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['To demonstrate that measurement of endogenous neopterin levels in unstimulated lymphoblasts identifies inherited GTP cyclohydrolase 1 (GCH1) dysfunction and can be a diagnostic test for dopa-responsive dystonia (DRD).', 'DRD results from decreased dopamine biosynthesis due to dysfunctional GCH1. GCH1 is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for catecholamine synthesis. Mutations in the GCH1 coding region are identified in 60 to 70% of DRD cases; in others, the cause of GCH1 dysfunction is unknown.', 'Using HPLC, we measured endogenous neopterin, the main byproduct of the GCH1 reaction, in lymphoblasts under basal conditions and following GCH1 stimulation conditions.', "In a four-generation family, all identified carriers of dysfunctional GCH1 had basal neopterin levels that were below those of controls. The spouse of one carrier had a mutation in exon 6 of GCH1. Although this man's GCH1 function appeared unaffected by this, his daughter, who was a compound heterozygote with her mother's dysfunctional GCH1 and this mutation, had a phenotype that was more severe than that of typical DRD. Cytokine or phytohemagglutinin (PHA) did not induce GCH1 activity in any carrier of dysfunctional GCH1; controls who did not respond to PHA had increased neopterin levels following cytokine induction."] Does reduced lymphoblast neopterin detect GTP cyclohydrolase dysfunction in dopa-responsive dystonia? | qiaojin/PubMedQA | 2 | [
-2.473456621170044,
-1.288314700126648,
2.7854056358337402
] |
['Heel lancing has hitherto been the method of choice for screening tests of inborn errors of metabolism in neonates. Eutectic mixture of local anesthetic has little, if any, analgesic effect when applied to the heel of pre- and full-term infants. Today there seems to be no practical method that effectively alleviates the pain caused by heel lancing. The aim of this study was to investigate whether other methods, such as venipuncture of the dorsal side of the hand, are less painful and more efficient than heel lancing in neonates.', 'One hundred twenty healthy, full-term infants who underwent testing for phenylketonuria (PKU) were included in the study. They were randomized into three groups: a venipuncture group (VP) (n = 50), a heel-lance group with a small lancet (SL) (n = 50), or a large lancet (LL) (n = 20). Pain reactions were assessed by the Neonatal Facial Coding System (NFCS). The latency and duration of the first cry as well as the total screaming time was analyzed. The efficacy of the method was assessed by the time taken to complete the PKU test and number of times the skin had to be punctured.', 'Nociceptive response. The NFCS scores after the first skin puncture were: VP, 247; SL, 333; and LL, 460. The NFCS scores were significantly lower in the VP than in the groups subjected to heel lancing. During the first 60 seconds after skin puncture, 44% of the infants cried in the VP group, compared with 72% and 85% in the SL and LL groups, respectively. Efficacy. A successful PKU test with only one skin puncture was performed in 86% of the VP group, but in only 19% in the SL group and 40% in the LL group. The total time needed to obtain the PKU blood sample was 191 seconds (median) in the VP group, 419 seconds in the SL group, and 279 seconds in the LL group.'] Is venipuncture more effective and less painful than heel lancing for blood tests in neonates? | qiaojin/PubMedQA | 2 | [
-1.4634900093078613,
-1.5827385187149048,
2.0150997638702393
] |
['Premature infants are susceptible to bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy that appears to be caused in part by oxidative stress from hyperoxia. To investigate the possible role of nitric oxide-derived oxidants such as peroxynitrite in the etiology of BPD, we measured levels of plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with proteins.', "Ten premature infants who developed BPD, defined as requiring supplemental oxygen beyond 36 weeks' postmenstrual age, were identified retrospectively from a group of subjects enrolled in a clinical trial of antenatal therapy. Serial plasma samples had been collected on these infants during the first month of life as part of the trial. Sixteen comparison premature infants were identified from the same population: 5 had no lung disease, 6 had respiratory distress syndrome that resolved, and 5 had residual lung disease at 28 days of life that resolved by 36 weeks' postmenstrual age. Plasma 3-nitrotyrosine levels were measured using a solid phase immunoradiochemical method.", 'All 3-nitrotyrosine values in infants without BPD were <0.25 ng/mg protein, and levels did not change with postnatal age. Plasma 3-nitrotyrosine concentrations were significantly higher in infants with BPD, increasing approximately fourfold during the first month of life. For the 20 infants who had blood samples available at 28 days of life, plasma 3-nitrotyrosine levels correlated with the fraction of inspired oxygen that the infant was receiving (r = 0.7).'] Is plasma 3-nitrotyrosine elevated in premature infants who develop bronchopulmonary dysplasia? | qiaojin/PubMedQA | 2 | [
-1.6816898584365845,
-1.4748334884643555,
2.173381805419922
] |
['To determine the clinical, hormonal, and biochemical effects of 4-6 months of metformin therapy in obese patients with polycystic ovary syndrome (PCOS).', 'Prospective study.', 'The Gynecological Endocrine Unit of University Central Hospital, Oulu, Finland.', 'Twenty obese patients with PCOS.', 'Patients were treated with 0.5 g of metformin three times daily for 4-6 months.', 'Clinical symptoms, menstrual pattern, and hirsutism, as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, and lipids were assessed during the treatment.', 'Eleven women (68.8% of the women with menstrual disturbances) experienced more regular cycles during therapy. No changes in hirsutism, body mass index, or blood pressure occurred. The mean testosterone level was decreased significantly after 2 months of treatment but returned to the starting level by 4-6 months. Free testosterone levels decreased significantly during the treatment. There was no significant change in the levels of other sex steroids or lipids measured at 4-6 months of treatment.'] Does metformin therapy improve the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome? | qiaojin/PubMedQA | 2 | [
-2.3707854747772217,
-0.942999541759491,
2.3224053382873535
] |
['The present investigation examined the speech perception skills of pediatric cochlear implant users who changed from their original speech processors and strategies to the Spectral Peak (SPEAK) strategy.', "A within-subjects design was used to compare individual subject's performance using the SPEAK strategy with that obtained with their previous speech strategy (FOF1F2 or Multipeak) in this retrospective study. The subjects demonstrated a wide range of perceptual abilities and had used a cochlear implant for varying lengths of time before converting to the SPEAK strategy.", 'Nine of the 11 subjects showed significant improvement on at least one of the open-set word recognition measures, whereas two subjects showed no change on any of the open-set measures when using the SPEAK strategy.'] Do the effects of processor strategy on the speech perception performance of pediatric nucleus multichannel cochlear implant users? | qiaojin/PubMedQA | 2 | [
-2.4593665599823,
-0.4066927134990692,
1.9490305185317993
] |
['Apoptosis in vivo has been identified in developing cartilage from embryonic chick sterna and avian and murine growth plates. To date, no evidence exists that chondrocytes in articular cartilage undergo apoptosis.', 'We examined the distribution of cells demonstrating fragmented DNA in the articular knee cartilage of C57BL/6 mice (aged 11, 18, 24, and 30 months) and Wistar rats (aged 6, 12, and 24 months) using a DNA end-labeling technique.', 'Control experiments utilizing retinoic acid-induced apoptosis in a chondrocyte cell line, established that DNA end-labeling correlated with DNA ladder formation. In vivo, apoptotic cells were detected in articular cartilage tissue in both species examined. The percentage of apoptotic cells increased significantly (P < 0.05 with age) for all joint surfaces in both species. No significant difference was found between the medial and lateral or femoral and tibial joint surfaces of the knee. Apoptotic cells were observed in both the calcified and uncalcified regions of the articular cartilage of C57 mice. In the rat, only the calcified region of articular cartilage contained apoptotic cells.'] Does chondrocyte apoptosis increase with age in the articular cartilage of adult animals? | qiaojin/PubMedQA | 2 | [
-2.2738001346588135,
-1.1233916282653809,
2.444840669631958
] |
['There is a high incidence of varicocele or dilatation of the spermatic vessels associated with reflux in the male population varying, according to statistics, from 4.5 to 30.7%. Among the numerous hypotheses put forward to explain infertility in approximately 50% of patients with varicocele, it has recently been shown that there is an increased concentration of noradrenalin in the spermatic vessel which might be responsible for chronic arterial vasoconstriction affecting the gonads, leading to endothelial hyperplasia and consequent infertility.', 'In this study the authors have evaluated the bilateral flow of spermatic arteries at the level of the scrotum in patients with varicocele and in the healthy (varicocele-free) population with normal and hypospermatogenesis.', 'In all groups and in the absence of other major pathologies (including arterial hypertension), no significant differences were found in systolic peak velocity (SPV) in relation to the presence or otherwise of varicocele and the degree of reflux. Mean SPV ranged between 3.5 and 4 cm/sec in patients with hypo- and/or normal zoospermia both in the varicocele and healthy population.'] Do [ Volocimetric evaluation of spermatic vessels with echo color doppler in patients with idiopathic varicocele ]? | qiaojin/PubMedQA | 2 | [
-2.472935438156128,
-1.1786761283874512,
2.7454094886779785
] |
['To examine early midtrimester amniotic fluid for its significance in pregnancy outcomes, especially with connection to the pathogenesis of preeclampsia.', 'A prospective, nested, case-control study was conducted. Fetal fibronectin in early midtrimester (16-20 weeks gestation) amniotic fluid was measured by EIA method. Results were compared by their pregnancy outcomes.', 'Amniotic fluid levels of fetal fibronectin were significantly higher in the group subsequently developing severe preeclampsia (106.8 +/- 13.2 micrograms/ml, mean +/- SD, n = 12) compared with matched controls (66.7 +/- 7.1 micrograms/ml, n = 12) (p < 0.05).'] Is elevated fetal fibronectin in midtrimester amniotic fluid involved with the onset of preeclampsia? | qiaojin/PubMedQA | 2 | [
-1.8985408544540405,
-1.4400482177734375,
2.455359697341919
] |
['We hypothesized that the hyperexcitability of occipital cortex neurons may predispose migraine subjects to develop spreading depression, the putative basis of migraine with aura (MwA). To date there is no direct physiologic correlate confirming this in patients. Accordingly, we evaluated the differences in the threshold of occipital cortex excitation between MwA patients and normal controls (C) using transcranial magnetic stimulation (TMS).', 'TMS was performed using the Cadwell MES 10 stimulator. A circular coil 9.5 cm in diameter was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulation intensity was then fine-tuned to determine the threshold at which phosphenes were just visualized.', 'Eleven MwA patients, mean age 37 +/- 7 years, were compared with 11 C, mean age 37.7 +/- 7 years. The difference in the proportion of subjects with phosphene generation between MwA patients and C was significant (MwA patients 100% versus C 27.3%, p = 0.001). The mean threshold level for MwA patients was 44.2 +/- 8.6 versus 68.7 +/- 3.1 for C (p = 0.0001). All threshold levels for MwA patients were lower than the lowest threshold for C; the MwA patient with the lowest threshold had an aura after stimulation.'] Does transcranial magnetic stimulation confirm hyperexcitability of occipital cortex in migraine? | qiaojin/PubMedQA | 2 | [
-1.3914717435836792,
-1.5862928628921509,
1.9446468353271484
] |
['Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer.', 'At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery.', 'Absent or severely reduced expression of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038).'] Does reduced expression of plakoglobin indicate an unfavorable prognosis in subsets of patients with non-small-cell lung cancer? | qiaojin/PubMedQA | 2 | [
-2.314471960067749,
-1.4473206996917725,
2.8237721920013428
] |
['It is not clear whether the laparoscopic approach does decrease the incidence of postoperative infectious complications after appendectomy.', 'One hundred sixty-nine patients were randomized, 87 with laparoscopic (LA) and 82 with open appendectomy (OA). Patients in the OA group had a McBurney incision; LA was performed in the lithotomy position.', 'Acute appendicitis was confirmed in 75% of patients. The appendix was perforated in 5 patients of the LA versus 2 patients of the OA group. No conversion to the open procedure was necessary. The median operating time was 35 minutes in the LA group and 31 minutes in the open group (P = 0.58). The median postoperative hospital stay was shorter after laparoscopic than after open surgery (3 days versus 4 days, P = 0.026), whereas the time required for return to work was not significantly different (14 versus 15 days). There were 5 (6%) patients with superficial wound infection following LA and 6 (7%) after OA (P = 0.67). Intra-abdominal fluid collections were found in 2 (2%) patients following LA and 3 (4%) patients following OA (P = 0.60). In the LA group, 3 patients presented with intra-abdominal hemorrhage and another 3 developed a paralytic ileus that was treated conservatively.'] Does laparoscopic appendectomy change the incidence of postoperative infectious complications? | qiaojin/PubMedQA | 2 | [
-1.7620811462402344,
-1.20327627658844,
1.980690598487854
] |
['The purpose of this study was to examine the dimensions of physician work satisfaction across a variety of medical specialties and practice settings.', "A modified version of the Scheckler et al survey instrument was mailed to all physicians in Marion County, Indiana. Forty-two percent (777) of the eligible physicians responded. Exploratory factor analysis and internal consistency measures were used to assess the instrument's validity and reliability. Multivariable linear regression was used to predict global and summary scale scores.", 'Four dimensions of physician work satisfaction were identified: relationships with patients (k = 6, alpha = 0.81), autonomy in clinical decision-making (k = 8, alpha = 0.81), office resources (k = 7, alpha = 0.87), and professional relationships (k = 5, alpha = 0.82). Most (73%) of the physicians were satisfied with their overall practice, and the majority were also satisfied with their income. Significant differences were observed in the sources and magnitude of physician work satisfaction across medical specialty, practice setting, and financial arrangement. Physicians in private practice were most satisfied with their overall practice and office resources, whereas physicians in health maintenance organizations (HMOs) were most satisfied with their autonomy in clinical decision-making. Physicians not working in HMOs but having a large percentage of patients with capitated reimbursement were not enthusiastic about the effect of managed care on their medical practice. Among primary care physicians, family practitioners and general internists were generally less satisfied, and general pediatricians were generally more satisfied with most aspects of their medical practices.'] Does dimensions and correlate of physician work satisfaction in a midwestern city? | qiaojin/PubMedQA | 2 | [
-1.1973893642425537,
0.24361976981163025,
0.253787636756897
] |
['Clinical hypothyroidism has been associated with prolonged survival in several types of malignancies, but the mechanism of this effect is unknown.', 'In vitro studies of thyroid hormone depletion (via culture in medium containing 5% thyroid hormone-depleted fetal bovine serum (FBS)) were carried out using a human glioblastoma cell line (WITG3) which expresses a mutant, non-functional p53.', 'Thyroid hormone depletion inhibited WITG3 proliferation compared to control medium containing 5% euthyroid FBS. There was no evidence of apoptosis and viability was not compromised. Cell cycle analysis by flow cytometry indicated that thyroid hormone depletion accumulated WITG3 cells in G1, with fewer cells progressing into S than in euthyroid medium. By immunoblotting, p21 (WAF1/CIP1) was only slightly detectable in lysates from WITG3 cells grown in control euthyroid medium; however, in thyroid hormone-depleted FBS, a marked induction of p2 1 occurred which could be reversed by exogenous thyroid hormone'] Does thyroid hormone depletion inhibit astrocytoma proliferation via a p53-independent induction of p21 ( WAF1/CIP1 )? | qiaojin/PubMedQA | 2 | [
-2.3891966342926025,
-1.3806304931640625,
2.842395782470703
] |
