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['Impairments in physical and social functioning are often associated with distress for the cancer survivor. Impaired functioning may also lead individuals to question previously held beliefs about meaning in life. Meaning in life was hypothesized to mediate the relationship between functioning and distress.', 'Two studies were conducted. In the cross-sectional study (I), cancer survivors (N=420) were accrued via the Internet and completed measures of social and physical functioning, meaning and distress. In the longitudinal study (II), breast cancer survivors (N=167) completed measures of functioning at 18 months, meaning at 24 months and distress at 30 months post-diagnosis.', 'In Study I, meaning in life was a significant, partial mediator for both of the effects of physical and social functioning impairments on heightened distress. In Study II, significant indirect effects of functioning impairments on distress through meaning were replicated even when functioning and distress were measured 1 year apart. The relationship of social functioning and distress was fully mediated by meaning in life, whereas the relationship of physical functioning and distress was partially mediated by meaning.'] Does meaning in life mediate the relationship between social and physical functioning and distress in cancer survivors?
qiaojin/PubMedQA
1
[ -2.287543773651123, 1.254016637802124, 0.23207131028175354 ]
['Serum levels of aldosterone in heart failure are increased up to 20 times compared to normal subjects. After an acute myocardial infarction, aldosterone increases progressively as well as interstitial fibrosis and collagen synthesis from cardiac fibroblasts, forming a patchy heterogeneous interstitial collagen matrix that affects ventricular function. Even if angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARA) can reduce aldosterone levels early during treatment, they increase again after a 12 week treatment. The aim of this study was to evaluate the changes in structure and function of the left ventricle in symptomatic (NYHA I-III) diastolic heart failure patients receiving an aldosterone receptor antagonist.', 'Twenty-eight subjects with diastolic heart failure, on BB, ACEI and/ or ARA were randomized to receive spironolactone (group A) on a mean dose of 37.5 mg once a day (n = 14, age 63.7 +/- 21.6 years and body mass index, BMI 27.5 +/- 9.4), or not (group B, n = 14, Age 64.8 +/- 11.9, BMI 26.9 +/- 4.7). All patients were followed-up for a mean of 13.79 +/- 0.99 months.', 'Group A showed a 42.8% ischemic origin of heart failure, while in group B was 55% (p = 0.2). No other co-morbidities were significativelly different among both groups. Mean percentage of changes by echocardiogram was as follows: Interventricular septum (IVS) -12.2 +/- 11% vs. 1.3 +/- 15.2 (p = 0.03), pulmonary systolic artery pressure (PSAP was 0.99 +/- 3.8% vs. 10.5 +/- 9.1, p = 0.05). Other parameters did not show statistically significant differences.'] Do aldosterone receptor antagonists induce favorable cardiac remodeling in diastolic heart failure patients?
qiaojin/PubMedQA
2
[ -1.9020990133285522, -1.5387938022613525, 2.4520773887634277 ]
['African Americans commonly have normal high-density lipoprotein cholesterol (HDL-C) and low triglyceride levels despite having insulin resistance and obesity. The higher than expected HDL-C levels are usually attributed to low levels of hepatic triglyceride lipase (HTGL) activity. Factors that regulate HTGL in African Americans are not well delineated.', 'In the current study, HTGL activity was examined in relation to indices of body fat (body mass index [BMI] and waist circumference [WC]), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR] index), and adipokines (adiponectin and leptin). Sixty-three African Americans (33 men, 30 women; median age 31 years, range 20-50 years; median BMI 28.6 kg/m2, range 19.7-54.7 kg/m2) had anthropometry and measurement of postheparin lipase activities (HTGL), plasma HDL-C, triglycerides, and plasma adiponectin.', 'HTGL correlated strongly with HDL-C (r = -.52, p < .0001) and adiponectin (r = -.49, p < .001). HTGL increased with BMI and WC (r = .297, p = .018 and r = .301, p = .016, respectively). Adiponectin correlated strongly with HDL-C (r = .50, p < .0001) and triglycerides (r = -.493, p < .001). From multiple regression models, 28% of HTGL variability among African Americans can be explained by adiponectin levels in combination with gender and 35% of HTGL is explained with HDL-C included in the model.'] Is variability in postheparin hepatic lipase activity associated with plasma adiponectin levels in African Americans?
qiaojin/PubMedQA
2
[ -1.2984070777893066, -1.587721824645996, 1.82811439037323 ]
['Blastocyst biogenesis occurs over several cell cycles during the preimplantation period comprising the gradual expression and membrane assembly of junctional protein complexes which distinguish the outer epithelial trophectoderm (TE) cells from the inner cell mass (ICM). In the human, TE integrity and the formation of a junctional seal can often be impaired. Embryos likely to result in a successful pregnancy after transfer are mostly selected according to morphological criteria. Recent data suggest that non-invasive measurement of amino acid turnover may be useful to complement such morphological scores. Whether morphological and metabolic criteria can be linked to poor TE differentiation thereby underpinning developmental predictions mechanistically remains unknown.', 'We examined TE intercellular junction formation in human embryos by immunofluorescence and confocal microscopy and correlated this process with morphological criteria and amino acid turnover during late cleavage.', 'Our results show that TE differentiation may be compromised by failure of membrane assembly of specific junction constituents. This abnormality relates more closely to metabolic profiles than morphological criteria.'] Are human embryos developing in vitro susceptible to impaired epithelial junction biogenesis correlating with abnormal metabolic activity?
qiaojin/PubMedQA
2
[ -2.835026264190674, -0.6675333380699158, 2.6192638874053955 ]
['The possible functions of the human IIIb-messenger RNA splice variant of fibroblast growth factor (FGF) receptor 1 (FGFR-1 IIIb) are yet to be delineated. In this study, the expression and functionality of the human FGFR-1 IIIb were characterized in the pancreas.', 'In situ hybridization with a specific FGFR-1 IIIb probe in human pancreatic tissues demonstrated that FGFR-1 IIIb localized in normal pancreatic acinar and in ductal-like pancreatic cancer cells. To further assess the potential role of this receptor, a full-length human FGFR-1 IIIb was stably expressed in TAKA-1 pancreatic ductal cells not expressing endogenous FGFR-1.', 'The FGFR-1 IIIb-expressing TAKA-1 cells synthesized a glycosylated 110-kd protein capable of inducing proliferation on incubation with exogenous FGF-1, -2, and -4. These effects were paralleled by tyrosine phosphorylation of FGFR substrate 2 and association of FGFR substrate 2 with FGFR-1 IIIb. The FGF-1, -2, and -10 induced the activation of p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, and c-Jun N-terminal kinase. Pharmacological inhibition revealed that FGF-induced proliferation was dependent on the concomitant activation of p44/42 MAPK and c-Jun N-terminal kinase. The FGFR-1 IIIb expression enhanced single-cell movement and plating efficacy.'] Is human fibroblast growth factor receptor 1-IIIb a functional fibroblast growth factor receptor expressed in the pancreas and involved in proliferation and movement of pancreatic ductal cells?
qiaojin/PubMedQA
2
[ -2.3680944442749023, -1.2845189571380615, 2.657651424407959 ]
['To investigate whether the increase of the retroperitoneal compartment pressure, as in the case of peripancreatic fluid accumulation in severe acute pancreatitis, simulated by infusing a colloid fluid into the retroperitoneum, has any effect on pancreatic tissue blood flow.', 'Six male anesthetized swine were subjected to a transcutaneous placement of catheters into the retroperitoneal space. Through these catheters, a colloid solution was infused, under continuous retroperitoneal pressure monitoring, to achieve a pressure up to 20 mm Hg. Pancreatic tissue blood flow was assessed by colored microsphere injection technique, and pancreatic interstitial pressure was measured by means of a commercially available pressure monitor system before and after the distension of the retroperitoneal space, allowing the appropriate time for the animals to be stabilized from any intervention.', 'The increase in the retroperitoneal compartment pressure was found to significantly increase pancreatic interstitial pressure (from 8 +/- 1 to 20 +/- 2.4 mm Hg, P = 0.001) as well as reduce pancreatic tissue blood flow (from 1.75 +/- 0.4 to 0.56 +/- 0.12 mL . min . g, P = 0.002).'] Does retroperitoneal compartment pressure elevation impair pancreatic tissue blood flow?
qiaojin/PubMedQA
2
[ -2.2283499240875244, -1.2898426055908203, 2.564563274383545 ]
['We investigated the effect of branched-chain amino acids (BCAA) supplementation on tissue damage during distance running.', 'Eight male distance runners (mean +/- standard deviation; age: 20.4+/-1.2 years, body weight: 58.4+/-4.2 kg) participated in a double blinded cross over designed study conducted during training camp. During each intervention period, the subjects were asked to participate in a 25-km run, and the blood BCAA and lactate dehydrogenase (LDH) level, an index of tissue damage, were measured pre- and post-run. Either a drink containing BCAA (0.4% BCAA in a 4% carbohydrate solution) or an iso-calorie placebo drink was provided to the subjects 5 times during the run without any restriction in the volume.', 'The total volume of the drink consumed by the subjects did not differ substantially between the trials: 591+/-188 (2.36 g BCAA) vs 516+/-169 mL in BCAA and placebo trial, respectively. During the run, the blood BCAA concentration was maintained in the BCAA trial. However, the blood BCAA concentration level tended to decrease in the placebo trial (P<0.1). The extent of the blood LDH increase in the BCAA trial was significantly less than that of the placebo trail (48% vs 58%, P<0.05).'] Does branched-chain amino acids supplementation attenuate the accumulation of blood lactate dehydrogenase during distance running?
qiaojin/PubMedQA
2
[ -1.181353211402893, -1.327944040298462, 1.5953643321990967 ]
['To analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin-like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis.', 'Formalin-fixed specimens of bladder cancer (40 whole-mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12).', 'Of the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q-RT-PCR showed significantly higher levels of steady-state IGF1R mRNA in tumours (all cases, Ta-T4) than in normal bladder (P < 0.05), indicating up-regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta-T1) or invasive (T2-4) tumours; only the latter showed significant IGF1R over-expression at the RNA level (P < 0.05 vs normal bladder).'] Is the type 1 insulin-like growth factor receptor over-expressed in bladder cancer?
qiaojin/PubMedQA
2
[ -2.135345458984375, -1.4813278913497925, 2.6456170082092285 ]
['To determine whether socioeconomic status (SES) is associated with catecholamine levels (epinephrine [E] and norepinephrine [NE]-indicators of sympathetic nervous system [SNS] activity) in a community-based sample of men and women, Blacks and Whites, with a broad range of income; and to test whether such a relationship is mediated by psychosocial factors and/or health behaviors.', 'A total of 672 participants from the Coronary Artery Risk Development in Young Adults study (CARDIA) provided 12-hour, overnight urine samples, and completed sociodemographic, health behavior, and psychosocial questionnaires.', 'Regardless of whether measured in terms of income, education, or occupation, higher SES was associated with lower urinary catecholamine levels, independent of age, race, and gender. These relationships were stronger in men than in women but were similar across Blacks and Whites. Smoking and greater levels of depressive symptoms accounted for some of the association of SES with E and, to a lesser extent, with NE.'] Is socioeconomic status related to urinary catecholamines in the Coronary Artery Risk Development in Young Adults ( CARDIA ) study?
qiaojin/PubMedQA
2
[ -2.532808542251587, -0.35522177815437317, 2.037426710128784 ]
['Extracorporeal photochemotherapy (ECP) produces clinical improvements in refractory/resistant graft-versus-host disease (GvHD). Immunological mechanisms of ECP are still under investigation.', 'We have evaluated the changes in frequency and immunophenotype of circulating regulatory T cells (T-regs) in 10 patients undergoing allogeneic hematopoietic stem cell transplantation, receiving ECP for acute (n=4) or chronic (n=6) GvHD. T-regs were monitored for expression of surface CD4, CD25, GITR, CD45RO, CD62L and intracytoplasmic Foxp3. T-regs were sorted by fluorescence-activated cell sorting to perform functional assays by interferon (IFN)-gamma enzyme-linked immunospot and real-time quantitative polymerase chain reaction (RQ-PCR) to measure Foxp3, transforming growth factor (TGF)-beta, and interleukin (IL)-10 mRNA.', 'ECP was accompanied by a significant increase of CD4+CD25+ T-regs after six procedures, increasing from 8.9% to 29.1% of total CD4 (P<0.05), with a simultaneous increase of glucocorticoid induced tumor necrosis factor receptor expression on CD4+CD25+ cells (from 15% to 40.8%, P<0.05). This increase was sustained after 12 procedures. T-regs expressed high levels of CD62L, CD45RO, and Foxp3. Sorted CD4+CD25+ T-regs were potently inhibitory toward the CD4+CD25- fraction, when matched with an allogeneic target (IFN-gamma secretion was reduced by 79%). Trans-well experiments showed that cell-to-cell contact was necessary to exert inhibitory activity. RQ-PCR revealed a significant expression of Foxp3 in CD4+CD25+ T-regs, but there was virtually no detection of TGF-beta and IL-10. GvHD improved in all patients, allowing tapering or discontinuation of immunosuppressive drugs.'] Is extracorporeal photochemotherapy accompanied by increasing levels of circulating CD4+CD25+GITR+Foxp3+CD62L+ functional regulatory T-cells in patients with graft-versus-host disease?
qiaojin/PubMedQA
2
[ -2.1265218257904053, -1.5327928066253662, 2.678062915802002 ]
['To examine the headache characteristics of women with migraine and endometriosis (EM), and differences in the prevalence of comorbid conditions between female migraineurs with EM, without EM and nonheadache controls.', 'Migraine and EM are common conditions in women of reproductive age, and both are influenced by ovarian hormones. The comorbidity of migraine and EM is newly recognized, but reasons for the association are uncertain.', 'This is a cross-sectional study of female headache outpatients and healthy controls conducted at University of Toledo and Duke University in 2005 and 2006. After a headache specialist determined headache frequency and diagnosis (based on criteria of the second International Classification of Headache Disorders), patients completed a self-administered electronic survey with information on demographics, headache-related disability, menstrual disorders, premenstrual dysphoric disorder (PMDD), vascular event risk, and comorbid conditions, including irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), interstitial cystitis (IC), depression, and anxiety.', 'Study enrolled 171 women with migraine and 104 controls. EM was reported more commonly in migraineurs than in controls (22% vs 9.6%, P < .01). Frequency of chronic headache was higher in migraineurs with EM compared to without EM (P= .002) and median headache-related disability scores were also higher in the EM group (P= .025). Symptoms of PMDD were more common in migraineurs, but frequency did not differ by EM status. Migraineurs with EM reported more menorrhagia, dysmenorrhea, and infertility compared to the migraine cohort without EM and to controls. Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls. Anxiety (OR = 2.2, 95% CI 1.0-4.7), IC (OR = 10.6, 95% CI 1.9-56.5), and CFS (OR = 3.6, 95% CI 1.1-11.5) were more common in migraine with EM group, than in the cohort with migraine without EM.'] Is endometriosis associated with prevalence of comorbid conditions in migraine?
qiaojin/PubMedQA
2
[ -1.7638596296310425, -1.2511439323425293, 1.9692586660385132 ]
['To evaluate left ventricular (LV) dyssynchrony in patients with left ventricular hypertrophy (LVH), and to compare abnormalities associated with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) using 2D speckle tracking imaging.', 'Basal, middle, and apical 2D LV short-axis images were acquired in 43 patients with LVH including 20 with HCM and 23 with HHD, and in 15 age-matched controls. Radial strain, circumferential strain, time interval from the R-wave to peak radial strain (Trs), and time to peak circumferential strain (Tcs) were measured in six equidistant segments at each level of the 3 LV short-axis views using 2D speckle tracking analysis. To assess LV dyssynchrony, Trs(cs)-18SD, the standard deviation (SD) of Trs(cs) in all 18 segments, was calculated.', 'Regional radial strain in the middle and apical short-axis segments was significantly less in patients with HCM than in those with HHD. Regional circumferential strain in the apical short-axis segments was also less in HCM. Trs-18SD and Tcs-18SD were significantly longer in patients with HCM than in age-matched controls and patients with HHD (Trs-18SD: HCM: 88 +/- 32 ms, HHD: 51 +/- 20 ms, control: 45 +/- 12 ms P < 0.001, Tcs-18SD: HCM: 71 +/- 27 ms, HHD: 46 +/- 14 ms, control: 45 +/- 14 ms P < 0.001).'] Is hypertrophic cardiomyopathy associated with more severe left ventricular dyssynchrony than is hypertensive left ventricular hypertrophy?
