by small hairpin RNA-mediated silencing of NTSR1 and neurotensin.', 'Transcriptome analysis carried out in a series of 74 patients showed that the positive regulation of NTSR1 put it within the top 50 genes related with relapse-free survival. Immunohistochemistry revealed neurotensin- and NTSR1-positive staining in 60.4% and 59.7% of lung adenocarcinomas, respectively. At univariate analysis, NTSR1 expression was strongly associated with worse 5-year overall survival rate (P = 0.0081) and relapse-free survival (P = 0.0024). Multivariate analysis showed that patients over 65 years of age (P = 0.0018) and NTSR1 expression (P = 0.0034) were independent negative prognostic factors. Experimental tumor xenografts generated by neurotensin- and NTSR1-silenced human lung cancer cells revealed that neurotensin enhanced primary tumor growth and production of massive nodal metastasis via autocrine and paracrine regulation loops.'] Does neurotensin receptor 1 determine the outcome of non-small cell lung cancer?
|
qiaojin/PubMedQA
| 2 |
[
-2.203282117843628,
-1.4204117059707642,
2.676102638244629
] |
['Increased proliferation of airway smooth muscle cells (ASMCs) are observed in asthmatic patients and smoking can accelerate proliferation of ASMCs in asthma. To elucidate the molecular mechanisms leading to these changes, we studied in vitro the effect of cigarette smoke extract (CSE) on the proliferation of ASMCs and the expression of cyclin D1, an important regulatory protein implicated in cell cycle.', 'ASMCs cultured from 8 asthmatic Brown Norway rats were studied. Cells between passage 3 and 6 were used in the study and were divided into control group, pcDNA3.1 group, pcDNA3.1-antisense cyclin D1 (ascyclin D1) group, CSE group, CSE + pcDNA3.1 group and CSE + pcDNA3.1-ascyclin D1 group based on the conditions for intervention. The proliferation of ASMCs was examined with cell cycle analysis, MTT colorimetric assay and proliferating cell nuclear antigen (PCNA) immunocytochemical staining. The expression of cyclin D1 was detected by reverse transcriptase-PCR (RT-PCR) and Western blotting.', '(1) The percentage of S + G2M phase, absorbance value at 490 nm wavelength (A(490)) and the expression rate of PCNA protein in CSE group were (31.22 +/- 1.17)%, 0.782 +/- 0.221, (90.2 +/- 7.0)% respectively, which were significantly increased compared with those of control group ((18.36 +/- 1.02)%, 0.521 +/- 0.109, and (54.1 +/- 3.5)%, respectively) (P < 0.01). After the transfection with antisense cyclin D1 plasmid for 30 hours, the percentage of S + G2M phase, A(490) and the expression rate of PCNA protein in ASMCs were much lower than in untreated cells (P < 0.01). (2) The ratios of A(490) of cyclin D1 mRNA in CSE group was 0.288 +/- 0.034, which was significantly increased compared with that of control group (0.158 +/- 0.006) (P < 0.01). After the transfection with antisense cyclin D1 plasmid for 30 hours, the ratios of A(490) of cyclin D1 mRNA in ASMCs was much lower than in untreated cells (P < 0.01). (3) The ratios of A(490) of cyclin D1 protein expression in CSE group was 0.375 +/- 0.008, which was significantly increased compared with that of control group (0.268 +/- 0.004) (P < 0.01). After the transfection with antisense cyclin D1 plasmid for 30 hours, the ratios of A(490) of cyclin D1 protein expression in ASMCs was much lower than in untreated cells (P < 0.01).'] Does cigarette smoke extract promote proliferation of airway smooth muscle cells in asthmatic rats via regulating cyclin D1 expression?
|
qiaojin/PubMedQA
| 2 |
[
-1.3251038789749146,
-1.68927800655365,
1.9617156982421875
] |
['Transplantation of adult bone marrow-derived mesenchymal stem cells (MSCs) has been proposed as a strategy for cardiac repair following myocardial damage. However cell transplantation strategies to replace lost myocardium are limited by the inability to deliver large numbers of cells that resist peritransplantation graft cell death. Accordingly, we set out to isolate and expand adult swine bone marrow-derived MSCs, and to engineer these cells to overexpress AKT1 (protein kinase B), to test the hypothesis that AKT1-engineered MSCs are more resistant to apoptosis and can enhance cardiac repair after transplantation into the ischemic swine heart.', 'The CDS (regulation domain of AKT1) AKT1-cDNA fragment was amplified, and MSCs were transfected following synthesis with a pCDH1-AKT1 shuttling plasmid. Western blotting analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed. Myocardial infarction (MI) models were constructed in Meishan pigs, and cardiac function was evaluated by magnetic resonance imaging (MRI) measurements and echocardiography 4 weeks later. All pigs were assigned to four groups: control (A), DMEM (B), MSC (C), and AKT-transfected (D). MSCs were transfected with the AKT1 gene, and autologous BrdU-labeled stem cells (1 x 10(7)/5 ml) were injected into left anterior descending coronary atery (LAD) of the infarct heart in groups C and D. In group B, DMEM was injected using the same approach. In group A, there was no injection following LAD occlusion. After 4 weeks, cardiac function and regional perfusion measurements were repeated by MRI and echocardiography, and histological characteristics of the hearts were assessed. Connecxin-43 (CX-43), BrdU, and von Willebrand factor (VWF) immunoreactivity was tested using enzyme linked immunosorbent assay (ELISA). Vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1) were analyzed at the same time.', 'AKT1-cDNA was cloned into pCDH1-MCS1-EF1-copGFP and the sequence was confirmed. AKT mRNA expression was detected at 24 hours after transfection. AKT1 expression in MSCs remained strong after 2 weeks, according to real-time RT-PCR and Western blotting. Prior to cell implantation, end-diastolic left ventricular dimension (EDLVd) increased and stroke volume (SV) decreased in the MI hearts. MRI scans revealed significantly improved cardiac function following implantation, and implanted MSCs prevented thinning and expanding in the infarct region, as well as improved contraction and increased perfusion in all groups compared to control hearts. The left ventricular chamber size was smaller in cell-transplanted hearts than in control hearts. Moreover, group D exhibited significant improvement. The expression of CX-43, BrdU, and VWF could be found in the immunohistochemical pathological sections of group C and group D. The level of VEGF reached a high level 1 week after implanting the MSCs, but the level of TGF-beta1 decreased gradually.'] Do aKT-modified autologous intracoronary mesenchymal stem cells prevent remodeling and repair in swine infarcted myocardium?
|
qiaojin/PubMedQA
| 2 |
[
-2.2720792293548584,
-1.4825177192687988,
2.7797646522521973
] |
['Early studies showed that naloxone infusion decreases the incidence of morphine-related side effects from intravenous patient-controlled analgesia. This study aimed to determine whether naloxone preserved analgesia while minimizing side effects caused by intravenous tramadol administration.', 'Eighty patients undergoing general anesthesia for cervical vertebrae surgery were randomly divided into four groups. All patients received 1 mg/kg tramadol 30 minutes before the end of surgery, followed by a continuous infusion with 0.3 mg x kg(-1) x h(-1) tramadol with no naloxone (group I, n = 20), 0.05 microg x kg(-1) x h(-1) naloxone (group II, n = 20), 0.1 microg x kg(-1) x h(-1) naloxone (group III, n = 20) and 0.2 microg x kg(-1) x h(-1) naloxone (group IV, n = 20). Visual analog scales (VAS) for pain during rest and cough, nausea five-point scale (NFPS) for nausea and vomiting, and ramsay sedation score (RSS) for sedation were assessed at 2, 6, 12, 24 and 48 hours postoperatively. Analgesia and side effects were evaluated by blinded observers.', 'Seventy-eight patients were included in this study. The intravenous tramadol administration provided the satisfied analgesia. There was no significant difference in either resting or coughing VAS scores among naloxone groups and control group. Compared with control group, sedation was less in groups II, III, and IV at 6, 12, and 24 hours (P < 0.05); nausea was less in groups II, III and IV than group I at 2, 6, 12, 24 and 48 hours postoperatively (P < 0.05). The incidence of vomiting in the control group was 35% vs. 10% for the highest dose naloxone group (group IV) (P < 0.01).'] Does a small-dose naloxone infusion alleviate nausea and sedation without impacting analgesia via intravenous tramadol?
|
qiaojin/PubMedQA
| 2 |
[
-1.7880146503448486,
-1.533806324005127,
2.341670036315918
] |
['Tobacco taxes are one of the most effective ways to reduce tobacco use. Transnational tobacco companies (TTCs) claim they wish to develop and secure excise systems that benefit both governments and the profitability of the companies themselves. The objective of the paper is to use the case of Ukraine, with its inconsistent history of excise tax changes in 1992-2008, to explore tobacco industry taxation strategies and tactics, and their implications for governmental revenues.', 'Details of tobacco industry policy on tobacco taxation in Ukraine were obtained by searching tobacco industry internal documents and various published reports.', 'Even before entering the market in Ukraine, TTCs had made efforts to change the excise system in the country. In 1993-1994, TTCs lobbied the Ukrainian Government, and succeeded in achieving a lowering in tobacco tax. This, however, did not produce revenue increase they promised the Government. In 1996-1998, Ukrainian authorities increased excise several times, ignoring the wishes of TTCs, caused significant growth in revenue. Due to TTCs lobbying activities in 1999-2007 the tax increases were very moderate and it resulted in increased tobacco consumption in Ukraine. In 2008, despite the TTCs position, excise rates were increased twice and it was very beneficial for revenues.'] Is `` The lobbying strategy to keep excise as low as possible '' - tobacco industry excise taxation policy in Ukraine?
|
qiaojin/PubMedQA
| 1 |
[
-2.5318801403045654,
3.2386763095855713,
-1.1957412958145142
] |
['Age-related muscle atrophy is characterized by increased oxidative stress, diminished Akt enzymatic function, and reduced phosphorylation of the mammalian target of rapamycin (mTOR), which can be attenuated by chronic acetaminophen ingestion. Here we hypothesize that age-related impairments in Akt/mTOR function are associated with reduced protein translational signaling, and that these changes, if present, can be attenuated by acetaminophen treatment.', 'Compared to 6- and 27-month old animals, the expression of the mTOR-complex proteins raptor and GβL and the phosphorylation of tuberin/TSC2 (Thr1462) were reduced in the soleus muscles of very aged rats (33 months old). These changes in Akt/mTOR pathway signaling proteins were in turn associated with decreased phosphorylation of S6 kinase p85S6K (Thr412) and eukaryotic translation initiation factor-4E (eIF4E) binding protein-1 (4EBP1, Thr37/46), reduced phosphorylation of S6 ribosomal protein (Ser235/236), and increased inhibition of eIF4E by binding to 4EBP1. Age-associated alterations in the Akt/mTOR pathway signaling and in the phosphorylation of the stress-responsive eIF2α protein were attenuated by chronic acetaminophen treatment (30 mg/kg body weight per day). Ex vivo incubation of adult muscles with hydrogen peroxide mimicked the age-related decreases seen in eIF4E and 4EBP1 phosphorylation, whereas the inclusion of acetaminophen in the muscle bath attenuated this effect.'] Does acetaminophen improve protein translational signaling in aged skeletal muscle?
|
qiaojin/PubMedQA
| 2 |
[
-2.445096492767334,
-1.2857686281204224,
2.7268850803375244
] |
['Our aim was to investigate effects of bosentan on hand perfusion in patients with systemic sclerosis (SSc) with pulmonary arterial hypertension (PAH), using laser Doppler perfusion imaging (LDPI).', 'We enrolled 30 SSc patients with PAH, 30 SSc patients without PAH, and 30 healthy controls. In SSc patients and healthy controls at baseline, skin blood flow of the dorsum of the hands was determined with a Lisca laser Doppler perfusion imager. The dorsal surface of the hands was divided into 3 regions of interest (ROI). ROI 1 included 3 fingers of the hand from the second to the fourth distally to the proximal interphalangeal finger joint. ROI 2 included the area between the proximal interphalangeal and the metacarpophalangeal joint. ROI 3 included only the dorsal surface of the hand without the fingers. LDPI was repeated in SSc patients and controls after 4, 8, and 16 weeks of treatment. In SSc patients, nailfold videocapillaroscopy and Raynaud Condition Score (RCS) were performed at baseline and at 4, 8, and 16 weeks.', 'SSc patients with PAH enrolled in the study received treatment with bosentan as standard care for PAH. In these patients with PAH, after 8 and 16 weeks of treatment, bosentan improved minimum, mean, and maximum perfusion and the perfusion proximal-distal gradient. Bosentan seems to be most effective in patients with the early and active capillaroscopic pattern than in patients with the late pattern. Bosentan improved skin blood flow principally in the ROI 1 compared to the ROI 2 and ROI 3. Bosentan restored the perfusion proximal-distal gradient in 57% of SSc patients with the early capillaroscopic pattern. No significant differences from baseline were observed in the RCS in SSc patients with PAH.'] Does bosentan improve skin perfusion of hands in patients with systemic sclerosis with pulmonary arterial hypertension?
|
qiaojin/PubMedQA
| 2 |
[
-1.950126051902771,
-1.5130438804626465,
2.483008861541748
] |
['There has been strong recent interest in the association between serum ferritin concentrations and increased risk of cardiovascular events. Surplus nutrition and convenience-seeking behavior has contributed to emergence of an increasingly obese population, with a concurrent increase in the prevalence of cardiovascular diseases. To date, few studies have specifically examined the association between serum ferritin and aortic stiffness in healthy populations, thus we investigated the association between serum ferritin and aortic stiffness according to sex and obesity in healthy subjects.', 'From a register of 196 healthy subjects (146 males, 50 females) 23 to 76 years of age, we measured BMI, serum ferritin, blood pressures, metabolic variables, and brachial ankle pulse wave velocity (baPWV). The average baPWV, serum ferritin and the sociodemographic prevalence (smoking, alcohol, and exercise) were higher in men than women. There was a positive association between serum ferritin and baPWV (R = 0.02) in total subjects after adjusting for age, sex, and blood pressures. The association between serum ferritin and baPWV (R = 0.099) in women was positive, yet negative in men (R = -0.007). The average baPWV and serum ferritin were highest in obese men, on the other hand lowest in nonobese women among 4 groups according to sex and obesity.'] Is serum ferritin linked with aortic stiffness in apparently healthy Korean women?
|
qiaojin/PubMedQA
| 2 |
[
-1.4066253900527954,
-0.8144728541374207,
1.2810041904449463
] |
['To investigate oxidative damage and antioxidant enzyme status in the liver of guinea pigs exposed to mobile phone-like radiofrequency radiation (RFR) and the potential protective effects of N-acetyl cysteine (NAC) and epigallocatechin-gallate (EGCG) on the oxidative damage.', 'Nine groups of guinea pigs were used to study the effects of exposure to an 1800-MHz Global System for Mobile Communications (GSM)-modulated signal (average whole body Specific Absorption Rate (SAR) of 0.38 W/kg, 10 or 20 min per day for seven days) and treatment with antioxidants.', 'Significant increases in malondialdehyde (MDA) and total nitric oxide (NO(x)) levels and decreases in activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) were observed in the liver of guinea pigs after RFR exposure. Only NAC treatment induces increase in hepatic GSH-Px activities, whereas EGCG treatment alone attenuated MDA level. Extent of oxidative damage was found to be proportional to the duration of exposure (P < 0.05).'] Is mobile phone radiation-induced free radical damage in the liver inhibited by the antioxidants N-acetyl cysteine and epigallocatechin-gallate?