['To examine the effects of a weight training program on the resting metabolic rate, fat-free mass, strength, and dietary intake of untrained young women.', 'A 12-week weight training program was completed by 20 previously untrained women aged 19 through 44 years.', 'Twenty-three study subjects and 14 control subjects were recruited on a volunteer basis. Twenty study subjects and 10 control subjects completed the study.', 'Study subjects participated in a 12-week moderate-intensity, progressive resistance weight training program consisting of 2 supervised sessions per week with 6 types of lifting exercises per session. Resting metabolic rate, fat-free mass, strength, and dietary intake were measured before and immediately after the study.', 'Repeated measures analysis of variance and t tests (unequal variance and paired) were used to determine interaction effects and differences within and between groups.', 'The study group increased their fat-free mass (mean+/-standard deviation) from 44.2+/-5.4 kg to 46.2+/-6.0 kg (P<.001). Elbow flexion, elbow extension, and knee flexion strength all increased from 28.9+/-5.3 to 34.5+/-3.8, 16.9+/-4.9 to 22.1+/-5.3, and 39.5+/-8.6 to 48.6+/-7.3 ft-lb, respectively (P<.001). Percent body fat decreased from 29.8+/-2.8 to 27.2+/-2.6 (P<.001) without a significant change in body weight. Resting metabolic rate did not change significantly (P>.05).'] Does weight training increase fat-free mass and strength in untrained young women? | qiaojin/PubMedQA | 0 | [
0.13556665182113647,
-0.6681936383247375,
-0.34919458627700806
] |
['Nausea and vomiting during spinal anaesthesia for caesarean section are common and unpleasant complications. This study was undertaken to evaluate the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, for prophylactic treatment of nausea and vomiting in parturients undergoing nonemergent caesarean section under spinal anaesthesia.', 'In a randomized, double-blind, placebo-controlled trial, 100 patients, 21-38 years, received either placebo (saline) or granisetron at 3 different doses (20 micrograms.kg-1, 40 micrograms.kg-1 or 80 micrograms.kg-1) (n = 25 for each) intravenously immediately after clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments were performed during spinal anaesthesia for caesarean section.', "The treatment groups were similar with regard to maternal characteristics and operative management. The incidence of nausea and vomiting was 64%, 52%, 14% and 12% after administration of placebo and granisetron in a dose of 20 micrograms.kg-1, 40 micrograms.kg-1 and 80 micrograms.kg-1, respectively (P < 0.05; overall Fisher's exact probability test). No clinically important adverse effects were observed in any group."] Does granisetron prevent nausea and vomiting during spinal anaesthesia for caesarean section? | qiaojin/PubMedQA | 2 | [
-1.9144684076309204,
-1.5141675472259521,
2.5254933834075928
] |
['Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates.', 'Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays.', 'Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA-seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA.'] Does transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrate of C1 inhibitor? | qiaojin/PubMedQA | 2 | [
-1.4337379932403564,
-1.6914448738098145,
2.0881824493408203
] |
['Diminished postprandial portal hyperemia has been demonstrated by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic role is unclear. This prospective study was therefore undertaken in patients with varying severity of portal hypertension and degree of liver cirrhosis.', 'Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Hemodynamic parameters were related to the degree of esophageal varices, variceal bleeding, portal hypertensive gastropathy and Child-Pugh score.', 'The postprandial portal blood velocity increment was low in patients with esophageal varices of any degree (22-24%), compared to patients without varices (49%, p<0.01) and healthy controls (65%, p<0.001), but was not different in patients with or without variceal bleeding (22% vs. 20%). In contrast, the congestion index (CI; ratio of portal vein cross-sectional area and portal blood velocity) pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/-0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive gastropathy was not related to any of the portal flow parameters. The portal blood velocity increment was comparable in controls (65%) and patients with Child-Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease in congestion index in patients with the most severe cirrhosis (p<0.01 class C vs. class A and B).'] Is the postprandial portal flow related to the severity of portal hypertension and liver cirrhosis? | qiaojin/PubMedQA | 2 | [
-1.8250712156295776,
-1.518859624862671,
2.3907763957977295
] |
['Biliary proteins are promoters of cholesterol crystallization in artificial model bile. However, their pathogenic importance for cholesterol precipitation in native gallbladder bile (GB) is uncertain. The aim of this study was to evaluate the significance of biliary lipids and proteins on cholesterol crystal detection time (ChCDT) of GB in patients with gallstones.', 'ChCDT and concentrations of lipids, albumin, mucins, aminopeptidase N, alpha1-acid glycoprotein, haptoglobin, and immunoglobulins (Igs) were measured in GB of 92 patients, 52 of whom had cholesterol gallstones.', 'ChCDT was markedly reduced in gallstone patients. Compared with patients without gallstones, they had a significant increase in cholesterol saturation and total protein, albumin, mucin, and IgG biliary concentrations. In univariate analysis, ChCDT of GB was significantly correlated with cholesterol saturation and total lipid, protein, Ig, aminopeptidase N, and alpha1-acid glycoprotein concentrations. However, stepwise logistic regression analysis showed that only cholesterol saturation independently correlated to ChCDT. Gallbladder inflammation correlated with the concentration of Igs, but subtraction of IgG from GB did not modify the ChCDT.'] Is cholesterol saturation , not proteins or cholecystitis , critical for crystal formation in human gallbladder bile? | qiaojin/PubMedQA | 2 | [
-2.2540290355682373,
-1.3509716987609863,
2.638301372528076
] |
['To determine the value of plasma HIV-1 RNA and CD4 cell count as predictors of the clinical benefit of antiretroviral treatment.', 'The CAESAR (Canada, Australia, Europe, South Africa) trial randomized 1840 patients [inclusion CD4 cell count, 25-250 x 10(6)/l] to add either placebo, lamivudine (3TC) or 3TC plus loviride in a double-blinded fashion to baseline treatments (zidovudine, zidovudine-didanosine or zidovudine-zalcitabine) for 1 year.', 'This analysis included 487 patients with data on CD4 cell count and HIV-1 RNA after 12-20 weeks of treatment and subsequent follow-up for clinical progression.', 'The correlation between 12-20-week change in CD4 cell count, HIV-1 RNA and progression to AIDS or death in the placebo group was used to predict the clinical benefit of the 3TC-containing arms of the trial, given their effects on CD4 cell count and HIV-1 RNA.', 'After 12-20 weeks of treatment, HIV-1 RNA fell by 0.37 log10 copies/ml in the 3TC arms versus a rise of 0.05 log10 copies/ml in the placebo arm. The 12-20-week CD4 cell count rose by 35 x 10(6)/l in the 3TC arm versus a fall of 8 x 10(6)/l in the placebo arm. After 12-20 weeks of treatment, a reduction in HIV-1 RNA of 1 log10 at 12-20 weeks predicted a 49% reduction in progression [hazard ratio (HR), 0.51; 95% confidence interval (CI), 0.30-0.87] and a rise in CD4 cell count of 50 x 10(6)/l predicted a 51% reduction in progression (HR, 0.49; 95% CI, 0.33-0.73). Using the model from the placebo arm, the rises in CD4 cell count and reductions in HIV-1 RNA during 3TC treatment predicted a 59% reduction in progression to AIDS or death. The observed clinical benefit was a 57% reduction in progression for the 3TC arms versus placebo (HR, 0.43; 95% CI, 0.26-0.71).'] Are the effects of lamivudine treatment on HIV-1 disease progression highly correlated with plasma HIV-1 RNA and CD4 cell count? | qiaojin/PubMedQA | 2 | [
-1.4618109464645386,
-1.6171019077301025,
2.1177010536193848
] |
['The relation between psychosomatic and psychosocial symptoms and blood pressure was studied in Swedish schoolchildren.', 'Blood pressure was measured in 122 healthy Swedish schoolchildren, aged 6-16 years. Psychosomatic and psychosocial symptoms, delinquent behaviour, parental health and employment status were assessed.', 'Children with systolic blood pressure above + 1 SD of mean reported significantly less symptoms (x = 1.4) than children with blood pressure below -1 SD of the mean (x = 2.7; p < 0.05). Children with three or more self-reported symptoms had significantly lower blood pressure than children without symptoms both in the supine (110 +/- 12 vs. 120 +/- 18 mm Hg; p < 0.05) and in the standing position (117 +/- 17 vs. 127 +/- 18 mm Hg; p < 0.05).'] Are psychosomatic and psychosocial symptoms associated with low blood pressure in Swedish schoolchildren? | qiaojin/PubMedQA | 1 | [
-0.5192971229553223,
0.15577104687690735,
-0.4393613636493683
] |
['A number of proteins make up the Cdc28 complex in Saccharomyces cerevisiae, and regulate CDK activity. The cell cycle regulator Nik1 (Hsl1) is a protein kinase that interacts with the Cdc28 complex. The growth inhibitor Gin4 is structurally similar to Nik1 and may play a redundant role in the regulation of the cell cycle. We investigated the functions of Gin4 with respect to those of Nik1.', 'GIN4 was not essential for growth, and cells deficient in the GIN4 gene displayed no obvious defects in cell cycle regulation. The delta(gin)4 delta(nik)1 strain was temperature sensitive and showed an abnormal cell shape and FACS profile at permissive temperatures. GFP-fused Gin4 was localized at the bud-neck from late G1 to the M phase. Over-production of the C-terminal portion of Gin4 was toxic for cell growth, and this domain was required for the bud-neck localization of Gin4-GFP. High copy expression of Gin4-GFP disturbed the bud-neck localization of Gin4 in the abnormally elongated cells. Cytokinesis was defective in the delta(gin)4 cdc28 double mutants. The GST-Gin4 fusion protein physically associates with the Cdc28 complex.'] Is gin4 of S. cerevisiae a bud neck protein that interacts with the Cdc28 complex? | qiaojin/PubMedQA | 2 | [
-2.3875908851623535,
-1.0261919498443604,
2.449591636657715
] |
['To investigate whether immunization with recombinant HIV-1 envelope protein derived from a clinical isolate could protect macaques from infection with an in vivo passaged chimeric simian-human immunodeficiency virus (SHIV).', 'A total of 16 animals were studied from which three groups of four animals were immunized with vaccine formulations of the CC-chemokine receptor-5-binding recombinant gp120 of HIV-1W6.1D. Four weeks after the last immunization, all 16 animals were intravenously challenged with in vivo passaged SHIV derived from the same HIV-1 group B clinical isolate (W6.1D) as the vaccines.', 'Vaccine protection from infection was demonstrated in 10 out of 12 macaques immunized with recombinant gp120. Complete protection from infection was achieved with all of the animals that received the SBAS2-W6.1D formulation, a potent inducer of both T-cell and humoral immune responses. Partial protection was achieved with SBAS1-W6.1D, a formulation based on immunomodulators known to induce T-cell responses in humans. In vaccinated animals that were infected, virus load was reduced and infection was delayed.'] Does a clinically relevant HIV-1 subunit vaccine protect rhesus macaques from in vivo passaged simian-human immunodeficiency virus infection? | qiaojin/PubMedQA | 2 | [
-2.3555572032928467,
-0.9601682424545288,
2.39312744140625
] |
['To determine markers that are associated with the durability of virologic response to therapy with HIV protease inhibitors in HIV-infected individuals.', 'This study encompassed two retrospective analyses of the duration of virologic response to protease inhibitor therapy. The first analysis included 29 patients receiving either monotherapy or combination therapy with the protease inhibitor ritonavir whose plasma HIV RNA levels rebounded from the point of greatest decline with mutations associated with resistance to ritonavir. The second analysis included a cohort of 102 patients who initially responded to randomized treatment with either monotherapy with ritonavir or combination therapy with ritonavir and zidovudine.', 'Durability of response was defined as the time from the initiation of therapy to the point at which plasma HIV RNA displayed a sustained increase of at least 0.6 log10 copies/ml from the nadir value. In the first analysis, durability of response was analyzed with respect to baseline HIV RNA, HIV RNA at the nadir, and the drop in HIV RNA from baseline to the nadir. In the second analysis, time to rebound was examined using Kaplan-Meier analysis, stratifying by either baseline HIV RNA or HIV RNA at the nadir.', 'In both analyses, the durability of response was not highly associated with either baseline RNA or the magnitude of RNA decline from baseline. Instead, a strong relationship was observed between the durability of response and the nadir plasma HIV-1 RNA value (P < 0.01). The nadir in viral load was generally reached after 12 weeks of randomized therapy.'] Is the duration of viral suppression during protease inhibitor therapy for HIV-1 infection predicted by plasma HIV-1 RNA at the nadir? | qiaojin/PubMedQA | 2 | [
-2.026370048522949,
-1.436324119567871,
2.456465244293213
] |
['The incidence of cervical metastases after surgery for Stages I/II carcinoma of the tongue is 30-40%. Postoperative cervical metastases are an adverse prognostic factor for patients with this malignancy. The purpose of this study was to evaluate the clinicopathologic factors associated with late cervical metastases in patients with carcinoma of the tongue.', 'The clinicopathologic features of 44 patients with previously untreated Stage I/II carcinoma of the tongue were reviewed. All patients were treated with partial glossectomy only.', 'Cervical metastases developed in 21 of 44 patients within 5 years. Factors significantly associated with the development of cervical metastases were invasive growth, differentiation, nuclear polymorphism in the deep portion, tumor border, nest formation, infiltrative growth ratio, depth, and thickness. No statistical correlations between cervical metastases and age, gender, tumor location, clinical stage, Brinkman index, alcohol index, mitosis, connective tissue, lymphocytic infiltration, or perineural invasion were found. Multivariate analysis demonstrated that only tumor thickness > 4 mm had a predictive value for cervical metastasis (risk ratio 9.4; 95% confidence interval, 1.5-57.7).'] Does tumor thickness predict cervical metastasis in patients with stage I/II carcinoma of the tongue? | qiaojin/PubMedQA | 2 | [
-2.11323618888855,
-1.4096260070800781,
2.6132733821868896
] |
['Prostate cancer is the most frequent cancer among men in the US. Histological grading is an important part of the diagnostic evaluation aside from clinical staging and serum PSA. The most commonly used grading system is the one described by Gleason. From a prognostic point of view, it is of considerable interest to know how accurate the needle biopsy Gleason score is in predicting the final score of the radical prostatectomy specimen. From an outcome research point of view, it is important to recognize that a stratification of patients by Gleason score may prove correct in patients undergoing radical prostatectomy, while in patients undergoing radiation or conservative management some of the well-differentiated cancers could actually be moderately and poorly differentiated, and some of the moderately differentiated might be poorly differentiated, thus favoring radical prostatectomy in a direct comparison of treatment efficacy. We aimed to determine (1) whether such undergrading exists, (2) what the magnitude of the bias is, and (3) whether it is common and similar in different institutions.', 'We retrospectively reviewed the records of 415 patients who underwent radical prostatectomy in three Dallas area hospitals, excluding patients who received neoadjuvant therapy prior to surgery. Data of Gleason grades and score were collected from the needle biopsy and the radical prostatectomy specimen. Analysis was done using three categorization schemes for mild, moderate and poor differentiation for the three individual hospitals and the entire group.', "The most common Gleason score by needle biopsy and prostatectomy was five. 37.2% of all patients had no change in score assignment, while 12.7% were 'overgraded' and 50.1% 'undergraded' by needle biopsy. The most common undergrading was by 1 or 2 score points. Only 23.7% of the category 'well' cancers remained so after surgery. Between 65.0 and 88.4% of the category 'moderate' cancers remained so after surgery. To determine the degree of agreement between needle biopsy and surgery category, kappa statistics were employed. The kappa value ranged from 0.148 to 0.328 for all categories and classification schemes indicating poor reproducibility. Serum prostate-specific antigen was not helpful in predicting Gleason score upgrading."] Do gleason scores from prostate biopsies obtained with 18-gauge biopsy needles poorly predict Gleason scores of radical prostatectomy specimens? | qiaojin/PubMedQA | 2 | [
-1.615034818649292,
-1.3533875942230225,
1.9908745288848877
] |
['This study aimed to determine whether patients with stage 1 testicular non seminomatous germ cell tumours (NSGCT) with high vascular density have a greater risk of disease recurrence than those with a low vascular density.', 'Orchidectomy specimens from 42 patients with stage 1 NSGCT, treated by orchidectomy and surveillance alone, were studied. Vessel density was counted in tumour sections immunohistochemically stained for CD34. The mean of the three highest counts (x250, field size 0.67 mm2) for each tumour was used. Tumour vessel density was very similar for relapsing and non relapsing patients. Vascular invasion was the only variable significantly predictive of disease recurrence at 2 years post-orchidectomy (P = 0.025). There was wide variation of vessel counts between different blocks of a tumour, compared with interobserver variation. The tumour tissue type in the area of highest vessel density was embryonal carcinoma in 50% and teratoma (mature or immature) in 38%.'] Does vascular density predict future metastatic disease in clinical stage 1 non-seminomatous germ cell tumours of the testis? | qiaojin/PubMedQA | 2 | [