qiaojin/PubMedQA
2
[ -1.615750789642334, -1.6654255390167236, 2.225153923034668 ]
['Stroke-work loss (SWL) represents the amount of energy the left ventricle dissipates as heat because of outflow obstruction. Recent studies suggest that SWL > 25% was the most clinically efficient Doppler measure for predicting hemodynamic significance, symptomatic status, and outcome in patients with aortic stenosis (AS). However, SWL may be affected by systolic blood pressure (SBP).', 'To determine if SWL reliably predicts hemodynamic significance of AS in patients with hypertension.', 'We studied 42 consecutive patients with hemodynamically significant AS requiring aortic valve replacement (AVR). Data on demographics, preoperative hemodynamics, and echocardiographic parameters were obtained. SWL was measured using the formula SWL = 100 x mean PG/ (mean PG + SBP), where PG is transaortic pressure gradient. Patients were considered hypertensive if their BP > 140/90 mmHg or if they are on antihypertensive medications.', 'There were 27 males (64%) and mean age was 68 +/- 11 years. Twenty-four patients (57%) were hypertensive. Mean SBP was 134 +/- 24 mmHg, mean transaortic PG 47 +/- 20 mmHg, effective valve orifice area (EOA) by Doppler estimation 0.74 +/- 0.23 cm(2), and SWL 26 +/- 9%. Patients with hypertension had smaller SWL than normotensives (table I). SWL was >25% in 20 (49%) patients, and fewer patients with hypertension have SWL >25% (33% vs 71%, P = 0.019). Of note, patients with SWL < or =25% had significantly higher SBP (145 +/- 21 mmHg vs 122 +/- 22 mmHg, P = 0.02).'] Does stroke-work loss underestimate hemodynamic significance of aortic stenosis in patients with hypertension?
qiaojin/PubMedQA
2
[ -0.7722009420394897, -1.7200675010681152, 1.459688663482666 ]
['Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT.', 'We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features.', 'Visceral and subcutaneous AT samples were obtained from morbid obese men (n=8), age: 42+/-13 years and body mass index>/=40 kg/m(2), undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR.', 'Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (P<0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (P<0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (P<0.01).'] Are clock genes implicated in the human metabolic syndrome?
qiaojin/PubMedQA
2
[ -2.013280153274536, -1.3061919212341309, 2.3477113246917725 ]
['Aortic valve pathology is often associated with proximal aortic dilatation. Even after valve surgery, the proximal aorta can continue to dilate and thus be at risk for rupture, dissection, or later aortic replacement. We hypothesized that the addition of proximal aortic intervention adds no further risk to aortic valve surgery, which may avoid subsequent proximal aortic procedures or catastrophes.', 'Between 1996 and 2004, 430 aortic valve interventions alone and 146 aortic valves with proximal aortic replacements were identified in elective adult patients. The age in the valve-alone patients (68.8 years) was slightly higher than the valve-plus-aorta group (valve/aorta, 60.5 years; p < 0.01), but comorbidities were similar between groups. We compared groups based on hospital mortality and incidence of complications.', 'The 30-day mortality was similar between groups (valve-alone, 3.8% versus valve/aorta, 2.7%; p = 0.5), as were rates for bleeding and operative revision (valve-alone, 6.7% versus valve/aorta, 9.5%; p = 0.5). Pulmonary (valve-alone, 23.0% versus valve/aorta, 11.6%) and renal complications (valve-alone, 8.2% versus valve/aorta, 2.7%) were higher in the valve-alone group (p = 0.02). Logistic regression demonstrated no additional risk of death, neurologic, or cardiac event with replacement of the proximal aorta.'] Does replacement of the proximal aorta add no further risk to aortic valve procedures?
qiaojin/PubMedQA
2
[ -1.2569862604141235, -1.5351686477661133, 1.7716360092163086 ]
['Low capacity of the central serotonergic system has been associated with impulsive behaviour. Both low platelet monoamine oxidase (MAO) activity and the short (S) allele of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) are proposed to be markers of less efficient serotonergic functioning.', 'The effect of the two markers for serotonin system efficiency on performance in a visual comparison task (VCT) and self-reported impulsiveness (Barratt Impulsiveness Scale, BIS-11) were investigated in healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study. Possible confounding effect of general cognitive abilities on the performance in VCT was controlled for.', 'Low platelet MAO activity and carrying of the S allele of 5-HTTLPR were both associated with higher error-rate and more impulsive performance in VCT. Platelet MAO activity and 5-HTTLPR S allele had a significant interactive effect on self-reported impulsivity (BIS-11). The effect of platelet MAO activity on both self-reported and performance impulsivity was significant only in the S allele carriers. The effect of 5-HTTLPR S allele on impulsive performance remained significant after controlling for general cognitive abilities.'] Are platelet MAO activity and the 5-HTT gene promoter polymorphism associated with impulsivity and cognitive style in visual information processing?
qiaojin/PubMedQA
2
[ -2.3929760456085205, -1.1503607034683228, 2.541064739227295 ]
['The ideal hematocrit (HCT) level during hypothermic selective cerebral perfusion (SCP)--to ensure adequate oxygen delivery without excessive perfusion--has not yet been determined.', "Twenty pigs (26.0+/-2.6 kg) were randomized to low or high HCT management. The cardiopulmonary bypass (CPB) circuit was primed with crystalloid in the low HCT group (21+/-1%), and with donor blood in the high HCT group (30+/-1%). Pigs were cooled to 20 degrees C and SCP was carried out for 90 min. During rewarming, whole blood was added in the low HCT group and crystalloid in the high HCT group to produce equivalent HCT levels by the end of the procedure. Using fluorescent microspheres and sagittal sinus sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at baseline, after cooling, at two points during SCP (30 and 90 min), and at 15 min and 2 h post-CPB. In addition, a range of physiological and metabolic parameters, including intracranial pressure (ICP), were recorded throughout the procedure. The animals' behavior was videotaped and assessed blindly for 7 days postoperatively (maximum score=5).", 'HCT levels were equivalent at baseline, 2 h post-CPB, and at sacrifice, but significantly different (p<0.0001) during cooling and SCP. Mean arterial pressure, pH and pCO2, and CMRO2 were equivalent between groups throughout. ICP was similar in the two groups throughout cooling, SCP, and rewarming, but was significantly higher in the low HCT animals after the termination of CPB. CBF was similar at baseline, but thereafter markedly higher in the low HCT group. Neurobehavioral performance was significantly better in the high HCT animals (median score 3.5 vs 4.5 on day 3, and 4.5 vs 4.75 on day 7, p=0.003).'] Does avoidance of hemodilution during selective cerebral perfusion enhance neurobehavioral outcome in a survival porcine model?
qiaojin/PubMedQA
2
[ -1.8402904272079468, -1.6022570133209229, 2.3908166885375977 ]
['Common carotid artery intima-media thickness (CCA-IMT) is a valid index of atherosclerosis, which is viewed as an inflammatory disease. It is unknown if various modes of inflammation (cyclooxygenase [COX]-mediated, cytokine-mediated), oxidative stress and anti-oxidants are independently related to CCA-IMT.', 'We investigated cross-sectional relations between CCA-IMT measured by B-mode ultrasound and COX-mediated inflammation (as measured by 15-keto-dihydro-prostaglandin F(2alpha) [PGF(2alpha)], cytokine-mediated inflammation (interleukin-6 [IL-6], high sensitivity C-reactive protein [hsCRP] and serum amyloid A protein [SAA]), oxidative stress (8-iso-PGF(2alpha), an F(2)-isoprostane; a non-enzymatic, free radical-induced product of arachidonic acid), and tocopherols (anti-oxidants) in a small subset of a population-based sample of elderly men (n=234) stating no use of anti-inflammatory medications. In a backward-stepwise regression analysis of correlates of CCA-IMT (with PGF(2alpha), hsCRP, IL-6, SAA, F(2)-isoprostanes, tocopherols, diabetes, body mass index (BMI), beta-blocker, statin treatment, smoking, hypertension and cholesterol), PGF(2alpha), CRP, beta-blocker treatment, diabetes and BMI were independently associated with CCA-IMT. There were no associations between F(2)-isoprostanes or tocopherols and CCA-IMT in this study.'] Do both cyclooxygenase- and cytokine-mediated inflammation are associated with carotid intima-media thickness?
qiaojin/PubMedQA
2
[ -2.402486562728882, -1.414406180381775, 2.8751447200775146 ]
['Glucagon-like peptide-1 (GLP-1) rescues insulin secretory deficiency in type 2 diabetes partly via cAMP actions on exchange protein directly activated by cAMP (Epac2) and protein kinase A (PKA)-activated Rab3A-interacting molecule 2 (Rim2). We had reported that haplodeficient Munc13-1(+/-) mouse islet beta-cells exhibited reduced insulin secretion, causing glucose intolerance. Munc13-1 binds Epac2 and Rim2, but their functional interactions remain unclear.', 'We used Munc13-1(+/-) islet beta-cells to examine the functional interactions between Munc13-1 and Epac2 and PKA. GLP-1 stimulation of Munc13-1(+/-) islets normalized the reduced biphasic insulin secretion by its actions on intact islet cAMP production and normal Epac2 and Rim2 levels.', "To determine which exocytotic steps caused by Munc13-1 deficiency are rescued by Epac2 and PKA, we used patch-clamp capacitance measurements, showing that 1) cAMP restored the reduced readily releasable pool (RRP) and partially restored refilling of a releasable pool of vesicles in Munc13-1(+/-) beta-cells, 2) Epac-selective agonist [8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate] partially restored the reduced RRP and refilling of a releasable pool of vesicles, and 3) PKA blockade by H89 (leaving Epac intact) impaired cAMP ability to restore the RRP and refilling of a releasable pool of vesicles. Conversely, PKA-selective agonist (N(6)-benzoyladenosine-cAMP) completely restored RRP and partially restored refilling of a releasable pool of vesicles. To determine specific contributions within Epac-Rim2-Munc13-1 interaction sites accounting for cAMP rescue of exocytosis caused by Munc13-1 deficiency, we found that blockade of Rim2-Munc13-1 interaction with Rim-Munc13-1-binding domain peptide abolished cAMP rescue, whereas blockade of Epac-Rim2 interaction with Rim2-PDZ peptide only moderately reduced refilling with little effect on RRP."] Is interaction between Munc13-1 and RIM critical for glucagon-like peptide-1 mediated rescue of exocytotic defects in Munc13-1 deficient pancreatic beta-cells?
qiaojin/PubMedQA
2
[ -2.3789165019989014, -1.3369296789169312, 2.691711902618408 ]
['Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT) and MIF knockout (KO) mice given N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression.', '5-month old male C57Bl/6 MIF WT and KO mice were treated with and without BBN. Animals were sacrificed at intervals up to 23 weeks of treatment. Bladder tumor stage and grade were evaluated by H&E. Immunohistochemical (IHC) analysis was performed for MIF and platelet/endothelial cell adhesion molecule 1 (PECAM-1), a measure of vascularization. MIF mRNA was analyzed by quantitative real-time polymerase chain reaction.', 'Poorly differentiated carcinoma developed in all BBN treated mice by week 20. MIF WT animals developed T2 disease, while KO animals developed only T1 disease. MIF IHC revealed predominantly urothelial cytoplasmic staining in the WT control animals and a shift toward nuclear staining in WT BBN treated animals. MIF mRNA levels were 3-fold higher in BBN treated animals relative to controls when invasive cancer was present. PECAM-1 staining revealed significantly more stromal vessels in the tumors in WT animals when compared to KOs.'] Is null mutation for macrophage migration inhibitory factor ( MIF ) associated with less aggressive bladder cancer in mice?
qiaojin/PubMedQA
2
[ -2.2405896186828613, -1.4806642532348633, 2.754607677459717 ]
['Lithium and carbamazepine (CBZ) are used to treat mania in bipolar disorder. When given chronically to rats, both agents reduce arachidonic acid (AA) turnover in brain phospholipids and downstream AA metabolism. Lithium in rats also attenuates brain N-methyl-D-aspartic acid receptor (NMDAR) signaling via AA. We hypothesized that, like chronic lithium, chronic CBZ administration to rats would reduce NMDAR-mediated signaling via AA.', 'We used our fatty acid method with quantitative autoradiography to image the regional brain incorporation coefficient k* of AA, a marker of AA signaling, in unanesthetized rats that had been given 25 mg/kg/day I.P. CBZ or vehicle for 30 days, then injected with NMDA (25 mg/kg I.P.) or saline. We also measured brain concentrations of two AA metabolites, prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TXB(2)).', 'In chronic vehicle-treated rats, NMDA compared with saline increased k* significantly in 69 of 82 brain regions examined, but did not change k* significantly in any region in CBZ-treated rats. In vehicle- but not CBZ-treated rats, NMDA also increased brain concentrations of PGE(2) and TXB(2).'] Does chronic carbamazepine administration reduce N-methyl-D-aspartate receptor-initiated signaling via arachidonic acid in rat brain?
qiaojin/PubMedQA
2
[ -2.284879684448242, -1.29967200756073, 2.6009721755981445 ]
['Intravitreal anti-vascular endothelial growth factor (VEGF) treatment with bevacizumab (Avastin) has emerged as a promising therapy for the treatment of choroidal neovascularisation in age-related macular degeneration. Intravitreal administration of bevacizumab is "off-label," and only very limited data regarding short-term toxicity exist. Therefore, we investigated the safety of different doses of bevacizumab on the anterior- and posterior-segment cells of the human eye.', 'Primary human retinal pigment epithelium (RPE) cells, human optic nerve head astrocytes (ONHA), human trabecular meshwork cells (TMC), and cornea buttons not suitable for transplantation were treated with bevacizumab (25 microg/ml, 250 microg/ml, and 2,500 microg/ml) for 48 h, corresponding to 0.1x, 1x, and 10x the dosage used intravitreally. Bevacizumab-related toxicity was evaluated by a colorimetric test (MTT) measuring inhibition of RPE, ONHA, and TMC cell proliferation. Additionally, cell viability was quantified by live/dead fluorescence assay. Corneal endothelium was quantified by phase-contrast microscopy.', 'Bevacizumab showed adverse effects on primary RPE cell proliferation as well as on cell viability at a concentration of 2,500 microg/ml. The lower concentrations of 25 microg/ml and 250 microg/ml had no influence on RPE cell proliferation or cell viability. There was no toxicity for any investigated concentration on human ONHA, TMC, or corneal endothelium.'] Is [ Bevacizumab toxic to human anterior- and posterior-segment cultured cells ]?
qiaojin/PubMedQA
2
[ -2.2192044258117676, -1.3747186660766602, 2.7121994495391846 ]
['Transplantation of stem cells has been proposed as a strategy for repair of lung fibrosis. Nevertheless, many studies have yielded controversial results that currently limit the potential use of these cells as an efficient treatment. Alveolar type II cells are the progenitor cells of the pulmonary epithelium and usually proliferate after epithelial cell injury. During lung fibrosis, however, the altered regeneration process leads to uncontrolled fibroblast proliferation.', 'To investigate whether intratracheal transplantation of isolated alveolar type II cells can halt and reverse the fibrotic process in an experimental model of bleomycin-induced lung fibrosis in rats.', 'Lung fibrosis was induced in syngeneic female Lewis rats by a single intratracheal instillation of bleomycin (2.5 U/kg). Animals were transplanted with alveolar type II cells from male animals at a dose of 2.5 x 10(6) cells per animal 3, 7, and 15 days after endotracheal bleomycin instillation. Animals were killed 21 days after the induction of lung fibrosis.', 'Lung fibrosis was assessed by histologic study and determination of hydroxyproline content. Engraftment of transplanted cells was measured by real-time polymerase chain reaction for the Y chromosome and by fluorescence in situ hybridization for the Y chromosome. Transplantation of alveolar type II cells into damaged lung 3, 7, or 15 days after bleomycin instillation led to reduced collagen deposition, and reduction in the severity of pulmonary fibrosis.'] Does intratracheal transplantation of alveolar type II cells reverse bleomycin-induced lung fibrosis?
qiaojin/PubMedQA
2
[ -2.5563158988952637, -1.1857519149780273, 2.786132335662842 ]
['Angiotensin II (Ang II) promotes atherosclerotic vascular diseases, in which proinflammatory and proliferative effects play a major pathogenic role. Ang II up-regulates chemokines, such as monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha, which are important pro-inflammatory factors mediating infiltration of inflammatory cells into atherosclerotic lesion. The aim of the present study was to determine whether the presence of MCP-1 or MIP-1alpha is essential in Ang II-induced intimal hyperplasia in the carotid artery ligation model.', 'Six-month-old male C57BL/6-, MCP-1-, or MIP-1alpha-deficient mice underwent ligation of the common left carotid artery and were randomly assigned to receive either vehicle or Ang II (1.4 mg kg(-1) day(-1)) via a subcutaneously implanted osmotic infusion pump (model 2004, Alzet) for 4 weeks.', 'Ang II not only increased MCP-1 and MIP-1alpha production but also enhanced neo-intimal formation, media thickness, and adventitia development in the ligated carotid arteries in C57BL/6 mice. However, MCP-1 or MIP-1alpha deficiency failed to affect intimal hyperplasia in vascular remodeling.'] Does monocyte chemoattractant protein-1 or macrophage inflammatory protein-1alpha deficiency affect angiotensin II-induced intimal hyperplasia in carotid artery ligation model?
