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['Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Among the pathogenetic factors leading to atherosclerosis, the role of insulin resistance and hyperinsulinemia as independent risk factors is still under debate. In this study, we examined the association between ED and insulin resistance in normotensive and normoglycemic first-degree relatives (FDRs) of patients with type 2 diabetes mellitus (DM).', 'Endothelium-dependent and -independent vasodilation of the brachial artery was measured with high-resolution ultrasound (13 MHz) in 53 normotensive FDRs (21 men, 32 women; mean age, 35 years) with normal oral glucose tolerance, 10 age- and sex-matched normal control subjects, and 25 DM patients (mean age, 57 years). According to the tertiles of the clamp-derived glucose metabolic clearance rate (MCR), the FDRs were further classified as insulin resistant with an MCR <or =5.8 mL. kg(-1). min(-1), insulin sensitive (IS) with an MCR > or =7.8 mL. kg(-1). min(-1), and borderline with an MCR of 5.9 to 7.7 mL. kg(-1). min(-1). Flow-associated dilation was 4.1+/-0.9% in insulin-resistant FDRs, 6.7+/-1.1% in borderline FDRs, 9.0+/-1.2% in insulin-sensitive FDRs (P=0.002), 7.7+/-2.9% in control subjects (P=NS versus FDRs), and 3.8+/-1.0% in DM patients (P=0.03). In multiple regression analysis, low MCR was significantly correlated with ED independent of age, sex, smoking, body mass index, percent body fat, serum insulin, and lipids.'] |
['Previous studies in our laboratory have shown that long-term (a period of weeks) increases in pain-related behavior were correlated with the activation of spinal microglia after subcutaneous injection of formalin into the dorsal surface of 1 hind paw. The present study examined whether intrathecal delivery of suramin (a P2 receptor antagonist) blocks microglia activation and long-term hyperalgesia induced by formalin injection. Suramin was administered by using an osmotic pump attached to an intrathecal catheter. Suramin delivery (1.25 microg/kg/h) began 1 day before the formalin injection and lasted for 4 days. Rats were observed by using a modified hot plate test before and at different times after formalin injection. The spinal cord was surveyed for changes in microglia labeling as shown by OX-42 staining at different times after formalin injection. Suramin decreased both the hyperalgesic sensitivity to the thermal stimuli and microglial activation induced by formalin injection as compared to the saline-treated group. This suggests that adenosine triphosphate is one potential mediator that activates spinal cord microglia and enhances pain-related behavior in the formalin model.'] |
['Fifteen minutes of physiological MS induces FGF-2 in osteogenic cells. Here, we show that MS induced proliferation in both MC3T3-E1 and BMOp cells isolated from Fgf2(+/+) mice; Fgf2(-/-) BMOp cells required exogenous FGF-2 for a normal proliferation response. The induction of fgf-2 is mediated by PKA and ERK pathways.', 'Mechanical stress (MS) induces gene expression and proliferation of osteogenic MC3T3-E1 cells. We have previously shown that physiological levels of MS in MC3T3-E1 cells causes extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Here we evaluate the induction and importance of fibroblast growth factor-2 (FGF-2) for MS-induced proliferation.', 'We characterized the MS induction of fgf-2 using a 15-minute pulse of 120 mustrain and studied the stability of fgf-2 message using actinomycin D. Bone marrow stromal cells (BMOp) isolated from Fgf2(-/-) and Fgf2(+/+) mice were used to study the importance of FGF-2 in MS-induced proliferation.', 'We found that the induction of fgf-2 by MS is dependent on both protein kinase A (PKA) and ERK pathways. MS transiently induces fgf-2 within 30 minutes. FGF-2 receptor (FGFR2) was also significantly increased within 1 h. All three isoforms of FGF-2 (24, 22, and 18 kDa) were significantly increased by MS. The MS-mediated increase of fgf-2 mRNA was caused by new synthesis and not stabilization. Pretreatment of MC3T3-E1 cells with cycloheximide showed that the induction of fgf-2 did not require new protein synthesis. Pretreating MC3T3-E1 cells with the mitogen-activated protein kinase (MAPK)/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, or H-89, a PKA inhibitor, significantly inhibited the induction of fgf-2, showing that mechanical induction of fgf-2 is dependent on ERK and PKA signaling pathways. The downstream consequence of a single 15-minute stress pulse was a 3.5-fold increase in cell number in MC3T3-E1 compared with growth in nonstressed control cells. In studies using bone marrow osteoprogenitor cells (BMOp) isolated from Fgf2(+/+)and Fgf2(-/-) mice, we found that FGF-2 was necessary for a full proliferative response to MS.'] |
['To evaluate the impact of smoking on endocrine, metabolic, and clinical parameters in women with polycystic ovary syndrome (PCOS).', 'Cohort analysis.', 'University hospital.', '346 women with PCOS, including 98 smokers and 248 nonsmokers.', 'Screening panel, including physical examination, weight and height measurement, and ultrasound examination of the ovaries, and hormone and insulin measurements.', 'Clinical, metabolic, and endocrine parameters, oral glucose tolerance test, calculation of insulin resistance indexes.', 'In women with PCOS, smoking was associated with statistically significantly increased levels of fasting insulin and calculated free testosterone (cFT) and with a raised free androgen index (FAI) score, which resulted in aggravated scores on the homeostatic model for assessment of insulin resistance (HOMA-IR). However, no differences were observed between the smoking and nonsmoking groups with regard to the clinical parameters for hirsutism, acne, ovulatory function (classified as eumenorrhea, oligomenorrhea, and amenorrhea), or polycystic ovaries using the ultrasound criteria recommended according to the Rotterdam definition.'] |
['The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.', 'Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion.'] |
['Microcirculatory alterations play a central role in the pathophysiology of sepsis. We investigated probe-based confocal laser endomicroscopy (pCLE) to assess alterations in mucosal microcirculatory perfusion in vivo in a porcine model of septic shock and in patients fulfilling consensus criteria for severe sepsis.', 'Septic shock was induced using a faecal peritonitis model in anaesthetized, mechanically ventilated pigs. Mucosal microcirculation was assessed using pCLE in the stomach, duodenum, terminal ileum, and rectum. Duodenal microcirculation was further evaluated in 10 patients with severe sepsis and in 8 healthy controls to quantify capillary diameter, capillary length, and functional capillary density (FCD).', 'In the animal model, FCD was markedly decreased in duodenal (P<0.001), ileal (P<0.001), gastric (P<0.001), and rectal mucosa (P<0.005) 4 h after induction of sepsis. After volume therapy, FCD partially recovered to 90.0% (duodenum), 94.4% (ileum), 95.4% (gastric), and 97% (rectum) of baseline values, indicating decoupling of microvascular and macrovascular flow. In septic patients, the mean capillary diameter (P<0.01) and FCD (P<0.05) in duodenal mucosa were decreased compared with healthy controls.'] |
['Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, hyperandrogenemia and insulin resistance. Hyperreninemia is observed in insulin resistance and hyperandrogenemic states.', 'To investigate the levels of total plasma renin and their possible relationship with insulin resistance and hyperandrogenemia and to explore the effect of metformin on these parameters in PCOS women.', '48 PCOS women who were age- and body mass index (BMI)-matched with 21 healthy women were studied. Total renin, aldosterone levels, glucose and insulin levels were measured at basal state and during an oral glucose tolerance test in all subjects. A subgroup of women with PCOS was evaluated 6 months after metformin administration.', 'Total renin levels were significantly higher in PCOS women compared to controls. PCOS women compared to controls displayed higher areas under the curve for glucose, insulin and total renin (AUCREN). Mean AUCREN was correlated significantly with insulin resistance indices and positively with free testosterone levels. Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment.'] |
['The purpose of this study was to investigate the therapeutic potential of the anti-CD2 mAb OX34 first with regard to bone protection in established rat adjuvant arthritis (AA) and secondly with regard to prevention of AA induction.', 'Established AA was treated with dexamethasone (1 mg/kg body weight) for two days plus OX34 mAb or control mAb over three days (2 mg and then 1 mg) starting at different time points of the disease. For prevention studies animals were injected as above with mAb before induction of AA. Arthritis score (AS), hindpaw thickness, and body weight were blindly measured three times per week. Flow cytometry and hindpaw radiography were performed at the end of the study (day 29).', "Treatment of early AA with OX34 mAb combined with dexamethasone but not dexamethasone plus control mAb dramatically suppressed established AA as assessed by AS and hind paw thickness (> 65% and > 80% reduction, respectively; p < 0.05). Most importantly, early treatment in the course of AA almost completely prevented bone destruction in established AA. When given before AA induction OX34 alone prevented the initiation of arthritis compared with controls (AS reduction 83-95%, p < 0.05). In addition, OX34 plus dexamethasone treatment resulted in depletion of CD4+ T cells but not CD8+ T cells. IL2R+ and CD45RC- ('memory') T cells were significantly reduced."] |
['The commonest bacteria, causing infection across the world is Helicobacter pylori, which colonizes the human stomach. This bacteria has also been detected in some extra-gastric ecological niches such as the oral cavity and water. However, the results of H. pylori detection in extra-gastric ecological niche are controversial. The improvement of the sensitivity and the specificity of the detection methods appear to be some of the main bottleneck issues in providing compelling evidence. The aim of this study was to detect the presence of this organism in dental plaque samples using an analytically sensitive and specific Polymerase Chain Reaction (PCR) as well as a new nucleic acid detection method termed the Loop-mediated Isothermal Amplification (LAMP).', 'In a descriptive cross-sectional study 45 participants enrolled and dental plaque samples were collected from at least two teeth surfaces (one anterior and one posterior tooth) using a sterile periodontal curette. The DNA content was extracted from the samples and the presence of H. pylori was determined by PCR and LAMP reactions.', 'The frequency of detection of H. pylori in the dental plaque samples were 44% (20/45), 66.67% (30/45) and 77.78% (35/45) using PCR, LAMP and positivity for both tests, respectively.'] |
['Tumor response to radiochemotherapy (RCT) varies considerably, even among patients treated in accordance with the same protocol. The aim of the present study was to test the predictive value of the cell-cycle inhibitor p27kip1 with regard to neoadjuvant RCT response in rectal cancer.', 'P27kip1 was evaluated by immunohistochemistry in pretreatment biopsy material obtained from 42 patients with rectal cancer treated uniformly in accordance with an identical prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Four expression patterns (staining intensity [-,+,++,+++] and the percentage of positive cells, evaluated separately for nuclei and cytoplasm) of p27kip1 were investigated for correlation with tumor response, which was assessed in the resected surgical specimen using a histopathological five-point grading system. Additionally, p27(kip1) expression was investigated for correlation with several pathological features, overall survival, and disease-free survival.', 'p27kip1 expression was as follows: nuclear intensity: -: 8, +: 19, ++: 11, +++: 4 cases, median percentage of positive cells: 18.75%; cytoplasmic intensity: -: 0, +: 25, ++: 12, +++: 3 cases, median percentage of positive cells: 70%. Histopathological tumor regression was acceptable in 30 patients (3 complete; 27 good) and inadequate in 12 patients (7 moderate; 5 minimal). No tumor failed to show some regression. No significant correlation was found between any of the p27kip1 expression patterns and RCT response, tumor differentiation (low grade versus high grade), cT- and ypT-category, UICC stage, overall survival, and disease-free survival.'] |
['Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults.', 'One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography.', 'Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62.8 +/- 16.0 mg/l vs. 51.7 +/- 14.6 mg/l, P < 0.0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0.0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0.3097, P = 0.0002).'] |
['Creatine (Cr) supplementation has been shown to attenuate increases in plasma ammonia and hypoxanthine during intense endurance exercise lasting 1 h, suggesting that Cr supplementation may improve muscle energy balance (matching of ATP resynthesis to ATP demand) during such exercise. We hypothesized that Cr supplementation would improve muscle energy balance (as assessed by muscle inosine monophosphate (IMP) accumulation) during intense endurance exercise.', 'Seven well-trained men completed two experimental trials involving approximately 1 h of intense endurance exercise (cycling 45 min at 78+/-1% & OV0312;O2 peak followed by completion of 251+/-6 kJ as quickly as possible (performance ride)). Subjects ingested approximately 42 g.d dextrose for 5 d before the first experimental trial (CON), then approximately 21 g Cr monohydrate plus approximately 21 g.d dextrose for 5 d before the second experimental trial (CREAT). Trials were ordered because of the long washout time for Cr. Subjects were blinded to the order of the trials.', 'Creatine supplementation significantly (P< 0.05) increased muscle total Cr (resting values: CREAT: 138.1+/-7.9; CON: 117.7+/- 6.5 mmol.kg dm). No difference was seen between treatments in any measured muscle or blood metabolite after the first 45 min of exercise. Despite the performance ride completion time being similar in the two treatments ( approximately 13.5 min, approximately 86% & OV0312;O2 peak), IMP at the end of the performance ride was significantly (P<0.05) lower in CREAT than in CON (CREAT: 1.2+/- 0.6; CON: 2.0+/- 0.7 mmol.kg dm).'] |
['To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats.', 'Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA).', 'High-dose JXR signififi cantly reduced FBG and HbA1c level at the 8th week of administration (P <0.01, P <0.05). JXR signififi cantly increased insulin level (P <0.05), and decreased glucagon level (P <0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment.'] |
['During the last 5 years, an increasing body of evidence on the association between adherence to the Mediterranean diet (MD), calculated through specific diet scores, and health status have been accumulated, but limited data are available regarding the association between MD scores and biomarkers. Similarly, many studies have demonstrated a significant protection against chronic diseases from a global healthy lifestyle (HL) pattern which includes not only dietary habits but also physical activity and abstinence from smoking, whereas few data regarding the influence of a HL pattern on circulating biomarkers are available. Using the framework of an epidemiological study conducted in Florence, Italy between 2002 and 2004 we evaluated the association between two different scores (a score of adherence to the MD and a score of adherence to a healthful life which includes abstinence from smoking and a moderate-to-high physical activity level) and some circulating parameters linked to chronic diseases.', 'Dietary habits and anthropometric and biochemical profiles were studied in 932 individuals (365 M; 567 F) with a median age of 47.5 years. Subjects who reported a greater adherence to the MD were found more frequently to be male, married and over 45 years of age. A general linear model dividing the study population into quartiles of scores was used. After adjustment for age, gender, educational status, body mass index and total energy intake, we observed no influence of adherence to the MD on circulating levels of biomarkers. On the other hand, an inverse association between circulating levels of lipid parameters (namely total cholesterol, LDL-cholesterol and triglycerides) and higher scores of adherence to a HL, was reported. In addition, a significant difference between the highest and the lowest quartiles of HL scores for homocysteine plasma levels was observed (p=0.04).'] |