-1.99639093875885,
-1.3863177299499512,
2.5029499530792236
] |
['Recent reports suggest that genetic examination of K-ras or p53 mutation is more sensitive for the detection of occult lymph node metastasis in colorectal carcinomas than conventional examination by haematoxylin and eosin (H & E) staining or immunohistochemistry for gene products. The aim of this study was, first, to define the microscopic characteristics of metastatic cancer cells in lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8 and 18, and, second, to compare the detection rate of occult lymph node metastasis for immunohistochemical vs genetic methods.', 'K-ras mutations were first examined in primary tumours of seven cases which showed distant metastasis or local recurrence within 5 years of the initial surgery in spite of the original reporting of no lymph node metastasis by routine H & E staining. K-ras mutations were positive in three cases in primary tumours and lymph nodes, and the remaining four primary tumours were negative for p53 mutation as well as K-ras mutation. Therefore, genetic analysis of occult lymph node metastasis was uninformative, but occult metastasis was detected by cytokeratin staining in two of these four cases. Comparative study of cytokeratin-positive cells was performed on each of the 43 lymph nodes from three cases with K-ras mutations. Cancer cells were detected in 28 of the 43 lymph nodes (65.1%) by cytokeratin staining and in 10 of the 43 corresponding lymph nodes (23.3%) by genetic analysis. Artefactual contamination by cancer cells was present in eight of the 28 cytokeratin positive lymph nodes, and three of the eight nodes were genetically positive.'] Is immunoperoxidase staining for cytokeratins 8 and 18 very sensitive for detection of occult node metastasis of colorectal cancer : a comparison with genetic analysis of K-ras? | qiaojin/PubMedQA | 2 | [
-2.169581174850464,
-1.3944158554077148,
2.629863977432251
] |
['To investigate long-term regulation of leptin expression in adipose tissues of obese JCR:LA-corpulent rats, which have been shown to overexpress leptin.', 'Manipulation of adipose tissue growth in obese rats by dietary restriction.', 'Weanling female obese rats were maintained on 1 of 3 diets until 8 months old. One group was allowed to feed ad libitum, the second was pair-fed with lean rats, and the third had food intake restricted to maintain weights equal to those of age-matched lean rats.', 'Body and fat pad weights, leptin messenger RNA (mRNA) levels, and size and number of adipocytes in retroperitoneal fat pads.', 'Adipose tissue mass was increased 6-fold in the obese rats compared with the lean ones, despite equal body weight and intake restriction that was sufficient to impair growth. Although leptin mRNA level was down-regulated by intake restriction, it was still twice as elevated in the obese rats as in the lean ones, and was highly correlated with specific fat pad mass and adipocyte number, but not with size.'] Is long-term regulation of leptin expression correlated with adipocyte number in obese rats? | qiaojin/PubMedQA | 2 | [
-2.5651628971099854,
-0.14425313472747803,
1.7757620811462402
] |
["Pigeon fanciers' lung (PFL) is a form of extrinsic allergic alveolitis. Affected individuals produce antibodies to various pigeon antigens, and the resulting immune complexes are thought to initiate the disease. However, high antibody titres also occur in some asymptomatic individuals. Previously attention has focused on protein antigens, but we have recently identified pigeon intestinal mucin as a novel antigen in PFL.", "To determine the relationship between IgG subclass antibodies to pigeon intestinal mucin and the development of pigeon fanciers' lung.", 'Sera were collected from 250 pigeon fanciers, who also completed a clinical questionnaire. Sera were screened for precipitating antibodies to pigeon serum and droppings. Individuals with symptoms and precipitating antibodies were considered to have classical PFL. Serum IgG and IgG subclass antibodies to pigeon intestinal mucin and pigeon serum proteins were investigated by quantitative enzyme-linked immunosorbent assay (ELISA).', 'Very high titres of IgG antibodies against pigeon mucin were found in all precipitin-positive individuals. A strong positive correlation was seen between titres of antibodies to mucin and to serum proteins, but this was not due to crossreactivity. No significant differences in IgG titres to either mucin or pigeon serum proteins were found between individuals with PFL and asymptomatic precipitin positive fanciers. IgG1 and IgG2 were the major subclasses of anti-mucin, with lower titres of IgG3. Patients with PFL had significantly higher titres of IgG1 to mucin than asymptomatic, precipitin-positive individuals. In contrast, no significant differences were seen between PFL and asymptomatic precipitin-positive sera with respect to the subclass titres against pigeon serum proteins.'] Are igG subclass responses to pigeon intestinal mucin related to development of pigeon fanciers ' lung? | qiaojin/PubMedQA | 2 | [
-2.0826256275177,
-1.3841452598571777,
2.512411117553711
] |
['Grass group I consists of very potent allergenic components which are found in the pollen of all temperate grasses. Several post-translational modifications are predicted from the cDNA data.', 'The aim of this study was to identify sequential IgE-binding sites on the allergen Phl p 1 and to determine their influence on IgE reactivity.', 'Based on cDNA data and microsequencing results we synthesized overlapping decapeptides covering the complete Phl p 1 molecule and tested them for immunological reactivity by means of the PEPSCAN technique. In a dot test we determined the frequency of IgE reactivities to post-translationally modified structures (hydroxylated proline residues, carbohydrate structure, and disulphide formations).', 'Screening by overlapping peptides demonstrated an IgE binding site on the 10 N-terminal amino acids. Comprehensive studies showed that the two hydroxyproline residues of the native Phl p 1 allergen (at positions 5 and 8) and the N-glycan (at position 9) can result in an increased IgE reactivity; 3.3% of the sera exclusively bound to the hydroxyproline bearing peptide, while only 0.4% bound to the proline containing peptide. With regard to glycosylation, we estimated that 20% of sera recognized protein and carbohydrate epitopes, while one serum exclusively bound to the glycan. The formation of disulphide bonds has no detectable effect on the IgE reactivity to Phl p 1.'] Do post-translational modifications influence IgE reactivity to the major allergen Phl p 1 of timothy grass pollen? | qiaojin/PubMedQA | 2 | [
-2.13603138923645,
-1.3882616758346558,
2.558156967163086
] |
['Laboratory experiments suggest that endogenous opioids inhibit blood pressure responses during psychological stress. Moreover, there seem to be considerable individual differences in the efficacy of opioid blood pressure inhibition, and these differences may be involved in the expression of risk for cardiovascular disease. To further evaluate the possible role of opioid mechanisms in cardiovascular control, the present study sought to document the effects of the long-lasting oral opioid antagonist naltrexone (ReVia, DuPont, Wilmington, DE) on ambulatory blood pressure responses during naturally occurring stress.', 'Thirty male volunteers participated in a laboratory stress study using naltrexone followed by ambulatory blood pressure under placebo and during the subsequent 24-hour period. Within-subject analyses were performed on ambulatory blood pressures under placebo and naltrexone conditions.', 'Laboratory results indicate no significant group effects of naltrexone on blood pressure levels or reactivity. Ambulatory results indicate that during periods of low self-reported stress, no effect of opioid blockade was apparent. In contrast, during periods of high stress, opioid blockade increased ambulatory blood pressure.'] Do endogenous opioids inhibit ambulatory blood pressure during naturally occurring stress? | qiaojin/PubMedQA | 2 | [
-2.6106631755828857,
-0.8467023968696594,
2.5585198402404785
] |
['Epinephrine-containing test doses for detection of intravascular injection during epidural anesthesia may be unreliable or hazardous in beta-blocked, elderly, or pregnant patients. Subtoxic injections of lidocaine have been used as an alternative marker of intravascular injection in unpremedicated patients. We studied two groups of premedicated patients and unpremedicated subjects to evaluate the reliability of the local anesthetics bupivacaine (B) and 2-chloroprocaine (2-CP) as test dose injections.', 'Thirty ASA I and II subjects received blinded randomized injections of 2-CP, B, or normal saline via a peripheral vein.', 'In group I, 10 healthy unpremedicated volunteers universally recognized injection of 90 mg 2-CP or 25 mg B, but did not reliably detect the injection of 60 mg 2-CP. In group II, 20 patients premedicated with 1 microg/kg fentanyl and 30 microg/kg midazolam could not reliably detect similar injections. Sixteen responded to the injection of 90 mg 2-CP, while 13 detected the 25 mg B test dose. A blinded observer rated only 12 of the subjective reports as conclusive of detection of intravascular injection after each drug. There were no false-positive reports in any group.'] Are 2-Chloroprocaine and bupivacaine unreliable indicators of intravascular injection in the premedicated patient? | qiaojin/PubMedQA | 2 | [
-2.017139434814453,
-1.4731688499450684,
2.557579278945923
] |
['Macrophage subpopulations are differentially activated during sepsis, shock, or trauma; however, it is unknown whether inherent mechanistic and phenotypic differences exist between macrophage subpopulations that may account for region-specific inflammation. We hypothesized that macrophage expression/function of protein kinase C (PKC) isoforms is tissue specific (alveolar versus peritoneal). Rat alveolar and peritoneal macrophages were each probed for the expression of PKC isoforms alpha, beta1, beta2, gamma, delta, epsilon, zeta, and theta by immunoblot. PKC isoforms alpha, beta1, beta2, and zeta were detected in both populations; however, isoforms epsilon, gamma, and eta were found in alveolar macrophages only. To investigate the functional role of the Ca2+-dependent PKC (cPKC) versus Ca2+-independent PKC (nPKC) isoforms, pan-PKC isoform inhibition (cPKC and nPKC), or cPKC isoform selective inhibition (alpha, beta1, beta2, gamma) was performed before endotoxin (lipopolysaccharide, Salmonella minnesota, 100 ng/mL) stimulation in vitro. Pan-PKC isoform inhibition attenuated TNFalpha and IL-1beta production by each population; however, selective cPKC (alpha, beta1, beta2, gamma) inhibition decreased peritoneal, but not alveolar, macrophage TNFalpha production. IL-1beta production was not affected by cPKC inhibition in either population.'] Do tissue-specific protein kinase C isoforms differentially mediate macrophage TNFalpha and IL-1beta production? | qiaojin/PubMedQA | 2 | [
-2.337634801864624,
-1.383991003036499,
2.7717974185943604
] |
['Not only the facilitation of inhibitory synapses but also the suppression of excitatory synapses may be effective in treating convulsion induced by local anesthetics. The effects of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, on bupivacaine-induced convulsion and hemodynamic changes were studied.', 'Cortex and hippocampal (A4; L5.5; H8) electroencephalogram (EEG), heart rate, and mean arterial pressure were measured in 21 cats anesthetized with urethane. Blood samples were obtained when cats demonstrated arrhythmias, convulsed, and became hypotensive. In the control group (n = 7), bupivacaine was continuously infused until a hypotensive state of 40 mm/Hg was reached. In the MK-801 pretreated group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously 15 minutes before the bupivacaine injection. In the MK-801 treatment group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously at the appearance of convulsive EEG after the bupivacaine injection.', 'Bupivacaine produced convulsion in the control group (17.1 +/- 2.4 microg/mL), but not in the MK-801 pretreated group. In the treatment group, convulsive EEG was suppressed gradually after injection of MK-801. The mean plasma bupivacaine concentrations (microg/mL) reaching arrhythmia and hypotension were 9.5 +/- 2.9 and 23.0 +/- 3.0, respectively, in the control group; 10.9 +/- 3.5 and 22.5 +/- 4.9, respectively, in the MK-801 pretreated group; and 7.5 +/- 1.6 and 21.0 +/- 3.0, respectively, in the MK-801 treatment groups. The mean arterial pressure and heart rate did not differ among the three groups.'] Is bupivacaine-induced convulsion suppressed by MK-801? | qiaojin/PubMedQA | 2 | [
-1.8808945417404175,
-1.5652859210968018,
2.4479594230651855
] |
['Postoperative nausea and vomiting after anesthesia is an distressing side effect. This study was undertaken to determine to what extent spinal opioids contribute to postoperative nausea and vomiting (PONV) and secondly to how effectively metoclopramide can reduce the incidence of PONV after intrathecal administration of morphine.', 'Patients were allocated to three groups all undergoing major joint surgery of the lower limb. In group 1 (n = 200), intrathecal anesthesia was assessed by administration of 20 mg bupivacaine and 0.2 mg morphine. In Group 2 (n = 100) intrathecal anesthesia was assessed in the same way and in addition, 20 mg metoclopramide intramuscular during maintenance of anesthesia and a second dose of 20 mg metoclopramide was administered intramuscular after arrival at the recovery room. Finally, in group 3 (n = 100), intrathecal anesthesia was assessed after administration of 20 mg bupivacaine.', 'The maximum PONV percentages were 41.1%, 32.7%, and 37% in groups 1, 2, and 3, respectively. The consumption of antiemetics was similar in all groups. The number of patients who needed one or more additional antiemetics during the first 24 hours after surgery was 112 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, and 3, respectively.'] Is intrathecal addition of morphine to bupivacaine the cause of postoperative nausea and vomiting? | qiaojin/PubMedQA | 2 | [
-1.0484312772750854,
-1.625631332397461,
1.6498435735702515
] |
['Focal glomerulosclerosis (FGS) is characterized by the accumulation of mesangial matrix and lack of mesangial cells (MC). We studied the role of glomerular hypertension (GH) in the development of MC hypoplasia.', 'We used an in vitro model of GH to study the effect of GH on MC apoptosis. Cultured rat endothelial cells were grown in the intracapillary space and MCs were grown in the extracapillary space. MC proliferation as well as apoptosis was evaluated under simulated normal glomerular pressure (SNGP) as well as simulated glomerular hypertension (SGH). Apoptosis was determined morphologically by DNA fragmentation using Hoechst staining as well as with the use of DNA gel electrophoresis. MCs grown under SNGP and SGH were also evaluated for the expression of genes associated with active cell death. In addition, we evaluated the effect of direct applied pressure on MC apoptosis.', 'MCs grown under SGH were less elliptical and had a tendency to develop a dome in the center. Direct applied pressure promoted MC apoptosis in a dose and time dependent manner. DNA gel electrophoresis from MCs grown under SGH also showed integer multiples of 180 base pairs (ladder pattern); whereas cells grown under SNGP showed no DNA fragmentation. SGH increased mRNA expression of cathepsin-B (SNGP, 0.31 +/- 0.04 vs SGH, 0.57 +/- 0.03, P < 0.01, n = 3) and SGP-2 (SNGP, 0.55 +/- 0.05 vs SHG, 1.08 +/- 0.12, P < 0.01, n = 3) in MCs when compared to cells grown under SNGP.'] Does simulated glomerular hypertension promote mesangial cell apoptosis and expression of cathepsin-B and SGP-2? | qiaojin/PubMedQA | 2 | [
-1.7840455770492554,
-1.5531888008117676,
2.2798845767974854
] |
['The pS2 protein is involved in the maintenance of the integrity of the gastrointestinal tract. In breast cancer pS2 can be demonstrated in at least half of the tumors and probably reflects the functional status of ER. Several features make it likely that pS2 is involved in growth regulation.', 'We have investigated the value of immunohistochemical pS2 determination as a prognostic factor in 339 breast cancer patients with long follow-up from one hospital.', 'A prognostic role for pS2 could not be demonstrated considering disease-free and overall survival, although in pS2-negative tumors a trend for less locoregional relapse was found. However, in multivariate analysis pS2 showed independent prognostic value for post-relapse survival.'] Is pS2 an independent prognostic factor for post-relapse survival in primary breast cancer? | qiaojin/PubMedQA | 2 | [
-2.346036672592163,
-0.9422337412834167,
2.4279184341430664
] |
['To assess hematologic recovery and procedure-related mortality in patients who received high-dose therapy with stem-cell support, in whom the peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells < 1 x 10(6)/kg). The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC) measurements and the value of bone marrow obtained after PBSC collection failure was assessed.', 'The study group comprised 324 consecutive patients mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and G-CSF alone (14 patients). Between one and four aphereses were performed.', 'In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+ cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but platelet independence was delayed (> 28 days) in eight patients. Of 28 patients with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC alone and five had delayed engraftment. Twelve patients with less than 1 x 10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected after PBSC collection failure. Eleven patients were assessable for engraftment; four patients had slow (> 21 days) or delayed (> 28 days) neutrophil recovery and eight patients had delayed platelet recovery. In the group of patients who received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths.'] Is back-up bone marrow frequently ineffective in patients with poor peripheral-blood stem-cell mobilization? | qiaojin/PubMedQA | 2 | [