qiaojin/PubMedQA
2
[ -2.369154214859009, -1.4254748821258545, 2.8293275833129883 ]
['We previously reported that hypothermic machine perfusion (HMP) for liver preservation is feasible, but hepatic microcirculatory dysfunction and significant liver damage remain major obstacles in its application when the preservation is extended to 24 h. The underlying injury mechanism is not well understood. The present study sought to investigate the role of thromboxane A(2) (TXA(2)) in the pathogenesis of liver injury after prolonged HMP.', 'Livers isolated from Sprague-Dawley rats were subjected to continuous machine perfusion with University of Wisconsin (UW) solution at a flow rate of 0.4 mL/min/g liver at 4 degrees C for 24 h. A specific TXA(2) synthase inhibitor, OKY-046 (OKY), was added to UW solution during the preservation period and to the Krebs-Henseleit buffer during reperfusion. The performance of the livers after preservation was evaluated using an isolated liver perfusion system with Krebs-Henseleit buffer at a flow rate of 15 mL/min at 37 degrees C for 30 min.', 'Prolonged HMP induced a significant release of TXA(2) into the portal circulation as indicated by markedly increased levels of TXB(2) in the perfusate during reperfusion (at 30 min, 1447.4 +/- 163.6 pg/mL vs 50.91 +/- 6.7 pg/mL for control). Inhibition of TXA(2) synthesis with OKY significantly decreased releases of TXA(2) (69.8 +/- 13.4 pg/mL) concomitant with reduced lactate dehydrogenase (LDH) releases (at 30 min, HMP + OKY: 144.9 +/- 27.9 U/L; HMP: 369.3 +/- 68.5 U/L; simple cold storage or SCS: 884.4 +/- 80.3 U/L), decreased liver wet/dry weight ratio (HMP + OKY vs SCS and HMP: 3.6 +/- 0.3 vs 4.4 +/- 0.1 and 3.9 +/- 0.2, respectively) and increased hyaluronic acid uptake (at 30 min, HMP + OKY vs SCS, HMP: 33.1 +/- 2.9% vs 13.9 +/- 3.6%, 18.6 +/- 2.4%, respectively). Liver histology also showed significant improvement in tissue edema and hepatocellular necrosis with OKY compared with HMP without OKY.'] Does inhibition of TXA synthesis with OKY-046 improve liver preservation by prolonged hypothermic machine perfusion in rats?
qiaojin/PubMedQA
2
[ -2.045140504837036, -1.5166313648223877, 2.6089444160461426 ]
['Ventricular remodeling after myocardial infarction (MI) is largely dependent on renin-angiotensin system activity, which is determined by angiotensin II concentration and angiotensin II type 1 receptor (AT(1)R) density in target tissues. We have recently shown that AT(1)R density in the acute phase of MI determines post-MI ventricular remodeling at discharge (8 days). The aim of this study was to test whether this correlation is retained in a longer follow-up (6 months), in the same group of patients.', 'In 48 patients with first acute MI who did not undergo reperfusion therapy, angiotensin AT(1)R density on blood platelets (a presumable marker of cardiovascular AT(1)R density) was assessed 13+/-5 h after the onset of MI, using radioligand binding assay. Echocardiographic indices of left ventricular function and dimensions were used as measures of ventricular remodeling.', '6 months after the infarction patients who at baseline had AT(1)R density above median (N=17) as compared to those with AT(1)R density below median (N=20) had higher left ventricular end-systolic volume index (LVESVI, 41.3+/-2.7 vs. 33.2+/-2.3) and lower ejection fraction (LVEF 48.1+/-1.8 vs. 54.7+/-2.0). Moreover LVESVI positively and LVEF negatively correlated with AT(1)R density although the strength of these correlations was weaker than at discharge. Infarct size as reflected by a single troponin T measurement and post-MI therapy did not differ between high- and low-AT(1)R groups: over 85% patients received ACE-inhibitor, beta-blocker and statin.'] Is late ventricular remodeling in non-reperfused acute myocardial infarction in humans predicted by angiotensin II type 1 receptor density on blood platelets?
qiaojin/PubMedQA
2
[ -1.7887152433395386, -1.6508755683898926, 2.419548273086548 ]
['We studied prevalence, causes and consequences of worsening renal function (WRF) during hospitalization for acute heart failure (AHF).', 'Patients admitted for AHF were enrolled. Patients with severe chronic renal failure, cardiogenic shock and contrast medium-induced nephropathy were excluded. WRF was defined as an increase of 25 mumol/l or more in serum creatinine relative to the admission level. Survivors were monitored for 6 months, focusing on deaths and first unscheduled readmissions for heart failure.', 'Among the included 416 patients, WRF occurred in 152 cases (37%), 5+/-3 days after admission, and two-thirds of patients recovered their baseline renal function before discharge. Old age, diabetes, hypertension and acute coronary syndromes increased the risk of WRF. In-hospital furosemide doses as well as discharge treatment were similar in WRF and no-WRF patients. Serum creatinine elevation was the strongest independent determinant of a longer hospital stay (r=0.37, p=0.001). Adverse events occurred in 158 patients (38%) during follow-up, with 23 deaths and 135 readmissions. Cox analysis showed that WRF, transient or not, was an independent predictor of the risk of death or readmission (hazard ratio=1.74 [1.14-2.68], p=0.01).'] Does transient worsening of renal function during hospitalization for acute heart failure alter outcome?
qiaojin/PubMedQA
2
[ -1.5846694707870483, -1.4673413038253784, 2.132617950439453 ]
['During N-methyl-d-aspartate-induced cell death in the neural retina, levels of the nuclear isoform of CaMKIIalpha, CaMKIIalphaB, previously reported to be detected only in the midbrain and diencephalon, become elevated. The purpose of this study was to investigate whether CaMKIIalphaB is present specifically in retinal ganglion cells (RGCs) and to determine whether it can be implicated in the cell death or cell survival of signal transduction pathways.', 'Pan-purified RGCs were obtained from the retinas of postnatal day (P)6 to P8 Sprague-Dawley rats. The expression level of CaMKIIalphaB was investigated in RGCs with the aid of RT-PCR and immunostaining under normal and glutamate-stressed conditions. siRNA targeted to CaMKIIalphaB was used to knock down the level of endogenous mRNA in RGCs, and cell viability was tested. The putative role of CaMKIIalphaB in the downstream expression of survival genes such as BDNF was evaluated in CaMKIIalphaB knocked-down RGCs with the aid of RT-PCR, real-time PCR, and immunofluorescence microscopy.', 'Basal levels of CaMKIIalphaB were expressed in RGCs. Expression levels became increased in response to glutamate treatment and were translocated to the nuclei after a glutamate stimulus. In pan-purified RGCs with knocked down levels of CaMKIIalphaB, a glutamate stimulus led to an increase in cell death. When CaMKIIalphaB was knocked down in RGCs, a corresponding decrease occurred in the level of BDNF expression.'] Does caMKIIalphaB mediate a survival response in retinal ganglion cells subjected to a glutamate stimulus?
qiaojin/PubMedQA
2
[ -2.4065940380096436, -1.303243637084961, 2.760302782058716 ]
['The beta3-adrenergic receptor (ADRB3) is a transmembrane receptor highly expressed in adipose tissue and thought to be involved in the regulation of lipolysis. ADRB3 is also highly expressed in gallbladder tissue where it may be involved in gallbladder contraction. Because polymorphisms of ADRB3 are present in populations with a high prevalence of gallstones (e.g., Pima-Indians, obese subjects), we hypothesized that known polymorphisms for ADRB3 (Trp64Arg) may represent an independent risk factor for gallstone disease.', 'The EMIL cross-sectional study investigated the health behavior and prevalence of chronic diseases in a small Southwestern German town of 12,475 inhabitants. From 3,893 randomly selected citizens 2,147 subjects were enrolled and screened for gallstones employing ultrasonography. Blood samples were drawn for biochemical analysis and isolation of genomic DNA. ADBR3 genotypes were determined by TaqMan SNP Assay.', 'We identified 171 (8%) gallstone carriers of whom 143 participated (46 male, 97 female), with a mean age of 51.4, and mean BMI of 29.3 kg/m2. For these subjects an age, gender and BMI matched partner without gallstones was recruited from the study population. Genotyping for ADRB3 revealed an Arg64 allele frequency of 5.9 versus 0.7% (HR = 11.9, P < 0.05) compared with controls.'] Is arg64 variant of the beta3-adrenergic receptor associated with gallstone formation?
qiaojin/PubMedQA
2
[ -2.015388011932373, -1.4347455501556396, 2.4886481761932373 ]
["Thyrotropin-releasing hormone (TRH) is known to have anticonvulsant effects in several animal seizure models and is efficacious in treating patients with certain intractable epilepsies. However, the duration of TRH's action is limited due to low bioavailability and difficulty penetrating the blood-brain barrier (BBB). Since direct nose to brain delivery of therapeutic compounds may provide a means for overcoming these barriers, we utilized the kindling model of temporal lobe epilepsy to determine if intranasal administration of a TRH analog, 3-methyl-histidine TRH (3Me-H TRH), could significantly inhibit various seizure parameters.", 'Kindling was accomplished using a 1s train of 60 Hz biphasic square wave (200 microA peak to peak) administered daily to the basolateral amygdala until the animal was fully kindled. Afterdischarge duration (ADD) was assessed via electroencephalographs (EEGs) recorded bilaterally from bipolar electrodes in the basolateral amygdala and behavioral seizure severity (stage I-V) was simultaneously recorded digitally. Kindled subjects received 3Me-H TRH (10(-9), 10(-8), 10(-7) M) intranasally 60 and 30 min prior to amygdala stimulation. The ADD and seizure stage was compared to control kindled animals receiving physiological saline intranasally.', 'Intranasal application of 3Me-H TRH resulted in a concentration-dependent reduction in total seizure ADD. Additionally, the analog had significant concentration-dependent effects on behavioral stages I through IV (partial) and stage V (generalized) seizures. However, 3Me-H TRH significantly reduced clonus duration only at the highest concentration.'] Does intranasal delivery of a thyrotropin-releasing hormone analog attenuate seizures in the amygdala-kindled rat?
qiaojin/PubMedQA
2
[ -2.3424432277679443, -1.400219440460205, 2.749265432357788 ]
['Conditions accelerating muscle proteolysis are frequently associated with defective phosphatidylinositol 3-kinase (PI3K)/Akt signaling and reduced PI3K-generated phosphatidylinositol 3,4,5-triphosphate (PIP(3)). We evaluated the control of muscle protein synthesis and degradation in mouse models of type 1 and 2 diabetes to determine whether defects besides PI3K/Akt activities affect muscle metabolism.', 'We evaluated the expression and activity of PTEN, the phosphatase converting PIP(3) to inactive phosphatidylinositol 4,5-bisphosphate, and studied how PTEN influences muscle protein in diabetic wild-type mice and in mice with partial deficiency of PTEN(+/-).', 'In acutely diabetic mice, muscle PTEN expression was decreased. It was increased by chronic diabetes or insulin resistance. In cultured C2C12 myotubes, acute suppression of PI3K activity led to decreased PTEN expression, while palmitic acid increased PTEN in myotubes in a p38-dependent fashion. To examine whether PTEN affects muscle protein turnover, we studied primary myotubes cultures from wild-type and PTEN(+/-) mice. The proteolysis induced by serum deprivation was suppressed in PTEN(+/-) cells. Moreover, the sizes of muscle fibers in PTEN(+/-) and wild-type mice were similar, but the increase in muscle proteolysis caused by acute diabetes was significantly suppressed by PTEN(+/-). This antiproteolytic response involved higher PIP(3) and p-Akt levels and a decrease in caspase-3-mediated actin cleavage and activation of the ubiquitin-proteasome system as signified by reduced induction of atrogin-1/MAFbx or MurF1 (muscle-specific RING finger protein 1).'] Does pTEN expression contribute to the regulation of muscle protein degradation in diabetes?
qiaojin/PubMedQA
2
[ -2.3729119300842285, -1.2528512477874756, 2.617316484451294 ]
['The present study investigated how the triceps surae are controlled at the spinal level during the naturally occurring postural sway of quiet standing.', 'Subjects stood on a force platform as electrical stimuli were applied to the posterior tibial nerve when the center of pressure (COP) was either 1.6 standard deviations anterior (COP(ant)) or posterior (COP(post)) to the mean baseline COP signal. Peak-to-peak amplitudes of the H-reflex and M-wave from the soleus (SOL) and medial gastrocnemius (MG) muscles were recorded to assess the efficacy of the Ia pathway.', 'A significant increase in the H(max) : M(max) ratio for both the SOL (12 +/- 6%) and MG (23 +/- 6%) was observed during the COP(ant) as compared to the COP(post) condition. The source of the modulation between COP conditions cannot be determined from this study. However, the observed changes in the synaptic efficacy of the Ia pathway are unlikely to be simply a result of an altered level of background electromyographic activity in the triceps surae. This was indicated by the lack of differences observed in the H(max) : M(max) ratio when subjects stood without postural sway (via the use of a tilt table) at two levels of background activity.'] Do control of the triceps surae during the postural sway of quiet standing?
qiaojin/PubMedQA
2
[ -2.514861822128296, -0.9434858560562134, 2.526211977005005 ]
['To observe the correlation between vascular endothelial growth factor (VEGF) and CD147 expressed in the rheumatoid synovium and to investigate the effect of CD147 of cultured rheumatoid fibroblast-like synoviocytes (FLS) on the production of VEGF.', 'The presence of CD147 and VEGF in the rheumatoid synovium derived from 15 patients with RA and 4 patients with osteoarthritis (OA) was detected by streptavidin/peroxidase (SP) immunostaining. FLS were cultured by enzymatic digestion of synovial tissues and incubated in 24-well plates. Then different concentration of LY294002, PD98059, SP600125, SB203580 and HAb18G mAb was added to each well. VEGF in the culture supernatant was measured by sandwich ELISA.', 'CD147 and VEGF in synovium from 15 patients with RA showed high expression, while CD147 and VEGF in synovium from 4 patients with OA showed low expression. Macrophages, fibroblast-like synovial cells and lymphocytes were demonstrated to express CD147 while synovial lining cells, fibroblasts surrounding microvessels and vascular smooth muscle cells were demonstrated to express VEGF. Statistic analysis indicates that VEGF production was correlated with the levels of CD147 expression. VEGFproduction was suppressed when CD147 expression was inhibited by LY294002 or HAb18G mAb.'] Does [ CD147 stimulate the angiogenesis in rheumatoid synovium via the activation of vascular endothelial growth factor ]?
qiaojin/PubMedQA
2
[ -2.2771494388580322, -1.3346809148788452, 2.6729350090026855 ]
['To investigate whether irradiation before antisense Bcl-2 oligodeoxynucleotide (ODN) administration enhances tissue uptake, and whether periodic dosing enhances cellular uptake of fluorescently labeled ODN relative to constant dosing.', 'PC-3-Bcl-2 cells (prostate cancer cell line engineered to overexpress Bcl-2) were subjected to increasing doses of irradiation (0-10 Gy) with or without increasing concentrations of fluorescently labeled antisense Bcl-2 ODN (G4243). The fluorescent signal intensity was quantified as the total grain area with commercial software. In addition, PC-3-Bcl-2 subcutaneous xenograft tumors were treated with or without irradiation in combination with various dosing schemas of G4243. The uptake of fluorescent G4243 in tumors was quantitated.', 'The uptake of G4243 was increased in prostate cancer cells exposed to low doses of irradiation both in vitro and in vivo. Irradiation before G4243 treatment resulted in increased fluorescent signal intensity in xenograft tumors compared with those irradiated after G4243 treatment. A single weekly dose of G4243 produced higher G4243 uptake in xenograft tumors than daily dosing, even when the total dose administered per week was held constant.'] Does irradiation of human prostate cancer cells increase uptake of antisense oligodeoxynucleotide?
qiaojin/PubMedQA
2
[ -2.314443588256836, -1.231985092163086, 2.528496026992798 ]
['Int6 has been shown to be an interactive participant with the protein translation initiation complex eIF3, the COP9 signalosome and the regulatory lid of the 26S proteasome. Insertion of mouse mammary tumor virus into the Int6 locus creates a C-terminally truncated form of the protein. Expression of the truncated form of Int6 (Int6sh) in stably transfected human and mouse mammary epithelial cell lines leads to cellular transformation. In addition, decreased expression of Int6/eIF3e is observed in approximately one third of all human breast carcinomas.', 'To validate that Int6sh has transforming activity in vivo, a transgenic mouse model was designed using the whey acidic protein (Wap) promoter to target expression of truncated Int6 to differentiating alveolar epithelial cells in the mammary gland. Microarray analyses were performed on normal, premalignant and malignant WapInt6sh expressing tissues.', 'Mammary tumors developed in 42% of WapInt6sh heterozygous parous females at an average age of 18 months. In WapInt6sh mice, the contralateral mammary glands from both tumorous and non-tumorous tissues contained widespread focal alveolar hyperplasia. Only 4% of WapInt6sh non-breeding females developed tumors by 2 years of age. The Wap promoter is active only during estrus in the mammary tissue of cycling non-pregnant mice. Microarray analyses of mammary tissues demonstrated that Int6sh expression in the alveolar tissue altered the mammary transcriptome in a specific manner that was detectable even in the first pregnancy. This Int6sh-specific transcriptome pattern subsequently persisted in both the Int6sh-expressing alveolar hyperplasia and mammary tumors. These observations are consistent with the conclusion that WapInt6sh-expressing alveolar cells survive involution following the cessation of lactation, and subsequently give rise to the mammary tumors that arise in aging multiparous females.'] Does expression of truncated Int6/eIF3e in mammary alveolar epithelium lead to persistent hyperplasia and tumorigenesis?