['Thromboembolism resulting from coagulum formation on the catheter and electrode surfaces is a serious complication with radiofrequency ablation procedures for heart rhythm disorders. Why coagulum occurs despite therapeutic heparinization is unclear. In this report, we demonstrate a novel approach to minimize coagulum formation based on the electromolecular characteristics of fibrinogen.', 'Atomic force microscopy was used to establish that fibrinogen deposited on surfaces underwent conformational changes that resulted in spontaneous clot formation. We then immersed ablation catheters that were uncharged, negatively, or positively charged in heparinized blood for 30 minutes and noted the extent of clot formation. In separate experiments, ablation catheters were sutured to the ventricle of an excised porcine heart immersed in whole, heparinized blood and radiofrequency ablation performed for 5 minutes with and without charge delivered to the catheter tips. Electron microscopy of the catheter tips showed surface coverage of fibrin clot of the catheter to be 33.8% for negatively charged catheters, compared with 84.7% (P = 0.01) in noncharged catheters. There was no significant difference in surface coverage of fibrin clot between positively charged catheters (93.8%) and noncharged catheters (84.7%, P = ns). In contrast, the thickness of surface clot coverage for positively charged catheters was 87.5%, compared with 28.45% (P= 0.03) for noncharged catheters and 11.25% (P = 0.03) for negatively charged catheters, compared with noncharged catheters.'] |
['Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents.', 'Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme-linked immunosorbent assay.', 'The mean +/- 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 +/- 2,690 ng/ml; in patients with FMF, 6,720 +/- 4,960 ng/ml; in patients with NOMID, 720 +/- 450 ng/ml; in patients with MWS, 150 +/- 60 ng/ml; in patients with infections, 470 +/- 160 ng/ml; in patients with ALL, 130 +/- 80 ng/ml; in patients with AML, 45 +/- 60 ng/ml; in healthy control subjects, 50 +/- 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively.'] |
['Despite modern treatment programs, less than 20% of adult cases of acute lymphoblastic leukemia (ALL) are cured. For relapsing and/or refractory patients, use of high dose cytosine arabinoside (ara-C) and anthracyclin achieved a complete remission (CR) rate of up to a 75%. The aim of this study was to evaluate in adult patients with ALL 1) the CR rate of a chemotherapy schedule similar to a schedule for acute myeloblastic leukemia (AML) patients, 2) the antileukemic value and the tolerance of 3 intensive stage treatments, and 3) the impact of recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF) on chemotherapy-induced neutropenia and infectious complications, as well as the effect of dose intensity.', 'Between November 1990 and April 1992, 67 patients ages 15-55 years with de novo ALL were randomly assigned to receive either rGM-CSF or placebo. The induction treatment consisted of idarubicin, methylprednisolone, and high dose ara-C. After achieving CR, patients up to age 45 years who had an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation (BMT). All remaining patients received a first course of early intensification with high dose ara-C, mitoxantrone, etoposide, and methylprednisolone, followed by autologous, unpurged BMT.', 'Of the 64 eligible patients, 50 (78%) achieved CR. Sixteen allogeneic and 18 autologous BMTs were performed. The median survival was 10.2 months. The 4-year survival was 24%. rGM-CSF only improved the incidence of severe mucositis during the induction course (P = 0.003) and probably also improved the median duration of fever (P = 0.07).'] |
['Cardiopulmonary bypass induces a systemic inflammatory response, which in turn promotes a cascade of leukocyte and endothelial cell activity. We investigated whether differences in bypass temperature and flow rate affect endothelial cell and leukocyte adhesion in the cerebral microcirculation.', 'Thirty-six piglets (13.0 +/- 1.1 kg) had a cranial window placed over the parietal cortex to evaluate the microcirculation by means of intravital microscopy. Animals were cooled to a temperature of 15 degrees C, 25 degrees C, or 34 degrees C on cardiopulmonary bypass with hematocrit levels of 20% or 30% by using pH-stat management, followed by 60 minutes of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules.', 'Higher bypass temperature correlated with significantly more adherent and rolling leukocytes during the full 60 minutes of low-flow bypass (P <.05). Poisson regression revealed more adherent leukocytes at 34 degrees C than at 15 degrees C and at a flow rate of 10 mL.kg(-1).min(-1) compared with a flow rate of 50 mL.kg(-1).min(-1). There was an inverse correlation between flow rate and the number of adherent and rolling leukocytes at 30, 45, and 60 minutes of low-flow bypass (P <.05). Temperature was a multivariable predictor of histologic score, with greater neurologic damage found after bypass at 34 degrees C (P <.01).'] |
["Clinical risk stratification models, such as the CHA2DS2-VASc, are used to assess stroke risk in atrial fibrillation (AF) patients. No study has yet investigated whether and to which extent these patients have a realistic perception of their personal stroke risk. The purpose of this study was to investigate and describe the association between AF patients' stroke risk perception and clinical stroke risk.", 'In an observational cross-sectional study design, we surveyed 178 AF patients with a mean age of 70.6 years (SD 8.3) in stable anticoagulant treatment (65% treatment duration >12 months). Clinical stroke risk was scored through the CHA2DS2-VASc, and patients rated their perceived personal stroke risk on a 7-point Likert scale.', "There was no significant association between clinical stroke risk assessment and patients' stroke risk perception (rho = .025; P = .741). Approximately 60% of the high-risk patients had an unrealistic perception of their own stroke risk, and there was no significant increase in risk perception from those with a lower compared with a higher risk factor load (χ(2) = .010; P = .522)."] |
['We recently found an elevation in the pre-operative peritoneal lavage carcinoembryonic antigen (CEA) level to be associated with an earlier detection of recurrent peritoneal dissemination and a poor prognosis.', 'Two hundred and twenty-nine patients with gastric cancer were intraoperatively measured for tumor markers, CEA and CA125 based on peritoneal lavage using a chemiluminescent enzyme immunoassay.', 'The patients were divided into four groups. (A) The peritoneal lavage CEA (-) CA125 (-) group (CEA < 0.4 ng/ml, CA125 < 200 ng/ml, n = 129); (B) the peritoneal lavage CEA (-) CA125 (+) group (CEA < 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 50); (C) the peritoneal lavage CEA (+) CA125 (-) group (CEA >or= 0.4 ng/ml, CA125 < 200 ng/ml, n = 18); and (D) the peritoneal lavage CEA (+) CA125 (+) group (CEA >or= 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 32). The 5-year survival of the patients in groups C and D was 40 and 26%, respectively, which was lower than that of the patients in any other group (group A, B; p < 0.0001). Recurrent sites were both peritoneal dissemination and lymph node/liver in group C, while those were only peritoneal dissemination in group D.'] |
['The Danish Psychiatric Central Research Register (DPCRR) has been used extensively for research purposes during the past decades. The aim of this study was to investigate the validity of the International Classification of Diseases (ICD)-10 schizophrenia diagnosis in the DPCRR.', 'A random sample of 300 patients with a first-time diagnosis of schizophrenia (ICD-10 codes F20.0-F20.3 and F20.9) in 2009 was drawn from the register to assess its validity. The case records were reviewed by a Schedules for Clinical Assessment in Neuropsychiatry-certified psychiatric resident using the ICD-10 diagnostic criteria as reference.', 'The sample of 300 patients with schizophrenia represented 23.3% of all incident cases (n = 1,288) registered in 2009. We obtained 291 (97.0%) of the case records (nine were lost or inaccessible). Two case records (0.7%) were excluded because of foreign citizenship as these patients had prior episodes in other countries. Thirteen cases (4.3%) were erroneously registered as schizophrenia in the DPCRR. Of the remaining 276 patients, 269 (97.5%) fulfilled the ICD-10 diagnostic criteria for schizophrenia. In a worst case model including all 300 case records, the validity of the schizophrenia diagnosis was 89.7%.'] |
['To estimate the effects of antibiotic exposures in the first 6 months of life on short- and long-term growth.', 'In a prospective observational cohort study of 497 children from Vellore, India, we estimated short-term effects of antibiotics during the first 6 months using longitudinal general linear regression to model weight-for-age, height-for-age, and weight-for-height z-scores in monthly intervals. To estimate long-term effects, we modeled growth from 6 months to 3 years as a function of antibiotic use in the first 6 months. We also estimated the effects of antibiotics on the monthly relative risks of underweight, stunting, and wasting in the first 6 months and to 3 years.', 'Underweight, stunting, and wasting were common in this population: 31%, 32%, and 15% on average after 6 months of age, respectively. There was no association between antibiotic exposures before 6 months and growth during that period. From 6 months to 3 years, adjusted absolute differences in weight and height were small (approximately -100 g and no more than -2 mm overall, respectively) and not statistically significant.'] |
['This study investigated whether processing emotionally salient information such as emotional facial expressions influences the performance on a cognitive control task in pediatric anxiety and depression.', 'The sample included 68 participants between 8 and 16 years of age selected into three diagnostic groups: Anxiety Disorder (ANX, n = 23), Major Depressive Disorder (MDD, n = 19), and Low-Risk Normal Control (LRNC, n = 26). Participants completed an Emotional Go/NoGo task in which participants must either respond to (Go trials) or not respond to (NoGo trials) specific facial expressions (angry, fearful, sad, happy, neutral). In order to manipulate the level of cognitive control needed to perform the task, the probability of occurrence of the Go trials was varied across 3 probability conditions (low, moderate, high).', 'Analyses showed that the MDD group had significantly faster reaction times to sad face Go trials embedded in neutral face NoGo trials in the moderate probability condition and that the ANX group had significantly slower reaction times to neutral face Go trials embedded in angry face NoGo trials in the low probability condition.'] |
['There is growing interest in high-frequency oscillations (HFO) as electrophysiological biomarkers of the epileptic brain. We evaluated the clinical utility of interictal HFO events, especially their occurrence rates, by comparing the spatial distribution with a clinically determined epileptogenic zone by using subdural macroelectrodes.', 'We obtained intracranial electroencephalogram data with a high temporal resolution (2000 Hz sampling rate, 0.05-500 Hz band-pass filter) from seven patients with medically refractory epilepsy. Three epochs of 5-minute, artifact-free data were selected randomly from the interictal period. HFO candidates were first detected by an automated algorithm and subsequently screened to discard false detections. Validated events were further categorized as fast ripple (FR) and ripple (R) according to their spectral profiles. The occurrence rate of HFOs was calculated for each electrode contact. An HFO events distribution map (EDM) was constructed for each patient to allow visualization of the spatial distribution of their HFO events.', 'The subdural macroelectrodes were capable of detecting both R and FR events from the epileptic neocortex. The occurrence rate of HFO events, both FR and R, was significantly higher in the seizure onset zone (SOZ) than in other brain regions. Patient-specific HFO EDMs can facilitate the identification of the location of HFO-generating tissue, and comparison with findings from ictal recordings can provide additional useful information regarding the epileptogenic zone.'] |
['Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL.', 'This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling.', 'A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival.'] |
['In anticipation of future studies, we examined the pharmacokinetics profile of erythropoietin (EPO) in patients undergoing cardiac surgery.', 'Cardiac surgical patients were enrolled into one of six groups: four cardiopulmonary bypass (CPB) groups [placebo (n = 6), 250 IU/kg EPO (n = 3), 500 IU/kg EPO (n = 3), and 500 IU/kg EPO, two doses (n = 6)] and two off-pump coronary artery bypass (OPCAB) groups [placebo (n = 3) and 500 IU/kg EPO (n = 3)]. The EPO was administered prior to anesthesia and 10 min after CPB (if required). Blood samples for serum EPO were collected at baseline, 10 min after dosing, 5 min after sternotomy, during CPB or the equivalent for OPCAB (5, 15, 45, 60 min), and post-CPB (5, 15, 45, and 60 min, 6, 12 and 24 h, and daily until day 5).', 'Endogenous EPO increased within 24 h of surgery in the placebo group and remained elevated. There was approximately a 40% decrease in serum EPO concentration at the initiation of CPB due to an increase in circulatory blood volume. There were no differences in apparent volume of distribution in the plasma (Vc) (42.2 +/- 9.9, 39.8 +/- 6.3, 42.3 +/- 14.0 mL/kg), clearance (CL) (4.63 +/- 1.14, 3.44 +/- 0.68, 4.27 +/- 0.52 mL h/kg), and t((1/2)) (16.4 +/- 8.0 16.9 +/- 10.6, 22.4 +/- 9.3 h) between the CPB treatment groups. The pharmacokinetic profile of EPO in the OPCAB group was similar to that for the CPB groups: Vc = 39.3 +/- 7.0 mL/kg, CL = 4.98 +/- 0.17 mL h/kg and t((1/2)) = 17.1 +/- 18.1 h.'] |
['Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk.', 'In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation.'] |
['The enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) is key in tyrosine catabolism. Inhibition of HPPD results in tyrosinemia and increased urinary excretion of 3 phenylketones: 4-hydroxyphenylpyruvate (HPPA), 4-hydroxyphenyllactate (HPLA), and 4-hydroxyphenylacetate (HPAA). A previous study involving administration of a novel HPPD inhibitor to dogs resulted in detection of ketonuria in treated animals using urine dipsticks read by reflectance photometry. Dipstick-positive results were suspected to be false because high concentrations of urinary phenylketones have been reported to react with ketone test fields of urine dipsticks, but visual confirmation was not performed.', 'The purpose of this study was to determine which of the 4- hydroxyphenolic acids produced by HPPD inhibition react with ketone test fields of 3 commercially available urine dipsticks.', 'Canine urine samples were prepared with HPPA, HPLA, HPAA, and lithium acetoacetate (positive control) at 6 concentrations. Unmodified urine samples were used as negative controls. All samples were tested for ketones using Combur 10 Test M dipsticks read by a Miditron dipstick analyzer. Urinalysis was also performed by visually inspecting ketone test fields on the Combur 10 Test M, Multistix 10 SG, and Aution 10 EA dipsticks.', 'Urine samples containing HPPA were positive for ketones with Combur 10 Test M dipsticks read by the Miditron analyzer and produced a red–brown color change in ketone test fields of all 3 dipsticks. Urine samples containing HPLA and HPAA were negative by all methods.'] |