|
qiaojin/PubMedQA
| 2 |
[
-2.4682207107543945,
-1.2015107870101929,
2.739295244216919
] |
['Communication of signals from irradiated to non-irradiated fish has been demonstrated by our group for adults. Major questions are however, whether the effects persist for significant lengths of time (meaning there are memories or legacies of the exposure) and whether they are induced in young animals or very early stages in the life cycle.', "To address these questions we used a reporter cell clonogenic bioassay to detect the effects of radiation exposure and of 'bystander' signals, emitted from irradiated fish, on non-irradiated fish. The legacy of radiation exposure or receipt of bystander signals was investigated in rainbow trout irradiated as eggs at 48 h, eyed eggs at one month, yolk sac larvae (YSL) at two months and juveniles at three months after fertilisation. The irradiated and bystander fish together with shams and unhandled husbandry controls were grown on in a hatchery and examined as they reached each of the remaining life stages. They were also re-examined as one-year-olds with and without further irradiation and finally examined as sexually mature two-year-olds.", 'The data indicate a clear legacy effect of irradiation at any early life stage in the adult fish.'] Does irradiation of rainbow trout at early life stages result in legacy effects in adults?
|
qiaojin/PubMedQA
| 2 |
[
-2.869244337081909,
-0.03395074978470802,
1.9409511089324951
] |
["To analyze clinical manifestations, serum ferritin, and serum cytokine levels in patients with adult-onset Still's disease (AOSD) or bacterial sepsis and to evaluate their potential use for differential diagnosis.", 'Twenty-two consecutive patients with the first flare of AOSD and 6 patients with an established diagnosis of AOSD under immunosuppressive therapy were compared with 14 patients with bacterial sepsis. Clinical manifestations were scored in a Pouchot AOSD activity score including elevated serum ferritin levels to obtain a modified Pouchot score. Serum cytokine profiles were analyzed from each patient.', 'The scores of clinical manifestations using a modified Pouchot activity score were significantly higher in patients with active untreated AOSD (mean 5.60 ± 1.93) compared with patients with chronic AOSD (mean 1.16 ± 0.98; p < 0.001) and patients with sepsis (mean 2.38 ± 1.19; p < 0.001). A modified Pouchot score ≥ 4 shows a sensitivity of 92% and a specificity of 93% for active AOSD. Serum cytokine levels of interleukin 1ß (IL-1ß), IL-6, IL-8, IL-10, IL-12, IL-18, interferon-γ, tumor necrosis factor-α, and calprotectin were elevated in acute AOSD and sepsis. Significant differences were detected only in patients with sepsis who had higher levels of IL-6 and IL-8. The overlap of the 2 groups limits the use of cytokines for differential diagnosis in individual patients.'] Do clinical manifestations but not cytokine profiles differentiate adult-onset Still 's disease and sepsis?
|
qiaojin/PubMedQA
| 2 |
[
-2.291747570037842,
-1.2750937938690186,
2.6380763053894043
] |
['The aim of this study was to investigate the possible effect of somatostatin on the liver function of recipients undergoing living donor liver transplantation.', 'Forty recipients were randomized into group A (n = 20) and group B (n = 20). Recipients in group A received no somatostatin whereas somatostatin was administrated for recipients in group B perioperatively. Liver function, the plasma concentration of endothelin-1 and nitric oxide, the intragraft expressions of endothelin-1 and inducible nitric oxide syntheses at 2 hours after declamping of the portal vein were compared between the two groups.', 'Compared to group A, alanine transaminase values in group B were significantly reduced at 2 hours after portal vein declamping, at the end of the operation and postoperation day 1 (P < 0.05), whereas aspartate aminotransferase values in group B decreased at 30 minutes after portal vein clamping, at 2 hours after portal vein declamping and at the end of the operation (P < 0.05). Total bilirubin values in group B were reduced significantly at 2 hours after portal vein declamping and at the end of the operation when compared to group A (P < 0.05). Intragraft expression of endothelin-1 was significantly downregulated at 2 hours after declamping of the portal vein accompanied with a reduction of plasma concentration of endothelin-1 in the peripheral blood (P < 0.05).'] Does downregulation of endothelin-1 by somatostatin improve liver function of recipients undergoing adult-to-adult living donor liver transplantation?
|
qiaojin/PubMedQA
| 2 |
[
-1.8059104681015015,
-1.4689890146255493,
2.257157325744629
] |
['Pedicle screw loosening is a major safety concern in instrumented spinal surgery due to loosening with potential pseudarthrosis and possible loss of correction requiring revision surgery. Several cadaver studies have compared insertion torque of pedicle screws with resistance to pullout or cyclic loading. In most of these studies, a correlation has been found between these variables. Clinical studies have been made, comparing insertion torque to bone mineral density or radiological signs of screw loosening. There are no clinical studies comparing insertion torque to extraction torque or other biomechanical parameters in vivo. This study was designed to investigate whether the insertion torque of pedicle screws can be used to predict the purchase of the screws.', 'The insertion torque of stainless steel pedicle screws was recorded in eight patients undergoing lumbar fusion surgery with four-screw constructs. Torque gauge manometers were used for the recordings. The implants were removed after one year, and the extraction torque of the screws was recorded.', 'The mean insertion torque was 76 ± 41 Ncm and the mean extraction torque 29 ± 36 Ncm. The r value was 0.591, suggesting that there was a correlation between the insertion and extraction torque. However, the scattergram revealed that the screws could be divided into two groups, six screws with a high correlation between insertion and extraction torque, and 26 screws where no correlation could be demonstrated.'] Is insertion torque a good predictor of pedicle screw loosening after spinal instrumentation : a prospective study in 8 patients?
|
qiaojin/PubMedQA
| 2 |
[
-2.1686041355133057,
-1.1941636800765991,
2.5046186447143555
] |
['Conditional gene activation is an efficient strategy for studying gene function in genetically modified animals. Among the presently available gene switches, the tetracycline-regulated system has attracted considerable interest because of its unique potential for reversible and adjustable gene regulation.', 'To investigate whether the ubiquitously expressed Gt(ROSA)26Sor locus enables uniform DOX-controlled gene expression, we inserted the improved tetracycline-regulated transcription activator iM2 together with an iM2 dependent GFP gene into the Gt(ROSA)26Sor locus, using gene targeting to generate ROSA26-iM2-GFP (R26t1Δ) mice. Despite the presence of ROSA26 promoter driven iM2, R26t1Δ mice showed very sparse DOX-activated expression of different iM2-responsive reporter genes in the brain, mosaic expression in peripheral tissues and more prominent expression in erythroid, myeloid and lymphoid lineages, in hematopoietic stem and progenitor cells and in olfactory neurons.'] Does tetracycline-controlled transgene activation using the ROSA26-iM2-GFP knock-in mouse strain permit GFP monitoring of DOX-regulated transgene-expression?
|
qiaojin/PubMedQA
| 2 |
[
-2.423471212387085,
-1.0458041429519653,
2.4925127029418945
] |
['Picoplatin is a new generation platinum designed to overcome platinum resistance. The goal of this study was to assess picoplatin anti-tumor activity and measure various cellular parameters in small-cell lung cancer (SCLC) cells resistant to cell killing by cisplatin and carboplatin.', 'We developed several platinum-resistant SCLC cell lines to evaluate picoplatin activity and drug resistance mechanisms in vitro. Drug cytotoxicity was measured by MTS assay. Total cellular platinum accumulation was measured by inductively coupled plasma mass spectrometry (ICP-MS). Whole genome gene expression profiling was carried out by microarray analysis.', 'Picoplatin retained significant cytotoxic activity in platinum-resistant SCLC lines compared to cisplatin and carboplatin. Cellular picoplatin accumulation in platinum-resistant and parental cells was high relative to levels of cellular platinum found in the same cell lines after cisplatin or carboplatin treatment. Gene expression analyses revealed substantial differences in gene expression and highlighted specific annotation clusters in carboplatin-resistant cells. In addition, a similar gene expression pattern was observed in picoplatin-treated carboplatin-resistant and parental cells.'] Does picoplatin overcome resistance to cell toxicity in small-cell lung cancer cells previously treated with cisplatin and carboplatin?
|
qiaojin/PubMedQA
| 2 |
[
-2.364422559738159,
-1.189960241317749,
2.632772922515869
] |
['A dietary portfolio has been used to reduce blood lipids in hyperlipidemic subjects. To increase the effectiveness of these dietary treatments in specific populations, it is important to study the genetic variability associated with the development of certain types of hyperlipidemias. Low plasma high-density lipoprotein cholesterol (HDL-C) levels are the most common dyslipidemia in Mexican adults and are coupled with the presence of the ABCA1 R230C genotype. Therefore, the aim of this study was to assess the response of HDL-C concentration to a dietary portfolio in a group of Mexican hyperlipidemic subjects with ABCA1R230C (rs9282541) and R219K (rs2230806) polymorphisms.', 'Forty-three hyperlipidemic subjects (20 men and 23 women) were given a low saturated fat (LSF) diet for one month, followed by a LSF diet that included 25g of soy protein and 15g of soluble fiber daily for 2months. We analyzed two ABCA1 polymorphisms and studied their association with serum lipids before and after treatment.', 'Hyperlipidemic subjects with the ABCA1 R230C genotype showed lower HDL-C concentrations at the beginning of the study and were better responders to the dietary treatment than subjects with the ABCA1 R230R genotype (+4.6% vs. +14.6%) (p=.05). According to gender and the presence of the R230C genotype, women responded more significantly to the dietary treatment, reflected by an increase of 21.9% in HDL concentration (p=.022), than women with R230R genotype who only experienced an increase of 2.7% in HDL-C concentration. There was no association between the presence of the ABCA1 R219K variant (p=.544) and HDL concentration.'] Is increase in HDL-C concentration by a dietary portfolio with soy protein and soluble fiber associated with the presence of the ABCA1R230C variant in hyperlipidemic Mexican subjects?
|
qiaojin/PubMedQA
| 2 |
[
-1.6277892589569092,
-1.388214111328125,
1.970789909362793
] |
['GM is typically affected in HD since the presymptomatic stage. Our aim was to investigate with MT MR imaging the microstructural changes of the residual brain subcortical and cortical GM in carriers of the HD gene and to preliminarily assess their correlation with the clinical features.', 'Fifteen HD gene carriers with a range of clinical severity and 15 age- and sex-matched healthy controls underwent MT MR imaging on a 1.5T scanner. The MT ratio was measured automatically in several subcortical and cortical GM regions (striatal nuclei; thalami; and the neocortex of the frontal, temporal, parietal, and occipital lobes) by using FLS tools.', 'The MT ratio was significantly (P < .05 with Bonferroni correction for multiple comparison) decreased in all subcortical structures except the putamen and decreased diffusely in the cerebral cortex of HD carriers compared with controls. Close correlation was observed between the subcortical and cortical regional MT ratios and several clinical variables, including disease duration, motor disability, and scores in timed neuropsychological tests.'] Does magnetization transfer MR imaging demonstrate degeneration of the subcortical and cortical gray matter in Huntington disease?
|
qiaojin/PubMedQA
| 2 |
[
-2.326728105545044,
-1.2624549865722656,
2.7144417762756348
] |
['To examine themes associated with falls specific to older adult patients diagnosed with cancer.', 'Prospective, exploratory, qualitative study.', 'A senior adult oncology program at a cancer and research center in the southeastern United States.', 'Men and women aged 70 years and older with any cancer diagnosis who had experienced a fall within three months.', 'Patients were telephoned after research consent to participate in an interview about their falls. Frequencies were conducted on the biographic data. Themes were identified and grouped according to topic.', 'Eastern Cooperative Oncology Group performance status, cancer site, cancer treatment modality, location of fall, and fear of falls.', 'Mean age was 76.2 years. Most falls occurred at home (75%). The themes of physical problems, general weakness, and walking were found to be the most common motivations for falls. Themes associated with self-imposed activities as a result of falls included "being more careful" and "using an assistive device."'] Does an analysis of fall experienced by older adult patients diagnosed with cancer?
|
qiaojin/PubMedQA
| 1 |
[
-2.842007875442505,
1.5851414203643799,
0.43554502725601196
] |
['Postnatal expansion of the pancreatic β-cell mass is required to maintain glucose homeostasis immediately after birth. This β-cell expansion is regulated by multiple growth factors, including glucose, insulin, insulin-like growth factor (IGF-1) and epidermal growth factor (EGF). These mitogens signal through several downstream pathways (AKT, ERK, STAT3, and JNK) to regulate the survival and proliferation of β-cells. Survivin, an oncofetal protein with both pro-proliferative and anti-apoptotic properties, is a known transcriptional target of both IGF-1 and EGF in cancer cells. Here, we analyzed the effects of the β-cell mitogens IGF-1 and EGF on survivin regulation in the established pancreatic β-cell model cell lines, MIN6 and INS-1 and in primary mouse islets.', 'In pancreatic β-cells, treatment with glucose, insulin, or EGF increased survivin protein levels at early time points. By contrast, no significant effects on survivin were observed following IGF-1 treatment. EGF-stimulated increases in survivin protein were abrogated in the presence of downstream inhibitors of the Raf-1/MEK/ERK pathway. EGF had no significant effect on survivin transcription however it prolonged the half-life of the survivin protein and stabilized survivin protein levels by inhibiting surviving ubiquitination.'] Does eGF regulate survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells?
|
qiaojin/PubMedQA
| 2 |
[
-2.5193915367126465,
-1.1259472370147705,
2.6583824157714844
] |
['In Latin America, the medical attention directed to systemic autoimmune diseases competes with a budget designed to fight poverty, lack of education, etc. In this context, the access to treatments recommended internationally are expensive and limited; therefore, research of methods that make these treatments cheaper is of paramount importance.', 'Our objective was to describe the 24-month clinical outcome of patients with active systemic lupus erythematosus (SLE) who received low doses of rituximab (RTX), followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate mofetil (MMF).', 'Forty-six patients with active SLE received 500 mg of RTX (together with 500 mg of methylprednisolone as a premedication) administered on two occasions 2 weeks apart, followed by HCQ (200-400 mg/day), prednisone and MMF (500-1000 mg/day) during a 24-month follow-up period. Clinical outcome was assessed using the MEX-SLE Disease Activity Index (MEX-SLEDAI) and serial serologic measurements. Remission was defined as MEX-SLEDAI scores 0-1, mild disease activity 2-5, moderate disease activity 6-9, severe 10-13, and very severe 14 or more.', 'Disease activity decreased over time with treatment. At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, and 9 (19.6%) moderate disease activity. Improvement on disease activity was detected at 3 months, since 9 (19.6%) patients reached disease remission after this period of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at 1 year, and 23 (50%) at 2 years of follow-up (p<0.0001).'] Is the administration of low doses of rituximab followed by hydroxychloroquine , prednisone and low doses of mycophenolate mofetil an effective therapy in Latin American patients with active systemic lupus erythematosus?
|
qiaojin/PubMedQA
| 2 |
[
-1.9966200590133667,
-1.3450368642807007,
2.414675712585449
] |
['Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in vitro, in tissue homogenates in a concentration-dependent manner, the concentration of 400\u2009µg/ml demonstrating the most efficient lipid damaging effect . Both melatonin and its precursor, N-acetylserotonin, must possess antioxidant activities, both in vivo or in vitro, however, following some claims, N-acetylserotonin is a more effective extra- and intracellular antioxidant than melatonin. The aim of our study was to compare the effects of melatonin and N-acetylserotonin on the LPS-induced LPO in vitro.', 'Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indices of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and N-acetylserotonin were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration level of 400\u2009µg/ml.', 'In all the examined tissues, LPS stimulated LPO, while both melatonin and N-acetylserotonin decreased LPS-stimulated LPO. Furthermore, the capacity of N-acetylserotonin reducing LPO was higher than that of melatonin.'] Does n-acetylserotonin reduce lipopolysaccharide-induced lipid peroxidation in vitro more effectively than melatonin?