qiaojin/PubMedQA
2
[ -2.261112689971924, -1.3679026365280151, 2.6402077674865723 ]
['For patients with localized gastric cancer (LGC) who are receiving preoperative chemoradiation (CTRT), the postsurgical pathologic stage predicts overall survival (OS) better than the baseline stage. The authors hypothesized that presurgical (postCTRT) stage would also correlate better with patient outcome than the baseline stage.', 'The authors analyzed 74 LGC patients treated with preoperative CTRT receiving similar treatment. Patients were staged with baseline endoscopic ultrasonography (EUS) and laparoscopy. Patients received induction chemotherapy, then CTRT (45 Gy), and had an attempted surgery. After CTRT, patients had complete preoperative staging including EUS in 35 patients.', 'Thirty-five had all 3 sets of staging, baseline, presurgical, and postsurgical. Baseline stage did not associate with OS (P = .16) nor disease-free survival (DFS; P = .13). However, presurgical stage was associated with OS (P = .01), and DFS (P = .05). OS was also associated with postsurgical stage and was longer for stages 0 and I than for stages III and IV (P = .01 and .04, respectively). Similarly, DFS was longer in postsurgical pathologic stages 0, I, and II than in stage III or IV (P < .001, <.001, and <.01, respectively). Baseline staging did not correlate with the proportion of patients alive at 4 years; however, presurgical staging did. Patients with stage I or II survived longer than those with stage III or IV (81% vs 25%; P < .01).'] Is clinical stage after preoperative chemoradiation a better predictor of patient outcome than the baseline stage for localized gastric cancer?
qiaojin/PubMedQA
2
[ -0.9552510976791382, -1.803288459777832, 1.6349270343780518 ]
['Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells.', 'To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia.', 'Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction.'] Does liver repopulation with bone marrow derived cells improve the metabolic disorder in the Gunn rat?
qiaojin/PubMedQA
2
[ -2.4854209423065186, -1.329725742340088, 2.8785641193389893 ]
['Patients with Albright hereditary osteodystrophy (AHO) have defects in stimulatory G protein signaling due to loss of function mutations in GNAS. The mechanism by which these mutations lead to the AHO phenotype has been difficult to establish due to the inaccessibility of the affected tissues.', 'The objective of the study was to gain insight into the downstream consequences of abnormal stimulatory G protein signaling in human epithelial tissues.', 'We assessed transcription of GNAS and Gsalpha-stimulated activation of the cystic fibrosis transmembrane conductance regulator (CFTR) in AHO patients, compared with normal controls and patients with cystic fibrosis.', 'Relative expression of Gsalpha transcripts from each parental GNAS allele and cAMP measurements from nasal epithelial cells were compared among normal controls and AHO patients. In vivo measurements of CFTR function, pulmonary function, and pancreatic function were assessed in AHO patients.', 'GNAS was expressed equally from each allele in normals and two of five AHO patients. cAMP generation was significantly reduced in nasal respiratory epithelial cells from AHO patients, compared with normal controls (0.4 vs. 0.6, P = 0.0008). Activation of CFTR in vivo in nasal (P = 0.0065) and sweat gland epithelia (P = 0.01) of AHO patients was significantly reduced from normal. In three patients, the reduction in activity was comparable with patients with cystic fibrosis due to mutations in CFTR. Yet no AHO patients had pulmonary or pancreatic disease consistent with cystic fibrosis.'] Do patients with mutations in Gsalpha have reduced activation of a downstream target in epithelial tissues due to haploinsufficiency?
qiaojin/PubMedQA
2
[ -2.1632578372955322, -1.3875279426574707, 2.528252124786377 ]
['Pheochromocytomas and paragangliomas may be malignant either at presentation or during recurrence, but the clinical course of malignant tumors is unpredictable.', 'The objective was to analyze survival according to clinical characteristics at diagnosis of malignancy and the presence or absence of SDHB mutations.', 'This was a retrospective cohort study.', 'A total of 54 patients with malignant tumors were included. Malignancy was scored according to the presence of metastases or histologically documented lymph node invasion.', 'The main outcome was the specific survival after the diagnosis of the first metastasis.', 'Germline mutations were identified in SDHB (n = 23, including 21 patients with apparent sporadic tumors) and VHL (n = 1) genes, and two patients had neurofibromatosis 1. Patients were followed up from the diagnosis of primary tumor and from the diagnosis of the first metastasis to the present or to death with medians of 79 [interquartile range (IQR) 24; 190] and 39 [IQR 14; 94] months, respectively. The 5-yr probability of survival after the diagnosis of the first metastasis was 0.55 (95% confidence interval 0.39-0.69). Patients with SDHB mutations were younger, more frequently had extra-adrenal tumors, and had a shorter metanephrine excretion doubling time. The presence of SDHB mutations was significantly and independently associated with mortality (relative risk 2.7; 95% confidence interval 1.2, 6.4; P = 0.021).'] Do succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas?
qiaojin/PubMedQA
2
[ -2.142460346221924, -1.4428791999816895, 2.5782053470611572 ]
['Natriuretic peptide receptor-B (NPR-B, GC-B in rodents; gene name NPR2) is a guanylyl cyclase-coupled receptor that mediates the effect of C-type natriuretic peptide. Homozygous mutations in human NPR-B cause acromesomelic dysplasia, type Maroteaux (OMIM 602875), an autosomal recessive skeletal dysplasia. NPR-B has an intracellular kinase homology domain (KHD), which has no kinase activity, and its functional significance in vivo is currently unknown.', 'We examined the functional significance of a novel NPR-B KHD mutation in humans.', 'A 28-yr-old Japanese male presented with marked short stature (118.5 cm, -9.3 sd). His limbs showed marked shortening in the middle and distal segments. His parents had relatively short stature with height z-scores of -2.75 and -0.98 (his father and mother, respectively). Direct sequencing of coding region of the NPR2 gene of the family was performed. The mutant receptor activity was investigated by saturation binding assay and cGMP measurement. Additionally, interaction between the mutant and wild type allele was investigated by the titration experiments.', 'We identified a novel missense mutation L658F in KHD of NPR-B in homozygous and heterozygous states in the patient and his parents, respectively. The mutation conferred normal binding affinity for C-type natriuretic peptide but no discernible ligand-induced cGMP production. Furthermore, L658F mutant impaired wild-type NPR-B-mediated cGMP production in a dose-dependent manner, suggesting that short stature found in L658F heterozygote can be caused by its dominant-negative effect.'] Is intact kinase homology domain of natriuretic peptide receptor-B essential for skeletal development?
qiaojin/PubMedQA
2
[ -2.346595048904419, -1.3482446670532227, 2.7466299533843994 ]
['Accurate chromosome segregation depends on the establishment of correct-amphitelic-kinetochore orientation. Merotelic kinetochore orientation is an error that occurs when a single kinetochore attaches to microtubules emanating from opposite spindle poles, a condition that hinders segregation of the kinetochore to a spindle pole in anaphase. To avoid chromosome missegregation resulting from merotelic kinetochore orientation, cells have developed mechanisms to prevent or correct merotelic attachment. A protein called Pcs1 has been implicated in preventing merotelic attachment in mitosis and meiosis II in the fission yeast S. pombe.', 'We report that Pcs1 forms a complex with a protein called Mde4. Both Pcs1 and Mde4 localize to the central core of centromeres. Deletion of mde4(+), like that of pcs1(+), causes the appearance of lagging chromosomes during the anaphases of mitotic and meiosis II cells. We provide evidence that the kinetochores of lagging chromosomes in both pcs1 and mde4 mutant cells are merotelically attached. In addition, we find that lagging chromosomes in cells with defective centromeric heterochromatin also display features consistent with merotelic attachment.'] Are the kinetochore proteins Pcs1 and Mde4 and heterochromatin required to prevent merotelic orientation?
qiaojin/PubMedQA
2
[ -2.564763307571411, -0.5957667231559753, 2.206094741821289 ]
['Liver regeneration is suppressed in alcoholic patients; however, the underlying mechanisms are not fully understood. We examined liver regeneration and signal transducer and activator of transcription 3 (STAT3) activation (an important signal for liver regeneration) in cirrhotic livers from alcoholics, hepatitis C virus (HCV) infection, and alcoholic plus HCV infection. Liver regeneration and STAT3 activation were determined by immunohistochemistry analysis of Ki67 and STAT3 phosphorylation, respectively, in 20 alcoholic cirrhosis, 13 HCV cirrhosis, 13 alcoholic+HCV cirrhosis. Alcoholic or alcoholic plus HCV cirrhotic livers had significantly lower Ki67+ and phospho-STAT3+ (pSTAT3+) hepatocytes and bile duct cells than HCV cirrhotic livers. The pSTAT3 positive staining did not correlate with liver injury (elevation of serum levels of aspartate transaminase [AST] and alkaline phosphatase [ALP]) but correlated positively with cell proliferation (Ki67 positive staining).'] Is liver regeneration suppressed in alcoholic cirrhosis : correlation with decreased STAT3 activation?
qiaojin/PubMedQA
2
[ -2.3128912448883057, -1.3045411109924316, 2.731135845184326 ]
['Renal disease is common in the general population and whilst few people progress to end-stage renal failure, mortality is increased. The aim of this study was to examine all-cause mortality risk in relation to chronic kidney disease (CKD) stages defined by estimated glomerular filtration rate (eGFR).', 'Data were extracted from a computerized central laboratory system for a defined geographical area over a 3-year study period. The eGFR was calculated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and aligned to the MDRD laboratory. Average annual mortality and relative risk (RR) of all-cause mortality was determined and compared for defined age and CKD bands.', '106 366 participants (55.5% female; 85% White, 13% South Asian, 2% Black and others) were eligible and studied, representing 49% of the Coventry adult population. 12 540 (12%) of the sample had some evidence of decreased kidney function, with an eGFR <60 ml/min/1.73 m2. 7611 (7%) participants died and there were significantly elevated risks of mortality with increasing renal dysfunction; RR = 4.0, 8.3, 16.2 and 43.5 for eGFR 45-59, 30-44, 15-29 and <15 ml/min/1.73 m2, respectively. Within age bands, RRs were statistically significantly raised with CKD progression and within CKD stage, RR of death decreased as age increased.'] Does elevated relative mortality risk with mild-to-moderate chronic kidney disease decrease with age?
qiaojin/PubMedQA
2
[ -0.9482496976852417, -0.9962832927703857, 1.030355453491211 ]
['Antibodies specific for the beta1-adrenergic receptor (beta1AR) are highly prevalent in patients with idiopathic dilated cardiomyopathy (DCM) and known to contribute to the pathogenesis of heart failure, though the precise molecular mechanisms involved are largely unknown.', 'We have explored the effects of beta(1)AR autoantibodies obtained from DCM patients on extracellular signal-regulated kinase (ERK) activation in murine cardiomyocytes.', 'We find that human beta(1)AR autoantibodies potently stimulate ERK1/2 in cardiac cells by using signalling pathways different from those triggered by the classic beta-agonist isoproterenol, also leading to a different pattern of activated ERK subcellular localization. The extent of ERK stimulation by endogenous cardiac beta(1)AR is markedly enhanced in the presence of both beta(1)AR-autoantibodies and isoproterenol. Interestingly, beta(1)AR-autoantibody-mediated ERK activation is not blocked by some betaAR antagonists used in the treatment of heart failure.'] Are anti-beta1-adrenergic receptor autoantibodies potent stimulators of the ERK1/2 pathway in cardiac cells?
qiaojin/PubMedQA
2
[ -2.5115816593170166, -1.1660821437835693, 2.720400810241699 ]
['Clinical and experimental studies demonstrate that exercise training improves aerobic capacity and cardiac function in heart failure, even in patients on optimal treatment with angiotensin inhibitors and beta-blockers, but the cellular mechanisms are incompletely understood. Since myocardial dysfunction is frequently associated with impaired energy status, the aim of this study was to assess the effects of exercise training and losartan on myocardial systems for energy production and transfer in heart failure.', 'Maximal oxygen uptake, cardiac function and energy metabolism were assessed in heart failure after a myocardial infarction induced by coronary artery ligation in female Sprague-Dawley rats. Losartan was initiated one week after infarction and exercise training after four weeks, either as single interventions or combined. Animals were sacrificed 12 weeks after surgery.', 'Heart failure, confirmed by left ventricular diastolic pressure >15 mmHg and by >20 mmHg drop in peak systolic pressure, was associated with 40% lower aerobic capacity and significant reductions in enzymes involved in energy metabolism. Combined treatment yielded best improvement of aerobic capacity and ventricular pressure characteristics. Exercise training completely restored aerobic capacity and partly or fully restored creatine and adenylate kinases, whereas losartan alone further reduced these enzymes. In contrast, losartan reduced left ventricle diastolic pressure, whereas exercise training had a neutral effect.'] Does exercise training restore aerobic capacity and energy transfer systems in heart failure treated with losartan?
qiaojin/PubMedQA
2
[ -2.576615571975708, -1.0129848718643188, 2.6407196521759033 ]
['Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Pseudomonas-based immunotoxins have a direct cytotoxic effect. However, delayed and often dramatic antitumor responses seen in human studies with targeted toxins led us to hypothesize that immunologic responses may be a secondary mechanism that enhances the therapeutic efficacy of these novel drugs.', 'This hypothesis was tested in a murine system using an immunotoxin, MR1-1 [MR1-1(dsFv)-PE38KDEL], that targets a syngeneic murine homologue of the tumor-specific human epidermal growth factor mutation, EGFRvIII, expressed on a murine cell line.', 'Intratumoral treatment with MR1-1 eliminated EGFRvIII-expressing tumors (P < 0.0001). The antitumor activity of MR1-1 was dependent on the expression of EGFRvIII on some, but not all tumors cells, and was significantly inhibited in the absence of CD4+ (P = 0.0193) and CD8+ (P = 0.0193) T cells. MR1-1 induced EGFRvIII-specific immunity (P < 0.0005) and produced long lasting immunity against tumors expressing EGFRvIII as well as EGFRvIII-negative tumors.'] Does eGFRvIII-targeted immunotoxin induce antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells?
qiaojin/PubMedQA
2
[ -2.414987802505493, -1.2542059421539307, 2.7785258293151855 ]
['This study was designed to investigate the relationship between the second trimester maternal serum markers and adverse pregnancy outcomes in healthy newborns.', "A total of 749 women who delivered in our institution with complete follow up and second-trimester triple marker test data available were included in the study. Women with multiple pregnancies, chronic diseases, diabetes mellitus, obesity, smokers and infants with chromosomal and congenital abnormalities were excluded. Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated estriol (uE(3)) values were investigated in our cohort who developed preeclampsia (n = 28), gestational diabetes (GM) (n = 69), preterm labor-birth (n = 100), oligohydramnios (n = 37) and macrosomia (n = 59) by using receiver operating characteristic (ROC) curve analysis, with chi-square and Pearson's correlation tests.", 'Women with uE(3) < or = 1.26 MoM (P = 0.001, AUC = 0.666), HCG > 1.04 MoM (P = 0.032, AUC = 0.599) or AFP < or = 0.69 MoM (P = 0.049, AUC = 0.600) values significantly developed oligohydramnios. Also, macrosomic infants were observed in women who had HCG values > 0.86 MoM (P = 0.047, AUC = 0.578). Patients with HCG > 1.04 MoM (P = 0.04, AUC = 0.565) and uE(3) < or =0.88 MoM (P = 0.049, AUC = 0.571) developed GDM. HCG levels > or =2.5 or > or =3 MoM were significantly associated with the development of oligohydramnios [P = 0.005; OR = 4 (95% CI: 1.7-9.7)], [P = 0.008; OR = 4.9 (95% CI: 1.7-13.7)], respectively. When women with adverse (n = 237) and normal (n = 512) outcomes were compared there were significant differences in maternal serum AFP (1.40 +/- 0.84 vs. 1.23 +/- 0.75 MoM, P = 0.006) and uE(3) values (1.38 +/- 1.42 vs. 1.45 +/- 0.98 MoM, P = 0.001).'] Does the association of triple-marker test result with adverse pregnancy outcomes in low-risk pregnancies with healthy newborns?
qiaojin/PubMedQA
2
[ -1.1074036359786987, -1.6044063568115234, 1.7196615934371948 ]
['We have recently shown that moderate preterm birth, in the absence of respiratory support, altered the structure of lung parenchyma in young lambs, but the long-term effects are unknown.', 'To determine whether structural changes persist to maturity, and whether postnatal growth affects lung structure at maturity in sheep.', 'At approximately 1.2 years after birth, lung parenchyma of sheep born 14 days before term (n = 7) was stereologically compared with that of controls born at term (n = 8, term approx. 146 days).', 'Preterm birth per se had no significant effect on lung volume, alveolar number and size, and thicknesses of the alveolar walls and blood-gas barrier. After combining the preterm and term groups, we examined the effects of postnatal growth rates on lung parenchyma. Slower-growing sheep (SG; n = 7: 4 preterm, 3 term) were compared with faster-growing sheep (FG; n = 8: 3 preterm, 5 term). At approximately 1.2 years, the right lung volume, relative to body weight, was significantly lower in SG than FG sheep (p < 0.05) and alveolar number was significantly lower by approximately 44%. The total alveolar internal surface area of the right lung of SG sheep was 38% smaller than in FG sheep; it was also significantly lower when related to both lung and body weight.'] Is lung parenchyma at maturity influenced by postnatal growth but not by moderate preterm birth in sheep?