['Recently, angiopoietin-2 (Ang-2) was identified as a ligand of the endothelial receptor tyrosine kinase, Tie-2. Ang-2 is an angiopoietin-1 antagonist that plays a role in vascular destabilization and remodelling, which may increase in some diseases. However, serum Ang-2 levels have not been evaluated in patients with COPD. In this study, we examined serum Ang-2 concentrations in patients experiencing COPD exacerbations and in patients with stable COPD.', 'Serum samples were obtained from 49 patients experiencing COPD exacerbations, 22 patients with stable COPD and 18 healthy control subjects. Serum Ang-2 concentrations were measured by ELISA.', 'Serum Ang-2 concentrations were significantly higher in patients with acute exacerbations of COPD than in those with stable COPD or control subjects, and were significantly positively correlated with serum CRP levels but inversely correlated with PaO(2) in patients with exacerbations. In addition, Ang-2 levels decreased significantly after clinical recovery from the acute exacerbation.'] |
['Our previous study found that somatostatin (SST) inhibited the intestinal inflammatory injury in a macaque model of intestinal ischemia-reperfusion (IIR); however, the underlying mechanism was unclear.', 'The present study was aimed to investigate the effects of SST on IFN-γ and the systemic inflammatory response after IIR.', 'Fifteen macaques were randomly divided into controls, IIR and SST+ IIR groups. ELISA was performed to measure IFN-γ in ileum tissues, ileac epithelial cells (IECs) and ileal lymphocytes, as well as the systemic levels of IL-6, IL-1β, TNF-α and IFN-γ in the peripheral circulation and the portal vein. HE staining was performed to evaluate morphological changes in vital organs. Immunohistochemistry was performed to identify the distribution of IFN-γ, CD4, CD8 and CD57 in the ileum.', 'After IIR, IFN-γ level was significantly increased in the IECs. IL-6, IL-1β and TNF-α were significantly increased in both the portal vein and the peripheral circulation; in contrast, IFN-γ level was increased in the portal vein alone. Prophylactic SST reversed the change in IFN-γ in the IECs and portal vein. SST led to an alleviation of the pathological changes in systemic vital organs. The distribution of CD4(+), CD57(+) and CD8(+) cells was not positively correlated with the secretion of IFN-γ.'] |
['Our recent report indicates that breviscapine play a protective role of the kidney by down-regulating transforming growth factor-β1(TGF-β1), α-smooth muscle actin (α-SMA) and alleviating interstitial fibrosis following unilateral ureteral obstruction (UUO). In this study, we investigate the effect of breviscapine on changes of renal water and sodium transport proteins in response to UUO.', "Male Sprague-Dawley rats were divided into 3 groups, sham group, UUO group and UUO treat with breviscapine. After 4, 7 and 14 days, histologic changes and interstitial collagen were determined microscopically following hematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Aquaporins (AQP-2) and γ-epithelial sodium channel (γ-ENaC) were investigated using immunohistochemistry and Western blot in each group.", 'Breviscapine treatment decrease the tubular injury index and the degree of interstitial collagen deposition significantly compared with the UUO group (P<0.05). Breviscapine treatment also significantly reduced downregulation of AQP2 and γ-ENaC compared to those subjected to the same time course of obstruction in UUO group (P<0.05).'] |
["Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables.", 'A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates.', 'Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks.'] |
['Children raised in institutions are at increased risk of developing internalizing and externalizing problems. However, not all children raised in institutions develop psychopathology. Deficits in error monitoring may be one risk pathway for children with a history of institutionalization given that these skills are related to both internalizing and externalizing psychiatric disorders. Error monitoring and the neural circuitry that supports it have a protracted developmental time course and are highly susceptible to the effects of adversity. As such, they may play an important moderating role between a history of institutional rearing and subsequent psychopathology.', 'We investigated the impact of psychosocial deprivation on behavioral and neural responses (event-related potentials: ERPs) to a Flanker task assessing error monitoring and the relations between these measures and psychopathology for 12-year-old children in the Bucharest Early Intervention Project (BEIP). The BEIP involves two groups of institutionalized children randomly assigned in infancy to receive either a foster care intervention (FCG) or care as usual (CAUG).', 'Children who experienced institutional care, particularly those in the CAUG, showed perturbed behavioral performance and ERPs on the Flanker task. Additionally, an ERP measure of error monitoring [error-related negativity (ERN)] moderated the relations between time spent in institutions and externalizing and ADHD behaviors. When the amplitude of the ERN was smaller, time spent in institutional care was positively related to ADHD and externalizing behaviors, whereas time spent in institutions was unrelated to externalizing problems when children evidenced a larger ERN. Neural correlates of error monitoring did not moderate the relations between time spent in institutionalized care and internalizing behaviors.'] |
['Diabetes mellitus is gradually becoming a global health burden leading to an increase in the search for herbal hypoglycemic agents as alternatives to synthetic ones. Asystasia gangetica is one of the herbs used in folklore system of medicine for managing hypoglycaemia associated with diabetes.', 'The influence of the juice of A. gangetica leaf on alloxan-induced diabetic rats was assessed by treating diabetic rats with 25%, 50% and 75% fresh juice and glibenclamide for 5 weeks. Afterwards, the plasma concentrations of glucose, triacylglycerols, total cholesterol, high-density lipoprotein (HDL) cholesterol, thiobarbituric acid reactive substances and bicarbonate were assayed spectrophotometrically.', 'Treatment of the diabetic rats with the juice significantly (P < 0.05) reduced the elevated plasma levels of glucose to a level not significantly (P > 0.05) different from that of glibenclamide. The juice also significantly (P < 0.05) reduced the plasma lipid peroxidation and improved the lipid profile, as indicated by a significant (P < 0.05) reduction in the total cholesterol: HDL cholesterol ratio. However, there was a significant (P < 0.05) rise in the level of bicarbonate as result of the juice treatment from 28.15 ± 2.82 mmol/l in normal control to 60.83 ± 17.46 mmol/l in diabetic control and to 122.20 ± 34.68 mmol/l, 120.95 ± 35.09 mmol/l and 115.85 ± 11.79 mmol/l in 25%, 50% and 75% juice, respectively.'] |
['In Danish health care, secondary prevention after stroke is currently handled mainly by general practitioners using office blood pressure (OBP) assessment of hypertension. The aim of this study was to compare the OBP approach to 24-hour assessment by ambulatory blood pressure (ABP) monitoring. Furthermore, we aimed to record the degree of adherence to recommended therapy goals for blood pressure and plasma lipids.', 'In a prospective observational study, 45 stroke patients aged 25-64 years who were participating in specialized intensive outpatient rehabilitation were monitored by OBP and ABP on average 1.3 (0.14-4.3) years post stroke. Furthermore, data on additional risk factors and medication for secondary prevention were collected.', 'OBP and daytime ABP exceeded the therapy goal of 130/80 mmHg in 71% and 44% of the patients, respectively. ABP exceeded the night-time therapy goal of 115/65 in 57% of cases. Normal dipping at night was found in only 41% (systolic) and 32% (diastolic) of the patients. Considering both day- and night-time blood pressure, antihypertensive medication was absent or inadequate in 60%. Low density lipid (LDL) levels exceeded the recommended limit of 2.5 mmol/l in 49%.'] |
['Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in Breast Cancer (BRCA) deficient breast cancer, but not in molecularly unselected patient populations. Two lines of research in this field are needed: the identification of novel subsets of patients that could potentially benefit from PARP inhibitors and the discovery of suitable targeted therapies for combination strategies.', 'We tested PARP inhibition, alone or combined with the anti-HER2 antibody trastuzumab on HER2+ breast cancer. We used two PARP inhibitors in clinical development, olaparib and rucaparib, as well as genetic downmodulation of PARP-1 for in vitro studies. DNA damage was studied by the formation of γH2AX foci and comet assay. Finally, the in vivo anti-tumour effect of olaparib and trastuzumab was examined in nude mice subcutaneously implanted with BT474 cells.', 'In a panel of four HER2 overexpressing breast cancer cell lines, both olaparib and rucaparib significantly decreased cell growth and enhanced anti-tumour effects of trastuzumab. Cells exposed to olaparib and trastuzumab had greater DNA damage than cells exposed to each agent alone. Mechanistic exploratory assays showed that trastuzumab downmodulated the homologous recombination protein proliferating cell nuclear antigen (PCNA). Combination treatment in the BT474 xenograft model resulted in enhanced growth inhibition, reduced tumour cell proliferation, and increased DNA damage and apoptosis.'] |
['Post-cardiac arrest management has seen significant advances with profound improvements in survival and neurologic outcome. However, early prognostication after return of spontaneous circulation remains most challenging. Biomarkers have evolved as helpful tools in identifying patients who are at increased risk of adverse outcome. While fibroblast growth factor 23 (FGF-23) has recently emerged as a promising predictor of mortality in patients with cardiogenic shock, its role in risk stratification in post-resuscitation management remains unresolved.', 'This study included 90 patients who had been resuscitated and transferred to the ICU of the University Hospital Heidelberg. Survivors and non-survivors were retrospectively analyzed for known prognostic biomarkers as well as FGF-23 serum levels 24h and 72 h post cardiac arrest (CA).', 'FGF-23 levels were significantly elevated in non-survivors compared to survivors. ROC analysis of FGF-23 levels at 24h and 72 h post CA yielded an AUC of 0.759 and 0.726, respectively, for prediction of overall survival after 6 months. FGF-23 levels remained as significant prognosticators after adjusting for age, renal function, and initial cardiac rhythm. FGF-23 levels did not show significant differences in patient outcome after stratification for cardiac origin of CA or left ventricular dysfunction. Furthermore, FGF-23 levels were moderately predictive of poor neurologic outcome in ROC analysis on day 1 and day 3 post CA with an AUC of 0.738 and 0.687, respectively.'] |
['Stretching is a widely accepted standard-of-care therapy following spinal cord injury (SCI) that has not been systematically studied in animal models.', 'To investigate the influence of a daily stretch-based physical therapy program on locomotor recovery in adult rats with moderate T9 contusive SCI.', 'A randomized treatment and control study of stretching in an animal model of acute SCI. Moderate SCIs were delivered with the NYU Impactor. Daily stretching (30 min/day, 5 days/wk for 8 weeks) was provided by a team of animal handlers. Hindlimb function was assessed using the BBB Open Field Locomotor Scale and kinematically. Passive range-of-motion for each joint was determined weekly using a goniometer.', 'Declines in hindlimb function during overground stepping were observed for the first 4 weeks for stretched animals. BBB scores improved weeks 5 to 10 but remained below the control group. Stretched animals had significant deficits in knee passive range of motion starting at week 4 and for the duration of the study. Kinematic assessment showed decreased joint excursion during stepping that partially recovered beginning at week 5.'] |
['Transient receptor potential melastatin 2 (TRPM2) highly expressed in immunocytes is a Ca(2+)-permeable non-selective cation channel activated by oxidative stress. Myocardial ischaemia/reperfusion (I/R) injury is characterized by acute inflammation associated with the augmentation of oxidative stress. We hypothesized that TRPM2 is implicated in the exacerbation of myocardial I/R injury.', 'Wild-type (Trpm2(+/+)) and Trpm2 knockout (Trpm2(-/-)) mice were subjected to ligation of the left main coronary artery followed by reperfusion. Myocardial infarction following I/R, but not ischaemia alone, was reduced more in Trpm2(-/-)mice than in Trpm2(+/+) mice and cardiac contractile functions were also improved in Trpm2(-/-)mice. TRPM2 was highly expressed in the polymorphonuclear leucocytes (PMNs) rather than in the heart. The number of neutrophils and myeloperoxidase (MPO) activity in the reperfused area following ischaemia was lowered in Trpm2(-/-) mice. When Trpm2(+)(/+) or Trpm2(-/-) PMNs were administered to the Trpm2(-/-) heart ex vivo through the perfusate or in vivo by iv injection, Trpm2(+)(/+) PMNs produced enlargement of the infarct size. Following in vitro regional I/R, a pharmacological inhibitor of TRPM2 reduced the infarct size. The combination of H(2)O(2) and leukotriene B(4) (LTB(4)) increased intracellular Ca(2+) concentration and their adhesion to endothelial cells in Trpm2(+)(/+) but not in Trpm2(-/-)PMNs.'] |
['The aim of this study was to investigate if ischemic stroke final infarction volume and location can be used to predict the associated functional outcome using a multi-class support vector machine (SVM).', 'Sixty-eight follow-up MR FLAIR datasets of ischemic stroke patients with known modified Rankin Scale (mRS) functional outcome after 30 days were used. The infarct regions were segmented and used to calculate the percentage of lesioned voxels in the predefined MNI, Harvard-Oxford cortical and subcortical atlas regions as well as using four problem-specific VOIs, which were identified from the database using voxel-based lesion symptom mapping. An overall of 12 SVM classification models for predicting the corresponding mRS score were generated using the lesion overlap values from the different brain region definitions, stroke laterality information, and the optional parameters infarct volume, admission NIHSS, and patient age.', 'Leave-one-out cross validations revealed that including information about the stroke location in terms of lesion overlap measurements led to improved mRS prediction results compared to classification models not utilizing the stroke location information. Furthermore, integration of the optional features led to improved mRS prediction results in all cases tested. The problem-specific brain regions and additional integration of the optional features led to the best mRS predictions with a precise multi-value mRS prediction accuracy of 56%, sliding window multi-value mRS prediction accuracy (mRS±1) of 82%, and binary mRS (0-2 vs. 3-5) prediction accuracy of 85%.'] |