-1.31368887424469,
-1.6064884662628174,
1.9026970863342285
] |
['To compare the antiemetic efficacy of a single dose of an oral antiemetic (granisetron 2 mg) with a single dose of an intravenous (i.v.) antiemetic (ondansetron 32 mg) given before cisplatin-based chemotherapy.', 'This was a multicenter, randomized, double-blind, parallel-group study. Patients (N = 1,054) scheduled to receive cisplatin (> or = 60 mg/m2)-based chemotherapy were randomized to receive either 2 mg of oral granisetron tablets 1 hour before chemotherapy (n = 534) or i.v. ondansetron (32 mg) 30 minutes before chemotherapy (n = 520). The primary efficacy end point was total control (no emesis, no nausea, and no use of antiemetic rescue medication) over the initial 24 hours after the start of chemotherapy. Dexamethasone or methylprednisolone were permitted, but not required, as concomitant prophylactic antiemetics.', 'Total control was equivalent 24 hours after cisplatin chemotherapy for single-dose oral granisetron (54.7%) and i.v. ondansetron (58.3%) (95% confidence interval [CI], -9.6 to 2.4). Similar proportions of patients remained nausea-free in the granisetron group (55.4%) and the ondansetron group (59%) (95% CI, -9.6 to 2.4). The rate of complete control of emesis was 61.2% in the granisetron group and 67.1% in the ondansetron group (95% CI, -11.7 to -0.1). Both treatment regimens were well tolerated, with similar patterns of adverse reactions, generally of a mild degree. The most common side effects included constipation (14%), headache (15%), and diarrhea (10%).'] Does single-dose oral granisetron have equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy? | qiaojin/PubMedQA | 2 | [
-1.8430384397506714,
-1.5475060939788818,
2.4650492668151855
] |
['Comorbidity is a frequent and often therapeutically limiting problem in older cancer patients. However, to date, there is no standard measure of the comorbidity burden available for these patients. We tested the performance of two comorbidity scales and their relationship with functional status.', 'The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was compared with the Charlson scale in 203 patients who received a comprehensive geriatric assessment (CGA) in our Senior Adult Oncology Program (SAOP). Study end points were variability, reliability, correlation with Eastern Cooperative Oncology Group (ECOG) performance status (PS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL). The relative weight of comorbidity versus tumor stage in the correlations with functional status was assessed.', 'Median age was 75 years (range, 63 to 91). Sixty-four percent of patients scored 0 on the Charlson scale versus 6% on the CIRS-G. The correlation between the Charlson and CIRS-G was fair (p = 0.25 to 0.39). CIRS-G grade 3/4 had a fair correlation with ADL (p = 0.27). Otherwise, there was low or no correlation between comorbidity and functional status across the measures. Tumor stage was not correlated with functional status either. Correlation of ECOG PS with ADL (p = 0.51)c and IADL (p = 0.61) was moderate. Interrater and test-retest correlations were good or very good for both the Charlson and CIRS-G.'] Are comorbidity and functional status independent in older cancer patients? | qiaojin/PubMedQA | 2 | [
-1.2949830293655396,
-1.5293655395507812,
1.84112548828125
] |
['Bacterial peritonitis is a frequent complication during treatment of end-stage renal failure by continuous ambulatory peritoneal dialysis. Local host defence mechanisms including the secretion of proinflammatory cytokines by peritoneal macrophages are of particular importance in the pathogenesis of infectious complications. LPS-binding protein (LBP) and soluble CD14 (sCD14) are serum factors known to regulate the endotoxin-induced cellular immune response. However, it is still unknown whether LBP and sCD14 are also present in the peritoneal effluent of CAPD patients.', 'Using specific immunoassays, we examined the concentration of LBP, sCD14 and the proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 in the dialysis effluents of 31 patients with CAPD-associated peritonitis. Twenty patients without peritonitis served as controls. Intraperitoneal LPS concentrations were determined using the limulus amebocyte lysate assay.', 'Bacterial lipopolysaccharide could be detected in 42% of the infected dialysis effluents. In comparison to controls (0.2 +/- 0.05 microg/ml), LBP was significantly elevated in both gram-negative/LPS-positive (1.03 +/- 0.3 microg/ml) and gram-positive infections (0.5 +/- 0.14 microg/ml) (P<0.05). No significant differences were detected concerning the intraperitoneal sCD14 levels in the three patient groups. Levels of TNF-alpha, IL-1beta and IL-6 were significantly increased in the effluents of patients with bacterial peritonitis compared to noninfected controls. Moreover the respective cytokine concentrations were significantly higher in the gram-negative/LPS-positive compared to the gram-positive bacterial infections (P<0.01).'] Is lipopolysaccharide-binding protein present in effluents of patients with Gram-negative and Gram-positive CAPD peritonitis? | qiaojin/PubMedQA | 2 | [
-2.031585693359375,
-1.5753300189971924,
2.6217265129089355
] |
['Diabetic foot problems due to angiopathy and neuropathy account for 50% of all nontraumatic amputations and constitute a significant economic burden to society. Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation. We investigated the influence of low-intensity laser irradiation by means of infrared thermography on skin blood circulation in diabetic patients with diabetic microangiopathy.', 'Thirty consecutive patients with diabetic ulcers or gangrenes and elevated levels of glycosylated hemoglobin were randomized by blocks of two to receive either a single low-intensity laser irradiation with an energy density of 30 J/cm2 or a sham irradiation over both forefoot regions in a double-blind placebo-controlled clinical study. Skin blood circulation as indicated by temperature recordings over the forefoot region was detected by infrared thermography.', 'After a single transcutaneous low-intensity laser irradiation, a statistically significant rise in skin temperature was noted (P < 0.001 by ANOVA for repeated measurements), whereas in the sham-irradiated control group, a slight but significant drop in temperature (P < 0.001) was found. Subsequently performed contrasts for comparison of measurements before and after irradiation revealed significant temperature increases at 20 min of irradiation time (P < 0.001), at the end of the irradiation (P < 0.001), and 15 min after stopping the irradiation (P < 0.001). In the sham-irradiated feet, the drop in local skin temperature was not significant at 20 min (P = 0.1), but reached significance at the end of the sham-irradiation procedure (P < 0.001) and 15 min after the end of sham irradiation (P < 0.001).'] Does low-intensity laser irradiation improve skin circulation in patients with diabetic microangiopathy? | qiaojin/PubMedQA | 2 | [
-1.9091721773147583,
-1.4671330451965332,
2.3993983268737793
] |
['Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates protein and/or amylase secretion from isolated rat pancreatic acini. The effect of PACAP on pancreatic secretion in vivo and its mechanism of action were studied.', 'Rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into duodenum, and 2.5, 5, and 10 nmol/kg PACAP-27 was administered intravenously while pancreatic juice was collected for 30 minutes. In other groups of rats, the effect of 10 nmol/kg PACAP-27 was studied under the influence of either atropine; loxiglumide, an antisecretin serum; a combination of both loxiglumide and the antiserum; or a PACAP antagonist (PACAP 6-38). Plasma secretin and cholecystokinin concentrations were measured by radioimmunoassay.', '(1) PACAP dose-dependently increased pancreatic secretion of fluid, bicarbonate, and protein; (2) the increase in pancreatic secretion paralleled that of plasma secretin and cholecystokinin; (3) a combination of loxiglumide and antisecretin serum eliminated the PACAP-stimulated pancreatic secretion, whereas loxiglumide or antisecretin serum alone partially but significantly blocked pancreatic secretion; (4) atropine failed to influence PACAP-induced pancreatic secretion; and (5) PACAP antagonist profoundly suppressed the PACAP action.'] Does pituitary adenylate cyclase-activating peptide stimulate rat pancreatic secretion via secretin and cholecystokinin releases? | qiaojin/PubMedQA | 2 | [
-2.4461255073547363,
-1.2848864793777466,
2.7633392810821533
] |
['During pre-mRNA splicing, dynamic rearrangement of RNA secondary structure within the spliceosome is crucial for intron recognition and formation of the catalytic core. Splicing factors belonging to the DExD/DExH-box family of RNA-dependent ATPases are thought to have a central role in directing these rearrangements by unwinding RNA helices. Proof of this hypothesis has, however, been conspicuously lacking.', 'Prp16 is a DEAH-box protein that functions in the second step of splicing in vitro. Using various RNA duplexes as substrate, we have shown that Prp16 has an ATP-dependent RNA unwinding activity. This activity is independent of sequence in either the single-stranded or duplexed regions of the RNA substrate. A mutation (prp16-1) near the ATP-binding motif of Prp16 inhibits both the RNA-dependent ATPase activity and the ATP-dependent RNA unwinding activity.'] Does the DEAH-box splicing factor Prp16 unwind RNA duplexes in vitro? | qiaojin/PubMedQA | 2 | [
-2.3557965755462646,
-0.5037001967430115,
1.87385892868042
] |
['Some patients experiencing near-fatal asthma present with extreme hypercapnia (PaCO2 > or = 100 mm Hg), whereas others do not. The influence of this factor on short- and long-term outcome and quality of life in these patients is still unknown.', 'A series of 39 consecutive patients who had had an episode of near-fatal asthma between 1978 and 1992 were followed up. Long-term outcome and quality of life of the 12 patients who had experienced extreme hypercapnia were compared with those of the 27 patients who had not.', 'Four patients died, but only 1 from asthma. Three patients were lost to follow-up. The remaining 32 patients had a median observation period of 12.7 years. The hypercapnic patients did not significantly differ from the others in past asthma history, subsequent hospitalizations, medication needs, pulmonary function tests, quality of life and impairment/disability. In the event of subsequent near-fatal asthma attacks, they tended to present with hypercapnia levels similar to those observed during the first episode.'] Is extreme hypercapnia a long-term prognostic factor after near-fatal asthma : a 12-year follow-up study? | qiaojin/PubMedQA | 2 | [
-2.0804860591888428,
0.336044043302536,
0.9123982191085815
] |
['Many investigators use prostate rebiopsy as an indicator of treatment efficacy and tumor response of localized prostate cancer for therapies in which the gland remains in situ. Because of the inherent sampling error of needle directed biopsies, however, some men will have a false-negative rebiopsy even if they have had no therapy or if the therapeutic intervention was unsuccessful in eradicating the malignancy. We evaluate the risk of a false-negative biopsy and the clinical factors that influence this risk.', 'A total of 90 patients undergoing radical prostatectomy for clinically localized disease underwent sextant biopsy of the prostate immediately after removal of the gland. Data collected included prostate specific antigen (PSA), hormonal status, age and biopsy core status.', 'Of the total study population 67.8% received neoadjuvant hormonal therapy. While all patients had pathologically confirmed adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false-negative rebiopsy. Within a combined predictive model, PSA and hormonal status demonstrated a statistically significant effect on the false-negative rebiopsy rate. Predictive power of this combined model was high across the spectrum of risk for a false-negative rebiopsy.'] Is prostate rebiopsy a poor surrogate of treatment efficacy in localized prostate cancer? | qiaojin/PubMedQA | 2 | [
-2.3524739742279053,
-1.232762336730957,
2.656466484069824
] |
['To determine whether children with epilepsy undergoing valproate (VPA) antiepileptic therapy and who are otherwise healthy have a lower serum level of carnitine (CAR) and a higher plasma level of plasma ammonia than do normal children.', 'A total of 45 children with epilepsy, 6.3 to 21.7 years of age, who were treated solely with VPA and were free of abnormal neurologic findings or nutritional problems were randomly selected (VPA-treated group). An age-matched control group (n = 45) was selected from subjects without epilepsy (control group). Total (T) and free (F) serum CAR, serum VPA concentration, and the plasma ammonia level were measured and analyzed.', 'Serum VPA concentration exhibited a weak negative correlation with both T- (r = -0.34) and F-CAR (r = -0.41). The T-CAR levels were 55.7 +/- 12.4 and 57.6 +/- 12.1 mM, and the F-CAR levels 42.7 +/- 9.9 and 44.4 +/- 9.9 mM in the VPA-treated and control groups, respectively. Thus, there was no significant difference in T- or F-CAR levels between the VPA-treated and control groups. Plasma ammonia levels were the same in the two groups: 26 +/- 9.2 and 29.4 +/- 11.8 mM in the VPA-treated and control groups, respectively. There was no significant correlation between blood ammonia and either T- (r = +0.024) or F-CAR (r = -0. 026).'] Does valproate therapy deplete carnitine levels in otherwise healthy children? | qiaojin/PubMedQA | 2 | [
-0.8408859968185425,
-1.6370680332183838,
1.5027896165847778
] |
['To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA).', 'The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score.', 'Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time.'] Are antibodies against mutated citrullinated vimentin a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides? | qiaojin/PubMedQA | 2 | [
-2.0561182498931885,
-1.480046033859253,
2.5646729469299316
] |
['The aetiology of ulcerative colitis is inadequately understood, and drug therapy has been empirical rather than based on sound understanding of disease aetiology. This has been a major factor for refractoriness and adverse drug effects as additional complications. However, ulcerative colitis by its very nature is exacerbated and perpetuated by inflammatory cytokines, which are released by peripheral granulocytes and monocytes as well. Additionally, active ulcerative colitis is often associated with elevated peripheral granulocytes and monocytes with activation behaviour and are found in vast numbers within the colonic mucosa. Hence, from the clinicopathologic viewpoint, granulocytes and monocytes are appropriate targets for therapy in ulcerative colitis. Based on this thinking, an Adacolumn has been developed for depleting excess granulocytes and monocytes by adsorption.', 'By colonoscopy, biopsy and histology, we investigated the impact of granulocyte and monocyte adsorption (GMA) on the mucosal level of granulocytes and monocytes in patients with active ulcerative colitis. Forty-five patients (26 steroid naïve and 19 steroid-dependent), mean age 44.7 yr, were included. Twenty patients had total colitis and 25 had left-sided colitis. Each patient was given up to 11 GMA sessions over 12 weeks. No patient received additional medications within 4 weeks (steroid) to 8 weeks (other immunosuppressants) prior to entry or during the GMA course. Colonoscopy together with biopsy was done at entry and within 2 weeks after the last GMA session.', 'At entry, the mean clinical activity index was 12.6; range 10-16. A total of 400 colonic biopsies were examined, which revealed massive infiltration of the colonic mucosa by granulocytes, and GMA was associated with striking reduction of granulocytes in the mucosa. At week 12, 33 of 45 patients (73.3%, P<0.01) had achieved clinical remission (the mean clinical activity index <or= 4). Colonoscopy revealed that most non-responders had deep colonic ulcers and extensive loss of the mucosal tissue. The response rate in steroid naïve subgroup was 22 of 26 patients (84.6%, P<0.005) and in steroid-dependent was 11 of 19 (57.9%, P<0.05 and P=0.02154 for steroid naïve vs. steroid-dependent). Patients who achieved remission could continue with their salicylates. On average, remission was sustained for 7.8 months in all 33 responders.'] Is in patients with ulcerative colitis , adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically most effective in steroid naïve patients? | qiaojin/PubMedQA | 2 | [
-2.1035354137420654,
-1.488682746887207,
2.6557321548461914
] |