qiaojin/PubMedQA
2
[ -1.245805263519287, -0.5029667019844055, 0.7900285124778748 ]
['Rheumatoid arthritis (RA) is a chronic autoimmune disease which is induced by proinflammatory cytokines or oxidative stress. The activation of nuclear factor-kappa B (NF-kappaB) that contributed to imbalance between apoptosis and proliferation of rheumatoid synovial cells (SC). Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of stroke. We aimed to investigate the suppressive effect of edaravone on collagen-induced arthritis (CIA) mice and on the activated molecules in SC stimulated by interleukin-1beta (IL-1beta).', 'Edaravone was administrated intravenously at a dose of 3mg/kg of body weight to CIA mice. The progression of CIA was evaluated by the macroscopic arthritis scoring system of paws. Interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3) concentrations in culture medium of human SC were measured by enzyme linked immunosorbent assays. Caspase-3/7 activity and nuclear factor-kappa B (NF-kappaB) protein level of cultured human SC were estimated by fluorometric assay and Western blot analysis, respectively.', 'Edaravone significantly decreased macroscopic arthritis score in CIA mice. Acceleration of IL-6 and MMP-3 productions and attenuation of caspase-3/7 activity in IL-1beta-stimulated SC were abated by edaravone. Activated NF-kappaB in IL-1beta-stimulated SC was suppressed by edaravone.'] Does edaravone inhibit collagen-induced arthritis possibly through suppression of nuclear factor-kappa B?
qiaojin/PubMedQA
2
[ -2.358903408050537, -1.4302458763122559, 2.814699649810791 ]
['Amplified MYCN oncogene defines a subgroup of neuroblastomas with poor outcome. However, a substantial number of MYCN single-copy neuroblastomas exhibits an aggressive phenotype similar to that of MYCN-amplified neuroblastomas even in the absence of high MYCN mRNA and/or protein levels.', 'To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN-amplified and single-copy high-risk neuroblastomas, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk neuroblastoma tumors (n = 49) using cDNA microarrays. Candidate gene expression was validated in a separate cohort of 117 patients using quantitative PCR, and protein expression was analyzed in neuroblastoma tumors by immunoblotting and immunohistochemistry.', 'We identified a genetic signature characterized by a subset of MYCN/MYC and E2F targets, including Skp2, encoding the F-box protein of the SCF(Skp2) E3-ligase, to be highly expressed in high-risk neuroblastomas independent of amplified MYCN. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n = 117) using quantitative PCR. High Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54; 95% confidence interval, 1.56-8.00; P = 0.002). Skp2 protein expression was inversely correlated with expression of p27, the primary target of the SCF(Skp2) E3-ligase, in neuroblastoma tumors.'] Does high Skp2 expression characterize high-risk neuroblastomas independent of MYCN status?
qiaojin/PubMedQA
2
[ -2.2194690704345703, -1.3985319137573242, 2.654144287109375 ]
['Given that inhibitors of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) are being introduced into treatment for melanoma, the present study was carried out to better understand the mechanism by which they may induce apoptosis of melanoma cells.', 'A panel of human melanoma cell lines and fresh melanoma isolates was assessed for their sensitivity to apoptosis induced by the MEK inhibitor U0126. The apoptotic pathways and regulatory mechanisms involved were examined by use of the inhibitor and small interfering RNA (siRNA) techniques.', 'Inhibition of MEK induced apoptosis in the majority of melanoma cell lines through a mitochondrial pathway that was associated with the activation of Bax and Bak, release of mitochondrial apoptogenic proteins, and activation of caspase-3. However, apoptosis was independent of caspases and instead was associated with mitochondrial release of AIF as shown by the inhibition of apoptosis when AIF was knocked down by siRNA. Inhibition of MEK resulted in the up-regulation of the BH3-only proteins PUMA and Bim and down-regulation of the antiapoptotic protein Mcl-1. These changes were critical for the induction of apoptosis by U0126 as siRNA knockdown of PUMA or Bim inhibited apoptosis, whereas siRNA knockdown of Mcl-1 increased apoptosis particularly in the apoptosis-resistant cell lines.'] Is apoptosis induction in human melanoma cells by inhibition of MEK caspase-independent and mediated by the Bcl-2 family members PUMA , Bim , and Mcl-1?
qiaojin/PubMedQA
2
[ -2.543189287185669, -1.0697665214538574, 2.6719069480895996 ]
['CYP3A2 is a male-specific isoform of cytochrome P450 enzyme which is expressed abundantly in male rats but not in intact female rats. Having previously reported that hepatic CYP3A2 promotes lipopolysaccharide (LPS)-induced liver injury in male rats, we further examined the impact of CYP3A on LPS-induced liver injury by comparing intact and hypophysectomized female rats. In hypophysectomized female rats, phenobarbital (PB), a cytochrome P450 inducer, markedly increased the hepatic content and activity of CYP3A1/2, but did not do so in intact rats. CYP2B1 increased to similar levels in PB-treated hypophysectomized and intact rats.', 'Rats were administered 10 mg/kg LPS intravenously and some were given PB for three days before LPS injection. Liver injury was analyzed 8 h after LPS injection.', 'PB-LPS increased plasma alanine aminotransferase significantly more in hypophysectomized female rats than in intact female rats. Ketoconazole, a CYP3A inhibitor, inhibited the increase of liver injury. Hepatic 8-hydroxydeoxyguanosine in nuclei and 4-hydroxy-2-nonenal-modified proteins, measured to evaluate oxidative stress by LPS treatment, increased markedly more in PB-treated, hypophysectomized female rats, than in intact female rats.'] Does overexpression of CYP3A aggravate endotoxin-induced liver injury in hypophysectomized female rats?
qiaojin/PubMedQA
2
[ -2.2526111602783203, -1.4429523944854736, 2.678621768951416 ]
['Fibronectin, an extracellular matrix protein, is associated with the general process of tissue repair and is present in heart valves. In order to understand the cellular mechanisms of heart valve repair, we hypothesized that fibronectin is produced and secreted by valvular interstitial cells (VICs), and when up-regulated in VICs involved in active repair, it is associated with prominent fibrillar adhesions composed of tensin and alpha(5)beta(1) integrin. We investigated the interaction of porcine mitral VICs with the underlying fibronectin matrix and the formation and localization of focal and fibrillar adhesion complexes in an in vitro wound model.', 'Confluent monolayers of VICs were wounded with a 1-mm-wide cell scraper, maintained in standard media and 10% fetal bovine serum, and fixed at various time points after wounding. Immunohistochemistry was used to localize fibronectin, paxillin, tensin, and alpha(5)beta(1) integrin. F-actin was localized with an Alexa-Fluor-568-labeled phalloidin. Cells were examined with a scanning confocal laser microscope.', 'In response to in vitro mechanical wounding, migrating VICs at the wound edge expressed cytoplasmic fibronectin compared to nonwounded confluent monolayers. Over 24 to 48 h, fibrils were deposited into the subcellular space. Coincident with this, staining for alpha(5)beta(1) appeared, and tensin redistributed from focal adhesions to fibrillar adhesions, which colocalized with alpha(5)beta(1).'] Do cardiac valve interstitial cells secrete fibronectin and form fibrillar adhesions in response to injury?
qiaojin/PubMedQA
2
[ -2.412602186203003, -1.4125934839248657, 2.9039764404296875 ]
['Constrictive remodeling of the neointima results in the late lumen loss and restenosis after balloon angioplasty. Intense expression of alpha8beta1 integrin in the contractile state of vascular smooth muscle cells (VSMCs) and in myofibroblasts led us to hypothesize that it might be involved in the process of late constrictive remodeling.', 'Balloon injury was used to induce neointima formation in the rat carotid artery. Immunohistochemical analysis and immunoconfocal studies showed that late lumen narrowing was concomitant with the up-regulation of smooth muscle alpha-actin and alpha8 integrin in the neointima. The transforming growth factor-beta (TGF-beta)-induced contractile properties of fibroblasts and VSMCs populated in a three-dimensional collagen matrix was associated with up-regulation of alpha8 integrin. TGF-beta-induced myofibroblastic features in Rat1 fibroblasts were impaired in cells pretreated with a small interference RNA silencing the alpha8 integrin gene.'] Is alpha8beta1 Integrin up-regulated in the neointima concomitant with late luminal loss after balloon injury?
qiaojin/PubMedQA
2
[ -2.5095436573028564, -1.2854176759719849, 2.836991310119629 ]
['Mother-to-child transmission (MTCT) of HIV-1 has been associated with symptomatic and asymptomatic mastitis and with the quantity of HIV-1 RNA and DNA in maternal milk. An improved understanding of the relationship between indicators of inflammation and HIV-1 loads in breast milk could improve MTCT prevention strategies.', 'In a cross-sectional study, laboratory indicators of mastitis (breast milk sodium [Na(+)] concentration, sodium : potassium ratio [Na(+) : K(+)], and leukocyte count) were related to breast milk HIV-1 RNA and DNA loads and were evaluated for predicting viral loads in milk.', 'Mastitis was present in 63 (15%) of 407, 60 (15%) of 407, and 76 (18%) of 412 milk specimens, as defined by Na(+) concentration >12 mmol/L, Na(+) : K(+) >1, and total leukocyte counts > or =10(6) cells/mL, respectively. Each indicator was associated with an increased milk HIV-1 RNA load (P<.05) but not with HIV-1 DNA load. Neutrophils correlated better with milk HIV-1 RNA load than total leukocytes. However, neither neutrophil count, Na(+) concentration, nor Na(+) : K(+) displayed a threshold that was both sensitive and specific for the detection of HIV-1 RNA in milk at thresholds of > or =50 or > or =10(4) copies/mL.'] Are laboratory indicators of mastitis associated with elevated HIV-1 DNA loads or predictive of HIV-1 RNA loads in breast milk?
qiaojin/PubMedQA
2
[ -1.2735055685043335, -1.600386619567871, 1.9153631925582886 ]
['The effect of rosiglitazone, an activator of peroxisome proliferator-activated receptor-gamma, on the growth of ectopic uterine tissue was assessed.', 'Endometriosis was surgically induced in 28 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Four weeks later, rats were randomly grouped and a second laparatomy was performed. The length, width, height and volume of the explants were measured. Rosiglitazone at 0.2 mg/kg/day was orally administered to one group, while vehicle treatment was given to the control group. Four weeks later, rats were sacrificed and ectopic uterine tissues were re-evaluated morphologically and histologically. Scoring system was used to evaluate the preservation of epithelia.', 'One rat in the study group and two rats in the control group died as a result of complications related to surgery. There was a significant difference in post-treatment length, width, height, and spherical volumes between control and rosiglitazone-treated groups. The epithelia were found to be preserved significantly better in the control group when compared with the rosiglitazone-treated group.'] Does peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduce the size of experimental endometriosis in the rat model?
qiaojin/PubMedQA
2
[ -2.279920816421509, -1.3499934673309326, 2.6773483753204346 ]
['To explore the predictive value of estrogen-regulated gene changes as indicators of sensitivity in ovarian cancer patients treated with the aromatase inhibitor Letrozole.', 'Expression of a range of proteins was assessed by semi-quantitative immunohistochemistry in tissue sections from the tumors of patients treated with Letrozole. Expression was correlated with clinical response to Letrozole. Corresponding mRNA in ovarian cancer cell lines treated with 17beta-estradiol (E2) was measured by quantitative RT-PCR.', 'In an estrogen receptor (ER)-positive ovarian cancer cell line, quantitative RT-PCR analysis demonstrated that PLAU, VIM, BIGH3, CDH6, FN1, CASP4, KRT4, KRT7, KRT13, TRAM and NGAL were down-regulated and TFF1, TFF3, TRAP1, TFAP4, MYC, CTSD, IL17BR, TOP2A, CCNB1, CCNB2, PDZK1 and UBE2C were up-regulated by E2. The E2 modulation of these genes was reversed by the anti-estrogen tamoxifen and was ERalpha-dependent. For ovarian cancer patients treated with Letrozole, we tested the predictive value of the majority of these genes in paraffin sections from their primary tumors by semi-quantitative immunohistochemistry. Significant differences in expression levels of TFF1, TFF3, BIGH3, TRAP1, VIM, TOP2A, PLAU and UBE2C were observed between tumors from CA125 responsive/stable patients as opposed to tumors from patients whose disease progressed, using serum levels of CA125 as an indicator of response. Aromatase expression in the ovarian cancers also differed between these 2 groups of patients.'] Does estrogen-regulated gene expression predict response to endocrine therapy in patients with ovarian cancer?
qiaojin/PubMedQA
2
[ -2.3642518520355225, -1.3631901741027832, 2.755659580230713 ]
['Protective autoimmunity attenuates secondary degeneration after central nervous system (CNS) injury. Such neuroprotection is achieved via activation of autoimmune CD4(+)CD25(-) effector T cells (Teffs) or suppression of naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs). In this study the ability of bacterial DNA, characterized by unmethylated CpG islands, to downregulate Treg activity and therefore, to confer neuroprotection was investigated.', 'The effects of CpG on suppressive activity of mouse Tregs were studied by coculturing Tregs with Teffs and measuring proliferation by radiolabeled thymidine. The neuroprotective effects of CpG-mediated Treg suppression was examined in rats after optic nerve crush.', 'Teff proliferation in response to T-cell receptor stimuli was significantly reduced when the Teffs were cocultured with Tregs, compared with Teff activation when cultured alone. Treating Tregs with CpG reduced their suppressive activity and restored Teff proliferation to baseline levels. CpG injection in rats with optic nerve crush conferred significant neuroprotection compared with that in untreated control rats (118 +/- 8 cells/mm(2) vs. 69 +/- 5 cells/mm(2), respectively; mean +/- SEM; P < 0.05). CpG-mediated neuroprotection was accompanied by significantly increased T-cell infiltration at the injury site. Similar CpG treatment of athymic nude rats yielded no neuroprotection, further suggesting a T-cell-dependent mechanism of CpG action.'] Does bacterial DNA confer neuroprotection after optic nerve injury by suppressing CD4+CD25+ regulatory T-cell activity?
qiaojin/PubMedQA
2
[ -2.2843196392059326, -1.4283418655395508, 2.7458720207214355 ]
['The anti-incontinence effect of desmopressin resides in its concentrating capacity and antidiuretic properties. We compared nighttime urine production on wet and dry nights in a highly selected study population of children with monosymptomatic nocturnal enuresis associated with proved nocturnal polyuria who responded only partially to intranasal desmopressin.', 'We retrospectively analyzed 39 home recordings of nocturnal urine production and maximum voided volume in children 7 to 19 years old (median 8.9) with monosymptomatic nocturnal enuresis with nocturnal polyuria who had a partial response to desmopressin. Nocturnal diuresis volume and maximum voided volume were documented at baseline (14 days) and during 3 months of followup.', 'Baseline nocturnal urine output (439 +/- 39 ml) was significantly higher than the maximum voided volume (346 +/- 93 ml, p <0.01). During desmopressin treatment nocturnal urine output on wet nights (405 +/- 113 ml) differed significantly from that on dry nights (241 +/- 45 ml). During treatment nocturnal urine output on wet nights did not differ from baseline values.'] Is partial response to intranasal desmopressin in children with monosymptomatic nocturnal enuresis related to persistent nocturnal polyuria on wet nights?
qiaojin/PubMedQA
2
[ -1.8918992280960083, -1.2660636901855469, 2.197719097137451 ]
['Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H. pylori) infection and host genetic factors on GC susceptibility in a population of Spanish white GC patients.', 'DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- (IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory (IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology.', 'Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77-3.66), smoking habit (OR 1.91, 95% CI 1.25-2.93), and positive family history of GC (OR 3.67, 95% CI 2.01-6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls.'] Is gastric cancer susceptibility linked to pro-and anti-inflammatory cytokine gene polymorphisms in whites : a Nationwide Multicenter Study in Spain?
qiaojin/PubMedQA
2
[ -2.4318954944610596, -1.253413200378418, 2.7838494777679443 ]
['Abnormalities of endogenous fibrinolysis are linked to diabetic macrovascular disease; whether key vascular endothelial regulatory proteins, such as tissue plasminogen activator (tPA), are altered in diabetic neuropathy microvasculature is unknown. This neuropathologic case: control study investigates the hypothesis that tPA expression is regionally deficient in microvessels in human diabetic neuropathy.', 'tPA and von Willebrand factor (vWF), a vascular endothelial cell marker, are detected on vascular endothelium by immunoperoxidase methods with specific antibodies on formalin fixed paraffin embedded sural nerve biopsies from six diabetic and six axonal neuropathy control nerves without vasculopathy. The proportion of microvessels in each nerve region expressing tPA is determined by the ratio of tPA positive vessels/total vWF positive vessels on serial sections.', 'tPA expression is lower in diabetic neuropathy cases compared to controls in all regions, including epineurial (62.4 +/- 8.6% vs 91.0 +/- 1.6%, p < 0.02) and endoneurial microvessels (51.7 +/- 7.1% vs 91.5 +/- 2.9%, p < 0.001).'] Is microvascular tissue plasminogen activator reduced in diabetic neuropathy?