['It is well recognized that the beta-adrenergic receptor-adenylylcyclase system is altered during myocardial ischemia/hypoxia. However, there are no data regarding either regulation of beta-adrenergic receptors, particularly at the mRNA level, or adenylylcyclase activity in isolated cardiac myocytes exposed to chronic hypoxia.', "In a chronic hypoxia model in which neonatal rat ventricular myocytes were exposed to a 1% O2 environment for 72 hours, we investigated (1) beta 1-mRNA and receptor expression and adenylylcyclase activity and (2) beta 1-mRNA and receptor downregulation and adenylylcyclase desensitization induced by prolonged norepinephrine incubation. We found that hypoxia for 72 hours increased myocardial membrane beta 1-adrenergic receptor density by 44%. This increase was not associated with a corresponding decrease in cytosolic beta 1-adrenergic receptors. RNase protection assays demonstrated that hypoxia increased the steady-state levels of beta 1-mRNA by 109%. Adenylylcyclase activity stimulated by isoproterenol, sodium fluoride, guanyl-5'-imidodiphosphate, and forskolin in hypoxic membranes was not altered compared with normoxic controls. Hypoxia for 72 hours also did not affect norepinephrine-induced beta 1-mRNA and receptor downregulation and adenylylcyclase desensitization in response to isoproterenol, guanyl-5'-imidodiphosphate, or forskolin."] |
['Collagen, as a component of the extracellular matrix, has been linked to atherosclerotic plaque formation and stability. Activation of LOX-1, a lectin-like oxidized low-density lipoprotein (LDL) receptor-1, exerts a significant role in collagen formation. We examine the hypothesis that LOX-1 deletion may inhibit collagen accumulation in atherosclerotic arteries in LDL receptor (LDLR) knockout (KO) mice.', 'We generated LOX-1 KO and LOX-1/LDLR double KO mice on a C57BL/6 (wild-type mice) background and fed a 4% cholesterol/10% cocoa butter diet for 18 weeks. Vessel wall collagen accumulation was increased in association with atherogenesis in the LDLR KO mice (P < 0.01 vs. wild-type mice), but much less so in the double KO mice (P < 0.01 vs. LDLR KO mice). Collagen accumulation data were corroborated with pro-collagen I measurements. Expression/activity of osteopontin, fibronectin, and matrix metalloproteinases (MMP-2 and MMP-9) was also increased in the LDLR KO mice (P < 0.01 vs. wild-type mice), but not in the mice with LOX-1 deletion (P < 0.01 vs. LDLR KO mice). The expression of NADPH oxidase (p47(phox), p22(phox), gp91(phox), and Nox-4 subunits) and nitrotyrosine was increased in the LDLR KO mice (P < 0.01 vs. wild-type mice) and not in mice with LOX-1 deletion (P < 0.01 vs. LDLR KO mice). Phosphorylation of Akt-1 and endothelial nitric oxide synthase and expression of haem-oxygenase-1 were found to be reduced in the LDLR KO mice (P < 0.01 vs. wild-type mice), but not in the mice with LOX-1 deletion (P < 0.01 vs. LDLR KO mice).'] |
['Besides the long-leg standing X-ray film focusing on static standing mechanical alignment of the lower extremity, dynamic alignment from full extension to 90° flexion after total knee arthroplasty (TKA) is rarely mentioned. Computer-assisted surgical technology enables surgeons to measure and assess knee behaviour during surgery. This study was designed to analyse the influences of femoral rotation on dynamic alignment of the lower extremity in TKA.', 'Seventy-six consecutive patients with end-stage knee osteoarthritis were enrolled. External rotation osteotomy of the distal femur during TKA was completed according to the pre-operative external rotation angle (ERA), intra-operative transepicondylar axis (TEA) and anteroposterior (AP) line. Passive dynamic alignment of the lower extremity during knee flexion was recorded. The variation trend of hip-knee-ankle (HKA) alignment and the influences of femoral external rotation osteotomy were analysed.', 'Postoperative deviation of HKA alignment from 0° to 90° flexion was associated with the rotational alignment of the femoral component (r\u2009=\u2009-0.769, p\u2009<\u20090.001). Variation trend of HKA alignment during knee flexion tended to be varus, valgus and neutral according to the selected angle of external rotation osteotomy of the distal femur.'] |
['Atherosclerosis is a chronic and progressive inflammatory disease of the arteries that is characterized by subendothelial accumulation of lipid-rich macrophages, called foam cells. We sought to identify the molecular details of cross-talk between liver X receptor α (LXRα) and hypoxia-inducible factor 1α (HIF-1α) for the formation of triglyceride-rich foam cells under hypoxic conditions.', 'We first observed that expression of LXRα and its target lipogenic genes was time-dependently induced in human primary macrophages and RAW 264.7 cells under hypoxia. Similarly, TO901317, an activator of LXRα, enhanced the expression level and the transcriptional activity of HIF-1α. Second, we demonstrated that LXRα increased HIF-1α protein stability through a physical interaction between the ligand binding domain of LXRα and the oxygen-dependent degradation domain of HIF-1α. Third, we found that the activation of HIF-1α or LXRα synergistically induced triglyceride accumulation in macrophages. Finally, we showed that LXRα and HIF-1α were codistributed in the macrophages of atherosclerotic lesions of patients.'] |
["The development of Tuber melanosporum mycorrhizal symbiosis is associated with the production of an area devoid of vegetation (commonly referred to by the French word 'brûlé') around the symbiotic plants and where the fruiting bodies of T. melanosporum are usually collected. The extent of the ecological impact of such an area is still being discovered. While the relationship between T. melanosporum and the other fungi present in the brûlé has been assessed, no data are available on the relationship between this fungus and the bacteria inhabiting the brûlé.", 'We used DGGE and DNA microarrays of 16S rRNA gene fragments to compare the bacterial and archaeal communities inside and outside of truffle brûlés. Soil samples were collected in 2008 from four productive T. melanosporum/Quercus pubescens truffle-grounds located in Cahors, France, showing characteristic truffle brûlé. All the samples were analyzed by DGGE and one truffle-ground was analyzed also using phylogenetic microarrays. DGGE profiles showed differences in the bacterial community composition, and the microarrays revealed a few differences in relative richness between the brûlé interior and exterior zones, as well as differences in the relative abundance of several taxa.'] |
['To examine the influence of stimulus motion on measured visual field extent of 3.5- to 30-month-old children and adults.', 'Each subject was tested with LED-hybrid and LED-kinetic perimetry procedures, using a black double-arc perimeter. Targets in both procedures were identical in size, color, luminance, contrast, and flicker rate. However, in the LED-hybrid procedure, peripheral targets were sequentially illuminated from more peripheral to more central locations, whereas in the LED-kinetic procedure, a peripheral target on a black wand was manually moved centrally along the perimeter arm. A subset of subjects was also tested with white sphere kinetic perimetry (WSKP).', 'The LED-kinetic procedure produced larger measured visual field extent than the LED-hybrid procedure in 3.5-, 11-, 17-, and 30-month-olds, but not in 7-month-olds or adults. Data from subjects tested with WSKP indicated that both stimulus motion and discrepancies in scoring methods contributed to the difference reported previously between visual field measurements obtained with WSKP vs. LED-hybrid perimetry.'] |
['The authors noted a significant increase in the diagnosis of atypical squamous cells of undetermined significance (ASCUS) in premenopausal women using oral contraceptive pills (OCP) (9%) versus women not on OCP (4%) using ThinPrep Pap smears (P = 0.02). The purpose of this study was to correlate these morphologic changes with human papillomavirus (HPV) DNA detection by in situ hybridization and clinical follow-up.', 'Eighty-four ThinPrep Pap smears diagnosed as ASCUS or ASCUS favor low-grade squamous intraepithelial lesions (LGSIL) in young women receiving OCP were studied by HPV in situ hybridization. This information was correlated with colposcopic follow-up and AutoCyte Pap smear results. The authors also studied 80 ThinPreps from young women with a Pap smear diagnosis of unequivocal LGSIL where there was a corresponding biopsy (positive controls) and 40 ThinPreps diagnosed as within normal limits and that rescreened as such (negative controls).', 'The detection rate of HPV DNA by in situ hybridization was 33% (28 of 84) in ASCUS cases versus 90% (72 of 80) for cases of unequivocal LGSIL. A blinded review of the 29 ASCUS Pap smears performed by AutoCyte showed that 66% (19 of 29) were diagnosed as within normal limits. The majority of the cervical biopsies in the women with ASCUS by ThinPrep Pap smears were negative for dysplasia (29 of 39 [74%]) whereas 71 of 80 biopsies (88%) showed dysplasia in women with Pap smears diagnosed as unequivocal LGSIL. The periodic acid-Schiff (PAS) stain demonstrated that many of the cells with halos in the ThinPrep Pap smears that mimicked LGSIL contained glycogen.'] |
['Henoch-Schönlein purpura nephritis (HSPN) is the most serious long-term complication of Henoch-Schönlein purpura and aberrant galactosylation of IgA1 plays a role in its development. However, the precise role of genetic factors contributing to the abnormal IgA1 galactosylation remains unknown.', 'In order to examine the effects of C1GALT1 gene encoding core 1 β1,3-galactosyltransferase, an important role in the β1,3 glycosylation of IgA1, on HSPN susceptibility, we conducted a case-control association genetic study in 269 HSP and 61 HSPN in China. Five tagging SNPs, SNP1(-734 C/T), SNP4(-465A/G), SNP6(-330 G/T), SNP7(-292 C/-), and SNP8(1365 G/A) in C1GALT1 were studied using single-locus and haplotype-based multilocus analysis.', "Our results demonstrated that 1365 G allele frequency was significantly higher in HSPN patients than in HSP patients without nephritis (0.459 vs 0.331, p = 0.0008, adjusted p' = 0.004) with an odds ratio (OR) = 1.716, 95%CI 1.151-2.560). The GG genotype of 1,365 G/A was significantly different in HSP without nephritis and HSPN (p = 0.008, adjusted p'' = 0.04). We did not observe statistically significant differences in haplotype frequencies between HSPN and HSP patients."] |
['During early HIV-1 infection of CD4 T-lymphocytes, many host protein tyrosine kinases become activated within minutes, including phosphoprotein pp60 (c-Src) and the focal adhesion kinase family member, proline-rich tyrosine kinase 2 (Pyk2). Whether their activation facilitates or impedes infection remains to be determined.', 'c-Src kinase inhibitors (SU6656, PP1, and PP2), adenovectors [wild-type and dominant-negative (DN) c-src] or siRNA (targeting c-src or pyk2) were used to inhibit, compete with or knockdown c-Src in Jurkat C, Jurkat E6-1, Hut 78 or Kit225 T-cell lines. Cells were then infected with HIV-1 luciferase reporter virus expressing VSV-G or HXB2(X4) envelope, and luciferase activity was measured after 2 days. Reverse transcriptase activity and viral cDNA were measured 1 hour after infection, whereas integrated virus was measured 12 hours after infection.', 'Pretreating Jurkat T-cells with SU6656 led to increased VSV-G luciferase activity. In the adenovector experiments, T-cells overexpressing dominant-negative c-Src, but not wild-type c-Src, showed increased luciferase activity after VSV-G infection. siRNA knockdown of c-Src or Pyk2, followed by HXB2 infection in Jurkat T-cells, lead to increased reverse transcriptase activity, viral cDNA, integrated virus, and increased luciferase activity.'] |
['Childhood overweight and obesity have increased substantially in the past two decades, raising concerns about their psychosocial and cognitive consequences. We examined the associations between academic performance (AP), cognitive functioning (CF), and increased BMI in a nationally representative sample of children.', 'Participants were 2,519 children aged 8-16 years, who completed a brief neuropsychological battery and measures of height and weight as a part of the Third National Health and Nutrition Examination Survey, a cross-sectional survey conducted between 1988 and 1994. Z-scores were calculated for each neuropsychological test, and poor performance was defined as z-score <2.', 'The association between BMI and AP was not significant after adjusting for parental/familial characteristics. However, the associations between CF remained significant after adjusting for parental/familial characteristic, sports participation, physical activity, hours spent watching TV, psychosocial development, blood pressure, and serum lipid profile. Z-scores on block design (a measure of visuospatial organization and general mental ability) among overweight children and children at risk of overweight were below those of normal-weight children by 0.22 (s.e. = 0.16) and 0.10 (s.e. = 0.10) unit, respectively (P for trend <0.05). The odds of poor performance on block design were 1.97 (95% confidence interval: 1.01-3.83) and 2.80 (1.16-6.75), respectively, among children at risk or overweight compared to normal-weight peers.'] |
['Intraoperative nerve lesions can lead to chronic postoperative pain. There are conflicting data as to whether or not anaesthetics administered intraoperatively are beneficial. We investigated if remifentanil administered at the time of nerve injury was able to attenuate neuropathic hypersensitivity.', 'Rats were anaesthetized with isoflurane, endotracheally intubated, and a tail vein catheter was inserted. Rats received an i.v. infusion of either saline or low- or high-dose remifentanil (2 or 20 μg kg(-1) min(-1), respectively) for 20 min. During this time, rats received a spinal nerve L5 transection to induce neuropathic pain or a sham procedure. Behavioural tests to assess mechanical and cold allodynia and heat hyperalgesia were performed on postoperative days 1, 3, 7, 14, 21, and 28.', 'Sham-operated animals exhibited no hypersensitivity regardless of the intraoperative remifentanil dose. In rats which received spinal nerve L5 transection, mechanical and cold allodynia developed with no significant differences between treatment groups. However, thermal hyperalgesia was reduced in rats given high-dose remifentanil: mean (standard deviation) area under the curve 426 (53) compared with 363 (34) and 342 (24) in saline or low-dose remifentanil treated rats, respectively (P<0.05).'] |
['Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases (IBD). Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD. We performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin.', 'We performed a single-blind, multicenter study of nonanemic patients who had completed the FERGIcor study. Serum levels of ferritin were assessed every second month, and patients were given FCM (total iron dose, 1181 ± 662 mg; n = 105) or placebo (n = 99) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months. Secondary end points included changes of quality of life, disease activity, results from laboratory tests, and adverse events.', 'Anemia recurred in 26.7% of subjects given FCM and in 39.4% given placebo. The time to anemia recurrence was longer in the FCM group (hazard ratio, 0.62; 95% confidence interval, 0.38-1.00; P = .049). Markers of body levels of iron increased or remained at normal levels in subjects given FCM (ferritin increased by 30.3 μg/L, transferrin saturation increased by 0.6%) but decreased in the group given placebo (ferritin decreased by 36.1 μg/L, transferrin saturation decreased by 4.0%). Changes in quality of life and disease activity were comparable between groups. Adverse events were reported in 59.0% of the FCM group and 50.5% of the placebo group, and serious adverse events were reported in 6.7% and 8.1%, respectively.'] |
['Conventional quality control studies of the shelf life of RBC units do not consider cold chain interruptions that occur during cross-matching or between the release of RBCs from the blood bank and their return from the ward. These interruptions may, however, lead to a considerable loss of quality. On the other hand, differences in the quality of RBCs may derive from the different manufacturing processes employed in various blood centres.', 'One day after the expiry date of the RBC unit, we analysed complete blood count, blood gas, potassium, LDH, hydroxybutyrate dehydrogenase, glucose, lactate, total and free haemoglobin (Hb) and ATP and compared the results with regard to the frequency of storage interruptions and to two manufacturers of these RBCs.', "We could not find any correlations between the frequency of interruptions (0-11) and these parameters in any of the data sets. However, we found significant differences when comparing the two suppliers. RBCs of manufacturer A ('A', inline filtration of whole blood) contained 25% more Hb than those of manufacturer B ('B', inline filtration after buffy coat reduction). Sixteen percentage of 'A'-RBC, but none of 'B'-RBC, exceeded a haemolysis of 0.8%."] |