|
qiaojin/PubMedQA
| 2 |
[
-1.8666987419128418,
-1.4566863775253296,
2.303138017654419
] |
['Exposure to community violence (ECV) has been associated with asthma morbidity of children living in inner-city neighborhoods.', 'To examine with prospective longitudinal data whether ECV is independently associated with asthma-related health outcomes in adults.', 'Adults with moderate-severe asthma, recruited from clinics serving inner-city neighborhoods, completed questionnaires covering sociodemographics, asthma severity, and ECV and were followed for 26 weeks. Longitudinal models were used to assess unadjusted and adjusted associations of subsequent asthma outcomes (emergency department [ED] visits, hospitalizations, FEV(1), quality of life).', 'A total of 397 adults, 47 +/- 14 years old, 73% women, 70% African American, 7% Latino, mean FEV(1) 66% +/- 19%, 133 with hospitalizations and 222 with ED visits for asthma in the year before entry, were evaluated. Ninety-one reported ECV. Controlling for age, sex, race/ethnicity, and household income, those exposed to violence had 2.27 (95% CI, 1.32-3.90) times more asthma-related ED visits per month and 2.49 (95% CI, 1.11-5.60) times more asthma-related hospitalizations per month over the 26-week study period compared with those unexposed. Violence-exposed participants also had 1.71 (95% CI, 1.14-2.56) times more overall ED visits per month and 1.72 (95% CI, 0.95-3.11) times more overall hospitalizations per month from any cause. Asthma-related quality of life was lower in the violence-exposed participants (-0.40; 95% CI, -0.77 to -0.025; P = .04). Effect modification by depressive symptoms was only statistically significant for the ECV association with overall ED visits and quality-of-life outcomes (P < .01).'] Is exposure to community violence associated with asthma hospitalizations and emergency department visits?
|
qiaojin/PubMedQA
| 2 |
[
-0.5245826244354248,
-0.8092020153999329,
0.3883500397205353
] |
["Patients with Parkinson's disease may present with severe or intractable pain, which can be more distressing than the motor disability. The aim of this prospective study was to assess the prevalence of pain and underlying causes in patients with idiopathic Parkinson's disease.", 'Ninety-six patients (42 female, 54 men) were interviewed and pain was assessed using patient descriptions, Visual Analog Scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). Stait Trait Anxiety Inventory (STAI-TX 1 and 2) and Beck Depression Scale were also administered.', 'Pain as the first symptom of PD was seen in 3 patients (2.8%), 63 (64.9%) out of 96 patients reported pain. Pain types included musculoskeletal type of different etiologies (28 patients, 44.4%), radicular or neuropathic pain (7 patients, 11.1%), pain secondary to dystonia (12 patients, 19.1%) and central pain (8 patients, 12.7%). Eight patients (12.7%) described more than one type of pain. Pain did not correlate with sex, duration of disease, disease stage, use of dopamine agonists and levodopa, years of levodopa treatment and current levodopa dosage, depression, anxiety, sleep disturbances, age at onset of PD or history of disease in first-degree relatives. Akathisia seemed to be correlated with presence of pain (p<0.02).'] Is pain common in Parkinson 's disease?
|
qiaojin/PubMedQA
| 2 |
[
-2.1801702976226807,
-1.0546119213104248,
2.298896551132202
] |
['Platelet-rich plasma (PRP) has been used to enhance tendon healing in clinical settings. However, the cellular mechanisms underlying PRP treatment of injured tendons remain unclear. The aim of this study was to determine the effects of PRP, in the form of PRP-clot releasate (PRCR), on tendon stem cells (TSCs), a newly discovered cell population in tendons.', 'The PRCR treatment promotes differentiation of TSCs into tenocytes that are activated to proliferate quickly and increase collagen production.', 'Controlled laboratory study.', 'After PRCR treatment, cell morphology, expression of stem/progenitor cell marker nucleostemin, and population doubling time were examined. In addition, gene and protein analyses were performed using reverse transcription-polymerase chain reaction, immunocytochemistry, and Western blot to characterize the type of cells that had differentiated after PRCR treatment.', 'The TSCs without PRCR treatment were small and exhibited an irregular shape, whereas with increasing PRCR dosage, TSCs became large, well spread, and highly elongated with downregulation of nucleostemin expression. The PRCR treatment also markedly enhanced TSC proliferation, tenocyte-related gene and protein expression, and total collagen production, all of which indicated that PRCR treatment induced differentiation of TSCs into activated tenocytes.'] Does platelet-rich plasma releasate promote differentiation of tendon stem cells into active tenocytes?
|
qiaojin/PubMedQA
| 2 |
[
-2.5538861751556396,
-1.1416348218917847,
2.7779734134674072
] |
['The neutrophil-lymphocyte ratio (NLR) reflects inflammatory status. An elevated NLR has been reported to be a prognostic indicator in some malignant tumors. The aim of this study was to evaluate the clinical significance of the preoperative NLR in patients with primary gastric cancer.', 'A total of 709 men and 319 women, with a mean age of 64.4 years, who underwent gastrectomy were included. The numbers of patients in each pathological stage were as follows: stage I, 584; stage II, 132; stage III, 153; and stage IV, 159. The mean NLR was 2.62 +/- 1.68. A total of 127 patients (12.4%) with an NLR of 4.0 or more were classified as high NLR individuals in this study. The prognostic significance of a high NLR, together with various clinicopathological factors, was evaluated by multivariate analysis.', 'The 5-year survival of patients with a high NLR was significantly worse than that of patients with a low NLR (57% vs 82%, P < 0.001). Univariate and multivariate analyses of clinicopathological factors affecting survival revealed that high NLR, depth of tumor, positive lymph nodes, distant metastasis, peritoneal metastasis, poorly differentiated type, and high platelet count were significant risk factors for reduced survival. On multivariate analysis, after adjusting for tumor stage, a high NLR was an independent risk factor for reduced survival (P = 0.003; adjusted hazard ratio, 1.845; 95% confidence interval, 1.236-2.747).'] Does high preoperative neutrophil-lymphocyte ratio predict poor survival in patients with gastric cancer?
|
qiaojin/PubMedQA
| 2 |
[
-1.7147694826126099,
-1.5833430290222168,
2.307939052581787
] |
['Recently backward walking is used by physical therapists to strengthen the hamstring muscles and thus improve the function of the knee joint of anterior cruciate ligament deficient patients. The aim of this study was to examine the stride-to-stride variability of anterior cruciate ligament deficient patients during backward walking. The variation of how a motor behavior emerges in time is best captured by tools derived from nonlinear dynamics, for which the temporal sequence in a series of values is the facet of interest.', 'Fifteen patients with unilateral anterior cruciate ligament deficiency and eleven healthy controls walked backwards at their self-selected speed on a treadmill while three-dimensional knee kinematics were collected (100 Hz). A nonlinear measure, the largest Lyapunov Exponent was calculated from the resulted knee joint flexion-extension data of both groups to assess the stride-to-stride variability.', 'Both knees of the deficient patients exhibited significantly lower Lyapunov Exponent values as compared to the healthy control group revealing more rigid movement pattern. The intact knee of the deficient patients showed significantly lower Lyapunov Exponent values as compared to the deficient knee.'] Is stride-to-stride variability altered during backward walking in anterior cruciate ligament deficient patients?
|
qiaojin/PubMedQA
| 2 |
[
-2.266177177429199,
-0.41711801290512085,
1.7581150531768799
] |
['Multipotent mesenchymal stromal cells raise great interest for regenerative medicine studies. Some MSC subpopulations have the potential to undergo neural differentiation, including marrow isolated adult multilineage inducible (MIAMI) cells, which differentiate into neuron-like cells in a multi-step neurotrophin 3-dependent manner. Epidermal and basic fibroblast growth factors are often used in neuronal differentiation protocols for MSCs, but with a limited understanding of their role. In this study, we thoroughly assessed for the first time the capacity of these factors to enhance the neuronal differentiation of MSCs.', 'We have characterized MIAMI cell neuronal differentiation program in terms of stem cell molecule expression, cell cycle modifications, acquisition of a neuronal morphology and expression of neural and neuronal molecules in the absence and presence of an EGF-bFGF pre-treatment.', 'EGF-bFGF pre-treatment down-regulated the expression of stemness markers Oct4A, Notch1 and Hes5, whereas neural/neuronal molecules Nestin, Pax6, Ngn2 and the neurotrophin receptor tyrosine kinase 1 and 3 were up-regulated. During differentiation, a sustained Erk phosphorylation in response to NT3 was observed, cells began to exit from the cell cycle and exhibit increased neurite-like extensions. In addition, neuronal β3-tubulin and neurofilament expression was increased; an effect mediated via the Erk pathway. A slight pre-oligodendrocyte engagement was noted, and no default neurotransmitter phenotype was observed. Overall, mesodermal markers were unaffected or decreased, while neurogenic/adipogenic PPARγ2 was increased.'] Does eGF and bFGF pre-treatment enhance neural specification and the response to neuronal commitment of MIAMI cells?
|
qiaojin/PubMedQA
| 2 |
[
-2.5053982734680176,
-1.24471116065979,
2.8208608627319336
] |
['We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS) increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study.', 'We genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y) from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI)-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error [SE] 0.012) kg/m(2) (p = 6.73 x 10(-37)) increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall). This association was significantly (p(interaction) = 0.005) more pronounced in inactive people (0.205 [SE 0.024] kg/m(2) [p = 3.62 x 10(-18); 592 g in weight]) than in active people (0.131 [SE 0.014] kg/m(2) [p = 7.97 x 10(-21); 379 g in weight]). Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26)) in the whole population, but significantly (p(interaction) = 0.015) more in inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(-16)]) than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1.15 x 10(-12)]). Consistent with the cross-sectional observations, physical activity modified the association between the genetic predisposition score and change in BMI during follow-up (p(interaction) = 0.028).'] Does physical activity attenuate the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study?
|
qiaojin/PubMedQA
| 0 |
[
0.4771125316619873,
-1.8466081619262695,
0.4405907690525055
] |
['Despite considerable efforts, a suitable vaccine against Onchocerca volvulus infection has remained elusive. Herein, we report on the use of molecular tools to identify and characterize O. volvulus antigens that are possibly associated with the development of concomitant immunity in onchocerciasis.', 'Third-stage larvae (L3) and molting L3 (mL3) O. volvulus stage-specific cDNA libraries were screened with a pool of sera from chronically infected patients who had likely developed such immunity. The 87 immunoreactive clones isolated were grouped into 20 distinct proteins of which 12 had already been cloned and/or characterized before and 4 had been proven to be protective in a small O. volvulus animal model. One of these, onchocystatin (Ov-CPI-2), a previously characterized O. volvulus cysteine proteinase inhibitor was, overall, the most abundant clone recognized by the immune sera in both the L3 and mL3 cDNA libraries. To further characterize its association with protective immunity, we measured the IgG subclass and IgE class specific responses to the antigen in putatively immune (PI) and infected (INF) individuals living in a hyperendemic area in Cameroon. It appeared that both groups had similar IgG3 and IgE responses to the antigen, but the INF had significantly higher IgG1 and IgG4 responses than the PI individuals (p<0.05). In the INF group, the IgG3 levels increased significantly with the age of the infected individuals (r = 0.241; p<0.01). The IgG1 responses in the INF were high regardless of age. Notably, culturing L3 in vitro in the presence of anti-Ov-CPI-2 monospecific human antibodies and naïve neutrophils resulted in almost complete inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.'] Is the Onchocerca volvulus cysteine proteinase inhibitor , Ov-CPI-2 , a target of protective antibody response that increases with age?
|
qiaojin/PubMedQA
| 2 |
[
-2.1204614639282227,
-1.4252867698669434,
2.5543901920318604
] |
['Partial amniotic carbon dioxide insufflation (PACI) during fetoscopic interventions greatly improves visualization of intraamniotic contents. The purpose of this study was to assess any histologically discernable effects from this approach on the fetal brain after long-term survival in sheep.', 'Six pregnant ewes between 63 and 92 days of gestation underwent PACI after fetoscopic intraamniotic access. Insufflation pressures ranged between 7 and 15 mm Hg (mean 11.7; median 12.5). Insufflation times ranged between 45 and 80 minutes (mean 55.8 minutes; median 52.5) and depended on the duration of various percutaneous fetoscopic maneuvers (e.g., posturing, fetal transesophageal electrocardiography, and chronic fetal vascular access) that were tested during these studies. After fetal spontaneous delivery between 147 and 150 days of gestation, 5 of the lambs were observed for abnormal neurological symptoms. The last ewe and her sheep were terminated at 133 days of gestation for humane reasons. All six brains were examined for hemorrhage, embolism, infarctions, inflammatory changes, and abnormal cortical maturation. An unoperated sibling was available as a control.', 'The 5 sheep that were spontaneously delivered exhibited no abnormal neurological findings. In all 6 sheep, PACI did not result in any histologically discernable damage to their brain in these long-term studies. Maternal and fetal complications were not observed during or after the approach.'] Does partial amniotic carbon dioxide insufflation during minimally invasive fetoscopic interventions seem safe for the fetal brain in sheep?
|
qiaojin/PubMedQA
| 2 |
[
-2.103703260421753,
-0.9111592173576355,
2.0460329055786133
] |
['The therapeutic potential of embryonic stem cells (ESCs) in ischaemic heart disease has been widely explored. However, tumourigenesis upon implantation interferes with the clinical application of ESC transplantation. This study aims to evaluate the influence of differentiation and enrichment of transplanted ESCs on tumourigenesis in infarcted rat hearts.', 'Mouse ESCs (mESCs) were cultured using a bioreactor system to develop embryoid bodies, which were then induced with 1% ascorbic acid to differentiate into cardiomyocytes. The mESCs-derived cardiomyocytes (mESCs-CMs) were enriched by Percoll density gradient separation. The specific markers (OCT-4, Sox2, and Nanog) of undifferentiated ESCs were detected by PCR both in mESCs and in mESCs-CMs, but not in the mESC-derived Percoll-enriched cardiomyocytes (mESC-PE-CMs). Immunosuppressed rats with infarcted hearts were randomly injected with the mESCs, mESC-CMs, or mESC-PE-CMs. Eight weeks after cell transplantation, histological and immunohistochemical analysis showed that the transplantation of both mESCs and mESC-CMs caused the formation of teratomas. The incidence of teratoma was markedly lower (P < 0.05) in the mESC-CMs group than in the mESCs group. The average tumour volume was significantly lower (P < 0.05) in the mESC-CMs group than in the mESCs group. Tumour formation was absent in the mESC-PE-CMs group.'] Is tumourigenesis in the infarcted rat heart eliminated through differentiation and enrichment of the transplanted embryonic stem cells?
|
qiaojin/PubMedQA
| 2 |
[
-2.050333261489868,
-1.5408655405044556,
2.5471136569976807
] |
['• To assess the clinical value of preoperative knowledge of the presence of extracapsular extension (ECE) or seminal vesicle invasion (SVI) in the planning for prostatectomy.', '• An institutional database of 1161 robotic-assisted laparoscopic prostatectomies (RALP) performed by a single surgeon (D.B.S.) was queried for those who underwent endorectal coil magnetic resonance imaging (erMRI) before robotic-assisted laparoscopic prostatectomy. • erMRI reports were dichotomized into positive or negative and compared with the final histopathology. The erMRIs performed at academic centres were compared with those performed in non-academic settings. • A sub-group of high-risk patients was also analyzed for erMRI accuracy.', '• The 179 patients who underwent erMRI had significantly worse disease compared to the 982 patients without imaging. Of the 110 patients with histopathologically organ-confined disease, 81 (74%) were correctly diagnosed as such on erMRI, whereas 29 (26%) were felt to have cT3 disease and constituted false-positives. Among the 69 patients with pT3 disease, erMRI correctly predicted 30 (43%), whereas 39 (57%) were incorrectly considered organ-confined. • The overall sensitivity and specificity for diagnosing pT3 disease was 43% and 73%. • When stratified by pT3a and pT3b, the sensitivity and specificity of erMRI to accurately diagnose ECE is 33% and 81%, respectively. In evaluating SVI, erMRI has a sensitivity and specificity of 33% and 89%, respectively. The positive predictive value of erMRI to assess for ECE and SVI is 50% in both, with a negative predictive value of 61% and 63%, respectively. • erMRIs performed at academic centres compared to non-academic locations demonstrated similar rates of sensitivity at 67% vs 77% and specificity at 39% vs 54%, respectively (P = 0.33).'] Does endorectal magnetic resonance imaging have limited clinical ability to preoperatively predict pT3 prostate cancer?