['Polyglandular failure or autoimmunity (PGA) involves at least two endocrine diseases. Several genes may play a role in its etiology. This study analyzed 1) whether HLA-DRB1, HLA-DQB1, and MHC class I chain-related gene A (MICA) polymorphisms are associated in PGA and 2) whether PGA patients display stronger associations with these immune genes than patients with monoglandular autoimmunity (MGA).', 'Association study.', 'HLA-DRB1, HLA-DQB1, and MICA alleles were analyzed in 73 patients with PGA, 283 with MGA, and 206 healthy controls. The HLA-DRB1 and HLA-DQB1 polymorphisms were determined with PCR-amplified DNA being hybridized with PCR-sequence-specific oligonucleotide probes. MICA microsatellites were typed by PCR amplification and fragment size analysis on a DNA sequencer.', 'HLA-DRB1*03 was strongly increased in patients with PGA (50.7%) versus both controls (21.8%, P(c)<0.0001; RR=2.32, 95% CI=1.62-3.33) and MGA (11.4%, P(c)<0.0001). HLA-DRB1*03 was highly prevalent in PGA patients with early versus late disease onset (P<0.05, logistic regression analysis). HLA-DRB1*04 allele carriers were more present in PGA versus controls (53.4% vs 22.4%, P(c)<0.0001, RR=2.38, 95% CI=1.68-3.38). Further, HLA-DQB1*02 was increased in PGA versus controls (P(c)<0.01), whereas HLA-DQB1*06 was decreased (P(c)<0.001). Patients with PGA showed more MIC A5.1 and less MIC A6 allele carriers than controls (NS). Presence of the MIC A5.1 allele was not associated with the HLA-DRB1*03 or HLA-DQB1 alleles.'] Is early onset of polyglandular failure associated with HLA-DRB1*03? | qiaojin/PubMedQA | 2 | [
-1.458533763885498,
-1.627436876296997,
2.0291171073913574
] |
['This study sought to evaluate whether increased left ventricular (LV) adenylyl cyclase VI (AC(VI)) expression, at a time when severe congestive heart failure (CHF) was present, would increase function of the actively failing heart.', 'Increased LV AC(VI) content markedly reduces mortality and increases LV function after acute myocardial infarction (MI) in mice. However, the effects of increased cardiac AC(VI) content in the setting of severe heart failure caused by ischemic cardiomyopathy are unknown.', 'Mice with cardiac-directed and regulated expression of AC(VI) underwent coronary artery ligation to induce severe CHF 5 weeks later. AC(VI) expression was then activated in 1 group (AC-On) but not the other (AC-Off). Multiple measures of LV systolic and diastolic function were obtained 5 weeks later, and LV samples were assessed for alterations in calcium and beta-adrenergic receptor signaling, apoptosis, and cardiac troponin I phosphorylation.', 'The LV systolic and diastolic function was increased 5 weeks after activation of AC(VI) expression. Improved LV function was associated with normalization of cardiac troponin I phosphorylation and reduced apoptosis.'] Does activation of cardiac adenylyl cyclase expression increase function of the failing ischemic heart in mice? | qiaojin/PubMedQA | 2 | [
-2.519465684890747,
-1.0840470790863037,
2.653655529022217
] |
['Human corticotrophin-releasing hormone (CRH) plays a pivotal role in the stress response. Its expression is under the control of various steroid hormones, such as estrogens. The transcriptional activity of the estrogen receptor (ER) may be modified by small-ubiquitin related modifier (SUMO1). In the present study, we aim to reveal the role of SUMO1 in the regulation of ER-mediated CRH promoter activation.', 'CHO-K1 cells were transfected with human ER and SUMO1 expressing plasmids together with the CRH promoter reporter gene. CRH mRNA was detected in BE(2)C cells by real time PCR.', 'We found that estradiol could elevate CRH promoter activity to a much higher level in cells co-transfected with ER and SUMO1 than that with ER alone, and that the enhancement was blocked by the ER inhibitor, ICI182,780. Furthermore, the endogenous CRH mRNA expression was also increased when the BE(2)C cell were transfected with ERalpha and SUMO1 in contrast to the transfection with ERalpha alone.'] Does sUMO1 enhance 17-beta estradiol 's effect on CRH promoter activation through estrogen receptors? | qiaojin/PubMedQA | 2 | [
-2.3693430423736572,
-1.0624147653579712,
2.4291677474975586
] |
['Eosinophilic chronic rhinosinusitis (ECRS) is one of the most common diseases worldwide. To date the underlying cause remains unclear and no drug has been accredited for first-line therapy. VCAM-1 has been reported to play a pivotal role in establishing ECRS. Other authors have reported that inflammatory cytokines may mediate changes in the underlying epithelium in the sinuses through hepatocyte growth factor HGF. In our study, the effect of VCAM-1 on HGF levels was investigated.', 'ECRS cell cultures were incubated with VCAM-1 and HGF levels were determined after 16, 24, 48 and 72 hours. RT-PCR was enrolled to depict the HGF-RNA levels.', 'Sixteen hours of incubation showed 28.5 pg/ml HGF, whereas in the control 16.3 pg/ml was detectable. After 24 and 36 hours, 37 pg/ml and 43.5 pg/ml HGF were measured in the incubated cell cultures, respectively; 72 hours of incubation with VCAM-1 resulted in 50.6 pg/ml HGF, whereas 23.5 pg/ml was determined in the controls. The RT-PCR for HGF also showed increased concentration in the incubated cells after 72 hours.'] Does vCAM-1 increase levels of HGF in eosinophilic chronic rhinosinusitis cell culture? | qiaojin/PubMedQA | 2 | [
-1.670112133026123,
-1.3854596614837646,
1.9925282001495361
] |
['Despite significant advances in the use of diagnosis and therapy to treat head and neck squamous cell carcinoma (HNSCC), the prognosis has improved only marginally in the last decades. Thus, there is an enormous need for better understanding of tumor biology and reversely novel immunotherapeutic approaches. It is becoming increasingly obvious that stem cells play an important role in tumor development and progression. The identity of these cells and the underlying cellular and molecular mechanisms are mostly unknown in HNSCC to date.', 'Solid HNSCC tumors, as well as permanent HNSCC cell lines, were analyzed by flow cytometry concerning the expression of different putative stem cell marker proteins.', 'Distinct populations of CD44 expressing potential stem cells could be identified in solid tumors of HNSCC patients with strong individual deviations. Surprisingly, the potential stem cell marker CD44 was found to be constitutively expressed on the surface of all the permanent HNSCC cell lines analyzed.'] Is potential stem cell marker CD44 constitutively expressed in permanent cell lines of head and neck cancer? | qiaojin/PubMedQA | 2 | [
-2.5836000442504883,
-0.9592357873916626,
2.7037906646728516
] |
['PCR can be used to detect T. whipplei (Tw) in samples from variable tissue types and body fluids. We report clinical, evolutive characteristics and final diagnosis in patients with positive Tw PCR assay.', 'Retrospective study of Tw PCR realized since 10years in a microbiology laboratory.', "Twenty-five Tw PCR assays were positive among 200 realized. Diagnosis was not confirmed in six cases. One patient was missing for follow up. Eighteen patients presented with Whipple's disease. Among these 18 patients, 14 had a classic Whipple's disease, three patients presented an endocarditis and one patient isolated neurological manifestations. Ten patients presented fever, seven a weight loss and 12 joint involvement. Four patients presented cutaneous manifestations, only six had gastrointestinal symptoms. Neurological involvement was reported in five cases, pulmonary symptoms in four cases, cardiac involvement in six cases and ocular signs in two cases. Anemia was reported in four patients and elevated levels of acute-phase reactants in 14 cases. Positive predictive value of Tw PCR for Whipple's disease diagnosis was 75%. Thirteen patients had a good evolution with antibiotics. Three patients presented recurrence and two cases with cardiovascular involvement died."] Are [ Tropheryma whipplei and Whipple disease : false positive PCR detections of Tropheryma whipplei in diagnostic samples rare ]? | qiaojin/PubMedQA | 2 | [
-2.2065820693969727,
-1.2864900827407837,
2.6311838626861572
] |
['Thermal balloon endometrial ablation (TBEA) is increasingly being performed in the outpatient setting under local anaesthesia (LA) rather than in a daycase setting under general anaesthesia (GA). Our aim was to compare the post operative rescue analgesia requirements and duration of hospital stay in women undergoing outpatient (LA) and daycase (GA) TBEA.', 'Prospective observational study of consecutively recruited women who underwent outpatient (LA) TBEA (n=51) and daycase (GA) TBEA (n=50) over the same time period. Analgesia that was provided additional to the standard administered analgesic regimen was considered rescue analgesia. The main outcome measures were requirement for rescue analgesia and duration of hospital stay in both cohorts.', 'LA compared to GA cohorts had shorter hospital stays (11 h [95% CI 9-13] vs. 17 h [95% CI 14-20]) and lower analgesia requirements. However, multivariate regression, correcting for all known confounders, showed that duration of stay was independent of setting for ablation or amount of rescue analgesia.'] Is hospital recovery following Thermachoice ablation dependent on setting ( outpatient or daycase ) or rescue analgesia : unexpected result? | qiaojin/PubMedQA | 2 | [
-2.323521852493286,
-1.143326759338379,
2.6408987045288086
] |
['Our aim was to establish whether the efficacy of post-conditioning is maintained in aging hearts.', 'Post-conditioning, or relief of myocardial ischemia in a stuttered manner, has been shown to reduce infarct size, in part because of up-regulation of survival kinases (extracellular-signal regulated kinase [ERK] 1/2 or PI3-kinase/Akt) during the early min of reperfusion. All of these data have, however, been obtained in adult populations; the question of whether post-conditioning-induced cardioprotection is maintained in aging cohorts is unknown.', 'Isolated buffer-perfused hearts were obtained from 3- to 4-month-old (adult) and 20- to 24-month-old C57BL/6J mice and subjected to 30 min of ischemia. For each cohort, hearts were randomized to receive standard, abrupt (control) reperfusion, or were post-conditioned with 3 or 6 10-s cycles of stuttered reflow. Primary end points were infarct size, cardiac expression of phospho-Akt, phospho-mitogen-activated protein kinase kinase 1/2 and phospho-ERK 1/2, and expression of mitogen-activated protein kinase-phosphatase-1 (MKP-1: phosphatase purported to play a primary role in ERK dephosphorylation).', 'In adult mouse hearts, post-conditioning significantly reduced infarct size via up-regulation of ERK (but not Akt) signaling. In contrast, in the 2-year-old cohort, post-conditioning failed to limit necrosis, possibly a consequence of the deficit in ERK phosphorylation and increased MKP-1 expression seen in old hearts. Indeed, infusion of sodium orthovanadate, a nonspecific MKP inhibitor, attenuated MKP-1 expression and restored the post-conditioned phenotype in old hearts.'] Are aging mouse hearts refractory to infarct size reduction with post-conditioning? | qiaojin/PubMedQA | 2 | [
-2.4491941928863525,
-1.278450846672058,
2.7483158111572266
] |
['The purpose of this study was to study aging-associated alterations in the inflammatory and reparative response after myocardial infarction (MI) and their involvement in adverse post-infarction remodeling of the senescent heart.', 'Advanced age is a predictor of death and ventricular dilation in patients with MI; however, the cellular mechanisms responsible for increased remodeling of the infarcted senescent heart remain poorly understood.', 'Histomorphometric, molecular, and echocardiographic end points were compared between young and senescent mice undergoing reperfused infarction protocols. The response of young and senescent mouse cardiac fibroblasts to transforming growth factor (TGF)-beta stimulation was examined.', 'Senescence was associated with decreased and delayed neutrophil and macrophage infiltration, markedly reduced cytokine and chemokine expression in the infarcted myocardium, and impaired phagocytosis of dead cardiomyocytes. Reduced inflammation in senescent mouse infarcts was followed by decreased myofibroblast density and markedly diminished collagen deposition in the scar. The healing defects in senescent animals were associated with enhanced dilative and hypertrophic remodeling and worse systolic dysfunction. Fibroblasts isolated from senescent mouse hearts showed a blunted response to TGF-beta1.'] Are aging-related defects associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction? | qiaojin/PubMedQA | 2 | [
-2.6146435737609863,
-1.0959383249282837,
2.755124807357788
] |
['In our study, we describe the use of spider silk fibres as a new material in nerve tissue engineering, in a 20-mm sciatic nerve defect in rats.', 'We compared isogenic nerve grafts to vein grafts with spider silk fibres, either alone or supplemented with Schwann cells, or Schwann cells and matrigel. Controls, consisting of veins and matrigel, were transplanted. After 6 months, regeneration was evaluated for clinical outcome, as well as for histological and morphometrical performance.', 'Nerve regeneration was achieved with isogenic nerve grafts as well as with all constructs, but not in the control group. Effective regeneration by isogenic nerve grafts and grafts containing spider silk was corroborated by diminished degeneration of the gastrocnemius muscle and by good histological evaluation results. Nerves stained for S-100 and neurofilament indicated existence of Schwann cells and axonal re-growth. Axons were aligned regularly and had a healthy appearance on ultrastructural examination. Interestingly, in contrast to recently published studies, we found that bridging an extensive gap by cell-free constructs based on vein and spider silk was highly effective in nerve regeneration.'] Do spider silk fibres in artificial nerve constructs promote peripheral nerve regeneration? | qiaojin/PubMedQA | 2 | [
-2.7617380619049072,
-0.604728639125824,
2.407514810562134
] |
['Atherosclerosis is a chronic inflammatory disease. Statins suppress the inflammation in the plaque. This cross-sectional study was planned to evaluate the effect of statins on plaque T cell activation markers in patients with stable angina pectoris undergoing coronary intervention and atherectomy procedures.', "Twenty-six patients with stable angina with suitable for atherectomy coronary lesions were enrolled in the study. Fourteen of 26 patients who had been taking statin treatment for at least six months were assigned to the Group 1 (Statin group) and 12 patients who had not received any lipid lowering treatment comprised the Group 2 (Control group). Atherectomy specimens were studied with single and double immunohistochemical staining (CD25, CD69, and CD40L). Statistical analysis was performed using Student's t-test and Fisher's exact test.", 'There was no significant difference between the total tissue area of sections (Group 1: 8.4+/-0.9 mm2, Group 2: 7.8+/-0.9 mm2, p>0.05). CD3, CD25, CD69, and CD40L positive cells did not show statistically significant difference between the groups in unit area (mm2). There was no significant difference between the groups for percentage of T lymphocytes expressing CD25 (Group 1: 7.8+/-4.6%, Group 2: 7.8+/-5.9%, p=0.97) and CD 69 (Group 1: 12.9+/-4.6%, Group 2: 15.5+/-5.2%, p=0.203). The expression of CD40L was significantly lower in Group 1 than in Group 2 (Group 1: 4.8+/-3.9%, Group 2: 11.2+/-8.7%, p=0.034).'] Is statin use associated with decreased CD-40 ligand expression on T lymphocytes of coronary atheroma plaque in patients with stable coronary artery disease? | qiaojin/PubMedQA | 2 | [
-1.4425455331802368,
-1.7096171379089355,
2.100398063659668
] |
['Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls.', 'Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits.', 'We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer.'] Are apoptosis induction in Jurkat cells and sCD95 levels in women 's sera related with the risk of developing cervical cancer? | qiaojin/PubMedQA | 2 | [
-1.9136945009231567,
-1.340254306793213,
2.2681703567504883
] |
['Tomato (Solanum lycopersicon) and potato (S. tuberosum) are two economically important crop species, the genomes of which are currently being sequenced. This study presents a first genome-wide analysis of these two species, based on two large collections of BAC end sequences representing approximately 19% of the tomato genome and 10% of the potato genome.', 'The tomato genome has a higher repeat content than the potato genome, primarily due to a higher number of retrotransposon insertions in the tomato genome. On the other hand, simple sequence repeats are more abundant in potato than in tomato. The two genomes also differ in the frequency distribution of SSR motifs. Based on EST and protein alignments, potato appears to contain up to 6,400 more putative coding regions than tomato. Major gene families such as cytochrome P450 mono-oxygenases and serine-threonine protein kinases are significantly overrepresented in potato, compared to tomato. Moreover, the P450 superfamily appears to have expanded spectacularly in both species compared to Arabidopsis thaliana, suggesting an expanded network of secondary metabolic pathways in the Solanaceae. Both tomato and potato appear to have a low level of microsynteny with A. thaliana. A higher degree of synteny was observed with Populus trichocarpa, specifically in the region between 15.2 and 19.4 Mb on P. trichocarpa chromosome 10.'] Does comparative BAC end sequence analysis of tomato and potato reveal overrepresentation of specific gene families in potato? | qiaojin/PubMedQA | 2 | [
-2.401732921600342,
-0.3625490963459015,
1.9015395641326904
] |
['Atherosclerosis is a chronic inflammatory disease that represents the primary cause of death through coronary disease and stroke. Chemokines are known to play a crucial role in this disease by recruiting inflammatory leukocytes to the endothelium. Recently, the chemokine variant [44AANA47]-RANTES was shown to impair inflammatory cell recruitment in vivo by interfering with heparin binding and oligomerization.', 'In this study we report that curative treatment with [44AANA47]-RANTES limits atherosclerotic plaque formation in LDLr-/- mice. This was associated with reduced infiltration of T cells and macrophages and reduced production of matrix metalloproteinase (MMP)-9. By contrast, the relative smooth muscle cell and collagen content was increased, indicating a more stable plaque phenotype. In addition, we provide evidence for direct inhibition of leukocyte recruitment into aortic root lesions, attenuated leukocyte rolling and arrest in mesenteric vessels, as well as a reduced proinflammatory response following Con A stimulation in vitro.'] Does a novel RANTES antagonist prevent progression of established atherosclerotic lesions in mice? | qiaojin/PubMedQA | 2 | [