['To investigate whether electroacupuncture (EA) produced analgesic effect and whether nuclear factor kappa B (NF-κB) and cystathionine β synthase (CBS) involved in EA-mediated analgesia in painful diabetic neuropathy in rats.', 'Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) in adult female rats. Mechanical pain threshold was measured by von Frey filaments. EA was applied at acupoint Zu-San-Li (ST-36) in both hindlimbs. Western blot analysis was employed to detect changes in protein levels of NF-κB and CBS in spinal dorsal root ganglion (DRGs).', 'Mechanical allodynia was developed 2\xa0weeks after STZ injection and lasted for another 4\xa0weeks. STZ injection significantly enhanced expression of p65 and CBS in lumbar L4-6 DRGs when compared with age-matched controls. EA markedly attenuated mechanical allodynia. Importantly, EA treatment remarkably inhibited p65 and CBS expression in DRGs. Additionally, intrathecal injection of the p65 antagonist pyrrolidine dithiocarbamate attenuated mechanical allodynia and markedly inhibited CBS expression in DRGs in STZ rats.'] |
['This study aimed to report falls and identify factors that might predict a fall in women aged between 40 and 80 years and thus provide evidence of earlier falls and need for morbidity preventive intervention.', 'A prospective cohort study design over 5 years. Personal demographic data of age, co-morbidities, number of prescribed medications, falls, activity level and living situation were obtained at face-to-face interview. Height, weight, body mass index and postural stability were measured in participating women living independently in the community.', 'Women were categorized into age decade cohorts, with 463 remaining at the year 5 assessment. At baseline, 8% of the women in their forties, 14% in their fifties, 25% in their sixties and 40% in their seventies had fallen in the previous 12 months. Over the 5-year study period, 21% of women in their forties and fifties, 31% of women in their sixties and 47% in their seventies had fallen. Multiple fallers mostly comprised women in their sixties and seventies. Parametric modeling and the classification tree approach revealed age and number of co-morbidities to be most predictive of a fall. Women < 60 years old had an increased risk of a fall by 8% and women > 60 years an increased risk of a fall by 35% with every additional co-morbidity. Stability and other demographics were not predictive of falling.'] |
['A negative relationship between anemia before coronary artery bypass graft (CABG) surgery and the perioperative mortality has been shown. We tried to clarify whether anemia only expresses an increased perioperative risk or is a risk factor per se in a two-institution database.', "In the years 2005 and 2006, 185 of 3,311 patients undergoing isolated first-time CABG surgery had anemia defined as hematocrit less than 33% or Hb≤11 g/dL. Preoperative and postoperative data of patients having anemia and patients having normal hematocrit were compared using χ2-tests or Fisher's exact tests regarding structural group differences. To determine factors influencing perioperative mortality, methods of logistic regression were used.", 'The 30-day mortality of anemic patients (12.9%) was significantly higher (p<0.001) than the mortality of nonanemic patients (2.2%). Patients having anemia, though, had a worse risk profile before surgery: high European System for Cardiac Operative Risk Evaluation values (median, 7 in anemic patients versus 4 in nonanemic patients), acute myocardial infarction (9.7% in anemic versus 2% in nonanemic patients), diabetes mellitus (45.4% in anemic versus 33.3% in nonanemic patients), and cardiogenic shock (5.4% in anemic versus 0.8% in nonanemic patients) were significantly more frequent in the anemic group. However, taking these risks in account, the logistic regression revealed preoperative anemia still to be a mortality-increasing factor in patients undergoing CABG surgery (odds ratio 3.727, confidence interval: 2.196 to 6.324). Furthermore, anemia was a risk factor for perioperative morbidity (major adverse cardiovascular events) after CABG surgery (odds ratio 2.199, confidence interval: 1.423 to 3.397).'] |
['Granulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in alpha motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti-apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti-apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy.', 'We performed sciatic nerve axotomy in neonatal mice overexpressing G-CSF in the CNS and found that G-CSF transgenic mice displayed significantly higher numbers of surviving lumbar motoneurons 4 days following axotomy than their littermate controls. Also, surviving motoneurons in G-CSF overexpressing animals were larger, suggesting additional trophic effects of this growth factor.'] |
['Twin studies have shown that age at menarche may be subject to hereditary influences but the specific determinants are unknown. Estrogens are known to have an important role in menarche. Since the enzyme aromatase is responsible for the conversion of androgens to estrogens, the aromatase (CYP19) gene could be a candidate gene for the regulation of menarche. The aim of this study was to investigate the possible association of the CYP19(TTTA)(n) polymorphism with age at menarche.', 'We studied 130 healthy adolescent females from a closed community in North-Western Greece. Information on menarche was obtained through interviews. The BMI was recorded. The CYP19(TTTA)(n) polymorphism was genotyped.', 'The mean age at menarche was 12.9 ± 1.2 years and the BMI = 19.8 ± 2.3 kg/m(2). Genotype analysis revealed 5 CYP19(TTTA)(n) alleles containing 7-11 TTTA repeats. Girls homozygous for the allele with 7 TTTA repeats had earlier menarche (12.45 ± 0.9 years) than girls carrying other genotypes (13.0 ± 1.2 years, P = 0.025), whereas the BMI was not different between these two subgroups. Carriers of the allele with 11 TTTA repeats had later menarche compared with non-carriers (14.1 ± 0.75 versus 12.8 ± 1.2 years, P< 0.001), whereas no difference was found in BMI values. Comparing girls with early menarche (<12 years, 25th percentile) with girls with late menarche (>13.75 years, 75th percentile), we found that 31% of the girls with early menarche were homozygous for the (TTTA)(7) allele compared with 6.9% among girls with late menarche (P = 0.018). In addition, none of the girls carrying the (TTTA)(11) allele was found among the subgroup with early menarche, whereas 24.1% of girls with late menarche had the (TTTA)(11) allele (P = 0.001). No association between other alleles and age at menarche was found.'] |
['BIM is essential for the response to tyrosine-kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations.', 'BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population) as a case-control study. Real-time quantitative PCR (RT qPCR) was performed to assess Bim expression in our reference population.', 'No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP) c465C>T (rs724710). A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p\u200a=\u200a0.0065). T allele frequency was higher in non responsive patients than in the reference population (p\u200a=\u200a0.0049). Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (p<0.001) and the presence of the T allele significantly lengthened the time to achieve a major molecular response (MMR). Finally, the presence of the T allele was related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy controls.'] |
['A significant prognostic difference exists among metastatic colorectal cancer (CRC) patients despite of any treatments. We identify the specific cytokines related to prognosis of metastatic CRC and assess their prognostic significance.', 'Stage IV CRC patients were divided into two groups according to their prognosis. Difference in serum cytokine level between these groups was determined by the cytokine array. Among the specific cytokines, macrophage inflammatory protein-3 alpha (MIP-3a) was measured using an enzyme-linked immunosorbent assay (ELISA) in the sera of 242 CRC patients.', 'Several cytokines related to prognostic difference in stage IV CRC were identified. The median MIP-3a level (28.2 pg/ml) was used as a cut-off value. Increased MIP-3a was significantly associated with synchronous liver metastases and age. In univariate analysis, high MIP-3a was correlated with poor prognosis (P < 0.001). Multivariate analysis showed that high MIP-3a was an independent prognostic factor in all CRC patients (P < 0.001). In subgroup analysis, high MIP-3a was significantly associated with poor survival in patients with stage II, II/III, and IV CRC, respectively.'] |
['We investigated whether a reduced estimated glomerular filtration rate (eGFR) was associated with cardiovascular disease (CVD) prevalence, independent of the effect of microalbuminuria in patients with diabetes.', 'In a multicentre, large-scale cohort including 3002 Japanese patients with Type 2 diabetes without macroalbuminuria, the relationship of a reduced eGFR and microalbuminuria with CVD was investigated.', 'Of those patients, 4.8% had a reduced eGFR and microalbuminuria, 12.7% had a reduced eGFR without microalbuminuria and 18.7% had microalbuminuria but normal eGFR. A reduced eGFR and microalbuminuria were each associated with a doubling of the prevalence of CVD. Compared with patients with no microalbuminuria/normal eGFR [odds ratio (OR) 1.0], the OR for CVD was significantly higher in those with a reduced eGFR without microalbuminuria (OR 1.97) and similarly higher in those with microalbuminuria without a reduced eGFR (OR 1.85). The OR was highest in those with both a reduced eGFR and microalbuminuria (OR 3.97, 95% confidence interval 2.55-6.20). The OR for CVD remained significant after adjustments for age, sex, hypertension, dyslipidaemia, smoking, body mass index, glycated haemoglobin and the duration of diabetes, and remained significant if the cut-off point for microalbuminuria was set at the median albumin : creatinine ratio (13.7 mg/g creatinine). In patients without microalbuminuria, a reduced eGFR was associated with CVD only in the older and male groups.'] |
['DNA methylation is a heritable covalent modification that is developmentally regulated and is critical in tissue-type definition. Although genotype-phenotype correlations have been described for different subtypes of renal cell carcinoma (RCC), it is unknown if DNA methylation profiles correlate with morphological or ontology based phenotypes. Here, we test the hypothesis that DNA methylation signatures can discriminate between putative precursor cells in the nephron.', 'We performed deep profiling of DNA methylation and transcriptome in diverse histopathological RCC subtypes and validated DNA methylation in an independent dataset as well as in The Cancer Genome Atlas Clear Cell and Chromophobe Renal Cell Carcinoma Datasets.', 'Our data provide the first mapping of methylome epi-signature and indicate that RCC subtypes can be grouped into two major epi-clusters: C1, which encompasses clear-cell RCC, papillary RCC, mucinous and spindle cell carcinomas and translocation RCC; C2, which comprises oncocytoma and chromophobe RCC. Interestingly, C1 epi-cluster displayed 3-fold more hypermethylation as compared with C2 epi-cluster. Of note, differentially methylated regions between C1 and C2 epi-clusters occur in gene bodies and intergenic regions, instead of gene promoters. Transcriptome analysis of C1 epi-cluster suggests a functional convergence on Polycomb targets, whereas C2 epi-cluster displays DNA methylation defects. Furthermore, we find that our epigenetic ontogeny signature is associated with worse outcomes of patients with clear-cell RCC.'] |
['The Krd mouse has a deletion in chromosome 19 that includes the Pax2 gene locus. The aim of this study was to characterize in detail how these retinas differ from normal.', 'Both electroretinographic and anatomic methods were used to assess visual function. Full-field flash electroretinograms (ERGs) and planimetric densities were obtained from Krd and control animals.', 'Measurements of the ERG show that in the Krd mice, both a- and b-wave amplitudes are attenuated relative to control by amounts that vary from animal to animal. The b-wave of the ERG generally is affected more severely than the a-wave. However, there is little or no shift of the curves relating the b-wave and a-wave amplitude to the intensity of the stimulus. Also, no change in the response kinetics seems to be associated with the attenuated responses. Estimates of planimetric cell density in the outer nuclear, inner nuclear, and ganglion cell layers show significant cell losses in affected animals that are more pronounced proportionally in the inner layers. Comparisons between electrophysiological and histologic measurements made on each eye show good correlation between the reduction in the ERG components and the magnitude of cell losses.'] |
['We sought to assess whether pharmacological inhibition of hypoxia-inducible transcription factor (HIF)-prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3) is a suitable strategy to stimulate liver regeneration after partial hepatectomy for colorectal liver metastases (CRLM).', 'Liver regeneration occurs in a hypoxic environment. PHD1 to PHD3 are molecular oxygen sensors and increasingly considered as putative therapeutic targets. However, little is known about the effect of pharmacological PHD inhibition on tumor expansion, and on liver regeneration after surgical resection.', 'Various mouse models of liver regeneration after extended partial hepatectomy and portal vein ligation for multiple bilobar CRLM were applied to assess the effect of the small molecule pan-PHD inhibitor ethyl-3,4-dihydroxybenzoate (EDHB) on liver regeneration and metastatic tumor growth. Metabolism and biodistribution of EDHB were analyzed using liquid chromatography coupled to tandem mass spectrometry.', 'EDHB selectively augmented liver regeneration after partial hepatectomy and portal vein ligation, and increased the expression of cell cycle-promoting cyclin proteins, without enhancing metastatic tumor growth. Systemically administered EDHB and its active metabolite 3,4-dihydroxybenzoic acid accumulated in the liver to selectively induce hepatoprotective effects in the liver, but not in tumor tissue, without humoral adverse effects.'] |
['More than one third of energy intake in Iran is provided from bread. Therefore, improving bread mineral bioavailability through dephytinization can play an important role in decreasing the prevalence of many mineral deficiencies. In this study, effect of phytase supplementation on zinc, iron and calcium status in growing rats fed with a diet containing high phytate Iranian bread (Sangak) was assessed.', "Thirty weanling Wistar male rats were assigned to phytase (Aspergillus niger) or control group for 6 weeks. The diet was designed based on Iranian's food pattern and 34.2% of the energy was supplied from Sangak bread. Food intake, body and organ weight and body height were measured. Zinc was measured in blood, liver and femur. Iron was assessed in blood and liver and calcium was titrated from femur bone. Statistical analyses were performed using SPSS software. Paired sample t-test, Wilcoxon signed-rank test and repeated measurement ANOVA were used for proper analysis of data.", 'Although weekly weight gain was not different between groups, final weight was in favor of control group. Food intakes, liver and femur bone weight did not differ between the two groups. However, the blood zinc was higher in the phytase group (26.2 ± 7.4 vs. 19.2 ± 5.2, P = 0.03). Thus positive effects of phytase supplementation on zinc, independent of growth was found. Other variables did not show any differences between groups.'] |