|
qiaojin/PubMedQA
| 2 |
[
-1.4718352556228638,
-1.377028465270996,
1.8150203227996826
] |
['Many countries use cooling plates to actively cool collected whole blood (WB) to room temperature. Until now, no paired comparison had been performed, and it was our aim to compare the effect of active versus no active cooling on the in vitro quality of WB and subsequently prepared blood components.', 'Two units of WB were pooled and divided shortly after donation. One unit was placed under a butane-1,4-diol plate to obtain active cooling; the other was placed in an insulated box with other warm units to mimic worst-case holding conditions. WB was held overnight and processed into a white blood cell (WBC)-reduced red blood cells (RBCs), buffy coat (BC), and plasma. The BCs were further processed into platelet (PLT) concentrates. RBCs were stored for 42 days, and PLT concentrates for 8 days (n\u2003=\u200312 paired experiments).', 'After overnight storage, ATP content of the RBCs was 4.9\u2003±\u20030.3\u2003µmol/g Hb for actively cooled WB versus 4.5\u2003±\u20030.4\u2003µmol/g\u2003Hb for not actively cooled WB (p\u2003<\u20030.001). On Day 42 of storage, RBCs prepared from this WB contained 3.1\u2003±\u20030.3\u2003µmol\u2003ATP/g\u2003Hb with active cooling versus 2.6\u2003±\u20030.3\u2003µmol/g\u2003Hb without (p\u2003<\u20030.001). Hemolysis on Day 42 was 0.35\u2003±\u20030.08% with active cooling and 0.67\u2003±\u20030.21% without (p\u2003<\u20030.001). No effect was observed on the in vitro quality of plasma, BC, or PLT concentrates.'] Does active cooling of whole blood to room temperature improve blood component quality?
|
qiaojin/PubMedQA
| 2 |
[
0.1429748833179474,
-1.8219960927963257,
0.6557642817497253
] |
['The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively).', 'In 17 patients (aged 18-60 years) with acute liver failure and severe hyperammonemia (182 ± 36 μM (mean ± SD)), cerebral microdialysis was performed, and ICP and CPP were monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and pyruvate were measured.', 'The hypoxanthine concentration was 23.0 ± 12 μM in early samples and 11.7 ± 6.8 μM in late samples (normal level ~2.0 μM). The inosine concentration was 7.2 ± 7.1 μM and 2.8 ± 1.6 μM, and the LP ratio was 55.8 ± 21.6 and 45.6 ± 20.8, respectively (normal level ~18). Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP, nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients without (n=8).'] Does brain hypoxanthine concentration correlate to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure?
|
qiaojin/PubMedQA
| 2 |
[
-0.9311674237251282,
-1.6716290712356567,
1.5690135955810547
] |
['Increased activity of the vascular Akt/eNOS signaling pathway is involved in the hemodynamic and renal complications developed by patients and rats with cirrhosis and ascites. This occurs in the setting of impaired Akt/eNOS activity within the cirrhotic liver. Here we assessed the feasibility of selectively inhibiting vascular eNOS without further impairing the intrahepatic activity of this enzyme. Ultimately, we sought to determine whether endothelial transduction of a constitutively inactive mutant of Akt (AA-Akt) improves circulatory function and sodium excretion in cirrhotic rats with ascites.', 'First, we administered recombinant adenoviruses that encode the β-galactosidase gene (β-gal) to 5 control rats and 5 cirrhotic rats with ascites and analyzed their tissue distribution by chemiluminescence. Next, urine samples were obtained from 18 cirrhotic rats with ascites and then the animal randomly received saline or adenoviruses containing the β-gal or the AA-Akt genes. Following a 24-h urine collection period, hemodynamic studies were performed and tissue samples were obtained to analyze Akt and eNOS expressions.', 'No β-gal activity was detected in the liver of cirrhotic rats compared to that of controls. This was paralleled by increased β-gal activity in other territories such as the thoracic aorta. AA-Akt transduction improved systemic hemodynamics, splanchnic perfusion pressure and renal excretory function in comparison with cirrhotic rats transduced with β-gal adenoviruses or receiving saline. Moreover, the AA-Akt transgene did not modify portal pressure.'] Does inactivation of extrahepatic vascular Akt improve systemic hemodynamics and sodium excretion in cirrhotic rats?
|
qiaojin/PubMedQA
| 2 |
[
-2.419020414352417,
-1.3743481636047363,
2.819803237915039
] |
["Cardiac resynchronization therapy (CRT) is generally associated with a low to moderate increase of the left ventricular ejection fraction (LVEF). In some patients, however, LVEF improves remarkably and reaches near-normal values. The aim of the present study was to further characterize these so called 'super-responders' with a special focus on the extent of intra- and interventricular asynchrony before and after device implantation compared to average responders.", '37 consecutive patients who underwent CRT device implantation according to current guidelines were included in the study. Patients were examined by echocardiography before, one day after and six months after device implantation. Pre-defined criterion for superior response to CRT was an LVEF increase > 15% after six months.', 'At follow-up, eight patients (21.6%) were identified as super-responders. There were no significant differences regarding age, gender, prevalence of ischemic heart disease and LVEF between average and super-responders at baseline. After six months, LVEF had significantly increased from 26.7% ± 5.7% to 33.1% ± 7.9% (p < 0.001) in average and from 24.0% ± 6.7% to 50.3% ± 7.4% (p < 0.001) in super-responders. Both groups showed a significant reduction of QRS duration as well as LV end-diastolic and -systolic volumes under CRT. At baseline, the interventricular mechanical delay (IVMD) was 53.7 ± 20.9 ms in average and 56.9 ± 22.4 ms in super-responders - representing a similar extent of interventricular asynchrony in both groups (p = 0.713). CRT significantly reduced the IVMD to 20.3 ± 15.7 (p < 0.001) in average and to 19.8 ± 15.9 ms (p = 0.013) in super-responders with no difference between both groups (p = 0.858). As a marker for intraventricular asynchrony, we assessed the longest intraventricular delay between six basal LV segments. At baseline, there was no difference between average (86.2 ± 30.5 ms) and super-responders (78.8 ± 23.6 ms, p = 0.528). CRT significantly reduced the longest intraventricular delay in both groups--with a significant difference between average (66.2 ± 36.2 ms) and super-responders (32.5 ± 18.3 ms, p = 0.022). Multivariate logistic regression analysis identified the longest intraventricular delay one day after device implantation as an independent predictor of superior response to CRT (p = 0.038).'] Is successful reduction of intraventricular asynchrony associated with superior response to cardiac resynchronization therapy?
|
qiaojin/PubMedQA
| 2 |
[
-1.489606499671936,
-1.6852891445159912,
2.106142520904541
] |
['the aim of this study was to determine the relative importance of Ca(2+) sensitization, ion channels, and intracellular Ca(2+) ([Ca(2+)](i)) in the mixed constrictor/relaxation actions of superoxide anion on systemic and pulmonary arteries.', 'pulmonary and mesenteric arteries were obtained from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8-quinolinequinone (LY83583). Following pre-constriction with U46619, 10 μmol/L LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries. Both constrictor and relaxant actions of LY83583 were inhibited by superoxide dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in α-toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot), was enhanced by LY83583 in pulmonary artery only. However, in both artery types, changes in tension were closely correlated with changes in phosphorylation of the 20 kDa myosin light chain as well as changes in [Ca(2+)](i) (as measured with Fura PE-3), with LY83583 causing increases in pulmonary and decreases in mesenteric arteries. When U46619 was replaced by 30 mmol/L K(+), all changes in [Ca(2+)](i) were abolished and LY83583 constricted both artery types. The K(V) channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in mesenteric artery without affecting constriction in pulmonary artery. However, LY83583 caused a similar hyperpolarizing shift in the steady-state activation of K(V) current in isolated smooth muscle cells of both artery types.'] Does superoxide differentially control pulmonary and systemic vascular tone through multiple signalling pathways?
|
qiaojin/PubMedQA
| 2 |
[
-2.3071420192718506,
-1.3701462745666504,
2.714573860168457
] |
['To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons.', 'Oxidative stress, which is implicated in diabetic retinopathy, was induced in mouse primary ganglion cells (GCs) and RGC-5 cells, and the effect of the σR1 ligand (+)-pentazocine on pro- and anti-apoptotic and endoplasmic reticulum (ER) stress gene expression was examined. Binding of σR1 to BiP, an ER chaperone protein, and σR1 phosphorylation status were examined by immunoprecipitation. Retinas were harvested from Ins2Akita/+ diabetic mice treated with (+)-pentazocine, and the expression of ER stress genes and of the retinal transcriptome was evaluated.', 'Oxidative stress induced the death of primary GCs and RGC-5 cells. The effect was decreased by the application of (+)-pentazocine. Stress increased σR1 binding to BiP and enhanced σR1 phosphorylation in RGC-5 cells. BiP binding was prevented, and σR1 phosphorylation decreased in the presence of (+)-pentazocine. The ER stress proteins PERK, ATF4, ATF6, IRE1α, and CHOP were upregulated in RGC-5 cells during oxidative stress, but decreased in the presence of (+)-pentazocine. A similar phenomenon was observed in retinas of Ins2Akita/+ diabetic mice. Retinal transcriptome analysis of Ins2Akita/+ mice compared with wild-type revealed differential expression of the genes critically involved in oxidative stress, differentiation, and cell death. The expression profile of those genes was reversed when the Ins2Akita/+ mice were treated with (+)-pentazocine.'] Does sigma receptor 1 modulate endoplasmic reticulum stress in retinal neurons?
|
qiaojin/PubMedQA
| 2 |
[
-2.389521598815918,
-1.3246357440948486,
2.720303535461426
] |
['The aim of this study was to determine the role of gangliosides in pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO).', 'The gangliosides profile and mRNA level of sialyltransferases of the orbital tissues from TAO patients (n = 5) and non-TAO subjects (n = 4) were investigated. In addition, the effect of exogenous gangliosides on the expression of hyaluronic acid was examined in orbital fibroblasts. For in vitro experiments, we used four different strains of cells obtained from non-TAO subjects with at least three replicates for each strain.', 'Trisialoganglioside 1b (GT1b) was significantly overexpressed in the orbital tissue of TAO patients compared with control tissue, whereas no significant difference was observed for either monosialoganglioside 1 (GM1) or disialoganglioside 1a (GD1a) by digital analyses of immunohistochemical images. Moreover, mRNA levels of sialyltransferase (SAT)-I and SAT II were increased in TAO patients compared with control. Exogenous GT1b strongly induced the morphologic changes related to an accumulation of sparse flocculent precipitates in lysosomes and increased the extracellular hyaluronic acid level in orbital fibroblasts with the induction of hyaluronic acid synthase, which were less by GD1a but not by GM1. The GT1b-induced morphologic changes of cells were due, at least in part, to an increase of intracellular hyaluronic acid. Co-treatment of hyaluronidase nicely attenuated the morphologic changes in orbital fibroblasts. Thy-1(+) orbital fibroblasts were more capable of producing hyaluronic acid by exogenous GT1b.'] Does altered ganglioside expression modulate the pathogenic mechanism of thyroid-associated ophthalmopathy by increase in hyaluronic acid?
|
qiaojin/PubMedQA
| 2 |
[
-2.4457976818084717,
-1.3370108604431152,
2.821610450744629
] |
['Toxoplasma gondii is a major cause of ocular disease, which can lead to permanent vision loss in humans. T cells are critically involved in parasite control, but little is known about the molecules that promote T-cell trafficking and migration in the retina. Thus, the aim of this study was to image and dissect the T-cell response during chronic toxoplasmic retinochoroiditis.', 'C57BL/6 mice were infected with the Me49 strain of T. gondii, and T cells that infiltrated the eye were analyzed by flow cytometry and imaged using multiphoton microscopy. IFN-γ, CXCL9, CXCL10, and CXCR3 mRNA levels were measured by real-time PCR. To investigate the role of CXCL10, mice were treated with anti-CXCL10 antibodies, and histopathology and immunohistochemistry were performed to monitor changes in pathology, cellular infiltration, and parasite burden in the eye.', 'Infection with T. gondii leads to the infiltration of highly activated motile T cells into the eye. These cells express CXCR3 and are capable of producing IFN-γ and TNF-α, and CD8+ T cells express granzyme B. The expression of CXCL9 and CXCL10 in the retina was significantly upregulated during chronic infection. Treatment of chronically infected mice with anti-CXCL10 antibodies led to decreases in the numbers of CD3+, CD4+, and CD8+ T cells and the amount of IFN-γ mRNA expression in the retina and an increase in replicating parasites and ocular pathology.'] Is cXCL10 required to maintain T-cell populations and to control parasite replication during chronic ocular toxoplasmosis?
|
qiaojin/PubMedQA
| 2 |
[
-2.443235397338867,
-1.289208173751831,
2.7690629959106445
] |
['Prostate specific membrane antigen (PSMA) is a suggested target for antibody-based therapy of prostate cancer potentially involved in the regulation of cell migration. This study was undertaken, to gain more insight on the role of PSMA in early prostate cancer and its distribution in various normal tissues.', 'A total of 1,700 different prostate cancers treated by radical prostatectomy and 612 samples from 76 different normal tissue types were successfully analyzed by immunohistochemistry (IHC) in a tissue microarray (TMA) format. PSMA immunostaining in cancers was also compared with clinical follow-up, preexisting HER2 expression and Ki67 labeling index data.', 'PSMA staining was only found in prostate epithelium and expression was higher in cancer cells than in benign tissue. PSMA staining was found in 94.1% of cancers and was significantly associated with tumor stage, high Gleason grade, preoperative PSA, and HER2 expression (P\u2009<\u20090.0001 each). Tumors with strong PSMA expression had a higher risk of biochemical recurrence than cancers with only weak PSMA staining intensity (P\u2009=\u20090.0483). There was no significant association between PSMA expression and Ki67 labeling index (P\u2009=\u20090.442).'] Is high level PSMA expression associated with early PSA recurrence in surgically treated prostate cancer?
|
qiaojin/PubMedQA
| 2 |
[
-2.0220069885253906,
-1.461087942123413,
2.5564417839050293
] |
['Donor T lymphocytes are directly responsible for graft-versus-host disease. Molecules important in T-cell function may, therefore, be appropriate targets for graft-versus-host disease therapy and/or prophylaxis. Here we analyzed whether nuclear factor-κ B inducing kinase might have a role in graft-versus-host disease.', 'We studied the expression of nuclear factor-κ B inducing kinase in human samples from patients with graft-versus-host disease. We also explored the effect of nuclear factor-κ B inducing kinase in a murine model of graft-versus-host disease using donor cells from aly/aly mice (deficient in nuclear factor-κ B inducing kinase) and C57BL/6 mice (control).', 'We detected expression of nuclear factor-κ B inducing kinase in T-lymphocytes in the pathological lesions of patients with acute graft-versus-host disease. Mice transplanted with aly/aly T lymphocytes did not develop graft-versus-host disease at all, while mice receiving C57BL/6 cells died of a lethal form of the disease. Deficiency of nuclear factor-κ B inducing kinase did not affect the engrafting ability of donor T cells, but severely impaired their expansion capacity early after transplantation, and aly/aly T cells showed a higher proportion of apoptosis than did C57BL/6 T cells. Effector T lymphocytes were the T-cell subset most affected by nuclear factor-κ B inducing kinase deficiency. We also detected lower amounts of inflammatory cytokines in the serum of mice receiving aly/aly T cells than in the serum of mice receiving C57BL/6 T cells.'] Is nuclear factor-kappaB inducing kinase required for graft-versus-host disease?
|
qiaojin/PubMedQA
| 2 |
[
-2.3227903842926025,
-1.2474050521850586,
2.5985169410705566
] |
["Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1", 'To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells.', "Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease."] Are dynamic chromosomal rearrangements in Hodgkin 's lymphoma due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles?