-2.5091097354888916,
-1.2563401460647583,
2.814249038696289
] |
['Reduced activity of the sarcoplasmic reticulum Ca ATPase-2a (SERCA-2a) contributes to myocardial dysfunction. Exercise training improves myocardial Ca-handling, but SERCA-2a function is uncertain. We assessed SERCA-2a activity after exercise training.', 'SERCA-2a function was assessed by sarcoplasmic reticulum Ca uptake in cardiomyocytes with other Ca uptake mechanisms blocked, in mice after aerobic interval training versus sedentary controls.', 'We established protocols to assess SERCA-2a function, and show that aerobic interval training increases the maximal rate of Ca uptake by 30%. This is at least partly explained by reduced phospholamban-to-SERCA-2a ratio.'] Does myocardial sarcoplasmic reticulum Ca2+ ATPase function is increase by aerobic interval training? | qiaojin/PubMedQA | 2 | [
-2.3546102046966553,
-0.9947255849838257,
2.431149959564209
] |
['To examine the kinetic ability of embryonic human epithelial INT-407 cells to express messenger ribonucleic acid mRNA for various cytokines and chemokines in response to Campylobacter jejuni C. jejuni stimulation.', 'In an experimental single-blind study, cultured embryonic human epithelial INT-407 cells were treated with different concentrations of viable C. jejuni, its sonicated, and filtered supernatant. A modified non-radioactive in situ hybridization using probe cocktails was used to measure mRNA levels for the pro-inflammatory cytokines interleukin IL-1beta, IL-6, interferon-gamma IFN-gamma, tumour necrosis factor TNF-alpha, transforming growth factor TGF-beta1, and IL-8, and the anti-inflammatory cytokines, IL-4 and IL-10. The study was carried out from September 2005 to March 2007 at the Department of Microbiology, Immunology, and Infectious Diseases, College of Medicine, Arabian Gulf University, Bahrain.', 'Viable C. jejuni, sonicated bacteria and filtered supernatant induced high mRNA expression for the pro-inflammatory cytokines IL-1beta, IL-6, IFN-gamma, TNF-alpha, TGF-beta1, and IL-8, which peaked at the 12 hours post stimulation. Anti-inflammatory cytokines IL-4 and IL-10 mRNA expression were induced maximally at 3 hours post stimulation mainly by sonicated bacteria and filtrated supernatant, however, not with living bacteria. Untreated embryonic human epithelial INT-407 cells expressed low amount of mRNA for the various cytokines and chemokines at all time points. For each cytokine, 4 samples were used per time hour.'] Does campylobacter jejuni induce diverse kinetics and profiles of cytokine genes in INT-407 cells? | qiaojin/PubMedQA | 2 | [
-2.383885622024536,
-1.3651435375213623,
2.7829060554504395
] |
['To compare the efficiency of apoptosis and other modes of cell death in killing tumor cells after the induction of DNA damage by topoisomerase inhibitors like etoposide.', 'This study was carried out in the Tumor Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt, from September 2005 to August 2007. The breast cancer MCF7, the cervix carcinoma, human cervical adenocarcinoma Hela, and the brain tumor U251 cell lines were exposed to etoposide. Apoptosis was detected using the flow cytometry and the DNA ladder formation methods. Cell viability was determined by a colorimetric assay, and the residual DNA double-strand breaks dsb were measured by gel electrophoresis.', "The Hela cells were the most, the MCF7's were moderately, whereas the U251's were the least sensitive to etoposide. Apoptosis was detected only in Hela cells whereas the other 2 cell lines showed a very low level of apoptosis only 3% increase above the control cells. At equitoxic drug concentrations namely IC50, the Hela cells showed the lowest amount of non-repaired DNA dsb, and the MCF7's showed the highest amount, whereas the U251 cells showed a moderate amount."] Is apoptosis the most efficient death-pathway in tumor cells after topoisomerase II inhibition? | qiaojin/PubMedQA | 2 | [
-2.408541679382324,
-1.1156070232391357,
2.518996238708496
] |
["It has been reported that salicylates (sodium salicylate and aspirin) inhibit the replication of flaviviruses, such as Japanese encephalitis virus and dengue virus. Therefore, we considered it important to test whether acetylsalicylic acid (ASA) had anti-hepatitis C virus (HCV) activity. To this end, we examined the effects of ASA on viral replication and protein expression, using an HCV subgenomic replicon cell culture system. We incubated Huh7 replicon cells with 2-8 mM ASA for different times and measured HCV-RNA and protein levels by northern blot, real-time polymerase chain reaction, and western analysis, respectively. We found that ASA had a suppressive effect on HCV-RNA and protein levels (nearly 58%). ASA-dependent inhibition of HCV expression was not mediated by the 5'-internal ribosome entry site or 3'-untranslated regions, as determined by transfection assays using bicistronic constructs containing these regulatory regions. However, we found that HCV-induced cyclooxygenase 2 (COX-2) messenger RNA and protein levels and activity and these effects were down-regulated by ASA, possibly by a nuclear factor kappa B-independent mechanism. We also observed that the ASA-dependent inhibition of viral replication was due in part to inhibition of COX-2 and activation of p38 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) mitogen-activated protein kinases (MAPKs). Inhibition of these kinases by SB203580 and U0126, respectively, and by short interfering RNA silencing of p38 and MEK1 MAPK prevented the antiviral effect of ASA. Taken together, our findings suggest that the anti-HCV effect of ASA in the Huh7 replicon cells is due to its inhibitory effect on COX-2 expression, which is mediated in part by the activation of MEK1/2/p38 MAPK."] Does acetylsalicylic acid inhibit hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways? | qiaojin/PubMedQA | 2 | [
-2.385605812072754,
-1.2406370639801025,
2.6871395111083984
] |
['Hepatitis C virus (HCV) infects over 3% of the world population and is the leading cause of chronic liver disease worldwide. HCV has long been known to associate with circulating lipoproteins, and its interactions with the cholesterol and lipid pathways have been recently described. In this work, we demonstrate that HCV is actively secreted by infected cells through a Golgi-dependent mechanism while bound to very low density lipoprotein (vLDL). Silencing apolipoprotein B (ApoB) messenger RNA in infected cells causes a 70% reduction in the secretion of both ApoB-100 and HCV. More importantly, we demonstrate that the grapefruit flavonoid naringenin, previously shown to inhibit vLDL secretion both in vivo and in vitro, inhibits the microsomal triglyceride transfer protein activity as well as the transcription of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and acyl-coenzyme A:cholesterol acyltransferase 2 in infected cells. Stimulation with naringenin reduces HCV secretion in infected cells by 80%. Moreover, we find that naringenin is effective at concentrations that are an order of magnitude below the toxic threshold in primary human hepatocytes and in mice.'] Is apolipoprotein B-dependent hepatitis C virus secretion inhibited by the grapefruit flavonoid naringenin? | qiaojin/PubMedQA | 2 | [
-2.5485074520111084,
-1.0606651306152344,
2.652132034301758
] |
['Local anesthetics which preferentially interact with voltage-gated sodium channels (VGSCs) were shown to have a clinical beneficial effect in ulcerative colitis and to regulate the secretion of inflammatory mediators from intestinal epithelial cells. However, expression of VGSCs in epithelial cells was not demonstrated. Herein we assessed whether intestinal epithelial cells express VGSCs.', 'The expression of VGSCs in normal human colonic tissue and in the TNFalpha-treated or untreated intestinal epithelial cell line HT-29 was studied by immunofluorescence staining and FACS analysis, Western blot, immunohistochemistry, and RT-PCR using primers specific for several VGSC alpha subunits. The function of VGSCs was assessed by measuring changes in the membrane potential of the intestinal epithelial cells following incubation with lidocaine, veratridine, or both.', 'HT-29 cells were shown to express the VGSC alpha protein. mRNA analysis revealed the expression of nine of ten VGSC alpha isoforms. Immunohistochemical staining of normal colonic tissue confirmed the expression of VGSCs in colonic epithelial cells, smooth muscle cells, and nerves. Lidocaine induced membrane depolarization of HT-29 cells and its effect was blocked by veratridine.'] Are functional voltage-gated sodium channels expressed in human intestinal epithelial cells? | qiaojin/PubMedQA | 2 | [
-2.4727556705474854,
-1.270263671875,
2.8338794708251953
] |
['To review evidence on the workplace prevalence and correlates of major depressive episodes, with a particular focus on the National Comorbidity Survey Replication, the most recent national survey to focus on these issues.', 'Nationally representative survey of Diagnostic and Statistical Manual, 4th Revision Mental Disorders.', 'A total of 6.4% of employed National Comorbidity Survey Replication respondents had 12-month major depressive disorder. An additional 1.1% had major depressive episodes due to bipolar disorder or mania-hypomania. Only about half of depressed workers received treatment. Fewer than half of treated workers received care consistent with published treatment guidelines.'] Does the prevalence and correlate of workplace depression in the national comorbidity survey replication? | qiaojin/PubMedQA | 1 | [
-1.7769532203674316,
0.8916245698928833,
0.2679218053817749
] |
['Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in insulin sensitivity, lipid metabolism and inflammation. However, the effects of PPARgamma agonist on renal inflammation have not been fully examined in type 2 diabetic nephropathy.', 'In the present study, we investigated the effect and molecular mechanism of the PPARgamma agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats. Inflammatory markers including NF-kappaB, MCP-1 and pro-fibrotic cytokines were determined by RT-PCR, western blot, immunohistochemical staining and EMSA. In addition, to evaluate the direct anti-inflammatory effect of PPARgamma agonist, we performed an in vitro study using mesangial cells.', 'Treatment of OLETF rats with pioglitazone improved insulin sensitivity and kidney/body weight, but had a little effect on blood pressure. Pioglitazone treatment markedly reduced urinary albumin and MCP-1 excretion, and ameliorated glomerulosclerosis. In cDNA microarray analysis using renal cortical tissues, several inflammatory and profibrotic genes were significantly down-regulated by pioglitazone including NF-kappaB, CCL2, TGFbeta1, PAI-1 and VEGF. In renal tissues, pioglitazone treatment significantly reduced macrophage infiltration and NF-kappaB activation in association with a decrease in type IV collagen, PAI-1, and TGFbeta1 expression. In cultured mesangial cells, pioglitazone-activated endogenous PPARgamma transcriptional activity and abolished high glucose-induced collagen production. In addition, pioglitazone treatment also markedly suppressed high glucose-induced MCP-1 synthesis and NF-kappaB activation.'] Does pioglitazone attenuate diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats? | qiaojin/PubMedQA | 2 | [
-2.4264917373657227,
-1.353446125984192,
2.790600299835205
] |
['Ventilator-induced lung injury (VILI) leads to airway epithelial cell apoptosis and lung inflammation. High tidal volume ventilation in vivo has been shown to induce MIP-2 production, lung neutrophil sequestration and apoptotic airway cell death. This study aimed to determine the effect of N-acetylcysteine (NAC), a scavenger of oxygen radicals, on lung inflammation and apoptosis in an in vivo model of VILI.', 'Sprague-Dawley rats (n = 5 per group) were ventilated at low tidal volume (V(T) 7 mL/kg) or high tidal volume (V(T) 20 mL/kg) with or without administration of 140 mg/kg of intravenous NAC. Animals were ventilated for 30 min, 1 or 2 h, then allowed to recover for 2 h, at which time neutrophil infiltration, MIP-2, TNF-alpha and IL-6 in BAL fluid, as well as the percentage of apoptotic airway epithelial cells, were measured.', 'Ventilation at V(T) 20 mL/kg increased oxidant release, as measured by serum isoprostane, and decreased lung glutathione, the major antioxidant in the lung. NAC treatment during ventilation at V(T) 20 mL/kg prevented the decrease in lung glutathione and significantly lowered serum isoprostane levels, neutrophil infiltration, cytokines in the BAL and apoptosis in the airways as compared with animals ventilated at V(T) 20 mL/kg without NAC (P < 0.05).'] Does oxidant stress mediate inflammation and apoptosis in ventilator-induced lung injury? | qiaojin/PubMedQA | 2 | [
-1.9748402833938599,
-1.490898847579956,
2.4274494647979736
] |
['There is evidence that the tea catechin epigallocatechin-3-gallate (EGCG) modulates myocardial contractility. However, the underlying mechanisms remain to be determined.', 'To study potential signalling pathways involved in EGCG-induced contractile parameters.', 'EGCG increased fractional shortening in rat cardiac myocytes and enhanced intracellular systolic Ca2+ concentrations. In isolated rat hearts, perfusion with EGCG resulted in significant, dose-dependent increase in peak systolic left ventricular pressure, as well as in contraction and relaxation velocities. Heart rate did not change. Inhibition of the beta1-receptor with metoprolol had no influence on the contractile effects of EGCG. Furthermore, levels of cAMP and phosphorylation of phospholamban did not change with EGCG, indicating that the beta-receptor pathway is not involved. The L-type Ca2+ channel inhibitors, nifedipine and gallopamil, failed to modulate EGCG-induced increase in contractility. However, the myocardial effects and intracellular calcium transients stimulated by EGCG were significantly reduced by the antagonist of the Na+/H+ exchanger (NHE) methyl-N-isobutyl amiloride (MIA), and by blocking of the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R7943.'] Do positive inotropic effects of epigallocatechin-3-gallate ( EGCG ) involve activation of Na+/H+ and Na+/Ca2+ exchangers? | qiaojin/PubMedQA | 2 | [
-2.478691339492798,
-1.3007681369781494,
2.8064002990722656
] |
['Depressive episodes can have a very fast onset (< 1 hour) or start very slowly (> 1 month). This interesting aspect, pointing to different neurophysiological pathomechanisms, has not been systematically evaluated so far. The aim of this study was to describe speed of onset of depressive episodes in a consecutive sample of patients with at least 1 depressive episode and to investigate potential differences between patients with major depression versus bipolar affective disorders concerning this variable.', 'We examined 158 consecutive adult patients with major depression (N = 108) and bipolar disorder (N = 50) diagnosed according to criteria of the International Statistical Classification of Diseases, 10th revision, by applying the structured Onset-of-Depression Inventory. Patients with acute critical life events preceding the onset were excluded from final analyses. Data were collected between December 2001 and January 2007.', 'There was a significant positive association between speed of onset of the present depressive episode and that of the preceding depressive episode (rho = 0.66, p < .001). Patients with bipolar disorder developed full-blown depressive episodes significantly faster than patients with major depression (p < .001): Whereas depressive episodes began within 1 week in 58% of patients with bipolar disorder, this was the case in only 7.4% of patients with major depression.'] Is onset of depressive episodes faster in patients with bipolar versus unipolar depressive disorder : evidence from a retrospective comparative study? | qiaojin/PubMedQA | 2 | [
-1.7792004346847534,
-0.026731910184025764,
0.9925246834754944
] |
['C-reactive protein (CRP) is widely used as a sensitive biomarker for inflammation. Increasing evidence suggests that CRP plays a role in inflammation. High-mobility group box-1 (HMGB1), a primarily nuclear protein, is passively released into the extracellular milieu by necrotic or damaged cells and is actively secreted by monocytes/macrophages. Extracellular HMGB1 as a potent inflammatory mediator has stimulated immense curiosity in the field of inflammation research. However, the molecular dialogue implicated between CRP and HMGB1 in delayed inflammatory processes remains to be explored.', 'The levels of HMGB1 in culture supernatants were determined by Western blot analysis and enzyme-linked immunosorbent assay in macrophage RAW264.7 cells. Purified CRP induced the release of HMGB1 in a dose- and time-dependent fashion. Immunofluorescence analysis revealed nuclear translocation of HMGB1 in response to CRP. The binding of CRP to the Fc gamma receptor in RAW264.7 cells was confirmed by fluorescence-activated cell sorter analysis. Pretreatment of cells with IgG-Fc fragment, but not IgG-Fab fragment, efficiently blocked this binding. CRP triggered the activation of p38MAPK and ERK1/2, but not Jun N-terminal kinase. Moreover, both p38MAPK inhibitor SB203580 and small interfering RNA significantly suppressed the release of HMGB1, but not the MEK1/2 inhibitor U-0126.'] Does c-reactive protein induce high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells? | qiaojin/PubMedQA | 2 | [
-2.3220527172088623,
-1.304656744003296,
2.689775228500366
] |