['The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex but increased left ventricular (LV) diastolic stiffness plays a key role. A load-independent, non-invasive, direct measure of diastolic stiffness is lacking. The diastolic wall strain (DWS) index is based on the linear elastic theory, which predicts that impaired diastolic wall thinning reflects resistance to deformation in diastole and thus, increased diastolic myocardial stiffness. The objectives of this community-based study were to determine the distribution of this novel index in consecutive HFpEF patients and healthy controls, define the relationship between DWS and cardiac structure and function and determine whether increased diastolic stiffness as assessed by DWS is predictive of the outcome in HFpEF.', "Consecutive HFpEF patients (n = 327, EF ≥ 50%) and controls (n = 528) from the same community were studied. Diastolic wall strain was lower in HFpEF (0.33 ± 0.08) than in controls (0.40 ± 0.07, P < 0.001). Within HFpEF, those with DWS ≤ median (0.33) had higher LV mass index, relative wall thickness, E/e', Doppler-estimated LV end-diastolic pressure to LV end-diastolic volume ratio, left atrial volume index, and brain natriuretic peptide (BNP) levels than those with DWS > median. Heart failure with preserved ejection fraction patients with DWS ≤ median had higher rate of death or HF hospitalization than those with DWS > median (P = 0.003) even after the adjustment for age, gender, log BNP, LV geometry, or log E/e' (P < 0.01)."] |
["To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fibrostenosis in patients with Crohn's disease (CD).", 'In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective case-controlled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR, matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen.', 'The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with fibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a significantly shorter median time interval from diagnosis of CD to the first operation with fibrostenosis (32 vs 160 mo). At 10 years, the likelihood of remaining free of operation with fibrostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR.'] |
['Our aim was to determine whether sildenafil citrate (Viagra) unfavorably alters coronary perfusion in canine models of coronary artery stenosis.', 'Concern has been raised that sildenafil may exacerbate ischemia in patients with coronary artery disease. However, the effects of sildenafil on coronary perfusion are largely unexplored.', 'Using anesthetized dogs, a micromanometer constrictor was applied to either an intact coronary artery (model of stable hypoperfusion: Protocol 1) or a site of arterial injury (model of recurrent platelet-mediated thrombosis: Protocol 2). After monitoring coronary flow for 1 h, dogs received two escalating, clinically relevant doses of sildenafil or placebo. Perfusion was assessed during the initial hour pretreatment, for 1 h following dose 1 and 1 h following dose 2 by measuring the area of the flow-time profile, normalized to baseline flow x 60 min. Interaction between sildenafil and adenosine-mediated inhibition of platelet aggregation was evaluated by in vitro platelet aggregometry (Protocol 3).', 'In Protocol 1, flow-time area was maintained at 50% to 60% of baseline in both placebo- and sildenafil-treated groups. In Protocol 2, controls exhibited an expected modest, temporal adenosine-mediated improvement in flow-time area (from 40 +/- 5% to 61 +/- 7%; p < .05) while in contrast, perfusion in sildenafil-treated dogs remained unchanged (37 +/- 6% vs. 33% to 35% before vs. after treatment). In vitro aggregometry confirmed that sildenafil rendered platelets refractory to the inhibitory effects of adenosine receptor stimulation.'] |
['It is not fully elucidated whether obesity enhances hepatocarcinogenesis in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between body weight and risk of hepatocarcinogenesis in chronic hepatitis C patients.', 'We enrolled 1431 patients with chronic hepatitis C who visited our liver clinic between 1994 and 2004, excluding those with hepatocellular carcinoma (HCC) at their visit or with a previous history of HCC. They were divided into 4 groups according to body mass index (BMI): underweight (< or =18.5 kg/m(2), N = 112); normal (18.5 to less than 25 kg/m(2), N = 1023); overweight (25 to less than 30 kg/m(2), N = 265); and obese (>30 kg/m(2), N = 31). We assessed the impact of obesity on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis.', 'During the follow-up period (mean, 6.1 y), HCC developed in 340 patients, showing cumulative incidence rates of 10.5%, 19.7%, and 36.8% at 3, 5, and 10 years, respectively. The incidence differed significantly among the BMI groups (P = .007). Adjusting for other significant factors, overweight and obesity were shown to be an independent risk factor of HCC, with a hazard ratio of 1.86 (95% confidence interval, 1.09-3.16; P = .022) and 3.10 (95% confidence interval, 1.41-6.81; P = .005) as compared with the underweight patients.'] |
['Stromal-epithelial interactions play a fundamental role in tissue homeostasis, controlling cell proliferation and differentiation. Not surprisingly, aberrant stromal-epithelial interactions contribute to malignancies. Studies of the cellular and molecular mechanisms underlying these interactions require ex vivo experimental model systems that recapitulate the complexity of human tissue without compromising the differentiation and proliferation potentials of human primary cells.', 'We isolated and characterized human breast epithelial and mesenchymal precursors from reduction mammoplasty tissue and tagged them with lentiviral vectors. We assembled heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in corresponding monocultures by analyzing growth, differentiation potentials, and gene expression profiles.', 'We show that heterotypic culture of non-immortalized human primary breast epithelial and mesenchymal precursors maintains their proliferation and differentiation potentials and constrains their growth. We further describe the gene expression profiles of stromal and epithelial cells in co-cultures and monocultures and show increased expression of the tumor growth factor beta (TGFβ) family member inhibin beta A (INHBA) in mesenchymal cells grown as co-cultures compared with monocultures. Notably, overexpression of INHBA in mesenchymal cells increases colony formation potential of epithelial cells, suggesting that it contributes to the dynamic reciprocity between breast mesenchymal and epithelial cells.'] |
['Cerebral and flank near-infrared spectroscopy are used to monitor tissue oxygenation during cardiopulmonary bypass in pediatric patients. We sought to validate these noninvasive measurements as predictors of oxygen saturation in the superior and inferior venae cavae during cardiopulmonary bypass.', 'Eight patients underwent elective repair of congenital heart defects with bicaval cannulation. Ultrasonic flow probes and oximetric catheters were placed in the superior and inferior venae cavae limbs of the perfusion circuit. Cerebral and flank near-infrared spectroscopy and 12 additional variables were recorded each minute on cardiopulmonary bypass. Relationships between these variables and superior and inferior venae cavae oxygen saturation were analyzed by linear mixed modeling. The regression of superior vena cava oxygen saturation by current cerebral near-infrared spectroscopy and 1-minute lag cerebral near-infrared spectroscopy, which are equivalent to the regression of the superior vena cava saturation by the current cerebral near-infrared spectroscopy and the 1-minute change in cerebral near-infrared spectroscopy, were used to assess cerebral near-infrared spectroscopy as a trend monitor.', 'The mean number of observation time points per patient was 86 (median 72, range 34-194) for 690 total observations. The root mean square percentage error was 6.39% for the prediction model of superior vena cava saturation by single-factor cerebral near-infrared spectroscopy. The root mean square percentage error was 10.8% for the prediction model of inferior vena cava saturation by single-factor flank near-infrared spectroscopy.'] |
['To investigate the in vitro production of metal-chelating compounds by ectomycorrhizal fungi collected from pine plantations in southern Chile.', 'Scleroderma verrucosum, Suillus luteus and two isolates of Rhizopogon luteolus were grown in solid and liquid modified Melin-Norkans (MMN) media with and without iron addition and the production of iron-chelating compounds was determined by Chrome Azurol S (CAS) assay. The presence of hydroxamate and catecholate-type compounds and organic acids was also investigated in liquid medium. All isolates produced iron-chelating compounds as detected by CAS assay, and catecholates, hydroxamates as well as oxalic, citric and succinic acids were also detected in all fungal cultures. Scleroderma verrucosum produced the greatest amounts of catecholates and hydroxamates whereas the highest amounts of organic acids were detected in S. luteus. Nevertheless, the highest catecholate, hydroxamate and organic acid concentrations did not correlate with the highest CAS reaction which was observed in R. luteolus (Yum isolate).'] |
['The aim of this study was to evaluate whether sildenafil, used for treatment of erectile dysfunction (ED), affects the exercise tolerance and ischaemic threshold in men with exercise-induced angina not taking nitrates.', 'This was a double-blind placebo-controlled study in men with ED and chronic stable angina, assessing the effect of sildenafil on time to limiting angina during incremental treadmill exercise. Patients remained on their antianginal therapy and received a 100-mg dose of sildenafil or placebo 1h prior to treadmill exercise. Other measurements included times to onset of angina, 1-mm ST-segment depression, and total exercise time.', 'Adjusted treatment differences for the time to limiting angina, time to onset of angina, total exercise time, and time to 1-mm ST-segment depression were (mean+/-SE) 20+/-10s (95% CI, 1-39; P=0.040), 32+/-11s (95% CI, 11-53; P=0.004), 20+/-10s (95% CI, 0-39; P=0.049), and 12+/-17s (95% CI, -21 to 45, P=0.48), respectively, in favour of sildenafil. There were no serious treatment-related adverse events.'] |
['Colorectal cancer (CRC) is highly metastatic. Metastases spread directly into local tissue or invade distant organs via blood and lymphatic vessels, but the role of lymphangiogenesis in CRC progression has not been determined. Lymphangiogenesis is induced via vascular endothelial growth factor C (VEGFC) activation of its receptor, VEGFR3; high levels of VEGFC have been measured in colorectal tumors undergoing lymphangiogenesis and correlated with metastasis. We investigated VEGFC signaling and lymphatic barriers in human tumor tissues and mice with orthotopic colorectal tumors.', 'We performed immunohistochemical, immunoblot, and real-time polymerase chain reaction analyses of colorectal tumor specimens collected from patients; healthy intestinal tissues collected during operations of patients without CRC were used as controls. CT26 CRC cells were injected into the distal posterior rectum of BALB/c-nude mice. Mice were given injections of an antibody against VEGFR3 or an adenovirus encoding human VEGFC before orthotopic tumors and metastases formed. Lymph node, lung, and liver tissues were collected and evaluated by flow cytometry. We measured expression of vascular endothelial cadherin (CDH5) on lymphatic vessels in mice and in human intestinal lymphatic endothelial cells.', 'Levels of podoplanin (a marker of lymphatic vessels), VEGFC, and VEGFR3 were increased in colorectal tumor tissues, compared with controls. Mice that expressed VEGFC from the adenoviral vector had increased lymphatic vessel density and more metastases in lymph nodes, lungs, and livers, compared with control mice. Anti-VEGFR3 antibody reduced numbers of lymphatic vessels in colons and prevented metastasis. Expression of VEGFC compromised the lymphatic endothelial barrier in mice and endothelial cells, reducing expression of CDH5, increasing permeability, and increasing trans-endothelial migration by CRC cells. Opposite effects were observed in mice and cells when VEGFR3 was blocked.'] |
['Peripheral serotonin is involved in tumorigenesis and induces a pro-proliferative effect in hepatocellular carcinoma (HCC) cells; however, the intracellular mechanisms by which serotonin exerts a mitogenic effect remain unclear. In this research, we examined whether FOXO3a, a transcription factor at the interface of crucial cellular processes, plays a role downstream of serotonin in HCC cells.', 'The cell viability and expression of FOXO3a was assessed in three HCC cell lines (Huh7, HepG2 and Hep3B) during serum deprivation in the presence or absence of serotonin. Serum free media significantly inhibited HCC proliferation and led to reduced expression and nuclear accumulation of FOXO3a. Knockdown of FOXO3a enhanced the ability of serum deprivation to inhibit HCC cells proliferation. And overexpression of non-phosphorylated FOXO3a in HCC cells reversed serum-deprivation-induced growth inhibition. Serotonin reversed the serum-deprivation-induced inhibition of cell proliferation and upregulated FOXO3a in Huh7 cells; however, serotonin had no effect on the proliferation of serum-deprived HepG2 or Hep3B cells. In addition to proliferation, serotonin also induced phosphorylation of AKT and FOXO3a in serum-deprived Huh7 cells but not in HepG2 and Hep3B cells. However, the phosphorylation of FOXO3a induced by serotonin did not export FOXO3a from nucleus to cytoplasm in serum-deprived Huh7 cells. Consequently, we demonstrated that serotonin promoted the proliferation of Huh7 cells by increasing the expression of FOXO3a. We also provide preliminary evidence that different expression levels of the 5-HT2B receptor (5-HT2BR) may contribute to the distinct effects of serotonin in different serum-deprived HCC cells.'] |
['To investigate the fundamental nature of calcium release events (Ca2+ "sparks") evoked in rat ventricular myocytes during excitation-contraction (E-C) coupling.', 'High-resolution line-scan confocal imaging with the fluorescent calcium indicator and patch-clamp techniques were used to study the spontaneous Ca2+ sparks and sparks evoked by depolarization.', '1) Line scans oriented along the length of the cell showed that both spontaneous sparks and sparks evoked by depolarization to -35 mV appeared to arise at single sites spacing about 1.8 microm apart (ie, the sarcomere length), and measurements of their longitudinal spread (full-width at half-maximal amplitude: FWHM) followed single Gaussian distributions with means of 2.6 microm. 2) Different to this, transverse line scans often revealed spontaneous and evoked sparks that appeared to arise near-synchronously from paired sites. Measurements of transverse FWHM of both spontaneous and evoked sparks showed bimodal distributions, which were fit well by the sums of two Gaussian curves with means of 1.8 and 2.9 microm for spontaneous sparks and with means of 1.9 and 3.1 microm for evoked sparks. Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1, respectively, for spontaneous and evoked sparks.'] |