|
qiaojin/PubMedQA
| 2 |
[
-2.4193615913391113,
-1.077514886856079,
2.60868501663208
] |
['During the final stages of differentiation of mammalian erythroid cells, the chromatin is condensed and enucleated. We previously reported that Rac GTPases and their downstream target, mammalian homolog of Drosophila diaphanous 2 (mDia2), are required for enucleation of in vitro cultured mouse fetal liver erythroblasts. However, it is not clear how chromatin condensation is achieved and whether it is required for enucleation.', 'Mouse fetal liver erythroblasts were purified from embryonic day 14.5 pregnant mice and cultured in erythropoietin-containing medium. Enucleation was determined by flow-cytometry based analysis after treatment with histone deacetylase inhibitors or infection with lentiviral short hairpin RNA.', 'We showed that histone deacetylases play critical roles in chromatin condensation and enucleation in cultured mouse fetal liver erythroblasts. Enzymatic inhibition of histone deacetylases by trichostatin A or valproic acid prior to the start of enucleation blocked chromatin condensation, contractile actin ring formation and enucleation. We further demonstrated that histone deacetylases 1, 2, 3 and 5 are highly expressed in mouse fetal erythroblasts. Short hairpin RNA down-regulation of histone deacetylase 2, but not of the other histone deacetylases, phenotypically mimicked the effect of trichostatin A or valproic acid treatment, causing significant inhibition of chromatin condensation and enucleation. Importantly, knock-down of histone deacetylase 2 did not affect erythroblast proliferation, differentiation, or apoptosis.'] Is histone deacetylase 2 required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts?
|
qiaojin/PubMedQA
| 2 |
[
-2.45186185836792,
-1.261992335319519,
2.747354507446289
] |
['Exposure to γ-radiation causes rapid hematopoietic cell apoptosis and bone marrow suppression. However, there are no approved radiation countermeasures for the acute radiation syndrome. In this study, we demonstrated that natural δ-tocotrienol, one of the isomers of vitamin E, significantly enhanced survival in total body lethally irradiated mice. We explored the effects and mechanisms of δ-tocotrienol on hematopoietic progenitor cell survival after γ-irradiation in both in vivo and in vitro experiments.', 'CD2F1 mice and human hematopoietic progenitor CD34(+) cells were treated with δ-tocotrienol or vehicle control 24 h before or 6 h after γ-irradiation. Effects of δ-tocotrienol on hematopoietic progenitor cell survival and regeneration were evaluated by clonogenicity studies, flow cytometry, and bone marrow histochemical staining. δ-tocotrienol and γ-irradiation-induced signal regulatory activities were assessed by immunofluorescence staining, immunoblotting and short-interfering RNA assay.', 'δ-tocotrienol displayed significant radioprotective effects. A single injection of δ-tocotrienol protected 100% of CD2F1 mice from total body irradiation-induced death as measured by 30-day post-irradiation survival. δ-tocotrienol increased cell survival, and regeneration of hematopoietic microfoci and lineage(-)/Sca-1(+)/ckit(+) stem and progenitor cells in irradiated mouse bone marrow, and protected human CD34(+) cells from radiation-induced damage. δ-tocotrienol activated extracellular signal-related kinase 1/2 phosphorylation and significantly inhibited formation of DNA-damage marker γ-H2AX foci. In addition, δ-tocotrienol up-regulated mammalian target of rapamycin and phosphorylation of its downstream effector 4EBP-1. These alterations were associated with activation of mRNA translation regulator eIF4E and ribosomal protein S6, which is responsible for cell survival and growth. Inhibition of extracellular signal-related kinase 1/2 expression by short interfering RNA abrogated δ-tocotrienol-induced mammalian target of rapamycin phosphorylation and clonogenicity, and increased γ-H2AX foci formation in irradiated CD34(+) cells.'] Does delta-tocotrienol protect mouse and human hematopoietic progenitors from gamma-irradiation through extracellular signal-regulated kinase/mammalian target of rapamycin signaling?
|
qiaojin/PubMedQA
| 2 |
[
-2.3749287128448486,
-1.3960672616958618,
2.806028127670288
] |
['• To determine (i) the presence of fatty acid amide hydrolase (FAAH) in the urinary bladder; (ii) whether or not endogenous fatty acid ethanolamides are synthesized by the bladder; (iii) the effects of FAAH inhibition on referred hyperalgesia associated with acute bladder inflammation in rats.', '• Immunohistochemistry and immunoblotting were performed to detect FAAH in the bladder. Acrolein (1 mM, 400 µL) was instilled into bladders of female Wistar rats to induce cystitis. Referred mechanical hyperalgesia was assessed by application of Von Frey monofilaments to the hind paws. • Animals were killed 4, 24, 48 and 72 h after acrolein instillation, and the fatty acid ethanolamide content of bladders was measured using isotope-dilution liquid chromatography/mass spectrometry. • Other rats were treated with the FAAH inhibitor URB597 (0.3 mg/kg, i.p.) after the induction of cystitis, and the mechanical sensitivity of the hind paws was determined.', '• Immunohistochemistry and immunoblotting showed the presence of FAAH in the bladder, with greatest abundance in the urothelium. • Acrolein-induced cystitis increased fatty acid ethanolamide content (including anandamide) in the bladder in a time-dependent manner. Inhibition of FAAH diminished referred hyperalgesia associated with acute bladder inflammation.'] Does inhibition of fatty acid amide hydrolase suppress referred hyperalgesia induced by bladder inflammation?
|
qiaojin/PubMedQA
| 2 |
[
-2.5592589378356934,
-1.2191557884216309,
2.821885108947754
] |
['Reactive oxygen species are involved in the pathogenesis of congestive heart failure. We recently showed that coupling factor 6, a component of adenosine trisphosphate (ATP) synthase, induces hypertension by intracellular acidosis, which is related to reactive oxygen species generation. We investigated the effect of high-salt diet on the cardiac performance and reactive oxygen species generation in coupling factor 6-overexpressing transgenic mice.', 'Baseline echocardiographic findings, reactive oxygen species generation, protein expression of sarcoplasmic/endoplasmic reticulum of Ca-ATPase 2 and phospholamban, and ATP content in the heart were similar between 7-week-old transgenic and wild-type mice. When the mice were fed with 8% salt diet for 20-24 weeks, fractional shortening of the left ventricle was decreased in transgenic mice compared with wild-type mice and was recovered by intraperitoneal administration of anticoupling factor 6 antibody. Nicotinamide adenine dinucleotide phosphate oxidase activity in the heart was increased in transgenic mice after the high-salt diet concomitantly with c-Src activation. The level of 8-iso-prostaglandin F2α was increased in transgenic heart compared with wild-type heart. The protein expression of sarcoplasmic/endoplasmic reticulum of Ca-ATPase 2 was decreased and that of phospholamban was increased in transgenic heart. In cDNA microarray analysis, the genes related to ATP synthesis and glycolysis were decreased in transgenic heart, concomitantly with the decrease in ATP content and the increase in β-myosin heavy chain.'] Does overexpression of coupling factor 6 cause cardiac dysfunction under high-salt diet in mice?
|
qiaojin/PubMedQA
| 2 |
[
-2.4502177238464355,
-1.3118000030517578,
2.7793707847595215
] |
['Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media.', 'The effects of prolonged hypoxic culture on growth and pro-angiogenic properties were investigated using human ASC cultured at 1%, 5% and 21% oxygen. The effect of trypsinization on the expression of pro-angiogenic genes was also determined.', 'Trypsinization induced up-regulation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) genes independent of oxygen concentration. The expression of VEGF and IGF-1 was up-regulated in ASC cultured at 1% oxygen for 13 days compared with 4 days. The VEGF concentration in ASC-conditioned media was higher after prolonged hypoxic culture compared with short-term culture, while the IGF-1 and chemokine (CXC motif) ligand 12 (CXCL12) concentrations were unchanged. The VEGF receptor blocker SU5416 abolished angiogenesis in a cultured rat aortic ring model. Media from cells exposed to hypoxia increased angiogenesis, an effect that was dependent on factors other than just the VEGF concentration in the added media.'] Do prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells?
|
qiaojin/PubMedQA
| 2 |
[
-2.432583808898926,
-1.3266234397888184,
2.768178939819336
] |
['To determine whether docosahexaenoic acid can protect against hereditary retinal degenerations in transgenic mice expressing the V20G, P23H, and P27L (VPP) rhodopsin mutations.', 'Female transgenic mice expressing the VPP rhodopsin mutation, known to cause a retinal degeneration, were bred to male transgenic mice expressing the fat-1 gene, which can convert n6 to n3 polyunsaturated fatty acids (PUFA). Several weeks before breeding, the female mice were fed a standard diet containing 10% safflower oil (SFO), which is high in n6 and low in n3 PUFA (n6/n3=273). Offspring were genotyped and four groups identified: Fat1(+)/VPP(+), Fat1(-)/VPP(+), Fat1(+)/VPP(-), and Fat1(-)/VPP(-). Dams were maintained on the SFO diet during the nursing period and offspring were kept on the SFO diet after weaning. At 4, 16, and 28 weeks of age, retinal function was evaluated by electroretinography (ERG), photoreceptor cell loss was quantified by measuring outer nuclear layer thickness, and rhodopsin levels were determined. Fatty acid profiles were analyzed in whole retina, plasma, and liver at 4 and 28 weeks of age.', 'Expression of fat-1 in the absence of dietary n3 PUFA led to the generation of two groups of mice with distinctly different levels of n3 and n6 PUFA in the three tissues that were analyzed. Already at four weeks of age, the retinas of fat-1 positive animals had higher levels of n3 PUFA than their wild-type counterparts (23%-29% versus 6.4%-6.5%). In addition, by four weeks of age, there was a significant loss of rod photoreceptor cells in the VPP mice. Progression of retinal degeneration occurred with increasing age in VPP positive mice, with photoreceptor cell death occurring in both inferior and superior regions. Amplitudes of the a- and b-waves of the ERG were significantly reduced with age, with VPP positive mice showing the greatest change. Rhodopsin content was lower in the VPP transgenic mice. There were no significant differences in outer nuclear layer thickness or ERG amplitudes between Fat1(+)/VPP(+) and Fat1(-)/VPP(+), or between Fat1(+)/VPP(-)and Fat1(-)/VPP(-) mice at any of the three ages.'] Do high levels of retinal docosahexaenoic acid protect photoreceptor degeneration in VPP transgenic mice?
|
qiaojin/PubMedQA
| 2 |
[
-2.15729022026062,
-1.352542519569397,
2.4854278564453125
] |
['We identified a large Chinese family with X-linked juvenile retinoschisis. The purpose of this study was to report the clinical findings of the family and to identify the genetic mutation by screening the retinoschisis 1 (RS1) gene.', 'Family history was collected and all family members underwent routine ophthalmic examination. Venous blood was collected from family members and genomic DNA was extracted. The exons of RS1 were screened by PCR followed by direct sequencing and/or restriction enzyme digestion.', 'The pedigree of interest was a four-generation family with 52 family members, including seven affected individuals. The proband was a 5-year-old boy showing highly elevated bullous retinoschisis with moderate vitreous hemorrhage in both eyes. Vitrectomy was performed in the left eye of the proband. Five affected males showed large peripheral retinoschisis in both eyes, either involving the macula or combined with foveal stellate cystic change. One of the affected family members showed only a foveal stellate cystic change in both eyes without periphery retinoschisis. Visual acuity of affected individuals ranged from hand motion to 0.4. The R213W mutation in exon 6 of RS1 was identified in all affected individuals, predicting an amino acid substitution of arginine to tryptophan at codon 213.'] Does r213W mutation in the retinoschisis 1 gene cause X-linked juvenile retinoschisis in a large Chinese family?
|
qiaojin/PubMedQA
| 2 |
[
-2.238534688949585,
-1.402759313583374,
2.7139265537261963
] |
['Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin.', 'Commercial PDS containing 3.86% glucose (20 - 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H(2)O(2). Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR.', 'The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H(2)O(2) (200 μmol/L). In addition, H(2)O(2) downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes.'] Does glucose-based peritoneal dialysis solution suppress adiponectin synthesis through oxidative stress in an experimental model of peritoneal dialysis?
|
qiaojin/PubMedQA
| 2 |
[
-2.2930080890655518,
-1.4188206195831299,
2.7465007305145264
] |
['The angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose factor (Fiaf) is known as a regulator of peripheral lipid and glucose metabolism. In the present study, we investigated the physiological role of Angptl4 in central regulation of body weight homeostasis.', 'Hypothalamic Angptl4 expression levels were measured using immunoblot assay during feeding manipulation or after administration of leptin, insulin, and nutrients. The effects of Angptl4 on food intake, body weight, and energy expenditure were determined following intracerebroventricular (ICV) administration of Angptl4 in C57BL/6 mice. Food intake, energy metabolism, and feeding responses to leptin, insulin, and nutrients were compared between Angptl4-null mice and their wild littermates. Finally, the relationship of hypothalamic AMP-activated protein kinase (AMPK) and Angptl4 was studied.', 'Hypothalamic Angptl4 expression levels were increased upon food intake or administration of leptin, insulin, and nutrients. Furthermore, central administration of Angptl4 suppressed food intake and body weight gain but enhanced energy expenditure. These effects were mediated via suppression of hypothalamic AMPK activities. Consistently, Angptl4-null mice displayed increased body weight and hypothalamic AMPK activity but reduced energy expenditure. Food intake following a fast was significantly greater in Angptl4-null mice, which was normalized by centrally administered Angptl4. Moreover, anorectic responses to leptin, insulin, and glucose were diminished in Angptl4-null mice. In contrast, Angptl4-null mice were resistant to diet-induced obesity, indicating obesity-promoting effects of Angptl4 under the condition of fat-enriched diet.'] Is hypothalamic Angptl4/Fiaf a novel regulator of food intake and body weight?
|
qiaojin/PubMedQA
| 2 |
[
-2.2861902713775635,
-1.3028838634490967,
2.576801300048828
] |
['To examine uric acid (UA) as a possible predictor of the progression of coronary artery calcification (CAC) using data from the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.', 'CAC was measured by electron beam tomography at the baseline and at a follow-up 6.0±0.5 years later. The study population included 443 participants with type 1 diabetes and 526 control subjects who were free of diagnosed coronary artery disease at baseline. The presence of renal disease was defined by the presence of albuminuria and/or low glomerular filtration rate.', 'In subjects without renal disease, serum UA predicted CAC progression (odds ratio 1.30 [95% CI 1.07-1.58], P=0.007) independent of conventional cardiovascular risk factors including diabetes and the presence of metabolic syndrome.'] Does serum uric acid predict progression of subclinical coronary atherosclerosis in individuals without renal disease?
|
qiaojin/PubMedQA
| 2 |
[
-2.229679584503174,
-1.237361192703247,
2.5679898262023926
] |
['To observe the influence of carbachol on inflammatory cytokine release and its protective role on organ function in rat endotoxemia model, and, furthermore, to investigate its receptor mechanism in rat peritoneal macrophages in vitro.', 'In the animal experiments, Wistar rats were subjected to lipopolysaccharide (LPS) injection (5 mg/kg body weight) to establish an endotoxemia animal model, and carbachol/nicotine was given 15 minutes after LPS injection. Serum contents of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were determined with enzyme-linked immunosorbent assay 4 hours after LPS injection. Plasma alanine aminotransferase, creatine kinase-MB, and diamine oxidase contents were detected 24 hours after LPS injection. In cell experiments, rat peritoneal macrophages were collected and initially pretreated with atropine (muscarinic cholinergic receptor antagonist) or α-Bungarotoxin (an antagonist that specifically binds α7 subunit of nicotinic cholinergic receptor), then with carbachol or nicotine, and finally stimulated with LPS. Contents of TNF-α, IL-6, and IL-10 in supernatant were assayed by enzyme-linked immunosorbent assay. Furthermore, macrophages were exposed to nicotine and carbachol of high concentration and then stained with fluorescein isothiocyanate-labeled α-bungarotoxin and observed with fluorescent confocal microscopy.', 'Carbachol inhibited expression of TNF-α and IL-6 after LPS injection and had no significant effect on IL-10 in rat endotoxemia model. It also inhibited the increase of plasma alanine aminotransferase and creatine kinase-MB contents whereas restored the inhibited plasma diamine oxidase activity. Cell experiments also showed that increases of TNF-α and IL-6 after LPS stimulation could be significantly inhibited by carbachol or nicotine, whereas IL-10 was not apparently altered. Atropine did not downregulate the inhibitive effects of both carbachol and nicotine, whereas α-bungarotoxin significantly downregulated these effects. Fluorescent confocal microscopy showed that nicotine and carbachol pretreatment markedly reduced the intensity of binding between fluorescein isothiocyanate-labeled α-bungarotoxin and macrophages.'] Does carbachol alleviate rat cytokine release and organ dysfunction induced by lipopolysaccharide?