qiaojin/PubMedQA
2
[ -2.187033176422119, -1.473879337310791, 2.7310338020324707 ]
['The authors assessed options for vertebral body replacements with the Synex telescopic expansion cage. Autologic or homologic bone grafts, a titanium "Harm\'s" cage or a polymethylmetacrylate filling reinforced by Kirschner wires, may be used for vertebral body replacements. The cement filling is indicated in oncological patients, the Harm\'s cage requires filling with a quantity of bone grafts and, with massive bone grafts, the collection place or the graft availability may be a problem. The telescopic expansion implant is fairly easy to implant, is stable and requires to be filled with a minimum of spongious grafts.', 'From May 2001 to November 2005, 20 telescopic Synex cages were implanted in 18 patients. Vertebral body replacements were performed 14x for acute fractures, 4x for posttraumatic kyphosis and 2x for metastatic skeletal disorder in breast and prostate tumors.', 'Vertebral body replacement was completed with posterior transpedicular stabilization in 14 subjects, in 5 subjects, additional anterior Ventrofix stabilization was performed. Vertebral body replacements down to the L1 level were conducted through thoracotomy or video-assissted minithoracotomy, L2-L4 replacements from lumbotomy or anterior retroperitoneal approach.', 'The most requently affected and operated vertebrae included the L1 (4 patients), Th12 (4 patients), Th6 (3 patients). The minimal interval between the procedure and a follow- up was 12 months. No fatal outcome has been recorded. In one patient with a vertebral body metastasis, the disorder has generalized and in a second one, no further metastatic spread has been reported. In one subject, the left-sided L4 root injury was recorded postoperatively, a cauda equina syndrome, diagnosed after the injury, persits in one subject. No signs of deep infection have been recorded. There are no records of the Synex release or displacement. Correction loss (kyphotisation) of up to 2 degrees was recorded in patients with transpedicular stabilization, in Ventrofix patients the loss was up to 5 degrees, except one case, where the loss reached 10 degrees.'] Do [ Vertebral body replacement with a Synex implant ]?
qiaojin/PubMedQA
2
[ -2.2215168476104736, -1.4103240966796875, 2.713259220123291 ]
['Patients with left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) may develop stress-induced wall motion abnormalities (SWMA) with low-dose (10 microg/kg/min) dobutamine infusion. The clinical significance of low-dose SWMA is unknown.', 'We investigated the clinical, hemodynamic and angiographic correlates of low-dose SWMA in patients with chronic ischemic LV systolic dysfunction.', 'Seventy patients with chronic ischemic LV systolic dysfunction who had dobutamine stress echocardiography were studied. Clinical, hemodynamic, and angiographic parameters at rest and low-dose were compared between 38 patients (mean ejection fraction (EF) of 30 +/- 8%) with low-dose SWMA and 32 patients (EF 30 +/- 11%) without low-dose SWMA.', 'Multivariate analysis showed that the number of coronary territories with severe disease (stenosis > or =70%)(P = 0.001, RR = 6.3) was an independent predictor of low-dose SWMA. An increasing number of collateral vessels protected patients from low-dose SWMA (P = 0.011, RR = 0.25). A higher resting heart rate was a negative predictor of low-dose SWMA (P = 0.015, RR = 0.92) but no other hemodynamic variables were predictors. In the patients with low-dose SMA, regions with low-dose SWMA were more likely to be supplied by vessels with severe disease than regions without low-dose SWMA (92% vs 58%, P < 0.001).'] Do stress-induced wall motion abnormalities with low-dose dobutamine infusion indicate the presence of severe disease and vulnerable myocardium?
qiaojin/PubMedQA
2
[ -1.8521701097488403, -1.5715112686157227, 2.452857494354248 ]
['To investigate the relationship between the degree of week 24 HBV suppression and week 48 therapeutic response in entecavir-treated chronic hepatitis B patients in whom lamivudine treatment failed, so as to explore a useful predictor for efficacy of enticavir treatment.', 'Thirty-three patients with chronic hepatitis B refractory to lamivudine were enrolled to receive treatment with entecavir 1.0 mg once daily. The patients were divided into 4 groups according to serum HBV DNA levels (copies/mL) at week 24: PCR-undetectable (less than 300 copies/ml); QL- less than 3 log10 copies/ml; 3 log10(-4) log10 copies/ml; greater than 4 log10 copies/mL, and the efficacy achieved at week 48 was evaluated.', 'At week 48, mean reductions of serum HBV DNA from baseline was 4.91 log10. HBV DNA became undetectable by PCR assay in 33.3 percent patients and ALT became normal in 75.8%. The lower the HBV DNA level achieved at week 24, the higher the proportion of patients in whom HBV DNA became undetectable by PCR and ALT normalization were acquired at week 48, and viral breakthrough at week 48 also decreased.'] Is [ Week 24 suppression of HBV in entecavir-treated chronic hepatitis B patients in whom lamivudine treatment failed associated with efficacy at week 48 ]?
qiaojin/PubMedQA
2
[ -1.3388382196426392, -1.4770843982696533, 1.906587839126587 ]
['Recent studies suggest that volatile anaesthetics have anti-inflammatory and preconditioning properties and that beta-adrenoceptors are involved in the signalling pathways for these effects. Concurrently, the blockade of beta-adrenoceptors has been shown to augment the release of inflammatory mediators in response to pro-inflammatory stimuli. We therefore aimed to investigate whether the beta-adrenoceptor antagonist propranolol might modulate the anti-inflammatory effects of isoflurane on the systemic and pulmonary release of pro-inflammatory cytokines in endotoxemic rats.', 'Forty anaesthetized and ventilated Sprague-Dawley rats were randomly treated as follows. Lipopolysaccharide (LPS) only (n = 8), endotoxemia with LPS [5 mg/kg, intravenously (i.v.)]. LPS-isoflurane (n = 8): endotoxemia and continuous inhalation of 1 minimum alveolar concentration (MAC) of isoflurane. LPS-isoflurane-propranolol (n = 8): administration of propranolol (3 mg/kg) before continuous inhalation of isoflurane and induction of endotoxemia. LPS-propranolol (n = 8): administration of propranolol (3 mg/kg) before endotoxemia without inhalation of isoflurane. Sham (n = 8): control-group only with surgical preparation. After 4 h of endotoxemia, levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-10 (IL-10) in plasma and bronchoalveolar fluid (BALF) were analysed. Release of nitric oxide (NO) and amount of inducible nitric oxide synthase (iNOS) protein in alveolar macrophages was measured by Griess assay or determined by Western Blotting, respectively.', 'Inhalation of isoflurane reduced the release of TNF-alpha (P < 0.05) and IL-1beta (P < 0.05) in plasma and IL-1beta (P < 0.05) in BALF. Co-administration of propranolol significantly inhibited these effects. During inhalation of isoflurane, the increased release of NO and iNOS protein from alveolar macrophages was also completely inhibited by propranolol.'] Does the beta-adrenoceptor antagonist propranolol counteract anti-inflammatory effects of isoflurane in rat endotoxemia?
qiaojin/PubMedQA
2
[ -2.301116943359375, -1.4633761644363403, 2.8377676010131836 ]
['Corneal confocal microscopy (CCM) is a rapid, noninvasive, clinical examination technique that quantifies small nerve fiber pathology. We have used it to assess the neurological benefits of pancreas transplantation in type 1 diabetic patients.', 'In 20 patients with type 1 diabetes undergoing simultaneous pancreas and kidney transplantation (SPK) and 15 control subjects, corneal sensitivity was evaluated using noncontact corneal esthesiometry, and small nerve fiber morphology was assessed using CCM.', 'Corneal sensitivity (1.54 +/- 0.28 vs. 0.77 +/- 0.02, P < 0.0001), nerve fiber density (NFD) (13.8 +/- 2.1 vs. 42 +/- 3.2, P < 0.0001), nerve branch density (NBD) (4.04 +/- 1.5 vs. 26.7 +/- 2.5, P < 0.0001), and nerve fiber length (NFL) (2.23 +/- 0.2 vs. 9.69 +/- 0.7, P < 0.0001) were significantly reduced, and nerve fiber tortuosity (NFT) (15.7 +/- 1.02 vs. 19.56 +/- 1.34, P = 0.04) was increased in diabetic patients before pancreas transplantation. Six months after SPK, 15 patients underwent a second assessment and showed a significant improvement in NFD (18.04 +/- 10.48 vs. 9.25 +/- 1.87, P = 0.001) and NFL (3.60 +/- 0.33 vs. 1.84 +/- 0.33, P = 0.002) with no change in NBD (1.38 +/- 0.74 vs. 1.38 +/- 1.00, P = 1.0), NFT (15.58 +/- 1.20 vs. 16.30 +/- 1.19, P = 0.67), or corneal sensitivity (1.23 +/- 0.39 vs. 1.54 +/- 00.42, P = 0.59).'] Does corneal confocal microscopy detect early nerve regeneration after pancreas transplantation in patients with type 1 diabetes?
qiaojin/PubMedQA
2
[ -1.7126153707504272, -1.5793291330337524, 2.309805393218994 ]
['Patients with atopic diseases are characterized by high levels of specific IgE production. However, little is known about the composition of their B-cell repertoires.', 'We sought to analyze the complete PBMC-derived IgE repertoire and to compare clonal expansions between different patients.', 'We have analyzed the IgE-bearing B-cell receptor repertoire in highly atopic patients (>1000 IU/mL) using quantitative RT-PCR, complementarity determining region 3 spectratyping, and sequence analysis. Three representative patients were additionally followed during anti-IgE therapy.', 'Atopic patients exhibited 100 to 1000 times more IgE-specific transcripts than control individuals. These patients used a variable region of the heavy immunoglobulin chain (VH) epsilon repertoire highly similar to their IgM and IgG repertoires, with preference of VH3b, VH4, VH3a, and VH1 segments. Each patient harbored individual clonal expansions, most probably as correlation of allergen-specific IgE production. Common expansions within the complementary determining region 3 shared by several individuals with similar sensitization patterns were found in spectratyping analysis. However, these antigen-driven expansions showed differences on the sequence level. In omalizumab-treated patients the clinical improvement was paralleled by a clear increase in the ratio of IgG/IgE transcripts.'] Is the IgE repertoire in PBMCs of atopic patients characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias?
qiaojin/PubMedQA
2
[ -2.3995304107666016, -1.3162224292755127, 2.7983992099761963 ]
['Plasma total homocysteine (tHcy) is often elevated in patients with mental illness. Since patients with mental illness and vascular disease exhibit a higher plasma tHcy concentration than patients without vascular disease, it is possible that elevated plasma tHcy in mental illness is mainly due to concomitant vascular disease.', "We have investigated plasma tHcy, cobalamin/folate status, renal function and the presence of vascular disease in patients with vascular dementia (VaD, n = 501), Alzheimer's disease (AD, n = 300), depression (n = 259) and in healthy subjects (n = 144) stratified according to age (below and above 75 years).", 'Plasma tHcy concentration showed the highest increase in patients with VaD compared to patients with AD or depression. After the exclusion of patients with cobalamin/folate deficiencies and increased serum creatinine, patients with AD or depression above 75 years with vascular disease showed a similar elevation of plasma tHcy concentration as patients with VaD. Furthermore, patients with AD and depression without vascular disease showed a similar plasma tHcy concentration to healthy subjects.'] Is elevated plasma homocysteine concentration in elderly patients with mental illness mainly related to the presence of vascular disease and not the diagnosis?
qiaojin/PubMedQA
2
[ -2.1233911514282227, -0.8233298063278198, 2.0364792346954346 ]
['Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined.', 'In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically.', 'Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD.'] Do radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models?
qiaojin/PubMedQA
2
[ -2.0052192211151123, -1.4844228029251099, 2.5779354572296143 ]
['Transcranial magnetic stimulation (TMS) is a non-invasive method used in medical applications such as brain mapping or as a therapeutic tool in neurological and psychiatric disorders because it can stimulate defined regions of the brain without anaesthesia.', "The action of repetitive transcranial magnetic stimulation (rTMS) on HL-60 and PC12 cells has been investigated. The cells have been stimulated in vitro with different number of pulses (75 - 1250), different intensities (10, 20 and 40%) and different frequencies (0.25, 1 and 10 Hz) by using a double coil (2x70 mm) connected to the 'Magstim rapid'. At selected time points after treatment the following endpoints have been determined: viability, cyclic AMP (cAMP) and heat shock protein 72 (Hsp72) (HL-60 cells), and viability, cAMP, dopamine and noradrenaline (PC12 cells). Viability was measured with the alamarBlue assay, whereas cAMP, Hsp72, dopamine and noradrenaline were determined with enzyme-linked immunosorbent assay (ELISA).", 'In both cell lines viability was not influenced by rTMS treatment, the same was true for the cytosolic cAMP concentration. In HL-60 cells rTMS treatment did not change the Hsp72 content, also a protective effect of rTMS treatment on cell viability before toxic H(2)O(2) treatment was not observed. After high potassium treatment the release of the two neurotransmitters dopamine and noradrenaline in PC12 cells was enhanced 15- and 5-fold, respectively, but after rTMS treatment no change in the release of the two neurotransmitters was observed.'] Does repetitive transcranial magnetic stimulation influence immunological HL-60 cells and neuronal PC12 cells?
qiaojin/PubMedQA
2
[ -2.368152379989624, -1.3758455514907837, 2.820063352584839 ]
['Various studies suggest that deficiency of magnesium and potassium may be associated with increased risk of ischemic stroke. However, single time-point serum measurements may not be suitable for assessing long-term tissue levels.', 'We investigated Mg and K levels in hair of patients with acute ischemic stroke. The elements hair accumulation analysis might provide historical information on their concentrations over a longer period of time and probably reflects the corresponding nutritional condition. The concentrations of Mg and K in hair of 48 men with acute ischemic stroke and a control group were measured using spectroscopic methods.', 'The mean Mg and K concentrations in hair of patients were significantly higher than in the controls.'] Is high magnesium or potassium hair accumulation associated with ischemic stroke risk reduction : a pilot study?
qiaojin/PubMedQA
2
[ -2.5587477684020996, -0.4410242736339569, 2.2207529544830322 ]
['To study the effects of carvedilol on the transmural heterogeneity of ventricular repolarization in rabbits with congestive heart failure (CHF).', 'Rabbits were randomly divided into 3 groups: control, CHF and carvedilol treated CHF group. Monophasic action potential duration (MAPD) in the 3 myocardial layers was simultaneously recorded.', 'All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resistance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold (VFT) was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization (TDR) was significantly increased in CHF. Low-dose carvedilol (0.25 mg/kg, twice daily) had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Although the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF.'] Does low-dose carvedilol reduce transmural heterogeneity of ventricular repolarization in congestive heart failure?
qiaojin/PubMedQA
2
[ -2.106455087661743, -1.4389114379882812, 2.530864953994751 ]
['To investigate the neuroprotective effect of propofol and its intracellular mechanism on neurons in vitro.', 'Cell viability was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction. Apoptotic cell death was determined by Hoechst 33258 staining and a fluorescence-activated cell sorter. The caspase-3 activity was measured by fluorometric assay. Mitogen-activated protein (MAP) kinase phosphorylation was detected with Western blotting.', 'The pretreatment of rat pheochromocytoma cell line PC12 with propofol (1-10 micromol/L) resulted in a significant recovery from hydrogen peroxide (H2O2)-induced cell death and the inhibition of H2O2 induced caspase-3 activation and PC12 cell apoptosis. Propofol inhibited the H2O2-induced p38 MAP kinase, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1 and 2 activations.'] Does propofol attenuate oxidative stress-induced PC12 cell injury via p38 MAP kinase dependent pathway?
qiaojin/PubMedQA
2
[ -2.448984384536743, -1.3053455352783203, 2.800753116607666 ]
['To investigate the effect and mechanism of morphine on purine nucleotide catabolism.', 'The rat model of morphine dependence and withdrawal and rat C6 glioma cells in culture were used. Concentrations of uric acid in the plasma were measured by the uricase-rap method, adenosine deaminase (ADA) and xanthine oxidase (XO) in the plasma and tissues were measured by the ADA and XO test kit. RT-PCR and RT-PCR-Southern blotting were used to examine the relative amount of ADA and XO gene transcripts in tissues and C6 cells.', '(i) the concentration of plasma uric acid in the morphine-administered group was significantly higher (P<0.05) than the control group; (ii) during morphine administration and withdrawal periods, the ADA and XO concentrations in the plasma increased significantly (P<0.05); (iii) the amount of ADA and XO in the parietal lobe, liver, small intestine, and skeletal muscles of the morphine-administered groups increased, while the level of ADA and XO in those tissues of the withdrawal groups decreased; (iv) the transcripts of the ADA and XO genes in the parietal lobe, liver, small intestine, and skeletal muscles were higher in the morphine-administered group. The expression of the ADA and XO genes in those tissues returned to the control level during morphine withdrawal, with the exception of the skeletal muscles; and (v) the upregulation of the expression of the ADA and XO genes induced by morphine treatment could be reversed by naloxone.'] Does morphine enhance purine nucleotide catabolism in vivo and in vitro?