['Hypoactive sexual desire disorder (HSDD) is one of the most common sexual problems reported by women, but few studies have been conducted to evaluate treatments for this condition.', 'The objective of this study was to evaluate the efficacy and safety of a testosterone patch in surgically menopausal women with HSDD.', 'The design was a randomized, double-blind, parallel-group, placebo-controlled, 24-wk study (the Intimate SM 1 study).', 'The study was performed at private or institutional practices.', 'The subjects studied were women, aged 26-70 yr, with HSDD after bilateral salpingo-oophorectomy who were receiving concomitant estrogen therapy. Placebo (n = 279) or testosterone 300 microg/d (n = 283) was administered. There were 19 patients who withdrew due to adverse events in the placebo group and 24 in the 300 mug/d testosterone group.', 'Testosterone (300 microg/d) or placebo patches were applied twice weekly.', 'The primary end point was the change in the frequency of total satisfying sexual activity at 24 wk. Secondary end points included other sexual functioning end points and safety assessments.', 'At 24 wk, there was an increase from baseline in the frequency of total satisfying sexual activity of 2.10 episodes/4 wk in the testosterone group, which was significantly greater than the change of 0.98 episodes/4 wk in the placebo group (P = 0.0003). The testosterone group also experienced statistically significant improvements in sexual desire and a decrease in distress. The overall safety profile was similar in both treatment groups.'] |
["Behçet's disease is associated with an increased risk of thrombosis, although the prothrombotic mechanisms are unclear. Alterations in blood rheology, particularly increased erythrocyte aggregation, might play a role in the development of such thrombotic events.", 'We measured plasma lipids, fibrinogen, haematocrit, erythrocite aggregation, erythrocyte deformability, blood viscosity, plasma viscosity and erythrocyte indexes in patients with a nonactive disease at sampling, and in a well-matched control group. The patient group comprised 42 patients with BD (21 male, 21 female aged 43+/-12 years) and the control group comprised 46 healthy volunteers (23 male, 23 female aged 45+/-13 years). Twelve of the 42 patients with BD had a previous documented history of deep vein thrombosis at least 6 months before entering the study, and the other 30 did not.', 'Compared with controls, patients showed statistically higher fibrinogen concentrations (P=0.001), plasma viscosity (P=0.002), blood viscosity (P=0.006) and erythrocyte aggregation, both at stasis (P=0.001) and at a low shear rate (P=0.002): the other rheological parameters were not statistically significant. No differences were observed in the rheological parameters when patients with and without previous thrombotic episodes were compared.'] |
['Hypoxia in the portal vein may compromise the survival of intraportally transplanted pancreatic islets. We therefore examined the effect of inspired oxygen on the outcome of islet transplantation.', 'Blood glucose concentrations, glucose tolerance, and the size and number of surviving islets were measured in diabetic rats housed for 48 hr under hyperoxic (100% O(2)), hypoxic (11% O(2)), or normoxic (21%O(2)) conditions after intraportal transplantation of 350, 500, 700, or 1,000 syngeneic islets.', 'In normoxic diabetic rats, the smallest graft size to consistently restore normoglycemia was 1,000 islets. A graft size of 700 islets was effective in only three of nine animals, whereas 500 islets were ineffective in all eight animals undergoing transplantation. In contrast, in hyperoxically housed rats, graft sizes of 700 or 500 islets restored normoglycemia in eight of nine or five of eight animals, respectively. In those animals that became normoglycemic, the glucose tolerance of the hyperoxically treated rats receiving 700 islets was almost identical to that of normoxically housed animals receiving 1,000 islets. The average size of the islets 6 weeks after transplantation was the same in livers of hyperoxic and control rats. However, the total islet area and number of islets engrafted in hyperoxic rats was significantly increased when compared with livers from normoxic animals receiving the same graft size, so the area in hyperoxic rats receiving 700 islets was not significantly different from normoxic recipients of 1,000 islets.'] |
['Computed tomography (CT) substitute images can be generated from ultrashort echo time (UTE) MRI sequences with radial k-space sampling. These CT substitutes can be used as ordinary CT images for PET attenuation correction and radiotherapy dose calculations. Parallel imaging allows faster acquisition of magnetic resonance (MR) images by exploiting differences in receiver coil element sensitivities. This study investigates whether non-Cartesian parallel imaging reconstruction can be used to improve CT substitutes generated from shorter examination times.', 'The authors used gridding as well as two non-Cartesian parallel imaging reconstruction methods, SPIRiT and CG-SENSE, to reconstruct radial UTE and gradient echo (GE) data into images of the head for 23 patients. For each patient, images were reconstructed from the full dataset and from a number of subsampled datasets. The subsampled datasets simulated shorter acquisition times by containing fewer radial k-space spokes (1000, 2000, 3000, 5000, and 10,000 spokes) than the full dataset (30,000 spokes). For each combination of patient, reconstruction method, and number of spokes, the reconstructed UTE and GE images were used to generate a CT substitute. Each CT substitute image was compared to a real CT image of the same patient.', 'The mean absolute deviation between the CT number in CT substitute and CT decreased when using SPIRiT as compared to gridding reconstruction. However, the reduction was small and the CT substitute algorithm was insensitive to moderate subsampling (≥ 5000 spokes) regardless of reconstruction method. For more severe subsampling (≤ 3000 spokes), corresponding to acquisition times less than a minute long, the CT substitute quality was deteriorated for all reconstruction methods but SPIRiT gave a reduction in the mean absolute deviation of down to 25 Hounsfield units compared to gridding.'] |
['We evaluated whether ultrasound improves myocardial tissue perfusion in 14 animals with coronary artery occlusion.', 'A recent study demonstrated that low-frequency ultrasound improves tissue perfusion in the rabbit ischemic limb, but there are no data on ultrasound enhancement of myocardial perfusion.', 'Fourteen animals (9 dogs, 5 pigs) underwent thoracotomy and occlusion of a diagonal branch of the left anterior descending coronary artery. Myocardial tissue perfusion units (TPUs) and pH were measured before coronary occlusion, after occlusion, and after direct exposure of the ischemic myocardium in the presence of fixed occlusion to low-frequency ultrasound (27 kHz).', 'The TPU decreased from 100.9 +/- 13 at baseline to 71.1 +/- 13 (p < 0.01) after 60 min occlusion but rose by 19.7% to 85.1 +/- 8 (p < 0.01) after ultrasound exposure for 60 min. After 60-min coronary occlusion, myocardial pH fell from 7.43 +/- 14 to 7.05 +/- 0.15 (p < 0.01) but then improved to normal (7.46 +/- 0.32) after ultrasound for 60 min. Administration of L-Nomega-nitro-arginine methyl esther (L-NAME), an inhibitor of nitric oxide synthase, before ultrasound exposure, blocked improvement in myocardial tissue perfusion and pH by ultrasound. Quantitative histomorphology showed a significant increase in the capillary area of myocardium exposed to ultrasound versus non-exposed myocardium (16.2 +/- 7.9 vs. 8.2 +/- 2.1, p < 0.02).'] |
['The mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia.', 'We prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤40%, which were subgrouped as follows: New York Heart Association (NYHA) class II (n=59), NYHA class III without cachexia (n=41) and NYHA class III with cachexia (n=18). All patients underwent blood collection, echocardiography and exercise testing.', 'Reduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤15 mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (TAPSE 19 [16-23] vs. 16 [13-19] vs. 14 [9-15] mm, respectively; p<0.001) and an increase in right atrial pressure (RAP; >10 mm Hg: 6.8 vs. 27.5 vs. 75.0%, respectively; p<0.001), indicating a higher degree of congestive right HF in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p ≤ 0.002), suggesting cholestatic dysfunction due to liver congestion. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia.'] |
['To determine whether alpha 1 adrenergic receptor mediated myocyte contractility and growth are depressed acutely after non-occlusive coronary artery narrowing, the left coronary artery was constricted in rats and mechanical behaviour, cytosolic calcium, and regulation of alpha 1 adrenergic receptors were examined in myocytes seven days later.', 'Coronary artery stenosis was surgically induced in rats and following the estimation of global cardiac performance myocytes were enzymatically dissociated and radioligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients and noradrenaline stimulated inositol phosphate generation in myocytes were measured in the presence of WB 4101 or after chlorethylclonidine treatment.', 'Estimations of cell mechanics in vitro established that peak shortening was decreased by 36% and 18% in left and right ventricular myocytes of coronary stenosed rats. Time to peak shortening was prolonged by 29% in left and 20% in right myocytes, whereas velocity of shortening was decreased by 27% in left myocytes. These alterations were associated with increases in cell length and width, indicative of myocyte hypertrophy. In addition, coronary stenosis was accompanied by reductions in the expression of alpha 1a and alpha 1b receptor subtypes in myocytes. alpha 1 Adrenergic receptor density and noradrenaline stimulated phosphoinositol turnover were decreased by 30% and 34% in left myocytes. alpha 1a Adrenergic receptor subtype mediated cytosolic calcium concentration and myocyte mechanical performance were also impaired in left myocytes only. The alpha 1a adrenergic receptor subtype antagonist WB 4101 abolished noradrenaline stimulated inositol phosphate generation in myocytes, whereas chlorethylclonidine at large doses only partially inhibited this response.'] |
['The tuberization mechanism of sweet potato (Ipomoea batatas) has long been studied using various approaches. Morphological data have revealed that the tuberizing events result from the activation of the cambium, followed by cell proliferation. However, uncertainties still remain regarding the regulators participating in this signal-transduction pathway. An attempt was made to characterize the role of one MADS-box transcription factor, which was preferentially expressed in sweet potato roots at the early tuberization stage.', 'A differential expression level of IbMADS1 (Ipomoea batatas MADS-box 1) was detected temporally and spatially in sweet potato tissues. IbMADS1 responses to tuberization-related hormones were assessed. In order to identify the evolutionary significance, the expression pattern of IbMADS1 was surveyed in two tuber-deficient Ipomoea relatives, I. leucantha and I. trifida, and compared with sweet potato. In functional analyses, potato (Solanum tuberosum) was employed as a heterologous model. The resulting tuber morphogenesis was examined anatomically in order to address the physiological function of IbMADS1, which should act similarly in sweet potato.', 'IbMADS1 was preferentially expressed as tuberous root development proceeded. Its expression was inducible by tuberization-related hormones, such as jasmonic acid and cytokinins. In situ hybridization data showed that IbMADS1 transcripts were specifically distributed around immature meristematic cells within the stele and lateral root primordia. Inter-species examination indicated that IbMADS1 expression was relatively active in sweet potato roots, but undetectable in tuber-deficient Ipomoea species. IbMADS1-transformed potatoes exhibited tuber morphogenesis in the fibrous roots. The partial swellings along fibrous roots were mainly due to anomalous proliferation and differentiation in the xylem.'] |
['Near-infrared spectroscopy combined with a vascular occlusion test (VOT) could indicate an impairment of microvascular reactivity (MVR) in septic patients by detecting changes in dynamic variables of muscle O2 saturation (StO2). However, in the perioperative context the consequences of surgical trauma on dynamic variables of muscle StO2 as indicators of MVR are still unknown.', 'This study is a sub-analysis of a randomised controlled trial in patients with metastatic primary ovarian cancer undergoing debulking surgery, during which a goal-directed haemodynamic algorithm was applied using oesophageal Doppler. During a 3 min VOT, near-infrared spectroscopy was used to assess dynamic variables arising from changes in muscle StO2.', 'At the beginning of surgery, values of desaturation and recovery slope were comparable to values obtained in healthy volunteers. During the course of surgery, both desaturation and recovery slope showed a gradual decrease. Concomitantly, the study population underwent a transition to a surgically induced systemic inflammatory response state shown by a gradual increase in norepinephrine administration, heart rate, and Interleukin-6, with a peak immediately after the end of surgery. Higher rates of norepinephrine and a higher heart rate were related to a faster decline in StO2 during vascular occlusion.'] |
['Characteristics of surgeons and their hospitals have been associated with cancer treatments and outcomes. However, little is known about factors that are associated with referral pathways.', 'We analyzed tumor registry and survey data from women with breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries (n = 1,844; response rate, 77.4%) and their attending surgeons (n = 365; response rate 80.0%).', 'About half of the patients (54.3%) reported that they were referred to the surgeon by another provider or health plan; 20.3% reported that they selected the surgeon; and 21.9% reported that they both were referred and were involved in selecting the surgeon. Patients who selected the surgeon based on reputation were more likely to have received treatment from a high-volume surgeon (adjusted odds ratio [OR], 2.2; 95% CI, 1.5 to 3.4) and more likely to have been treated in an American College of Surgeons-approved cancer program or a National Cancer Institute (NCI) -designated cancer center (adjusted OR, 2.0; 95% CI, 1.3 to 3.1; adjusted OR, 3.4; 95% CI, 1.9 to 6.2, respectively). Patients who were referred to the surgeon were less likely to be treated in an NCI-designated cancer center (adjusted OR, 0.5; 95% CI, 0.3 to 0.9).'] |
['Autoimmune hepatitis (AIH) is historically classified into type 1 and type 2 on the basis of the autoantibody profile, anti-nuclear and/or anti-smooth muscle antibodies being the serological markers of type 1 AIH, whereas anti-liver/kidney microsomal antibody type 1 and/or anti-liver cytosol antibody type 1 characterise type 2 AIH.', 'To evaluate whether such a distinction is justified on the basis of different expression of the disease in adults.', 'Twenty-six adult patients with type 2 AIH and 52 age- and sex-matched patients with type 1 AIH, representative of the entire cohort of adults with type 1 AIH, were compared at onset and during follow-up.', 'At diagnosis, median age was 26\xa0years (range 17-53), female sex 86%, acute presentation 43%, severe liver histology 54%, cirrhosis 14%, complete response to treatment 52%, progression of the disease 17%, and median disease duration 72\xa0months (range 12-280). HLA-DRB1*0301 was present in 26%, HLA-DRB1*0401 in 23% and HLA-DRB1*0701 in 25%. Clinical presentation, biochemical parameters, severe liver histology, genetic profile, response rate and progression of the disease were identical between type 1 and type 2 AIH.'] |
['HIV-1 reverse transcriptase (RT) is a heterodimer composed of p66 and p51 subunits and is responsible for reverse transcription of the viral RNA genome into DNA. RT can be post-translationally modified in vitro which may be an important mechanism for regulating RT activity. Here we report detection of different p66 and p51 RT isoforms by 2D gel electrophoresis in virions and infected cells.', "Major isoforms of the p66 and p51 RT subunits were observed, with pI's of 8.44 and 8.31 respectively (p66(8.44) and p51(8.31)). The same major isoforms were present in virions, virus-infected cell lysates and intracellular reverse transcription complexes (RTCs), and their presence in RTCs suggested that these are likely to be the forms that function in reverse transcription. Several minor RT isoforms were also observed. The observed pIs of the RT isoforms differed from the pI of theoretical unmodified RT (p66(8.53) and p51(8.60)), suggesting that most of the RT protein in virions and cells is post-translationally modified. The modifications of p66(8.44) and p51(8.31) differed from each other indicating selective modification of the different RT subunits. The susceptibility of RT isoforms to phosphatase treatment suggested that some of these modifications were due to phosphorylation. Dephosphorylation, however, had no effect on in vitro RT activity associated with virions, infected cells or RTCs suggesting that the phospho-isoforms do not make a major contribution to RT activity in an in vitro assay."] |