|
qiaojin/PubMedQA
| 2 |
[
-2.3737387657165527,
-1.397233247756958,
2.7988498210906982
] |
['Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a major role in the sepsis and multiple organ dysfunction secondary to major trauma. The purpose of this article was to research the clinical relevance of the TNF gene polymorphism in patients with major trauma.', 'Three hundred six patients with major trauma were prospectively recruited. The TNF gene polymorphisms were genotyped using restriction fragment length polymorphism analysis. Plasma TNF-α levels were determined with enzyme-linked immunosorbent assay. Sepsis morbidity rate and multiple organ dysfunction scores were accessed.', 'The TNF-α/-308 polymorphism was shown to be well associated with increased capacity of peripheral leukocytes to produce TNF-α in response to ex vivo lipopolysaccharide stimulation in trauma patients at admission. Results from association study indicated that trauma patients carrying the TNF-α/-308/A allele were more likely complicated with sepsis.'] Is tumor necrosis factor alpha gene polymorphism associated with the outcome of trauma patients in Chinese Han population?
|
qiaojin/PubMedQA
| 2 |
[
-2.404975175857544,
-1.2325010299682617,
2.7725162506103516
] |
['Notch signal pathway plays a fundamental role in regulating haematopoietic development. It is also an important mediator of growth and survival in several cancer types, with Notch pathway genes functioning as oncogenes or tumor suppressors in different cancers. However, the clinical role of Notch signal pathway in acute myeloid leukemia (AML) remains unclear.', 'To address this problem, we investigated the gene expression levels of Notch signal pathway members (Notch1, Jagged1 and Delta1) in bone marrow mononuclear cells by real-time quantitative PCR in a cohort of 100 patients with newly diagnosed de novo AML and normal marrow donors. The prognostic values of the three molecules in AML were also analyzed.', 'Comparing with the normal controls, we show the transcriptional up-regulation of Notch1, Jagged1 and Delta1 in the bone marrow of AML patients with statistic differences (P = 0.008, 0.01 and 0.01, respectively). In addition, univariate analysis of factors associated with relapse-free survival and overall survival showed a significantly shorter survival in the patients with unfavorable karyotype, higher Notch1 expression, higher Jagged1 expression, or higher Delta1 expression. Moreover, Cox proportional hazards multivariate analysis of the univariate predictors identified karyotype and gene expression levels of Notch1, Jagged1 and Delta1 as independent prognostic factors for relapse-free survival and overall survival. Furthermore, the prognostic significance of Notch1, Jagged1 and Delta1 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics.'] Is activation of Notch signal pathway associated with a poorer prognosis in acute myeloid leukemia?
|
qiaojin/PubMedQA
| 2 |
[
-2.360961437225342,
-1.2239995002746582,
2.6822457313537598
] |
['Prevalence of metabolic syndrome (MS) is rapidly increasing worldwide. To investigate the spread of MS risks and its relationship with eating habits including fish intake, we carried out a health examination for young and middle-aged men.', 'The subjects were 97 healthy men (20 to 50 years) living in Mwanza, located on the shore of Lake Victoria in Tanzania. The health examination was conducted according to the basic protocol of WHO-CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study. This survey included anthropometric measurements, a dietary questionnaire, blood pressure measurement, and blood and 24-hour urine (24U) collection. Excretions of sodium, potassium and taurine (Tau) in 24U were estimated as the biomarkers of salt, vegetable and fish product intakes respectively.', 'In this survey, 62.5 % of the young and 63.3% of the middle-aged adults had MS risks. The most prevalent MS risk factor was increased blood pressure (50.0% of young adults and 53.1% of the middle-aged). Tau excretions in 24U and n-3 fatty acid levels in plasma were significantly lower in young adults than those in the middle-aged (both P < 0.05). The eating frequencies of non-traditional foods such as donuts and ice cream showed negative correlations with age (r = -0.282, P < 0.01 and r = -0.246, P < 0.05), while salt intake positively correlated with age (r = 0.236, P < 0.05). Tau excretion in 24U was inversely correlated with atherosclerosis index (r = -0.306, P < 0.01) and fasting blood glucose (r = -0.284, P < 0.05).'] Does deterioration of traditional dietary custom increase the risk of lifestyle-related diseases in young male Africans?
|
qiaojin/PubMedQA
| 2 |
[
-1.4913499355316162,
-0.9718753099441528,
1.5807108879089355
] |
['The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice.', 'To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters.'] Do cD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis?
|
qiaojin/PubMedQA
| 2 |
[
-2.525113582611084,
-0.9830695986747742,
2.573489189147949
] |
['Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP.', 'One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n = 56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined.', 'The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P < 0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9) days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05).'] Is rapid hemodilution associated with increased sepsis and mortality among patients with severe acute pancreatitis?
|
qiaojin/PubMedQA
| 2 |
[
-0.7612907886505127,
-1.7581902742385864,
1.4597053527832031
] |
['Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting beta(2)-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients.', 'An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups (1:1) to receive either the combination of 50 microg salmeterol and 500 microg fluticasone twice daily (n = 61), or the combination of 206 microg albuterol and 36 microg ipratropium q.i.d (n = 61) over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment.', "Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein (-1.73 vs. 0.08 mg/L, respectively, P < 0.05) after 6-month treatment. Forced expiratory volume in one second (FEV(1)) and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV(1) and St George's Respiratory Questionnaire total scores compared with those who did not (185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P < 0.01)."] Does salmeterol/fluticasone treatment reduce circulating C-reactive protein level in patients with stable chronic obstructive pulmonary disease?
|
qiaojin/PubMedQA
| 2 |
[
-1.8995250463485718,
-1.5463743209838867,
2.431682586669922
] |
['Deficits in face emotion recognition (FER) in schizophrenia are well documented, and have been proposed as a potential intermediate phenotype for schizophrenia liability. However, research on the relationship between psychosis vulnerability and FER has mixed findings and methodological limitations. Moreover, no study has yet characterized the relationship between FER ability and level of psychosis-proneness. If FER ability varies continuously with psychosis-proneness, this suggests a relationship between FER and polygenic risk factors.', 'We tested two large internet samples to see whether psychometric psychosis-proneness, as measured by the Schizotypal Personality Questionnaire-Brief (SPQ-B), is related to differences in face emotion identification and discrimination or other face processing abilities.', 'Experiment 1 (n=2332) showed that psychosis-proneness predicts face emotion identification ability but not face gender identification ability. Experiment 2 (n=1514) demonstrated that psychosis-proneness also predicts performance on face emotion but not face identity discrimination. The tasks in Experiment 2 used identical stimuli and task parameters, differing only in emotion/identity judgment. Notably, the relationships demonstrated in Experiments 1 and 2 persisted even when individuals with the highest psychosis-proneness levels (the putative high-risk group) were excluded from analysis.'] Is face emotion recognition related to individual differences in psychosis-proneness?
|
qiaojin/PubMedQA
| 2 |
[
-1.7630585432052612,
-0.04546879604458809,
0.9189060926437378
] |
['Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known.', 'Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD.', "SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified."] Do expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density?
|
qiaojin/PubMedQA
| 2 |
[
-2.2906229496002197,
-1.3828577995300293,
2.705756187438965
] |
['Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo.', 'The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases.', 'The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight) significantly suppressed the postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following starch challenge.'] Does antioxidant rich grape pomace extract suppress postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase?
|
qiaojin/PubMedQA
| 2 |
[
-2.4126570224761963,
-1.2178092002868652,
2.659928798675537
] |
['To investigate the effect of HCV DF (Double-shift F) protein on the expression p16 and p21 in HepG(2); cells.', 'DF gene was amplificated from the whole HCV 1b genome, and cloned into pCDNA3.0 vecter. The recombinant plasmid (pCDNA3.0/HCV-DF) and empty vector were transfected into HepG(2); cells. Screening was performed with G418. p16 and p21 mRNA were detected by semi-quantitative RT-PCR, and protein by Western blot.', 'Stable expression of the recombinant plasmid was found in HCV DF protein. The expression of p16 and p21 in HepG();2 cells transfected with pCDNA3.0/HCV-DF were lower than those with blank plasmid.'] Does [ HCV DF protein inhibit expression of p16 and p21 in HepG₂ cells ]?
|
qiaojin/PubMedQA
| 2 |
[
-1.8950440883636475,
-1.2006696462631226,
2.192089557647705
] |
['Cryptotanshinone is a major active component of Salvia miltiorrhiza, which is often used as Chinese herbal medicine in cancer therapy. Here, we systematically assessed the anti-tumor effect of Cryptotanshinone on two melanoma cell lines with low/high-metastatic capacity (B16/B16BL6).', 'MTT and LDH assays were used to evaluate cell growth and cytotoxicity. We assessed the effect of Cryptotanshinone on cell apoptosis or proliferation by Annexin V, TUNEL or BrdU assay. Cell cycle distribution was detected by flow cytometry. The integrity of cell cycle checkpoints was determined by mutational analyses of B-RAF and N-RAS, and the expression of cell cycle-associated proteins by western blotting.', 'Treatment with Cryptotanshinone had no obvious effect on cell apoptosis but significantly inhibited cell proliferation. Cryptotanshinone slightly increased the expression of p53, Chk1, and Chk2 in both B16 and B16BL6. Interestingly, Cryptotanshinone induced G1 arrest with a concomitant increase in p21 expression in B16BL6 cells. However, in B16 cells, Cryptotanshinone induced the G2/M arrest through its induction of Cdc25c. Regulation of Cyclin A1, Cyclin B1 and Cdk1/cdc2 expression might contribute to the different cell cycle patterns in B16 and B16BL6 after Cryptotanshinone treatment.'] Does cryptotanshinone have diverse effects on cell cycle events in melanoma cell lines with different metastatic capacity?
|
qiaojin/PubMedQA
| 2 |
[
-2.438286781311035,
-1.2566512823104858,
2.741875171661377
] |
["Research studies of the female response to intense stress are under-represented in the scientific literature; indeed, publications in female humans and animals number half those in male subjects. In addition, women have only recently entered more dangerous professions that were historically limited to men. The US Navy's survival course, therefore, offers a unique opportunity to examine, in a controlled manner, individual differences in the human female response to acute and realistic military stress.", 'The current study assessed the nature and prevalence of dissociative symptoms and other aspects of adaptive function in healthy female subjects experiencing acute, intense stress during US Navy survival training. Cognitive dissociation and previous exposure to traumatic events were assessed at baseline in 32 female service members prior to Navy survival training. At the conclusion of training, retrospectively rated levels of dissociation during peak training stress and current health symptoms were assessed.', 'Female subjects reported previous trauma (35%) and at least one symptom of dissociation at baseline prior to training (47%). Eighty-eight percent of subjects reported experiencing multiple symptoms of dissociation during peak training stress. Post-stress dissociation scores and stress-induced increases in dissociation, as well as prior cumulative exposure to potentially traumatic events, were significant predictors of post-stress health symptoms.'] Is dissociation During Intense Military Stress Related to Subsequent Somatic Symptoms in Women?
|
qiaojin/PubMedQA
| 1 |
[
-2.221081018447876,
1.1352894306182861,
0.2854934334754944
] |
["We investigated the involvement of MAPK signaling in the cell death mechanisms of classical microtubule interfering agents (MIA) and aryl-3-(2-chloroethyl)ureas (CEU) acting as antimitotics, along with CEU that don't affect directly microtubules (non-MIA CEU).", 'To ascertain the activated signaling pathway profile of MIA and non-MIA CEU, Western blot, immunoprecipitation and transfection experiments were performed.', 'Non-MIA CEU do not activate p38, as opposed to MIA, and the extent of ERK and JNK activation is lower than in response to MIA. The effect of MIA and non-MIA CEU on focal adhesion associated protein was also studied; MIA were shown to induce focal adhesion dismantlement associated with a sustained increase in paxillin phosphorylation and FAK cleavage, as opposed to non-MIA CEU. In addition, bcl-2 phosphorylation and AKT cleavage, induced by all MIA tested, was not observed in response to non-MIA CEU further emphasizing the differential cell death mechanisms induced by MIA and non-MIA CEU. Pharmacologic and genetic approaches emphasize that the ASK1-p38 pathway activation contributes to the cytotoxic mechanism of MIA, in contrast to non-MIA CEU. ASK1-p38 is important for increased paxillin phosphorylation and FAK cleavage, suggesting that ASK-1-p38 is an upstream event of FA structure dismantlement induced by MIA. Moreover, the endogen inhibitor of ASK-1, thioredoxin, is released from ASK-1 in response to MIA as opposed to non-MIA CEU.'] Is aSK1-P38 pathway important for anoikis induced by microtubule-targeting aryl chloroethylureas?
|
qiaojin/PubMedQA
| 2 |
[
-2.396153688430786,
-1.2858818769454956,
2.772261619567871
] |
['The objective of this study was to describe the epidemiology of burn injuries refered to Taleghani Burn hospital, Ahvaz and to provide information necessary for planning and implementing an effective prevention program.', 'The medical records of 6082 consecutive admissions for burn injury treated at Taleghani burn hospital over a five-year period (August 2003 to August 2007) were reviewed.', 'Our results shows that hospital stay in female was significantly longer than in male (p < 0.05). A positive significant correlation was observed between duration of hospital stay and %TBSA (chi2, p < 0.05). Of the 6082 patients, 486 deaths were recorded. The overall mortality rate of hospitalized burns patients was 8%. Mortality rate in female was higher than in male (p < 0.05). Our data showed E. coli in urine culture and Pseudomonas aeruginosa in blood and wound culture was the predominant isolated bacteria.'] Do epidemiology of hospitalized burn patients in Taleghani Hospital during 2003-2007?
|
qiaojin/PubMedQA
| 2 |
[
-2.0423989295959473,
-0.30242469906806946,
1.5589725971221924
] |
['Generally small renal masses grow at slow rate; some of them do not exhibit any growth. Does it mean that they are less aggressive? The aim of our study was to compare the growth of enhancing, non-enhancing solid renal masses, angiomyolipomas and complex renal cystic masses < or =4 cm in diameter.', '12 patients with solid enhancing, 20 with solid non-enhancing, 8 with angiomyolipomas and 25 with Bosniak II/IIF/III and IV masses were enrolled and prospectively studied during the surveillance period. The mean diameter of the lesion at presentation was 3.5; 3.1; 3.2 and 3.9 cm, the mean period of observation was 47; 48; 35 and 48 for each group respectively. All masses were detected incidentally. Progression rates (the largest diameter was calculated) were compared among the groups.', 'The range and mean growth rates among all groups after one year of observation were (0.0-0.3; 0.2 cm); (0.0-0.3; 0.2 cm); (0.0-0.4; 0.3 cm); (0.0-0.3; 0.1 cm); (0.0-0.2; 0.1 cm); (0.0-0.0; 0.0 cm) and (-0.6-0.0; -0.2 cm) for 7 groups respectively. Overall 55.4% of masses did not exhibit any growth. We did not monitor any pathological lymph node enlargement, distant metastases in any group of patients. Overall, 85% of masses that exhibited growth during the first year did so at the end of follow up.'] Are growth rates similar in potentially benign and malignant small renal masses detected incidentally?