qiaojin/PubMedQA
2
[ -2.5271291732788086, -1.1054110527038574, 2.6958789825439453 ]
['To investigate the expression of sonic hedgehog (SHH) and epidermal growth factor receptor (EGFR) signal molecules in pancreatic cancer cells, and to assess the inhibitory effects through the blockade of the SHH and EGFR signaling pathways by cyclopamine and Iressa, respectively.', 'The expression of SHH and EGFR in pancreatic cancer cell lines (PANC-1, SUIT-2, and ASPC-1) was detected by RT-PCR and Western blot analysis. After treatment with different concentrations of cyclopamine, alone or in combination with Iressa, the antiproliferative effect on pancreatic cancer cells was analyzed by methyl thiazolyl tetrazolium assays. A flow cytometry analysis was used to detect the cellular cycle distribution and apoptosis of pancreatic cancer cells.', 'All of the 3 pancreatic cancer cell lines expressed SHH, Smoothened (SMO), and EGFR. Cyclopamine could downregulate the expression of EGFR in all cell lines. Cyclopamine or Iressa could induce a growth inhibitory effect in a dose-dependent manner. Moreover, the combined use of 2.5 micromol/L cyclopamine and 1 micromol/L Iressa induced an enhanced inhibitory effect and a greater apoptosis rate than any agent alone. The percentage of the cell population of the G0/G1 and sub-G1 phases was significantly increased along with the increasing dose of cyclopamine and/or Iressa.'] Does blockade of sonic hedgehog signal pathway enhance antiproliferative effect of EGFR inhibitor in pancreatic cancer cells?
qiaojin/PubMedQA
2
[ -2.2889304161071777, -1.4174981117248535, 2.686990261077881 ]
['To examine the protective effect of propofol in renal ischemia/reperfusion (I/R) injury and the role of heme oxygenase-1 (HO-1) in this process.', 'Sprague-Dawley rats were randomly divided into 3 groups: (i) sham-operated group; (ii) I/R group; and (iii) propofol group. Bilateral renal warm ischemia for 45 min was performed. After 2, 6, and 24 h reperfusion, blood samples and kidneys were collected for assessment of renal injury, and HO-1 expressions were analyzed by immunohistochemical analysis, RT-PCR and Western blotting.', 'Blood urea nitrogen and serum creatinine levels in the propofol group were significantly lower than that in the I/R group at 24 h after reperfusion. The mean histological score by Palleros standard showed that propofol significantly attenuated renal I/R injury after 6 h reperfusion. Propofol increased HO-1 mRNA and protein levels 2 h after reperfusion, whereas HO-1 expressions were present at exceedingly low levels in the I/R group and the sham-operated group at same time point. Propofol also markedly increased HO-1 mRNA and protein levels than I/R at 6 and 24 h after reperfusion.'] Does propofol attenuation of renal ischemia/reperfusion injury involve heme oxygenase-1?
qiaojin/PubMedQA
2
[ -2.2358272075653076, -1.3983582258224487, 2.7036056518554688 ]
['This study compared the effect of 2 specific cervical flexor muscle exercise protocols on immediate pain relief in the cervical spine of people with chronic neck pain. In addition, the study evaluated whether these exercise protocols elicited any systemic effects by studying sympathetic nervous system (SNS) function and pain at a location distant from the cervical spine. Participants were randomly allocated into either a cranio-cervical flexion (CCF) coordination exercise group (n = 24) or a cervical flexion (CF) endurance exercise group (n = 24). Measures of pain and SNS function were recorded immediately before and after a single session of the exercise interventions. Pain measures included visual analogue scale (VAS) ratings of neck pain at rest and during active cervical motion and pressure pain threshold (PPT) and thermal pain threshold (TPT) recordings over the cervical spine and at a remote site on the leg. Measures of SNS function consisted of blood flow, skin conductance, skin temperature, heart rate, and blood pressure. Immediately after 1 session of exercise, there was a reasonably sized increase of 21% (P < .001, d = 0.88) and 7.3% (P = .03, d = 0.47) in PPT locally at the neck for the CCF exercise and the CF exercise, respectively. There were no changes in local neck TPT with either exercise. Pressure pain threshold and TPT at the leg and SNS did not change after exercise. Only the CCF exercise demonstrated a small improvement in VAS ratings during active movement (change on 10-cm VAS: CCF, 0.42 cm (P = .04). This study shows that specific CCF therapeutic exercise is likely to provide immediate change in mechanical hyperalgesia local to the neck with translation into perceived pain relief on movement in patients with chronic neck pain.'] Does specific therapeutic exercise of the neck induce immediate local hypoalgesia?
qiaojin/PubMedQA
2
[ -1.823851227760315, -1.413268804550171, 2.2453432083129883 ]
["There is no consensus on the pharmacological treatment of alcoholic hepatitis. The Glasgow alcoholic hepatitis score (GAHS) has been shown to be more accurate than the modified Maddrey's discriminant function (mDF) in the prediction of outcome from alcoholic hepatitis. This study aimed to determine whether the GAHS was able to identify those patients who would benefit from corticosteroids.", '225 patients with an mDF greater than or equal to 32 from five hospital centres in the United Kingdom were reviewed. Patient survival relative to the GAHS and the use of corticosteroids was recorded.', '144 patients with an mDF greater than or equal to 32 (64%) also had a GAHS greater than or equal to 9. There was no difference in survival between untreated or corticosteroid-treated patients for those with a GAHS less than 9. For patients with a GAHS greater than or equal to 9 the 28-day survival for untreated and corticosteroid-treated patients was 52% and 78% (p = 0.002), and 84-day survival was 38% and 59% (p = 0.02), respectively.'] Does the Glasgow alcoholic hepatitis score identify patients who may benefit from corticosteroids?
qiaojin/PubMedQA
0
[ -0.0673428401350975, -0.5040684342384338, -0.28808850049972534 ]
['International guidelines recommend that children who are managed at home with mechanical respiratory support (RS) should have sleep studies performed every 6-12 months. This recommendation is based on expert opinion, with little evidence to support it. No studies have been undertaken to examine the utility of sleep studies in children on RS.', 'A retrospective review of sleep studies performed over a 12-month period was undertaken at a New Zealand paediatric sleep medicine referral centre, to determine changes made to RS following sleep studies.', 'Sixty-one sleep studies were performed for assessment of RS in 45 children (27 boys; median age 8.3 years; range 0.4-18.6 years). Twenty-nine (64%) children were on continuous positive airway pressure, 14 (31%) on bi-level non-invasive ventilation, and two (4%) on tracheostomy ventilation. A change was made to RS settings after 66% of studies. No clinical parameters predicted which children would require a change in settings.'] Do sleep studies frequently lead to changes in respiratory support in children?
qiaojin/PubMedQA
2
[ -2.2151081562042236, 0.4025098383426666, 1.0071029663085938 ]
['To examine postictal breathing pattern in generalized convulsive nonepileptic seizures (GCNES) and generalized tonic-clonic seizures (GTCS) and evaluate this feature as a discriminating sign.', 'We reviewed the postictal breathing pattern seizures in 23 generalized tonic-clonic seizures in 15 consecutive patients with epilepsy and 24 convulsive nonepileptic seizures in 16 consecutive patients with pure psychogenic seizures. We also analyzed 21 frontal lobe hypermotor seizures (FLHS) in 9 patients with frontal lobe epilepsy.', 'The breathing after GTCS was deep with prolonged inspiratory and expiratory phases, regular, and loud (except for two short seizures). The breathing after GCNES was characterized by increased respiratory rate or hyperpnea with short inspiratory and expiratory phases, as can be noted after exercise. The breathing was often irregular, with brief pauses. The altered breathing lasted longer after GTCS. The two groups differed significantly in loudness of postictal respiration, postictal snoring (only with GTCS), respiratory rate (faster for the GCNES group), and duration of altered breathing (longer after GTCS) (p < 0.00001 for all features). FLHS shared postictal breathing features of GCNES, but had other distinguishing features.'] Does postictal breathing pattern distinguish epileptic from nonepileptic convulsive seizures?
qiaojin/PubMedQA
2
[ -1.9999479055404663, -1.057121753692627, 2.090458393096924 ]
['Stenosis at a vascular anastomotic site has been a significant clinical issue. We tested the hypothesis that rapamycin-eluting biodegradable poly L-lactic acid and epsilon-caprolactone copolymer (PLA-CL) film applied externally can inhibit neointimal hyperplasia in a canine vascular anastomosis model.', 'Femoral artery graft interposition was performed in 25 beagles. Beagles were divided into five groups (five in each): graft interposition without PLA-CL film (control); with PLA-CL film only; and PLA-CL containing rapamycin 8 microg, 80 microg, and 800 microg. Orthotopic arterial graft interposition was performed on the left side and vein graft from the ipsilateral femoral vein was interposed on the right. Morphometric and immunochemical analyses were performed at four-week intervals.', 'In arterial graft models, the ratio of intimal area (intimal area divided by the entire vessel area) was significantly reduced in all the three rapamycin-eluting film groups compared with control (0.19, 0.07, 0.05, and 0.38 in 8 microg, 80 microg, 800 microg groups and control, respectively, p < 0.05). In vein graft models, the ratio of intimal area was significantly decreased only in the 800 microg rapamycin group compared with control (0.33 vs 0.54, p < 0.05). Inhibition of neointimal growth was associated with reduced cell proliferation, as evidenced by proliferating cell nuclear antigen immunostaining and diminished alpha-actin positive vascular smooth muscle cells.'] Does external application of rapamycin-eluting film at anastomotic sites inhibit neointimal hyperplasia in a canine model?
qiaojin/PubMedQA
2
[ -2.0984041690826416, -1.556265115737915, 2.658376455307007 ]
['Cell cycle progression is driven by the coordinated regulation of cyclin-dependent kinases (CDKs). In response to mitogenic stimuli, CDK4 and CDK2 form complexes with cyclins D and E, respectively, and translocate to the nucleus in the late G(1) phase. It is an on-going discussion whether mammalian cells need both CDK4 and CDK2 kinase activities for induction of S phase.', 'In this study, we have explored the role of CDK4 activity during G(1) progression of primary rat hepatocytes. We found that CDK4 activity was restricted by either inhibiting growth factor induced cyclin D1-induction with the PI3K inhibitor LY294002, or by transient transfection with a dominant negative CDK4 mutant. In both cases, we observed reduced CDK2 nuclear translocation and reduced CDK2-Thr160 phosphorylation. Furthermore, reduced pRb hyperphosphorylation and reduced cellular proliferation were observed. Ectopic expression of cyclin D1 alone was not sufficient to induce CDK4 nuclear translocation, CDK2 activity or cell proliferation.'] Is cDK2 regulation through PI3K and CDK4 necessary for cell cycle progression of primary rat hepatocytes?
qiaojin/PubMedQA
2
[ -2.46600079536438, -0.8372664451599121, 2.3174312114715576 ]
['The retinoblastoma tumor suppressor (RB) is a key regulator of cell cycle progression and is functionally inactivated in the majority of human non-small cell lung cancers (NSCLC). The specific influence of RB on therapeutic response in NSCLC remains elusive.', 'We investigated the consequence of reintroduction of RB on checkpoint response and chemosensitivity in NSCLC cell lines. RB introduction into RB-proficient (NCI-H1299) and -deficient (H1734, H2172) NSCLC cells was achieved by adenoviral infection. RB/E2F target gene expression was determined by immunoblot analysis. Cell cycle response and viability after chemotherapeutic exposure were assessed by flow cytometry and MTT viability assay.', 'RB reconstitution in RB-deficient lines restored regulation of topoIIalpha, thymidylate synthase, and cyclin A. Similarly, RB overexpression in RB-proficient cells caused further regulation of some RB/E2F target genes including thymidylate synthase and topoIIalpha. In addition, RB overexpression resulted in restoration of the G1 arrest mechanism. Exposure of RB-proficient cells to cisplatin, etoposide, or 5-fluorouracil elicited arrest in various phases of the cell cycle while lines deficient for RB exhibited different checkpoint responses. However, introduction of RB restored ability to arrest following chemotherapeutic exposure. Chemotherapeutic challenge resulted in varying effects on cellular viability independent of RB status, yet restoration of RB activity conferred partial chemoresistance.'] Does rB activity alter checkpoint response and chemosensitivity in lung cancer lines?
qiaojin/PubMedQA
2
[ -2.445854902267456, -1.307174801826477, 2.8298797607421875 ]
['West syndrome is a severe epileptic encephalopathy of infancy characterized by a poor developmental outcome and hypsarrhythmia. The pathogenesis of hypsarrhythmia is insufficiently understood.', 'We investigated eight patients with infantile spasms and hypsarrhythmia (group I) and 8 children with complex partial seizures (group II) using simultaneous recordings of electroencephalogram (EEG) and functional MRI. Hemodynamic responses to epileptiform discharges and slow wave activity (EEG delta power) were analyzed separately.', 'In group I (mean age, 7.82 +/- 2.87 months), interictal spikes within the hypsarrhythmia were associated with positive blood oxygenation level-dependent (BOLD) changes in the cerebral cortex (especially occipital areas). This was comparable with cortical positive BOLD responses in group II (mean age, 20.75 +/- 12.52 months). Slow wave activity in group I correlated significantly with BOLD signal in voxels, which were localized in brainstem, thalamus, as well as different cortical areas. There was no association between BOLD effect and EEG delta power in group II. Moreover, as revealed by group analysis, group I differed from group II according to correlations between BOLD signal and slow wave activity in putamen and brainstem.'] Are different neuronal networks associated with spikes and slow activity in hypsarrhythmia?
qiaojin/PubMedQA
2
[ -2.3404128551483154, -1.1520507335662842, 2.5543837547302246 ]
['Haptoglobin is a glycoprotein produced mainly by the liver and secreted into the circulation. Haptoglobin, by virtue of its high affinity for hemoglobin, protects the tissues against hemoglobin-induced oxidative damage and allows heme iron recycling. Haptoglobin synthesis is controlled by various effectors, however, little is known concerning its regulation by iron. Haptoglobin regulation in C57BL/6 and 129sv mice fed on an iron-rich diet for 3 weeks was thus undertaken.', 'Iron induced a dramatic post-transcriptional decrease of liver and serum haptoglobin in C57BL/6 mice. In contrast, no alteration of haptoglobin expression was detected in 129sv mice. We assumed that the oxidative stress induced by iron in C57BL/6 mice altered the endoplasmic reticulum (ER) environment, leading to the incorrect folding of haptoglobin and its subsequent degradation. To test this hypothesis, the levels of the RE chaperone GRP78 were measured. This chaperone is known to assist protein folding in the RE during pathophysiological conditions. Interestingly, we found that the mRNA and protein levels of GRP78 were decreased in iron-fed C57BL/6 mice, while they were unchanged in iron-fed 129sv mice. These results suggest that the correct processing of haptoglobin (glycosylation, disulfide linkage, folding, and assembly) might be sensitive to ER stress and that, in the absence of GRP78-mediated assistance, Hp is degraded.'] Is haptoglobin degraded by iron in C57BL/6 mice : a possible link with endoplasmic reticulum stress?
qiaojin/PubMedQA
2
[ -2.3080456256866455, -1.2943778038024902, 2.5959019660949707 ]
['Twenty-five novel phosphoproteins, including Annexin I, triggered by Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) were identified when we previously combined phosphorylation enrichment with proteomics technology to elucidate signaling pathway activated by LMP1. This study was to map signal transduction pathway between LMP1 and phosphorylation of AnnexinI.', 'The expression of Annexin I in nasopharyngeal carcinoma cell lines (stably expressing LMP1) was analyzed by Western blot. Serine-and tyrosine-phosphorylation levels of AnnexinIwere detected through combining immunoprecipitation with Western blot. The activity of protein kinase C (PKC) was analyzed by non-radioactive protein kinase assay.', 'The protein level and tyrosine phosphorylation of Annexin I in CNE1 and CNE1-LMP1 cells were similar; the serine phosphorylation of annexin I was higher in CNE1-LMP1 cells than in CNE1 cells. The relative activity of PKC was significantly lower in CNE1 cells than in CNE1-LMP1 cells (0.97+/-0.05 vs. 1.22+/-0.10, P<0.01). The change of PKC activity was followed by the change of serine phosphorylation level of Annexin I.'] Does [ Epstein-Barr virus-encoded latent membrane protein 1 mediate serine-phosphorylation of annexin I by activating protein kinase C ]?