['Good cardiorespiratory fitness has been associated with a reduced risk for clinical events of atherosclerotic vascular diseases. It is still unclear how this relates to a slower progression of the early atherosclerosis wall process.', 'Using a dynamic model, we generated new parameters for describing the pathologic wall process in the carotid artery, based on an automatic layer detection system. In this study, we scrutinised the influence of two ultrasonographic parameters, intima-media thickness (IMT) and roughness, by comparing two groups: a healthy inactive group (PIP) (mean (SD) age 64.37 (5.10) years; n = 50) and a healthy lifelong physically active group (PA) (mean (SD) age 64.48 (3.45) years; n = 51). All subjects underwent a blood test, spiroergometry, echocardiography and carotid ultrasound examination.', 'There was a significant difference in the well known risk factors for cardiovascular disease (for example, high density lipoprotein cholesterol, triglyceride) between groups. PIP compared to PA had a significantly higher roughness (PIP 0.073 (0.015) vs PA 0.065 (0.0156); p<0.01). No significantly higher IMT was found for PIP (PIP 0.89 (0.18) vs PA 0.90 (0.22); p = 0.63) compared to PA. In this cross sectional study of middle aged men, Vo(2)max was inversely associated with carotid atherosclerotic parameters.'] Does physical activity throughout life reduce the atherosclerotic wall process in the carotid artery? | qiaojin/PubMedQA | 2 | [
-2.0942189693450928,
-1.4695454835891724,
2.6187334060668945
] |
['The aim of this study was to investigate the antitumour promoting effects and possible mechanisms of action of the most abundant polymeric black tea polyphenols (PBPs 1-5) or thearubigins, in vivo.', 'Effect of PBP pre-treatments on 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted skin papillomas was studied in 7,12-dimethylbenz(a)anthracene initiated mice over 40 weeks. Cell proliferation and apoptosis, in epidermis of the skin, were measured using appropriate immunohistochemical staining. Mitogen-activated protein kinase signalling studies were conducted with Western blot analysis at 10, 20, 30 and 40 weeks of promotion.', 'Pre-treatments with PBP fractions differentially altered latency, multiplicity and incidence of skin papillomas as compared to TPA treatments thereby exhibiting antipromoting effects. Most PBP fractions decreased TPA-induced cell proliferation by decreasing activation of signalling kinases (c-Jun N-terminal protein kinase, extracellular signal-regulated protein kinase, p38 protein kinase and Akt), transcription factors (activator protein-1 and nuclear factor kappa B) and inflammatory protein (cyclooxygenase 2). TPA-induced epidermal cell apoptosis was also decreased by pre-treatment with most PBP fractions. Higher levels of p53 and p21 in skin cells pre-treated with PBP fractions followed by TPA treatment as compared to only TPA-treated animals suggested possible activation of a cell cycle checkpoint.'] Do polymeric black tea polyphenols inhibit mouse skin chemical carcinogenesis by decreasing cell proliferation? | qiaojin/PubMedQA | 2 | [
-2.4288508892059326,
-1.3542516231536865,
2.8005056381225586
] |
['The aim of this study was to evaluate the association between severe periodontitis and sub-clinical atherosclerosis in young (< or =40 years) systemically healthy individuals.', 'Ninety systemically healthy subjects, 45 affected by severe periodontitis (mean age 36.35+/-3.65 years) and 45 controls without a history of periodontal disease (mean age 33.78+/-3.28 years), were enrolled in this study. Patients and controls were paired for age, gender, body mass index and smoking habits. Carotid intima-media thickness (IMT) was bilaterally assessed by ultrasonography at the level of common carotid artery. Traditional cardiovascular risk factors for atherosclerosis were also evaluated.', 'The overall mean carotid IMT was 0.82+/-0.13 mm in the test group and 0.72+/-0.07 mm in the control group ( p<0.0001). Stepwise regression analysis showed that periodontitis ( p<0.0001) and regular physical activity ( p=0.0009) were predictor variables of overall mean carotid IMT. When considering an IMT> or =0.82 mm as the critical index of increased cardiovascular risk, periodontal patients overcame this threshold compared with healthy patients by an odds ratio=8.55 [confidence interval 95%: 2.38; 39.81]. No investigated haemostatic variable was associated with increased carotid IMT.'] Is severe periodontitis in young adults associated with sub-clinical atherosclerosis? | qiaojin/PubMedQA | 2 | [
-1.7684723138809204,
-1.3804962635040283,
2.2109992504119873
] |
['In tropical lowland rain forest (TLRF) the leaves of most monocots differ from those of most dicots in two ways that may reduce attack by herbivores. Firstly, they are tougher. Secondly, the immature leaves are tightly folded or rolled until 50-100 % of their final length. It was hypothesized that (a) losses of leaf area to herbivorous invertebrates are generally greatest during leaf expansion and smaller for monocots than for dicots, and (b) where losses after expansion are appreciable any difference between monocots and dicots then is smaller than that found during expansion.', 'At six sites on four continents, estimates were made of lamina area loss from the four most recently mature leaves of focal monocots and of the nearest dicot shoot. Measurements of leaf mass per unit area, and the concentrations of water and nitrogen were made for many of the species. In Panama, the losses from monocots (palms) and dicots were also measured after placing fully expanded palm leaflets and whole dicot leaves on trails of leaf-cutter ants.', 'At five of six sites monocots experienced significantly smaller leaf area loss than dicots. The results were not explicable in terms of leaf mass per unit area, or concentrations of water or nitrogen. At only one site was the increase in loss from first to fourth mature leaf significant (also large and the same in monocots and dicots), but the losses sustained during expansion were much smaller in the monocots. In the leaf-cutter ant experiment, losses were much smaller for palms than for dicots.'] Are monocot leaves eaten less than dicot leaves in tropical lowland rain forests : correlations with toughness and leaf presentation? | qiaojin/PubMedQA | 1 | [
-0.6436702609062195,
1.4730414152145386,
-1.4990694522857666
] |
['Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-alpha) in prepubertal children.', 'Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1-3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test.', 'Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = -0.52; P < 0.01) and liver fat content (r = -0.44; P < 0.02) but not with visceral abdominal adipose tissue (VAT) (r = -0.193; P value not significant) and fat accumulation in skeletal muscle (r = -0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P < 0.01) as well as adiponectin (r = -0.53; P <0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P < 0.01; 20 and 16% of explained variance, respectively).'] Is insulin sensitivity correlated with subcutaneous but not visceral body fat in overweight and obese prepubertal children? | qiaojin/PubMedQA | 2 | [
-1.5756367444992065,
-1.3036298751831055,
1.9936784505844116
] |
['Churg-Strauss Syndrome (CSS) is characterized by excessive eosinophil accumulation in peripheral blood and affected tissues with development of granulomatous vasculitic organ damage. The contribution of eosinophil-chemotactic cytokines (eotaxin family) to eosinophilia and disease activity in CSS is unknown. Thus, we compared serum levels of the eotaxin family members in CSS patients with healthy and disease controls.', 'Forty patients with CSS diagnosed according to ACR 1990 criteria, 30 healthy controls (HC) and 57 disease controls (28 asthma, 20 small vessel vasculitis, 9 hypereosinophilic syndrome) were studied. Clinical data were collected and serum levels of eotaxin-1, -2 and -3 were determined by ELISA. Further, immunohistochemistry was applied to identify eotaxin-3 expression in tissue biopsies from patients with CSS.', 'In contrast to eotaxin-1 and -2, eotaxin-3 was highly elevated in serum samples of active CSS patients and correlated highly significantly with eosinophil counts, total immunoglobulin E (IgE) levels and acute-phase parameters. Moreover, eotaxin-3 was not elevated in other eosinophilic and vasculitic diseases. Immunohistochemical analysis revealed strong expression of eotaxin-3 in endothelial and inflammatory cells in affected tissues of active CSS patients.'] Is eotaxin-3 involved in Churg-Strauss syndrome -- a serum marker closely correlating with disease activity? | qiaojin/PubMedQA | 2 | [
-2.390340566635132,
-1.332406997680664,
2.8321006298065186
] |
['To probe into the law of acupuncture analgesic effect and specificities of acupoint action.', "Adult male Kunming mice were randomly divided into a control group, a model group, a model plus electroacupuncture (EA) group and a model plus sham EA group. Chronic inflammatory pain model was prepared by injection of complete Freund's adjuvant (CFA) into right posterior foot, and paw withdrawing latency (PWL) induced by radiation heat was used as pain threshold index, and changes of PWL in all the groups were investigated.", 'After modeling, PWL significantly shortened on the inflammatory side (P < 0.05); EA at bilateral "Zusanli" (ST 36) and "Kunlun" (BL 60) could significantly reverse the shortened PWL (P < 0.05), and this effect was prolonged along with increase of EA times, but in the sham EA group PWL did not significantly change; EA at bilateral "Shousanli" (LI 10) and Neiguan" (PC 6) could not reverse the shortened PWL (P > 0.05).'] Does [ Electroacupuncture alleviate complete Freund 's adjuvant peripheral chronic inflammatory pain in mice ]? | qiaojin/PubMedQA | 2 | [
-2.296929359436035,
-1.3169257640838623,
2.6570353507995605
] |
['The cell morphology, gene expression, and matrix synthesis of articular chondrocytes are known to vary with depth from the tissue surface. The objective of this study was to investigate if chondrocytes from different zones respond to in vitro oscillatory tensile loading in distinct ways and whether tensile strain, which is most prevalent near the articular surface, would preferentially stimulate superficial zone chondrocytes.', 'Chondrocytes were separately isolated from the superficial, middle, and deep zones of articular cartilage and seeded into three-dimensional fibrin hydrogel constructs. An intermittent protocol of oscillatory tensile loading was applied for 3 days, and the effects on extracellular matrix (ECM) synthesis were assessed by measuring the incorporation of radiolabed precursors, size exclusion gel chromatography, and western blotting.', 'Tensile loading was found to be a potent stimulus for proteoglycan synthesis only in superficial zone chondrocytes. Although overall biosynthesis rates by deep zone chondrocytes were unaffected by tensile loading, the molecular characteristics of proteins and proteoglycans released to the culture medium were significantly altered so as to resemble those of superficial zone chondrocytes.'] Do articular chondrocytes derived from distinct tissue zones differentially respond to in vitro oscillatory tensile loading? | qiaojin/PubMedQA | 2 | [
-2.6104025840759277,
-0.9756487011909485,
2.727151870727539
] |
['Expression of the angiotensin type 2 receptor (AT2-receptor) occurs in many animal models of atherosclerosis. However, its expression in human plaques and its functional role remains undetermined. This study examined AT2-receptor expression in human atherosclerotic plaque and also explored its potentially important functional role in atherosclerosis.', 'We analysed carotid atherosclerotic plaques obtained from 14 Caucasian patients who had previously undergone endarterectomy for symptomatic carotid artery stenosis. Half of all subjects received treatment with an angiotensin receptor blocker (ARB) (n=7); the remaining subjects received no intervention in the renin-angiotensin system (n=7). Immunohistochemistry measured tissue expression of smooth muscle cells (a-actin), macrophages (CD68 antibody), collagen (picro-sirius), and AT2-receptor (AT2-receptor antibody).', 'AT2-receptor expression occurred consistently in all specimens. Although cellular localisation varied, AT2-receptor expression levels correlated with macrophage levels (p<0.01). Compared to conventional treatment, ongoing ARB treatment affected neither AT2-receptor levels nor plaque composition.'] Is angiotensin type 2 receptor expressed in human atherosclerotic lesions? | qiaojin/PubMedQA | 2 | [
-2.3059017658233643,
-1.3978312015533447,
2.748114824295044
] |
['We have previously demonstrated a profound hypotensive response to the angiotensin II type 1 (AT1)-receptor antagonist losartan in rats consuming a normal salt diet that is not seen in salt-loaded rats, presumably due to a suppression of the renin-angiotensin system (RAS) by high sodium levels. The purpose of the present study was to examine the cardiovascular effects of changing dietary sodium intake during chronic treatment with losartan. We hypothesised that during blockade of AT1-receptors by chronic losartan infusion, when renin levels would be elevated regardless of dietary sodium, changing diets from high to normal or normal to high salt would have no effect on mean arterial pressure (MAP).', 'To test this hypothesis, groups of rats instrumented with radiotelemetry transducers for MAP monitoring and venous catheters for infusion were initially placed on either a 0.4% salt content diet, referred to as Losartan Normal diet - High salt diet (LosN-HI, n = 7), or a 4.0% salt content diet, referred to as Losartan High salt diet - Normal diet (LosHI-N, n = 9). After a thee-day control period, infusion of losartan was begun in all rats (10 mg/kg/day in 7 ml/day isotonic saline i.v.). After 10 days, diets were switched between groups and data were collected for another 10 days, after which losartan infusion was terminated for a 10-day recovery period.', 'At the start of losartan infusion MAP was observed to be similar between LosN-HI rats (101+/-2 mmHg) and LosHI-N rats (101+/-2 mmHg). By day seven of the first 10 day protocol, MAP in LosN-HI rats had fallen to 71+/-4 mmHg while decreasing to 90+/-2 mmHg in LosHI-N rats. Five days after switching diets, MAP in LosN-HI rats had risen back to 85+/-3 mmHg, while MAP in LosHI-N rats had fallen to 75+/-2 mmHg.'] Does changing dietary sodium alter the chronic cardiovascular effects of losartan in rats? | qiaojin/PubMedQA | 2 | [
-1.8178240060806274,
-1.4263134002685547,
2.225886344909668
] |
['In this study, the influence of anthropometric and training parameters on race performance in ultra-endurance runners in a 24-h run was investigated.', 'Descriptive field study.', '24-h run in Basel 2007.', '15 male Caucasian ultra-runners (mean (SD) 46.7 (5.8 years), 71.1 (6.8 kg), 1.76 (0.07 m), body mass index 23.1 (1.84 kg/m(2))).', 'None.', 'Age, body mass, body height, length of lower limbs, skin-fold thicknesses, circumference of extremities, skeletal muscle mass, body mass, percentage of body fat, and training volume in 15 successful finishers were determined to correlate anthropometric and training parameters with race performance.', 'No significant association (p>0.05) was found between the reached distance and the anthropometric properties. There was also no significant association between the reached distance with the weekly training hours, running years, the number of finished marathons and the number of finished 24-h runs. The reached distance was significantly (p<0.05) positively correlated with the personal best marathon performance (r(2) = 0.40) and the personal best 24-h run distance (r(2) = 0.58). Furthermore, the personal best marathon performance was significantly and positively correlated (p<0.01) with the best personal 24-h run distance (r(2) = 0.76).'] Is personal best marathon performance associated with performance in a 24-h run and not anthropometry or training volume? | qiaojin/PubMedQA | 0 | [
0.6348413228988647,
-0.971464216709137,
-0.4353063106536865
] |
['Changes in footwear and foot orthotic devices have been shown to significantly alter knee joint torques thought to be relevant to the progression if not the development of knee osteoarthritis (OA) in the medial tibiofemoral compartment. The purpose of this study was to determine if commonly prescribed arch support cushions promote a medial force bias during gait similar to medial-wedged orthotics, thereby increasing knee varus torque during both walking and running.', 'Twenty-two healthy, physically active young adults (age, 29.2 +/- 5.1 yr) were analyzed at their self-selected walking and running speeds in control shoes with and without arch support cushions. Three-dimensional motion capture data were collected in synchrony with ground reaction force (GRF) data collected from an instrumented treadmill. Peak external knee varus torque during walking and running were calculated through a full inverse dynamic model and compared.', 'Peak knee varus torque was statistically significantly increased by 6% (0.01 +/- 0.02 N.m.(kg.m)(-1)) in late stance during walking and by 4% (0.03 +/- 0.03 N.m.(kg.m)(-1)) during running with the addition of arch support cushions.'] Does the influence of arch support on knee torques relevant to knee osteoarthritis? | qiaojin/PubMedQA | 2 | [
-1.9357579946517944,
-0.9468163847923279,
1.9238829612731934
] |