|
qiaojin/PubMedQA
| 2 |
[
-0.29232287406921387,
-1.7139978408813477,
1.072967767715454
] |
['The aim was to investigate the growth of monozygotic twins with discordant birth weights and the predictive value of birth-weight, birth-length, and cord-blood concentration of growth factors on their catch-up growth up to the age of 4 yr.', 'Twenty-five monozygotic twin-pairs [14 with an intertwin birth-weight sd score (SDS) difference>1] were studied at birth and at 4 yr of age. In all pairs, several parameters including IGF-I were analyzed in cord blood, and in 20 pairs parameters were analyzed again at 4 yr of age. Intertwin differences (Δ) in birth weight, birth length, and growth at 3, 6, 12, 24, and 48 months were correlated with Δ of the parameters analyzed.', 'We found a reduction of Δ height SDS from birth to 4 yr, with the main catch-up occurring during the first year, but only a slight, statistically insignificant reduction of Δ body mass index SDS during the observation period. Correlation coefficients were used to identify factors predicting postnatal catch-up growth. Both birth-weight difference (r=0.653; P=0.001) and Δ IGF-I in cord blood (r=0.613; P=0.007) were of similar predictive value. Variance analysis showed no significant difference in individual impact between these two parameters, although both correlated strongly with actual height.'] Is insulin-like growth factor-I in cord blood predictive of catch-up growth in monozygotic twins with discordant growth?
|
qiaojin/PubMedQA
| 2 |
[
-1.3666744232177734,
-1.2087666988372803,
1.7015407085418701
] |
['Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells.', 'To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress.', 'Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined.', 'Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress.'] Does suppression of Par-4 protect human renal proximal tubule cells from apoptosis induced by oxidative stress?
|
qiaojin/PubMedQA
| 2 |
[
-2.55462646484375,
-1.0946944952011108,
2.6074318885803223
] |
['There has been a considerable increase in the need for psychiatric services for adolescents. Primary health care practitioners have a major role in detecting, screening and helping these adolescents. An intervention entitled SCREEN is described in this article. The SCREEN intervention was developed to help practitioners to detect and screen adolescent needs, to care for adolescents at the primary health care level and to facilitate the referral of adolescents to secondary care services in collaboration between primary and secondary health care. Secondly, the article presents the background and clinical characteristics of youths seeking help from the SCREEN services, and compares the background factors and clinical characteristics of those patients referred and not referred to secondary care services.', "The SCREEN intervention consisted of 1 to 5 sessions, including assessment by a semi-structured anamnesis interview, the structured Global Assessment Scale, and by a structured priority rating scale, as well as a brief intervention for each adolescent's chosen problem. Parents took part in the assessment in 39% of cases involving girls and 50% involving boys. During 34 months, 2071 adolescents (69% females) entered the intervention and 70% completed it. The mean age was 17.1 years for boys and 17.3 years for girls.", 'For 69% of adolescents, this was the first contact with psychiatric services. The most common reasons for seeking services were depressive symptoms (31%). Self-harming behaviour had occurred in 25% of girls and 16% of boys. The intervention was sufficient for 37% of those who completed it. Psychosocial functioning improved during the intervention. Factors associated with referral for further treatment were female gender, anxiety as the main complaint, previous psychiatric treatment, self-harming behaviour, a previous need for child welfare services, poor psychosocial functioning and a high score in the priority rating scale.'] Is a brief intervention sufficient for many adolescents seeking help from low threshold adolescent psychiatric services?
|
qiaojin/PubMedQA
| 2 |
[
-2.431626319885254,
0.29605624079704285,
1.2284984588623047
] |
['To compare efficacy and safety of bortezomib plus dexamethasone and vincristine plus doxorubicin plus dexamethasone (VAD) as induction before stem-cell transplantation in previously untreated myeloma.', 'Four hundred eighty-two patients were randomly assigned to VAD (n = 121), VAD plus dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation (n = 121), bortezomib plus dexamethasone (n = 121), or bortezomib plus dexamethasone plus DCEP (n = 119), followed by autologous stem-cell transplantation. Patients not achieving very good partial response (VGPR) required a second transplantation. The primary end point was postinduction complete response/near complete response (CR/nCR) rate.', 'Postinduction CR/nCR (14.8% v 6.4%), at least VGPR (37.7% v 15.1%), and overall response (78.5% v 62.8%) rates were significantly higher with bortezomib plus dexamethasone versus VAD; CR/nCR and at least VGPR rates were higher regardless of disease stage or adverse cytogenetic abnormalities. Response rates were similar in patients who did and did not receive DCEP. Post first transplantation, CR/nCR (35.0% v 18.4%) and at least VGPR (54.3% v 37.2%) rates remained significantly higher with bortezomib plus dexamethasone. Median progression-free survival (PFS) was 36.0 months versus 29.7 months (P = .064) with bortezomib plus dexamethasone versus VAD; respective 3-year survival rates were 81.4% and 77.4% (median follow-up, 32.2 months). The incidence of severe adverse events appeared similar between groups, but hematologic toxicity and deaths related to toxicity (zero v seven) were more frequent with VAD. Conversely, rates of grade 2 (20.5% v 10.5%) and grades 3 to 4 (9.2% v 2.5%) peripheral neuropathy during induction through first transplantation were significantly higher with bortezomib plus dexamethasone.'] Is bortezomib plus dexamethasone superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma : results of the IFM 2005-01 phase III trial?
|
qiaojin/PubMedQA
| 2 |
[
-1.5659815073013306,
-1.7367355823516846,
2.244009017944336
] |
['The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids are widely used as biological control agents in sustainable agricultural programs. Females of the gregarious endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae) inject venom along with eggs into their hosts. P. puparum does not inject polydnaviruses during oviposition. For this reason, P. puparum and its pupal host, the small white butterfly Pieris rapae (Lepidoptera: Pieridae), comprise an excellent model system for studying the influence of an endoparasitoid venom on the biology of the pupal host. P. puparum venom suppresses the immunity of its host, although the suppressive mechanisms are not fully understood. In this study, we tested our hypothesis that P. puparum venom influences host gene expression in the two main immunity-conferring tissues, hemocytes and fat body.', 'At 1 h post-venom injection, we recorded significant decreases in transcript levels of 217 EST clones (revealing 113 genes identified in silico, including 62 unknown contigs) derived from forward subtractive libraries of host hemocytes and in transcript levels of 288 EST clones (221 genes identified in silico, including 123 unknown contigs) from libraries of host fat body. These genes are related to insect immune response, cytoskeleton, cell cycle and apoptosis, metabolism, transport, stress response and transcriptional and translational regulation. We verified the reliability of the suppression subtractive hybridization (SSH) data with semi-quantitative RT-PCR analysis of a set of randomly selected genes. This analysis showed that most of the selected genes were down-regulated after venom injection.'] Is expression of immune-response genes in lepidopteran host suppressed by venom from an endoparasitoid , Pteromalus puparum?
|
qiaojin/PubMedQA
| 2 |
[
-2.3673629760742188,
-1.0625040531158447,
2.507796287536621
] |
['Investigate the effect of dietary vitamin E (Vit E) on the retinas of a rat model of induced glaucoma, in which surgically induced elevation of intraocular pressure (IOP) is associated with an increase in reactive oxygen species.', 'Rats were fed a standard chow, Vit E-supplemented diet, or Vit E-deficient diet and subjected to surgically induced IOP elevation (or sham surgery) for five weeks. The retinal ganglion cells (RGCs) were subjected to retrograde fluorescent tracer labeling.', 'The mean number of RGCs of rats on the standard chow, Vit E-supplemented diet, and Vit E-deficient diet were 79.6%, 78.6%, and 71.3% of controls, respectively. Lipid peroxidation of the retinas of rats given a Vit E-deficient diet were significantly higher after IOP elevation for three days (14.42 +/- 0.25 microM, P = 0.016) and five weeks (10.46 +/- 0.11 microM, p = 0.042), compared to rats given standard chow (11.37 +/- 0.31 microM; 8.95 +/- 0.16 microM). Compared with rats given standard chow, rats given a Vit E-deficient diet had significantly elevated concentrations of glutathione (p = 0.032), but no significant differences in the levels of total superoxide dismutase (SOD), Cu/Zn SOD, or catalase activities three days after IOP elevation.'] Does dietary deficiency of vitamin E aggravate retinal ganglion cell death in experimental glaucoma of rats?
|
qiaojin/PubMedQA
| 2 |
[
-2.0929558277130127,
-1.2029814720153809,
2.3201611042022705
] |
['The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium.', 'To test this hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS protein that can be produced to high yields in the E. coli expression system. Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the recombinant protein adjuvanted with Montanide ISA 720 and characterized using in vitro and in vivo analyses.'] Does immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicit cross-species protection against heterologous challenge with Plasmodium berghei?
|
qiaojin/PubMedQA
| 2 |
[
-2.517028570175171,
-1.1740916967391968,
2.8200337886810303
] |
['The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial.', 'To address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-beta2-glycoprotein I (isolated IgA anti-beta2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-beta2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-beta2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-beta2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-beta2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin).'] Are igA anti-beta2-glycoprotein I autoantibodies associated with an increased risk of thromboembolic events in patients with systemic lupus erythematosus?
|
qiaojin/PubMedQA
| 2 |
[
-2.3902783393859863,
-1.2927186489105225,
2.7143757343292236
] |
['A sedentary lifestyle with insufficient exercise is associated with cardiovascular disease. Previous studies have demonstrated that endurance exercise benefits atherosclerosis and cardiovascular disorders; however, the mechanisms by which physical activity, such as voluntary exercise (Ex), produces these effects are not fully understood.', 'Eight-week-old male apolipoprotein (ApoE)-deficient mice were fed a standard diet (STD) or high fat diet (HFD) for 10 weeks. The HFD+Ex group mice performed Ex on a running wheel for 10 weeks. No significant differences in lipid profiles were observed between the HFD and HFD+Ex groups. Although changes in body and brown adipose tissue weights were comparable between the HFD and HFD+Ex groups, white adipose tissue weight was significantly lower in the HFD+Ex group than in the HFD group. The areas of atherosclerotic lesions in the aortic sinus and thoracoabdominal aorta were significantly reduced in the HFD+Ex group than in the HFD group (p<0.001). There was a strong negative correlation between atherosclerotic areas and the mean running distance per day in the HFD+Ex group (r=-0.90, p=0.01). Endothelial function was significantly preserved in the HFD+Ex group (p<0.05). Serum interleukin-6 and macrophage chemoattractant protein-1 levels were significantly lower and those of adiponectin were significantly higher in the HFD+Ex group than in the HFD group (p<0.05).'] Does voluntary exercise ameliorate the progression of atherosclerotic lesion formation via anti-inflammatory effects in apolipoprotein E-deficient mice?
|
qiaojin/PubMedQA
| 2 |
[
-2.146815538406372,
-1.3934789896011353,
2.5406854152679443
] |
['Mitochondrial biogenesis includes both mitochondrial proliferation and differentiation and its regulation under different physiological conditions is not clear. Given the sexual dimorphism previously found in mitochondrial function, the aim of this study was to investigate the gender-dependent effect of chronic high-fat-diet (HFD) feeding on rat liver mitochondrial function and biogenesis.', 'Ten-week old male and female rats were fed a HFD (26% fat) or a control diet (2.9% fat) for 26 weeks. Mitochondrial morphology was studied. Mitochondrial DNA and protein content, hydrogen peroxide production, oxidative capacity, antioxidant defenses, as well as markers of oxidative damage and mitochondrial biogenesis were analyzed.', 'Female rats showed higher levels of mitochondrial protein and an enhanced oxidative capacity per mitochondrion than males. In both genders, HFD feeding increased mtDNA content and decreased mitochondrial differentiation markers.'] Does long-term high-fat-diet feeding impair mitochondrial biogenesis in liver of male and female rats?
|
qiaojin/PubMedQA
| 2 |
[
-2.5613598823547363,
-0.1102290004491806,
1.6999166011810303
] |
['The impact of single-nucleotide polymorphisms (SNPs) on tumour susceptibility and pathogenesis has gained enormous attention. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based genotyping facilitates the analysis of short DNA amplicons and is, therefore, a promising tool for the investigation of formalin-fixed paraffin-embedded (FFPE) tissue samples, particularly in targeted genotyping analysis.', 'To examine the applicability of genotyping FFPE DNA with MALDI-TOF MS in multiplex reactions, we investigated five DNA samples extracted from FFPE tumour specimens from follicular lymphoma patients using different extraction methods (phenol-chloroform, commercial kit). Thirty-one SNPs from 25 genes, integrated in different-sized multiplex assays (7-plex, 10-plex, 14-plex, 24-plex), were analyzed. To investigate the reliability of genotyping tumour-derived DNA extracted from FFPE tissue, we examined 64 FFPE tumour specimens in comparison with matched germline DNA samples.', 'Call rates of 99.6 (274/275) and 93.5% (257/275) were observed for the DNA extracted with the phenol-chloroform approach or the commercial extraction kit, respectively. Increasing the number of SNPs per assay resulted in reduced genotyping call rates and genotyping quality, especially in the DNA samples isolated with the commercial extraction kit. When comparing the genotypes of DNA derived from germline and tumour (FFPE) specimens, a perfect concordance rate of 100% was detected.'] Does a multiplex MALDI-TOF MS approach facilitate genotyping of DNA from formalin-fixed paraffin-embedded tumour specimens?
|
qiaojin/PubMedQA
| 2 |
[
-1.9637176990509033,
-1.4486470222473145,
2.4467618465423584
] |
['Synaptogenesis is a fundamental step in neuronal development. For spiny glutamatergic synapses in hippocampus and cortex, synaptogenesis involves adhesion of pre and postsynaptic membranes, delivery and anchorage of pre and postsynaptic structures including scaffolds such as PSD-95 and NMDA and AMPA receptors, which are glutamate-gated ion channels, as well as the morphological maturation of spines. Although electrical activity-dependent mechanisms are established regulators of these processes, the mechanisms that function during early development, prior to the onset of electrical activity, are unclear. The Eph receptors and ephrins provide cell contact-dependent pathways that regulate axonal and dendritic development. Members of the ephrin-A family are glycosyl-phosphatidylinositol-anchored to the cell surface and activate EphA receptors, which are receptor tyrosine kinases.', 'Here we show that ephrin-A5 interaction with the EphA5 receptor following neuron-neuron contact during early development of hippocampus induces a complex program of synaptogenic events, including expression of functional synaptic NMDA receptor-PSD-95 complexes plus morphological spine maturation and the emergence of electrical activity. The program depends upon voltage-sensitive calcium channel Ca2+ fluxes that activate PKA, CaMKII and PI3 kinase, leading to CREB phosphorylation and a synaptogenic program of gene expression. AMPA receptor subunits, their scaffolds and electrical activity are not induced. Strikingly, in contrast to wild type, stimulation of hippocampal slices from P6 EphA5 receptor functional knockout mice yielded no NMDA receptor currents.'] Does ephrin-A5 and EphA5 interaction induce synaptogenesis during early hippocampal development?