qiaojin/PubMedQA
2
[ -2.2185323238372803, -1.3264765739440918, 2.6329009532928467 ]
['Our objective was to characterize the heat shock response (HSR) in a model of traumatic brain injury (TBI) and to determine the association of HSR to cell death.', 'We used immunofluorescent detection of HSP-70 to characterize HSR and TUNEL labeling to determine the pattern of cell death.', 'HSP-70 immunofluorescence revealed a steady increase from 4 to 48 hours following TBI, culminating in a ubiquitous expression with the capillary bed 48 hours post-TBI. TUNEL labeling revealed a small subset of endothelial cell death and a most robust staining of putative pericyte cell death.'] Does brain endothelial HSP-70 stress response coincide with endothelial and pericyte death after brain trauma?
qiaojin/PubMedQA
2
[ -2.3951902389526367, -1.1795601844787598, 2.650087833404541 ]
['To study the cellular distribution of endothelin receptors A and B (ETrA and ETrB) in the post-traumatic sensorimotor cortex and hippocampus.', "We inflicted closed head trauma to male Sprague-Dawley rats and visualized ETrA and ETrB immunoreactivity with 3,3'-diaminobenzidine.", 'ETrA immunolabeling was the most prominent in pyramidal neurons 24 and 48 hours post-trauma, while it reached its peak in the microvasculature at hour 4. ETrB immunolabeling was observed in endothelial cells, perivascular neurons, smooth muscle cells (SM) and pericytes, the expression being the most pronounced 24 hours post-trauma.'] Are spatial alterations in endothelin receptor expression temporally associated with the altered microcirculation after brain trauma?
qiaojin/PubMedQA
2
[ -2.7151143550872803, -0.9938099384307861, 2.7778310775756836 ]
['The purpose of this study was to determine the molecular and biochemical changes in the contractile protein, calponin (Cp), which temporally coincide with a previously reported state of sustained contractility following traumatic brain injury (TBI).', 'Double immunofluorescence, western analysis and two-dimensional non-equilibrium pH gradient gel electrophoresis (NEPHGE)/SDS-PAGE techniques were utilized to determine both the location and extent of Cp within smooth muscle cells (SM) and the phosphorylation state of Cp following TBI, as induced using a weight drop acceleration impact model.', 'Double immunofluorescence for Cp and SM indicate that following injury, Cp migrates from the cytosol to a location subjacent to the SM membrane. Western analysis revealed a significant increase in Cp protein expression following injury that was maintained up to 48 hours post-injury. Combined Western analysis and NEPHGE indicated that Cp is phosphorylated following TBI.'] Does calponin phosphorylation in cerebral cortex microvessels mediate sustained vasoconstriction after brain trauma?
qiaojin/PubMedQA
2
[ -2.495804786682129, -1.1955373287200928, 2.7987937927246094 ]
['We investigated whether exercise pre-conditioning ameliorates stroke-induced blood-brain barrier (BBB) dysfunction by strengthening basal lamina.', 'Adult male Sprague-Dawley rats were subjected to a 30 minute exercise program on a treadmill each day for 3 weeks. Stroke was induced by a 2 hour middle cerebral artery (MCA) occlusion using an intraluminal filament in the exercised and non-exercised groups. BBB dysfunction was then determined by brain edema. Expression of collagen IV, the major component of basal lamina essential for maintenance of the endothelial permeability barrier, was quantitatively detected by Western blot and immunocytochemistry. Ex vivo techniques were used to compare collagen IV-labeled vessels in response to ischemic insult.', 'Brain edema was significantly (p<0.05) reduced after stroke in the exercised group. Western blot analysis indicated that exercise pre-conditioning enhanced collagen IV expression and reduced the loss after stroke. Immunocytochemistry demonstrated that collagen IV-positive vessels were significantly (p<0.01) increased in exercised rats. In ex vivo study, after exercised brain was incubated with ischemic brain tissue, a significantly (p<0.01) higher expression of collagen IV in cortex and striatum was observed compared to non-exercised brain following the same treatment. The ex vivo study also revealed that matrix metalloproteinase (MMP)-9 plays a key role in exercise-strengthened collagen IV expression against ischemia/reperfusion injury.'] Does exercise pre-conditioning ameliorate blood-brain barrier dysfunction in stroke by enhancing basal lamina?
qiaojin/PubMedQA
2
[ -2.3822362422943115, -1.2042186260223389, 2.632514476776123 ]
['Global transcript levels throughout the cell cycle have been characterized using microarrays in several species. Early analysis of these experiments focused on individual species. More recently, a number of studies have concluded that a surprisingly small number of genes conserved in two or more species are periodically transcribed in these species. Combining and comparing data from multiple species is challenging because of noise in expression data, the different synchronization and scoring methods used, and the need to determine an accurate set of homologs.', 'To solve these problems, we developed and applied a new algorithm to analyze expression data from multiple species simultaneously. Unlike previous studies, we find that more than 20% of cycling genes in budding yeast have cycling homologs in fission yeast and 5% to 7% of cycling genes in each of four species have cycling homologs in all other species. These conserved cycling genes display much stronger cell cycle characteristics in several complementary high throughput datasets. Essentiality analysis for yeast and human genes confirms these findings. Motif analysis indicates conservation in the corresponding regulatory mechanisms. Gene Ontology analysis and analysis of the genes in the conserved sets sheds light on the evolution of specific subfunctions within the cell cycle.'] Does combined analysis reveal a core set of cycling genes?
qiaojin/PubMedQA
1
[ -2.402007818222046, 0.8181354403495789, 0.7589429020881653 ]
["Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Abeta42 in cell culture and animal models, and that the effect of NSAIDs on Abeta42 is independent of the inhibition of cyclooxygenase by these compounds. Since Abeta42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Abeta42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Abeta42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Abeta loads in Tg2576 APP mice.", 'A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Abeta pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Abeta was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Abeta plaque burden but no significant improvement in spatial learning.'] Does chronic administration of R-flurbiprofen attenuate learning impairments in transgenic amyloid precursor protein mice?
qiaojin/PubMedQA
2
[ -2.3534109592437744, -1.3632795810699463, 2.7298359870910645 ]
['To determine the impact of novel invitation strategies on population participation in faecal immunochemical test (FIT)-based colorectal cancer (CRC) screening.', 'A community screening programme in Adelaide, South Australia.', 'In total, 2400 people aged 50-74 years were randomly allocated to one of four CRC screening invitation strategies: (a)', 'standard invitation-to-screen letter explaining risk of CRC and the concept, value and method of screening; (b) Risk: invitation with additional messages related to CRC risk; (c) Advocacy: invitation with additional messages related to advocacy for screening from previous screening programme participants and (d) Advance Notification: first, a letter introducing CONTROL letter messages followed by the standard invitation-to-screen. Invitations included an FIT kit. Programme participation rates were determined for each strategy relative to control. Associations between participation and sociodemographic variables were explored.', 'At 12 weeks after invitation, participation was:', '237/600 (39.5%); Risk: 242/600 (40.3%); Advocacy: 216/600 (36.0%) and Advance Notification: 290/600 (48.3%). Participation was significantly greater than CONTROL only in the Advance Notification group (Relative risk [RR] 1.23, 95% confidence interval [CI] 1.06-1.43). This effect was apparent as early as two weeks from date of offer; Advance Notification: 151/600 (25.2%) versus', '109/600 (18.2%, RR 1.38, 95% CI 1.11-1.73).'] Does an advance notification letter increase participation in colorectal cancer screening?
qiaojin/PubMedQA
2
[ -0.4295782446861267, -1.68886137008667, 1.0949293375015259 ]
['To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs.', 'Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices.', 'Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S.'] Is exposure to hardly soluble indium compounds in ITO production and recycling plants a new risk for interstitial lung damage?
qiaojin/PubMedQA
2
[ -0.5133192539215088, -1.7153693437576294, 1.3129968643188477 ]
['In this study, we employed chimeric human/mouse Proteinase 3 (PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice.', 'Rats and mice were immunised with recombinant human PR3 (HPR3), recombinant murine PR3 (mPR3), single chimeric human/mouse PR3 (HHm, HmH, mHH, mmH, mHm, Hmm) or pools of chimeric proteins. Antibodies to mPR3 and HPR3 were measured by ELISA. Antibodies to rat PR3 were determined by indirect immunofluorescence (IIF) on rat white blood cells. Urinalysis was performed by dipstick analysis. Kidney and lung tissue was obtained for pathological examination.', 'In mice, immunisation with the chimeric human/mouse PR3 Hmm led to an autoantibody response to mPR3. Rats immunised with the chimeric human/mouse PR3 Hmm, HmH and mmH, or a pool of the chimeric human/mouse PR3 proteins, produced antibodies selectively binding to rat granulocytes as detected by IIF. No gross pathological abnormalities could be detected in kidney or lungs of mice or rats immunised with chimeric human/mouse PR3.'] Do rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes?
qiaojin/PubMedQA
2
[ -2.4320950508117676, -1.063523769378662, 2.6041457653045654 ]
['To explore the relationship between serum sodium concentration and coronary atherosclerosis.', 'The study population consisted of 896 consecutive patients (684 males and 212 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. Smoking and drinking were investigated. The anthropometric measurements, including body mass index, systolic blood pressure and diastolic blood pressure, and the serum measurements, including sodium, potassium, chlorine, lipids, blood glucose, urea, creatinine, and uric acid for every patient were conducted. The severity of coronary atherosclerosis was defined by the Gensini score system. The statistical methods, including one-way ANOVA, Kruskal-Wallis test, Spearman correlation analysis, partial correlation analysis, multivariate stepwise linear regression analysis, and multinomial logistic regression analysis were employed to explore the relationship between serum sodium concentration and the Gensini score.', 'The analysis of the Kruskal-Wallis test indicated that the distribution of the Gensini score (P=0.000) differed among the groups according to serum sodium concentration, quartile values of which were used as cut-off points. The Spearman correlation and partial correlation analysis controlling for gender, smoking status, and drinking status indicated that the Gensini score significantly correlated with the sodium concentration (r=-0.241, P=0.000 for the Spearman correlation, r=-0.114, P=0.000 for the partial correlation). The results from the multivariate stepwise linear regression analysis showed that the left ventricular ejection fraction (beta=-0.228, P=0.000), age (beta=0.137, P=0.010), glucose level (beta=0.129, P=0.000), and sodium level (beta=-0.106, P=0.004) were significantly and independently associated with the Gensini score. The results of the multinomial logistic regression analysis suggested that the hyponatremia was the risk factor for the higher Gensini score.'] Is serum sodium concentration significantly associated with the angiographic characteristics of coronary atherosclerosis?
qiaojin/PubMedQA
2
[ -1.6672025918960571, -1.493579626083374, 2.1177401542663574 ]
["Avarol is a marine sesquiterpenoid hydroquinone with anti-inflammatory and antipsoriatic properties. The aim of this study was to evaluate the in vitro and in vivo pharmacological behaviour of the derivative avarol-3'-thiosalicylate (TA) on some inflammatory parameters related to the pathogenesis of psoriasis.", 'Human neutrophils and monocytes as well as the human keratinocyte cell line HaCaT were used to study the effect of TA on oxidative stress, the arachidonic acid pathway, tumour necrosis factor-alpha (TNF-alpha) release and nuclear factor-kappaB (NF-kappaB) activation. All these parameters were also determined in vivo using the zymosan induced mouse air pouch model and the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse epidermal hyperplasia model.', 'TA showed antioxidant properties in human neutrophils and in the hypoxanthine/xanthine oxidase assay. This compound reduced, in a concentration-dependent manner, leukotriene B(4), prostaglandin E(2) and TNF-alpha production in activated leukocytes. Oral and intrapouch administration of TA in the mouse air pouch model produced a dose-dependent reduction of all these inflammatory mediators. TA also inhibited secretory phospholipase A(2) activity and NF-kappaB DNA-binding in HaCaT keratinocytes. In TPA-induced mouse epidermal hyperplasia, topical administration of TA reduced oedema, leukocyte infiltration, eicosanoid levels and TNF-alpha in skin. In addition, interleukin (IL)-1beta and IL-2 production were also inhibited. Finally, TA was also capable of suppressing NF-kappaB nuclear translocation in vivo.'] Do antipsoriatic effects of avarol-3'-thiosalicylate are mediated by inhibition of TNF-alpha generation and NF-kappaB activation in mouse skin?
qiaojin/PubMedQA
2
[ -2.4529614448547363, -1.3535196781158447, 2.816863775253296 ]
['Sepsis is a systemic inflammatory response resulting from the inability of the host to restrict local infection. The failure of neutrophil migration to the infection site is one of the mechanisms involved in this process. Recently, it was demonstrated that this event is mediated by nitric oxide (NO). The present study addresses the possibility that peroxynitrite (ONOO(-)), a NO-derived powerful oxidizing and nitrating compound, could also be involved in neutrophil migration failure.', 'Male C57Bl/6 mice were subjected to moderate (MSI) or severe (SSI) septic injury, both induced by cecal ligation and puncture (CLP). The leukocyte rolling and adhesion in the mesentery was evaluated by intravital microscopy. Cytokines (TNF-alpha and MIP-1alpha) were measured by ELISA and 3-nitrotyrosine (3-NT) by immunofluorescence.', 'Compared with saline pretreatment of SSI mice, pre-treatment with uric acid, a ONOO(-) scavenger, partially restored the failure of neutrophil rolling, adhesion and migration to the site of infection. These mice also presented low circulating bacterial counts and diminished systemic inflammatory response. Pretreatment with uric acid reduced 3-NT labelling in leukocytes in mesenteric tissues and in neutrophils obtained from peritoneal exudates. Finally, uric acid pretreatment enhanced significantly the survival rate in the SSI mice. Similarly, treatment with FeTPPs, a more specific ONOO(-) scavenger, re-established neutrophil migration and increased mice survival rate.'] Does peroxynitrite mediate the failure of neutrophil migration in severe polymicrobial sepsis in mice?
qiaojin/PubMedQA
2
[ -2.4212863445281982, -1.3829123973846436, 2.8738441467285156 ]
['Palytoxin (PLT) is a potent toxin that binds to the Na,K-ATPase. Palytoxin is highly neurotoxic and increases the cytosolic calcium concentration ([Ca(2+)](c)) while decreasing intracellular pH (pH(i)) in neurons (Vale et al., 2006; Vale-Gonzalez et al., 2007). It is also a tumour promoter that activates several protein kinases.', 'The role of different protein kinases in the effects of palytoxin on [Ca(2+)](c), pH(i) and cytoxicity was investigated in cultured neurons.', 'Palytoxin-induced calcium load was not affected by inhibition of calcium-dependent protein kinase C (PKC) isoforms but it was partially ameliorated by blockade of calcium-independent PKC isozymes. Inhibition of the extracellular signal-regulated kinase (ERK) 2 eliminated the palytoxin-induced rise in calcium and intracellular acidification, whereas inhibition of MEK greatly attenuated the palytoxin effect on calcium without modifying the PLT-evoked intracellular acidification. Blockade of c-Jun N-terminal protein kinases (JNK) somewhat decreased the palytoxin-effect on calcium, whereas inhibition of the p38 mitogen activated protein kinases (MAPKs) delayed the onset of the palytoxin-evoked rise in calcium and acidification. Furthermore, the cytotoxicity of palytoxin was completely blocked by inhibition of ERK 2 and partially prevented by inhibition of MEK. PLT increased phosphorylated ERK immunoreactivity in a concentration-dependent manner.'] Do mitogen-activated protein kinases regulate palytoxin-induced calcium influx and cytotoxicity in cultured neurons?
qiaojin/PubMedQA
2
[ -2.451911687850952, -1.1317483186721802, 2.573195457458496 ]
['This retrospective study was performed to relate tunnel position as measured by plain radiographs and magnetic resonance imaging (MRI) to residual pivot shift and to determine its clinical relevance after anterior cruciate ligament reconstruction via central quadriceps tendon autograft.', "We reviewed 137 arthroscopic anterior cruciate ligament reconstructions via quadriceps tendon autograft with a minimum of 2 years' follow-up. Clinical results were evaluated by use of the Lachman test, pivot-shift test, Lysholm score, and Cybex dynamometer (Lumex, Ronkonkoma, NY). Anterior tibial translation was measured with the KT-1000 arthrometer (MEDmetric, San Diego, CA). Patients were classified into 3 groups based on postoperative pivot-shift and Lachman test findings: group I, both negative; group II, negative Lachman test and positive pivot shift; and group III, both positive. The radiographic analysis was performed via the angle between the tibial and femoral tunnels on plain anteroposterior radiographs, the angle between the tibial tunnel and anterior tibial cortex on the lateral view, and the femoral and tibial tunnel location by use of the ratio method. Postoperative knee MRI was performed, and the angle between the intercondylar anteroposterior axis and femoral tunnel on the axial view and the angle between the joint line and the graft on the oblique coronal and sagittal views were measured.", 'There were 100 patients in group I, 13 in group II, and 24 in group III. Patients in group I showed the greatest improvement in Lysholm score among the groups, and patients in group III had the greatest side-to-side difference by KT-1000 arthrometer. Tunnel obliquity as measured by the angle between the anteroposterior axis of the femur and the femoral tunnel in the axial view on MRI was greater (P < .05) and the angle between the joint line and the graft on the oblique coronal view was less in group I.'] Does vertical femoral tunnel placement result in rotational knee laxity after anterior cruciate ligament reconstruction?
qiaojin/PubMedQA
2
[ -1.9784992933273315, -1.48508882522583, 2.459542989730835 ]