['Beta-catenin, the central component of the canonical Wnt pathway, plays important roles in the processes of liver regeneration, growth, and cancer. Previously, we identified temporal expression of beta-catenin during liver development. Here, we characterize the hepatic phenotype, resulting from the successful deletion of beta-catenin in the developing hepatoblasts utilizing Foxa3-cyclization recombination and floxed-beta-catenin (exons 2 through 6) transgenic mice. Beta-catenin loss in developing livers resulted in significantly underdeveloped livers after embryonic day 12 (E12) with lethality occurring at around E17 stages. Histology revealed an overall deficient hepatocyte compartment due to (1) increased cell death due to oxidative stress and apoptosis, and (2) diminished expansion secondary to decreased cyclin-D1 and impaired proliferation. Also, the remnant hepatocytes demonstrated an immature phenotype as indicated by high nuclear to cytoplasmic ratio, poor cell polarity, absent glycogen, and decreased expression of key liver-enriched transcription factors: CCAAT-enhancer binding protein-alpha and hepatocyte nuclear factor-4alpha. A paucity of primitive bile ducts was also observed. While the stem cell assays demonstrated no intrinsic defect in hematopoiesis, distorted hepatic architecture and deficient hepatocyte compartments resulted in defective endothelial cell organization leading to overall fetal pallor.'] Does beta-catenin deletion in hepatoblasts disrupt hepatic morphogenesis and survival during mouse development? | qiaojin/PubMedQA | 2 | [
-2.4897139072418213,
-1.2889149188995361,
2.8396620750427246
] |
['Tube expansion defects like stenoses and atresias cause devastating human diseases. Luminal expansion during organogenesis begins to be elucidated in several systems but we still lack a mechanistic view of the process in many organs. The Drosophila tracheal respiratory system provides an amenable model to study tube size regulation. In the trachea, COPII anterograde transport of luminal proteins is required for extracellular matrix assembly and the concurrent tube expansion.', 'We identified and analyzed Drosophila COPI retrograde transport mutants with narrow tracheal tubes. gammaCOP mutants fail to efficiently secrete luminal components and assemble the luminal chitinous matrix during tracheal tube expansion. Likewise, tube extension is defective in salivary glands, where it also coincides with a failure in the luminal deposition and assembly of a distinct, transient intraluminal matrix. Drosophila gammaCOP colocalizes with cis-Golgi markers and in gammaCOP mutant embryos the ER and Golgi structures are severely disrupted. Analysis of gammaCOP and Sar1 double mutants suggests that bidirectional ER-Golgi traffic maintains the ER and Golgi compartments and is required for secretion and assembly of luminal matrixes during tube expansion.'] Is cOPI vesicle transport a common requirement for tube expansion in Drosophila? | qiaojin/PubMedQA | 2 | [
-2.600482702255249,
-1.025354027748108,
2.7235231399536133
] |
["Several drugs have recently been demonstrated to successfully treat diseases by activating cytolytic or suicidal cell molecular machineries. On the other hand, in healthy subjects cytolytic and suicidal machineries are able to maintain tissue homeostasis, thus preventing the onset of a number of diseases. These machineries include both the cytolysis, exerted by cytotoxic T lymphocytes, of cells 'altered' by infectious or neoplastic antigens (altered cell cytolysis [AlCC]), and the suicide of antigen-activated T cells when in antigen-excess (activated cell suicide [AcCS])."] Does therapeutic restoration of cytolytic and suicidal cell molecular machineries favour disease healing? | qiaojin/PubMedQA | 2 | [
-3.043941020965576,
-0.28828033804893494,
2.453784942626953
] |
['To investigate potential retinal neuroprotective effects of oral lamotrigine in rabbits after pars plana vitrectomy (PPV) and intravitreal silicone oil injection (SOI).', 'Twelve New Zealand rabbits (weight, 2.0-2.5 kg) underwent PPV with SOI on the right eye. For 30 days postoperatively, 6 rabbits received a daily oral dose of lamotrigine (25 mg/kg), and 6 rabbits received a daily oral dose of water. The animals were killed 30 days after surgery. All retinas were processed histologically, immunostained using glial fibrillary acidic protein (GFAP), and analyzed by fluorescence microscopy. Retina sections from all groups were analyzed by TUNEL for the presence of apoptosis and stained with hematoxylin-eosin for morphologic analysis and retina cell density measurements in each layer using a Zeiss Axiophot microscope and KS 400 software.', 'Retinas from water-operated eyes showed a significant decrease in cell density associated with cell death compared with retinas from water-control eyes; cell density was reduced by 56% in the outer nuclear layer (ONL), 49% in the inner nuclear layer (INL), and 64% in the ganglion cell layer (GCL). Lamotrigine-operated retinas showed a reduction in cell death when compared with water-operated retinas; cell death was reduced by 52% in the ONL, 25% in the INL, and 56% in the GCL. Water-operated retinas showed TUNEL-positive cells and GFAP immunofluorescence throughout Müller cell processes; lamotrigine-operated retinas showed no TUNEL-positive cells and decreased GFAP staining when compared with water-operated retinas.'] Do neuroprotective effects of oral lamotrigine administration on rabbit retinas after pars plana vitrectomy and silicone oil injection? | qiaojin/PubMedQA | 2 | [
-2.252002000808716,
-1.408665418624878,
2.6652486324310303
] |
['Glial cells and fibroblasts (FBs) play a key role in epiretinal membrane (ERM) development and progression. Myofibroblasts (myoFBs), arising from these cells, can lead to the hypertrophic scars and tissue contraction observed in ERMs. Nerve growth factor (NGF) and transforming growth factor-beta1 (TGF-beta1) play a crucial role in FB activities. Therefore, the authors evaluated myoFBs in ERMs and NGF, trkA(NGFR and p75(NTR) expression, as well as TGF-beta1/TGF-betaRII levels in both ERMs and vitreous.', 'Eight idiopathic ERMs and vitreous were obtained from patients at the time of vitrectomy for macular pucker. Ten control vitreous were from donors. Biochemical and molecular analyses were performed to identify alpha-smooth muscle actin (alpha-SMA, a defined myoFB marker), NGF, trkA(NGFR)/p75(NTR), and TGF-beta1/TGF-betaRII.', 'Every idiopathic ERM displayed alpha-SMA positive myoFBs, expressing NGF, trkA(NGFR), and p75(NTR). ERM vitreous showed a significant decrease in NGF protein coupled with a TGF-beta1 increase. In addition, vitreous cells showed an increase in trkA(NGFR)/p75(NTR) mRNA associated with a decrease in TGF-betaRII mRNA.'] Do human idiopathic epiretinal membranes express NGF and NGF receptors? | qiaojin/PubMedQA | 2 | [
-2.328829765319824,
-1.3951584100723267,
2.778432846069336
] |
['To investigate macular hole (MH) formation in patients with retinitis pigmentosa (RP) and to determine surgical prognosis for these patients.', 'Data for four RP patients with MHs were retrospectively reviewed. Comprehensive ocular examinations, including electroretinography, Goldmann perimetry, color funduscopy, B-scan ultrasonic tomography, and optical coherence tomography (OCT), were performed. All patients underwent par plana vitrectomy followed by peeling of the posterior inner limiting membrane and gas tamponade. Preoperative best-corrected visual acuity ranged from 20/1000 to 20/100.', 'Typical full-thickness MHs were evident by OCT for three patients. Two of these patients had posterior vitreous detachment or vitreoretinal traction; one had cystoid macular edema in the fellow eye. A fourth patient had extensive retinal detachment; ophthalmoscopy revealed a hole in the macular region. After surgery, significant improvement of visual acuity was recorded for three patients; the patient with retinal detachment had no change in visual acuity in the affected eye. OCT showed adequate sealing of the MHs.'] Do macular hole formation in patients with retinitis pigmentosa and prognosis of pars plana vitrectomy? | qiaojin/PubMedQA | 2 | [
-2.3816375732421875,
-1.352818489074707,
2.8079378604888916
] |
['Obesity and aging increase the risk of type 2 diabetes (T2D). We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults.', 'Twenty-four obese (BMI: 38 +/- 2 kg/m(2)) older (age: 70 +/- 2 years) adults completed a 6-month randomized, controlled trial. Participants were randomized to diet and exercise (treatment group) or no therapy (control group). beta-Cell function (assessed using the C-peptide minimal model), alpha-cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test.', 'Body weight decreased in the treatment group, but did not change in the control group (-9 +/- 1% vs. 0 +/- 1%; P < 0.001). Insulin sensitivity doubled in the treatment group and did not change in the control group (116 +/- 49% vs. -11 +/- 13%; P < 0.05). Even though indices of beta-cell responsivity to glucose did not change (P > 0.05), the disposition index (DI), which adjusts beta-cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 +/- 47% vs. -22 +/- 9%; P < 0.05). The glucagon response decreased in the treatment but not in the control group (-5 +/- 2% vs. 4 +/- 4%; P < 0.05). Insulin secretion rate did not change (P > 0.05), but insulin clearance rate increased (51 +/- 25%; P < 0.05), resulting in lower plasma insulin concentrations.'] Does weight loss therapy improve pancreatic endocrine function in obese older adults? | qiaojin/PubMedQA | 2 | [
-1.4840213060379028,
-1.516924262046814,
2.055209159851074
] |
['Rhodnius prolixus is the main vector of Chagas disease in Venezuela. Here, domestic infestations of poor quality rural housing have persisted despite four decades of vector control. This is in contrast to the Southern Cone region of South America, where the main vector, Triatoma infestans, has been eliminated over large areas. The repeated colonisation of houses by silvatic populations of R. prolixus potentially explains the control difficulties. However, controversy surrounds the existence of silvatic R. prolixus: it has been suggested that all silvatic populations are in fact Rhodnius robustus, a related species of minor epidemiological importance. Here we investigate, by direct sequencing (mtcytb, D2) and by microsatellite analysis, 1) the identity of silvatic Rhodnius and 2) whether silvatic populations of Rhodnius are isolated from domestic populations.', 'Direct sequencing confirmed the presence of R. prolixus in palms and that silvatic bugs can colonise houses, with house and palm specimens sharing seven cytb haplotypes. Additionally, mitochondrial introgression was detected between R. robustus and R. prolixus, indicating a previous hybridisation event. The use of ten polymorphic microsatellite loci revealed a lack of genetic structure between silvatic and domestic ecotopes (non-significant F(ST) values), which is indicative of unrestricted gene flow.'] Do molecular genetics reveal that silvatic Rhodnius prolixus do colonise rural houses? | qiaojin/PubMedQA | 2 | [
-2.5467982292175293,
-0.02434316650032997,
1.7430243492126465
] |
['CCN1 (Cyr61) is an extracellular matrix-associated protein involved in cell proliferation and survival. CCN1 is bound to vascular smooth muscle cells (VSMCs) via integrins and is expressed in VSMCs in atherosclerotic lesions, suggesting involvement in the regulation of vascular smooth muscle cell (VSMC) proliferation and atherosclerosis. We hypothesized that knockdown of CCN1 may inhibit VSMC proliferation and suppress neointimal hyperplasia.', "We examined the effect of the knockdown of CCN1 using rat cultured VSMCs and a rat balloon injury model. CCN1 stimulated adhesion and migration of VSMCs in a dose-dependent manner, and this was blocked by an antibody for integrin alpha(6)beta(1). Moreover, knockdown of endogenous CCN1 by lentiviral delivery of siRNA significantly inhibited proliferation of VSMCs and the uptake of 5-bromo-2'-deoxyuridine (BrdU). Replenishment with recombinant CCN1 reversed the effect of siRNA knockdown. Interestingly, knockdown of CCN1 significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at days 14 and 28 after injury. Gene transfer of CCN1 to smooth muscle reversed the effect of CCN1 knockdown on neointimal formation. These results suggest that endogenous CCN1 regulates proliferation of VSMCs and neointimal hyperplasia."] Does cCN1 knockdown suppress neointimal hyperplasia in a rat artery balloon injury model? | qiaojin/PubMedQA | 2 | [
-2.376971483230591,
-1.2483021020889282,
2.640446662902832
] |
['Estrogens may induce the proliferation of neoplastic cells by activating neo-angiogenesis.', 'To evaluate the effect of estrogens on the expression of vascular endothelial growth factor (VEGF) and related receptors (VEGF-R) in human cholangiocarcinoma and the role played by VEGF in mediating the proliferative effects of estrogens.', 'Seven biopsies of intra-hepatic cholangiocarcinoma and the HuH-28 cell lines were investigated. Cell proliferation was measured by both PCNA Western blot and MTS proliferation assay.', 'By immunohistochemistry, biopsies of human cholangiocarcinoma stained positively for VEGF-A and VEGF-C and related receptors. HuH-28 cells expressed VEGF-A, -C, and VEGFR-1, -2, -3 and, their protein level was enhanced by 17beta-estradiol in association with the stimulation of cell proliferation. 17beta-Estradiol-stimulated proliferation of HuH-28 cells was blocked by 70% by VEGF-TRAP, a receptor-based VEGF inhibitor. 17beta-Estradiol induced the secretion of VEGF in the supernatant of HuH-28 cells. The stimulatory effect of 17beta-estradiol on the protein expression of VEGF-A, VEGF-C and VEGFR-1, -2, -3 was blocked by antagonists of ER (Ici182,780) or insulin-like growth factor 1-receptor (alphaIR3).'] Do estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor? | qiaojin/PubMedQA | 2 | [
-2.456158399581909,
-1.2742063999176025,
2.7633233070373535
] |
['Neonatal stroke is associated with the N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxic brain injury. Src family kinases (SFKs) are considered to be the molecular hub for NMDAR regulation. We determined the relationship between SFKs activation and NMDAR tyrosine phosphorylation after neonatal hypoxia-ischemia (HI) and investigated the neuroprotective potential of a selective SFKs inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3, 4-d] pyramidine), against neonatal brain ischemic injury.', 'The Rice-Vannucci model was adapted for neonatal HI injury in postnatal day 7 CD1 mice. SFKs activity in the postsynaptic densities was measured by Western blot. NMDAR tyrosine phosphorylation and their association with SFKs were determined by coimmunoprecipitation. Brains from animals treated with PP2 or its inactive analog, PP3, were examined histologically with cresyl violet and iron stain to assess the degree of damage.', 'Neonatal HI resulted in a rapid and transient increase in tyrosine phosphorylation of NMDAR subunits NR2A and NR2B. This upregulation correlated with the enhanced association of Fyn and Src with NR2A and NR2B. SFKs were activated in the postsynaptic densities after HI. Inhibition of SFKs with PP2 attenuated brain injury after neonatal HI, whereas PP3 did not protect the brain from the HI insult.'] Do activated Src kinases interact with the N-methyl-D-aspartate receptor after neonatal brain ischemia? | qiaojin/PubMedQA | 2 | [
-2.444152355194092,
-1.3287434577941895,
2.7693300247192383
] |
['To evaluate the effects of three potentially anti-inflammatory probiotic bacteria from three different genera on immune variables in healthy adults in a clinical setting based on previous in vitro characterization of cytokine responses.', 'A total of 62 volunteers participated in this randomized, double-blind and placebo-controlled parallel group intervention study. The volunteers were randomized to receive a milk-based drink containing either Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis ssp. lactis Bb12 (Bb12), or Propionibacterium freudenreichii ssp. shermanii JS (PJS) or a placebo drink for 3 wk. Venous blood and saliva samples were taken at baseline and on d 1, 7 and 21. Fecal samples were collected at baseline and at the end of intervention.', 'The serum hsCRP expressed as the median AUC(0-21) (minus baseline) was 0.018 mg/L in the placebo group, -0.240 mg/L in the LGG group, 0.090 mg/L in the Bb12 group and -0.085 mg/L in the PJS group (P = 0.014). In vitro production of TNF-alpha from in vitro cultured peripheral blood mononuclear cells (PBMC) was significantly lower in subjects receiving LGG vs placebo. IL-2 production from PBMC in the Bb12 group was significantly lower compared with the other groups.'] Does probiotic intervention have strain-specific anti-inflammatory effects in healthy adults? | qiaojin/PubMedQA | 2 | [
-2.2965948581695557,
-1.3426225185394287,
2.6555161476135254
] |
['To use Diffusion Tensor Imaging (DTI) to explore structural integrity and connectivity of the uncinate fasciculus (UF) in patients with temporal lobe epilepsy (TLE) and its relationship to memory performance.', 'DTI and UF reconstruction were performed in 28 patients with TLE (18 left, 10 right) and 10 normal controls. Differences between left and right UF fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and correlations between DTI measures and memory scores in the TLE groups were computed.', 'In controls, FA was higher in the left than right UF (p < 0.01). In left TLE, FA values were lower and ADC values higher than controls in the left UF and ADC values were higher in the right UF (all p < 0.05). In right TLE, ADCs were higher in the left and right UF compared to controls, and FA was reduced in the left UF (all p < 0.05). In left TLE, ADCs in the left UF were negatively correlated with Auditory Immediate (p < 0.05) and Delayed Memory (p < 0.01). Visual Delayed Memory was positively correlated with reduced FA in the ROI of the right UF and increased radial diffusivities (p < 0.05). No significant correlations were found in right TLE. Thus, DTI values correlated with memory scores in the expected direction in patients with left TLE.'] Do abnormalities in diffusion tensor imaging of the uncinate fasciculus relate to reduced memory in temporal lobe epilepsy? | qiaojin/PubMedQA | 2 | [
-2.223842144012451,
-1.0621788501739502,
2.3623294830322266
] |
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