|
qiaojin/PubMedQA
| 2 |
[
-2.5422160625457764,
-1.1108497381210327,
2.6718690395355225
] |
['The 1555A > G mutation is the most common cause of aminoglycoside-induced and non-syndromic deafness. However, the variable clinical phenotype and incomplete penetrance of A1555G-induced hearing loss complicate our understanding of this mutation. Environmental factors, nuclear genes, mitochondrial haplotypes/variants and a possible threshold effect have been reported to may be involved in its manifestation.', 'Here, we performed a clinical, molecular, genetic and phylogenic analysis in a six-generation Chinese family.', 'A clinical evaluation revealed that affected individuals without aminoglycoside exposure developed hearing loss extending gradually from 12000 Hz to 8000 Hz and then to 4000 Hz. Using pyrosequencing, we detected an identical homoplasmic 1555A > G mutation in all individuals except one. We did not find any correlation between the mutation load and the severity of hearing loss. T123N coexisted with the 1555A > G mutation in six affected subjects in our pedigree. Analysis of the complete mtDNA genome of this family revealed that this family belonged to haplotype B4C1C and exhibited high penetrance. Upon the inclusion of subjects that had been exposed to aminoglycosides, the penetrance of the hearing loss was 63.6%.; without exposure to aminoglycosides, it was 51.5%. This pedigree and another reported Chinese pedigree share the same haplotype (B4C1C) and lack functionally significant mitochondrial tRNA variants, but nevertheless they exhibit a different penetrance of hearing loss.'] Does a six-generation Chinese family in haplogroup B4C1C exhibit high penetrance of 1555A > G-induced hearing Loss?
|
qiaojin/PubMedQA
| 2 |
[
-2.01440167427063,
-1.3111073970794678,
2.413879632949829
] |
['Coordinated efforts to collect large-scale data sets provide a basis for systems level understanding of complex diseases. In order to translate these fragmented and heterogeneous data sets into knowledge and medical benefits, advanced computational methods for data analysis, integration and visualization are needed.', 'We introduce a novel data integration framework, Anduril, for translating fragmented large-scale data into testable predictions. The Anduril framework allows rapid integration of heterogeneous data with state-of-the-art computational methods and existing knowledge in bio-databases. Anduril automatically generates thorough summary reports and a website that shows the most relevant features of each gene at a glance, allows sorting of data based on different parameters, and provides direct links to more detailed data on genes, transcripts or genomic regions. Anduril is open-source; all methods and documentation are freely available.', 'We have integrated multidimensional molecular and clinical data from 338 subjects having glioblastoma multiforme, one of the deadliest and most poorly understood cancers, using Anduril. The central objective of our approach is to identify genetic loci and genes that have significant survival effect. Our results suggest several novel genetic alterations linked to glioblastoma multiforme progression and, more specifically, reveal Moesin as a novel glioblastoma multiforme-associated gene that has a strong survival effect and whose depletion in vitro significantly inhibited cell proliferation. All analysis results are available as a comprehensive website.'] Does large-scale data integration framework provide a comprehensive view on glioblastoma multiforme?
|
qiaojin/PubMedQA
| 2 |
[
-2.555492639541626,
-0.20770207047462463,
1.9758416414260864
] |
['Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings.', 'Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided).', 'Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p = 0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated.'] Does prophylactic tetracycline diminish the severity of epidermal growth factor receptor ( EGFR ) inhibitor-induced rash : results from the North Central Cancer Treatment Group ( Supplementary N03CB )?
|
qiaojin/PubMedQA
| 2 |
[
-1.9750312566757202,
-1.459347128868103,
2.445673942565918
] |
['Safe esophageal closure remains a challenge in transesophageal Natural Orifice Transluminal Endoscopic Surgery (NOTES). Previously described methods, such as suturing devices, clips, or submucosal tunneling, all have weaknesses. In this survival animal series, we demonstrate safe esophageal closure with a prototype retrievable, antimigration stent.', 'Nine Yorkshire swine underwent thoracic NOTES procedures. A double-channel gastroscope equipped with a mucosectomy device was used to create an esophageal mucosal defect. A 5-cm submucosal tunnel was created and the muscular esophageal wall was incised with a needle-knife. Mediastinoscopy and thoracoscopy were performed in all swine; lymphadenectomy was performed in seven swine. A prototype small intestinal submucosal (SurgiSIS(®)) covered stent was deployed over the mucosectomy site and tunnel. Three versions of the prototype stent were developed. Prenecropsy endoscopy confirmed stent location and permitted stent retrieval. Explanted esophagi were sent to pathology.', 'Esophageal stenting was successful in all animals. Stent placement took 15.8 ± 4.8 minuted and no stent migration occurred. Prenecropsy endoscopy revealed proximal ingrowth of esophageal mucosa and erosion with Stent A. Mucosal inflammation and erosion was observed proximally with Stent B. No esophageal erosion or pressure damage from proximal radial forces was seen with Stent C. On necropsy, swine 5 had a 0.5-cm periesophageal abscess. Histology revealed a localized inflammatory lesion at the esophageal exit site in swine 1, 3, and 9. The mucosectomy site was partially healed in three swine and poorly healed in six. All swine thrived clinically, except for a brief period of mild lethargy in swine 9 who improved with short-term antibiotic therapy. The submucosal tunnels were completely healed and no esophageal bleeding or stricture formation was observed. All swine survived 13.8 ± 0.4 days and gained weight in the postoperative period.'] Does stent placement provide safe esophageal closure in thoracic NOTES ( TM ) procedures?
|
qiaojin/PubMedQA
| 2 |
[
-2.281529664993286,
-1.4470641613006592,
2.7990174293518066
] |
['Vitamin D deficiency is associated with susceptibility to active tuberculosis (TB) in many settings. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs, isoniazid and rifampicin, reduce 25-hydroxy vitamin D (25[OH]D) concentrations.', 'To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB (PTB).', 'We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment.', 'Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment (median increase 6.0 nmol/l, IQR -0.7-25.0, P = 0.001). Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l (median increase 0.46, IQR -0.2-1.1, P < 0.001).'] Do serum 25-hydroxy-vitamin D3 concentrations increase during tuberculosis treatment in Tanzania?
|
qiaojin/PubMedQA
| 2 |
[
-1.444712519645691,
-1.2787868976593018,
1.738782286643982
] |
['A tertiary care research centre in São Paolo, Brazil.', 'To quantify interleukin (IL) 8, tumour necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF) and transforming growth factor beta(1) (TGF-beta(1)) in pleural fluid from tuberculous patients, correlating its values with the histopathological patterns in pleural biopsies.', 'Cytokines were quantified in patients with transudates secondary to congestive heart failure (n = 8) and exudates secondary to tuberculosis (TB; n = 39). In parietal pleural biopsies from TB patients, the histological patterns of the inflammatory response were quantified by morphometric analysis (stereological point-counting method).', 'IL-8, TNF-alpha, VEGF and TGF-beta(1) levels were higher in TB than in transudates. A positive correlation existed between components of the fibrinoid exudative phase with pleural fluid IL-8 (R = 0.52, P = 0.004) and VEGF (R = 0.42, P = 0.0021) levels. A negative correlation existed between pleural fluid IL-8 (R = -0.37, P = 0.048) and VEGF (R = -0.44, P = 0.0015) levels with tissue components of fibroproliferation.'] Do pleural fluid cytokines correlate with tissue inflammatory expression in tuberculosis?
|
qiaojin/PubMedQA
| 2 |
[
-2.2489168643951416,
-1.3024057149887085,
2.577399253845215
] |
['To determine the effect of losartan on vascular remodeling and the underlying mechanism in spontaneously hypertensive rats(SHR).', 'SHR of 12 weeks old were given losartan orally [0, 15, 30 mg/(kg.d), n=12]. The tail arterial pressure was measured every week. Eight weeks later, the pathological changes and p22(phox) expression in the thoracic aorta, the activity of catalase (CAT), the contents of H(2)O(2) and Ang II in the plasma were evaluated.', 'Blood pressure was increased in the SHR accompanied by the thickened wall and increased p22(phox) expression in the thoracic aorta. The plasma levels of H(2)O(2) and Ang II were elevated while the CAT level was decreased in the SHR. Administration of losartan reversed the thickened wall and increased the CAT activity concomitantly with the decreased plasma levels of H(2)O(2) and p22(phox) expression in the SHR. The plasma level of Ang II increased after the losartan treatment.'] Does losartan attenuate vascular remodeling of the aorta in spontaneously hypertensive rats and the underlying mechanism?
|
qiaojin/PubMedQA
| 2 |
[
-2.2440755367279053,
-1.3719979524612427,
2.671476364135742
] |
['The goal of this study was to explore the molecular mechanisms of aberrant hypoxia inducible factor-1 (HIF-1) activation in lymphoma cells.', 'We analyzed the expression of the α subunit of HIF-1 in three lymphoma cell lines and in normal CD19-positive B cells by Western blotting. To investigate the role of nuclear factor (NF)-κB in abnormal HIF-1α expression in lymphoma cells, we performed a reporter assay using HIF-1α promoter constructs that contained or lacked an NF-κB binding site. We also used a chromatin immunoprecipitation assay to assess whether NF-κB binds the HIF-1α promoter. In addition, we took advantage of NF-κB inhibitors. To analyze the function of HIF-1 in lymphoma cells, we established stable HIF-1α knockdown cells using short-hairpin RNA.', 'Malignant lymphoma cells, but not normal B cells, demonstrated constitutive expression of HIF-1α. Inhibitors of NF-κB, however, drastically suppressed this HIF-1α expression at both the messenger RNA and protein levels. Furthermore, we found that exposure of lymphoma cells to ionizing radiation clearly induced NF-κB activation and increased HIF-1α expression. Suppressing HIF-1α expression by short-hairpin RNA increased the sensitivity of lymphoma cells to ionizing radiation-induced cell death. In searching for downstream targets of the NF-κB/HIF-1 axis, we identified survivin, a member of the IAP family of anti-apoptotic proteins.'] Does nF-κB mediate aberrant activation of HIF-1 in malignant lymphoma?
|
qiaojin/PubMedQA
| 2 |
[
-2.4114620685577393,
-1.2308626174926758,
2.658515453338623
] |
['\u2002 A hypoallergen of the major cat allergen Fel d 1, recombinant (r) Fel d 1 (DTE III), was previously shown to have retained T-cell reactivity and strongly reduced IgE-binding capacity compared to unmodified rFel d 1. Here, we evaluated the therapeutic capacity of rFel\u2003d 1 (DTE III) in a mouse model for cat allergy.', '\u2002 Mice were subcutaneously (s.c.) sensitized with rFel d 1 and subsequently treated (s.c.) with 50 or 200 μg rFel d 1 (DTE III), or 50 μg rFel d 1, prior to intranasal challenge with cat dander extract. Airway hyperreactivity (AHR), cells and cytokines in bronchoalveolar lavage fluid, splenocyte in vitro response, and serum immunoglobulins were analyzed. Seven cat-allergic patients and ten healthy controls were tested for skin prick test (SPT) reactivity to rFel d 1 (DTE III) and rFel d 1.', "\u2002 Mice treated with 50 and 200 μg rFel d 1 (DTE III), and 50 μg rFel d 1, produced increased serum levels of rFel d 1-specific IgG1 and IgG2a compared to sham-treated mice. IgG from all treatment groups could block binding of patients' IgE to rFel d 1. The 200 μg rFel d 1 (DTE III) treatment tended to reduce AHR. All mice tolerated treatment with rFel d 1 (DTE III), in contrast to only four of ten treated with rFel d 1. Compared to rFel d 1, the hypoallergen showed a tendency of reduced SPT reactivity."] Does treatment with a Fel d 1 hypoallergen reduce allergic responses in a mouse model for cat allergy?
|
qiaojin/PubMedQA
| 2 |
[
-1.9294474124908447,
-1.5797946453094482,
2.5024728775024414
] |
['The purpose of this study was to determine the anabolic response of a single bout of high intensity resistance exercise (RE) following 5 weeks of RE training.', 'To complete these studies, Sprague-Dawley rats were assigned by body mass to RE, exercise control (EC), or sedentary cage control (CC) groups and studied over 36 h after 5 weeks of RE (squat-like) training. Cumulative (final 36 h) fractional rates of muscle protein synthesis (FSR) were determined by ²H₂O, and acute (16 h post-RE) rates of muscle protein synthesis (RPS) were determined by flooding with l-[2,3,4,5,6-³H]phenylalanine. Regulators of peptide-chain initiation, 4E-BP1, eIF4E and the association of the two were determined by Western blotting and immunoprecipitation respectively.', 'No differences were observed with acute measures of RPS obtained 16 h following the final exercise bout in the plantaris or soleus muscles (P > 0.05). Consistent with this observation, 4E-BP1 was similarly phosphorylated and bound to eIF4E among all groups. However, upon determination of the cumulative response, FSR was significantly increased in the plantaris of RE vs. EC and CC (0.929±0.094, 0.384±0.039, 0.300±0.022% h(-1) respectively; P<0.001), but not the soleus.'] Are cumulative responses of muscle protein synthesis augmented with chronic resistance exercise training?
|
qiaojin/PubMedQA
| 2 |
[
-1.810305118560791,
-1.4939993619918823,
2.323029041290283
] |
['Osteopontin is a key cytokine involved in pro-inflammatory T helper type 1 (Th1)-associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia.', 'The concentrations of osteopontin and Th1- or Th2-associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug-induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin.', 'Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug-induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL-10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL-5, as well as IL-10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils.'] Are osteopontin levels elevated in patients with eosinophilic pneumonia?
|
qiaojin/PubMedQA
| 2 |
[
-2.30163836479187,
-1.4204740524291992,
2.688608169555664
] |
['The purpose of the study was to know the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) in critically ill patients with H1N1 influenza A virus pneumonia and to compare levels of these inflammatory mediators with patients with acute community-acquired bacterial pneumonia.', 'An observational study in a mixed intensive care unit (ICU) at a general university hospital was performed. All consecutive patients admitted to the ICU with a diagnosis of severe acute community-acquired pneumonia from September 2009 to December 2009 were included. Viral (H1N1 influenza A) and bacterial microbiological diagnoses were done in every patient. At admission, demographics, comorbidities, Simplified Acute Physiology Score, Sequential Organ Failure Assessment, Lung Injury Score, and Pao(2)/Fio(2) were recorded. At admission and after 24, 48, and 120 hours, WBC, CRP, and PCT levels were obtained. Finally, hospital and ICU length of stay and mortality were recorded.', 'No differences in CRP or WBC were found between H1N1-positive patients and H1N1-negative patients (patients with acute community-acquired bacterial pneumonia). Procalcitonin levels at admission were lower in H1N1-positive patients (PCT = 0.4 [0.1-6.1] ng/mL) than in the H1N1-negative patients (24.8 [13.1-34.5] ng/mL). Procalcitonin significantly decreased with time but remained lower in the H1N1-positive group at all measurements (P < .05 for all comparisons).'] Are procalcitonin levels lower in intensive care unit patients with H1N1 influenza A virus pneumonia than in those with community-acquired bacterial pneumonia . A pilot study?
|
qiaojin/PubMedQA
| 2 |
[
-1.6641374826431274,
-1.4802790880203247,
2.1522650718688965
] |
['Allergic rhinitis is a global health problem that causes major illnesses and disability worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. However, the precise mechanism underlying allergen-SIT is not well understood.', 'The aim of the current study was to identify protein expression signatures reflective of allergen-SIT-more specifically, sublingual immunotherapy (SLIT).', 'Serum was taken twice from patients with seasonal allergic rhinitis caused by Japanese cedar: once before the pollen season and once during the season. A\xa0total of 25 patients was randomly categorized into a placebo-treated group and an active-treatment group. Their serum protein profiles were analyzed by 2-dimensional electrophoresis.', 'Sixteen proteins were found to be differentially expressed during the pollen season. Among the differentially expressed proteins, the serum levels of complement C4A, apolipoprotein A-IV (apoA-IV), and transthyretin were significantly increased in SLIT-treated patients but not in placebo-treated patients. Among these proteins, the serum levels\xa0of apoA-IV correlated with the clinical symptom-medication scores (r\xa0= -0.635; P\xa0< .05) and with quality of life scores (r\xa0= -0.516; P\xa0< .05) in the case of SLIT-treated patients. The amount of histamine released from the basophils in vitro was greatly reduced after the addition of recombinant apoA-IV in the medium (P\xa0< .01).'] Is apolipoprotein A-IV a candidate target molecule for the treatment of seasonal allergic rhinitis?
|
qiaojin/PubMedQA
| 2 |
[
-2.1270573139190674,
-1.4979530572891235,
2.623566150665283
] |
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