['It has been hypothesized that people with subjective hypersensitivity to chemicals may indeed suffer from neuronal damage due to widely distributed environmental toxins and that such deficits of diagnostic importance can be demonstrated with the help of functional neuroimaging even in single cases. In this study, a small group of well-characterized patients with idiopathic environmental intolerance were examined in order to identify such changes.', 'Twelve patients with idiopathic environmental intolerance were investigated neuropsychologically and underwent cerebral F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET). The imaging results were compared with findings from 17 healthy controls.', 'Six patients showed deficits in verbal learning and memory, three of them also had a reduced information processing speed. In the individual analyses, 11 patients showed normal cerebral glucose metabolism. In the group analysis of the patients, no areas with significantly reduced glucose metabolism could be found.'] |
['This study investigated the correlation between the connective tissue graft size and the percentage of root coverage.', 'Fifteen patients with Miller Class I or II recession defects (one tooth/defect per patient) were treated using an envelope connective tissue graft procedure. Clinical parameters including gingival recession depth (RD), clinical attachment level (CAL), keratinized tissue width (KW), and the probing depth (PD) were measured. Visible denuded area (VDA) and graft tissue area (GTA) were indirectly measured in mm2 using computer software. Graft tissue thickness (GTT) and graft tissue width (GTW) were also measured. All clinical parameters and VDA were recorded at baseline and 3 and 6 months. The RD, CAL, KW, PD, and VDA were evaluated by Friedman test. The correlation between the percentage of root coverage (PRC) and factors related to graft size were determined by Spearman rank correlation and nonparametric regression analysis.', 'The percent of root coverage at 3 and 6 months postoperatively was statistically significantly associated with the GTA:VDA ratio (P<0.01); it did not correlate with GTA, GTT, or RD, and was inconsistently correlated to GTW and VDA. In patients who had 100% root coverage, the GTA:VDA ratio ranged between 10.92:1 and 21.95:1; in patients with <100% root coverage, the ratio was between 4.54:1 and 11.06:1.'] |
['To compare implant survival rates after total hip arthroplasty with Exeter matte or polished stems and to determine the relationship of synovitis/joint effusion to signs of implant loosening and stem type.', 'The first part of the study included retrospective revision rate analysis of 118 primary hip replacements performed during 1991-1995. Two different designs of Exeter stems were used: matte surface stems during 1991-1995 (matte surface group--47 cases), and polished stems during 1992-1995 (polished stem group--71 cases). During the second part of the study, 24 patients (11 in polished stem group and 13 in matte stem group) were prospectively examined with radiography and sonography. Sonography was performed in order to evaluate capsular distension, i.e. the distance between prosthetic femoral neck and anterior capsule. Capsular distension depends on synovitis and/or synovia in prosthetic hip. The relationship between capsular distension, stem type, and radiographic signs of loosening was assessed.', 'For the first part of our study, total implant survival was 78% with matte stems and 61% with polished stems 13 years postoperatively (P=0.27). Stem survival was 82% for matte stems, and 88% for polished stems (P=0.54). In the second part of study, a significant relationship between increased capsular distension and cup loosening was determined (P=0.04). We did not find significant difference in capsular distension when compared matte and polished stems.'] |
['Bayesian random-effects meta-analyses require the analyst to specify the prior distribution for between-study variance of the treatment effect. We assessed the sensitivity of prediction and other outputs of the meta-analysis to the choice of this prior.', 'We reanalyzed 7 published meta-analyses (5-14 trials) with rare (event rates <5%), moderate (15%-50%), and frequent binary outcomes (>50%). We examined 10 noninformative priors: inverse gamma on between-study variance (τ (2)), 2 uniforms on each of the between-study standard deviation (τ) and τ (2), uniform shrinkage on τ (2), DuMouchel shrinkage on τ, half-normal on τ (2), and half-normal priors on τ with large and small variances. For each analysis, we calculated the posterior distributions for τ, the population treatment effect in current studies, and the predicted treatment effect in a future study. We assessed goodness of fit using total residual deviance, the deviance information criterion, and predictive deviance (by cross-validations).', 'According to total residual deviance, the best-fitting priors were uniform on τ (2). According to predictive deviance, half-normal on τ (2) and the shrinkage priors were optimal. Across analyses with the 10 priors, there were no important differences in the posteriors for the population treatment effect, but there were substantial differences in the posteriors for τ and predictions. The priors that fitted best according to predictive deviance resulted in less uncertainty around predictions of future treatment effect.'] |
['Smoking has been associated with low serum levels of adiponectin, an adipocytokine with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. The objective of this study was to assess the early effect on adiponectin levels of smoking cessation supported by bupropion.', 'Apparently healthy smokers of both sexes with no additional cardiovascular risk factors were administered 150mg sustained-release bupropion twice daily for 9 weeks. Quitters constituted the active group and non-quitters the control group. Sandwich enzyme-linked immunosorbent assays were employed for the measurement of serum adiponectin and cotinine, the latter used for validation of self-reported abstinence.', "Among the 106 participants (mean age 44.5+/-11.3 years, 57 females, Brinkman index 512.2+/-98.4, basal adiponectin 7.2+/-1.5mg/L), 45 (42.5%) had quitted smoking at week 9. Quitters' post-cessation adiponectin levels were significantly increased (mean difference with baseline 1.9+/-0.8mg/L, 95% CI 1.2, 2.3; p<0.001), while non-quitters' adiponectin remained unaltered. A multiple regression model including female gender (standardized beta coefficient=0.480, p=0.002), age (0.355, p=0.003), body mass index (BMI) (-0.308, p=0.005), waist circumference (-0.276, p=0.008), smoking status (-0.255, p=0.010), and cotinine levels (-0.233, p=0.021) explained about two thirds of the variation in adiponectin levels (adjusted R(2)=0.656)."] |
['Cardiovascular disease (CVD) is increasing in HIV-infected patients. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population. We aimed to quantify the risk of CVD events associated with NT-proBNP at baseline in the Strategies for Management of Anti-Retroviral Therapy study.', 'In a nested case-control study, NT-proBNP was measured at baseline in 186 patients who experienced a CVD event over an average of 2.8 years of follow-up and in 329 matched controls. Odds ratios (ORs) associated with baseline levels of NT-proBNP for CVD were estimated using conditional logistic regression.', 'At baseline median NT-proBNP [interquartile range (IQR)] was 48.1 (18.5, 112.9) pg/ml in patients who developed a CVD event and 25.7 (12.4, 50.2) pg/ml in controls. The unadjusted OR for the highest versus the lowest quartile was 3.7 [95% confidence interval (CI) 2.1-6.5, P < 0.0001]. After adjustment for baseline covariates and CVD risk factors, OR was 2.8 (95% CI 1.4-5.6, P = 0.003); with additional adjustment for IL-6, high-sensitivity C-reactive protein and D-dimer, OR was 2.3 (95% CI 1.1-4.9, P = 0.02).'] |
['Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown.', 'We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells.', 'Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion.'] |
['To investigate the surgical methods and outcome of reshaping the nose by using autologous cartilage grafting-silicone gel complex combined with trimming the lower lateral cartilages and thinning the superfluous tissue of the tip.', 'Between May 2006 and July 2008, 36 patients with ugly nose shape received open nasal plasty by thinning the superfluous tissue and trimming the lower lateral cartilages combined with implant of auto-cartilage and silicone gel complex. There were 3 males and 33 females with an average age of 23 years (range, 18-36 years), including 20 cases of hypertrophy and obtuse round of nasal tip, 10 cases of flat of nasal tip, 2 cases of slight nostril exposure, and 4 cases of small whole nose with hypertrophy of nasal tip. Among them, 8 cases received 2-time operations.', 'All incisions achieved healing by first intention. No deformation and complication occurred at donor sites of cartilage. The appearance, contour, color, and touch sensation of the nose were satisfactory and no complications of prosthesis exposure and skin redness of the nasal tip occurred. At 3-5 months after operation, the appearance of the nasal tip was satisfactory when part of the soft tissue was absorbed. Thirty-two patients were followed up 3-12 months (6 months on average), who were satisfied with the appearance of nose with good correct rate.'] |
['In our previous studies, we found that intraglomerular deposition of fibrin and its metabolites was related to glomerular sclerosis and reduced renal function. It has been reported that both overlying and underlying fibrin may induce specific morphological changes of cultured endothelial cells from large blood vessels. The dependency of these morphological changes on the integrin alphavbeta3-arginyl-glycyl-aspartyl-serine (RGDS) interaction is still controversial. We hypothesized that glomerular endothelial cells (GECs) stimulated by fibrin might undergo morphological changes through an integrin alphavbeta3-RGDS interaction. Methods. In vitro studies were performed to examine the growing status of GECs stimulated by overlying and underlying fibrin gels in the presence or absence of the following: 50 microg/ml anti-alphavbeta3 integrin monoclonal antibody 23C6 or nonimmune mouse IgG, 1 mg/ml synthetic RGDS or arginyl-glycyl-glycyl-serine (RGGS) peptide, 10 mg/ml sodium heparin, 100 microg/ml cycloheximide, and 10 microM actinomycin D. Fast protein liquid chromatography (FPLC)-purified fibrinogen and the third to fifth passages of human GECs were also used in this study.', 'GECs developed capillary tube structure after 60 hours of culturing on fibrin gels, and GECs cultured on gelatin-coated plates displayed a monolayer of cobblestone-like cells in the presence or absence of 23C6 and synthetic RGDS peptide. Fibrin-induced capillary tube formation was promoted by 23C6 and inhibited by RGDS peptide, cycloheximide, and actinomycin D. Disorganization of the GEC monolayer was induced by overlying fibrin, but was not induced by overlying agarose gels and glass cover slips or culturing in fibrinogen, 0.05 NIH U/ml thrombin, fibrin supernatants, as well as in fibrin degradation products. Disorganization of GEC monolayer can be induced by both des-AA-fibrin and des-AABB-fibrin and was unaffected by heparin. Furthermore, both 23C6 and synthetic RGDS peptide prevented disorganization of GECs induced by overlying fibrin, whereas nonimmune mouse IgG, synthetic RGGS peptide, cycloheximide, and actinomycin D had no similar effect.'] |
['Interleukin-27 (IL-27) has been proposed to be useful for diagnosing tuberculous pleural effusion (TPE). Adenosine deaminase (ADA) has been long used for the same purpose. The aim of this study was to compare the performance of IL-27, ADA, and their product (IL-27 • ADA) in the diagnosis of TPE.', 'Pleural fluid samples from patients with exudative pleural effusions were assessed for IL-27 and ADA levels. Receiver operating characteristic (ROC) curves were constructed to compare the overall diagnostic accuracy of IL-27, ADA, and IL-27 • ADA. Curves of false-positive (FPR) and false-negative (FNR) rates as a function of TPE prevalence were also constructed, and mean rates of false results in low (1-10%), intermediate (11-40%), and high (41-70%) prevalences were estimated to evaluate the ability of the three markers in ruling in or ruling out TPE.', 'We studied 121 exudates. IL-27 and ADA were higher in TPEs compared with non-TPEs and they presented similar accuracies for the diagnosis of TPE. The product of IL-27 and ADA (IL-27 • ADA) was more accurate than ADA for the same purpose. IL-27 and IL-27 • ADA presented the lowest overall FPR and FNR, respectively. The FPR of IL-27, ADA and IL-27 • ADA was > 9%, even in high prevalence settings. Although their FNR was < 2% in low prevalence settings, only IL-27 • ADA exhibited sufficiently low FNR (< 1%) in intermediate and high prevalences.'] |
['Paternal age at childbirth has been increasing worldwide, and we assessed whether this increase affects growth, body composition and metabolism in their children.', 'We studied 277 children (aged 3-12 years) born to fathers aged 19·8-51·8 years. Clinical assessments were height and weight adjusted for parental measurements, DEXA-derived body composition, fasting lipids, glucose homoeostasis and hormonal profiles.', 'Children born to fathers aged 31-35 (P = 0·009) and >35 years (P = 0·021) were 2 cm taller than those of fathers aged ≤30 years. Children of fathers aged >35 years at childbirth had a lower body mass index (BMI) (-0·32 SDS) than offspring of fathers aged 31-35 (-0·01 SDS; P = 0·043) and ≤30 (0·22 SDS; P = 0·019). There were marked effects of paternal age at childbirth on childhood blood lipids. LDL-C concentrations in children born to fathers aged >35 years were 11% and 21% higher than in children of fathers aged 31-35 and ≤30 years, respectively (P < 0·01). Total cholesterol to HDL-C ratio was also higher among the children of fathers aged 31-35 (12%; P = 0·014) and >35 (16%; P = 0·004) years at childbirth compared with the ≤30 group. In addition, HOMA-IR in girls (but not boys) born of fathers aged 31-35 (0·99) and >35 years (1·11) indicated better insulin sensitivity compared with offspring in the ≤30 group (1·63; P < 0·05).'] |
['Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells and is implicated in the vascular response to injury and the pathogenesis of atherosclerosis. It is also a potent vasoconstrictor.', 'To examine whether acute myocardial ischemia increases the level of PDGF in the coronary circulation, we measured plasma levels of PDGF in the coronary sinus and the aortic root simultaneously in 14 patients with coronary spastic angina. These measurements were performed before and after the left coronary artery spasm induced by intracoronary injection of acetylcholine, and measurements were also taken in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Eleven patients with chest pain but normal coronary arteries and no coronary spasm served as controls.', 'Plasma PDGF levels increased significantly (P < 0.01) from 274 +/- 28 pg/mL to 364 +/- 27 pg/mL only in coronary sinus after anginal attacks in the patients with coronary spastic angina. However, plasma PDGF levels in coronary sinus remained unchanged after these attacks in the patients with stable exertional angina (from 230 +/- 27 pg/ml to 247 +/- 28 pg/mL) and after intracoronary injection of acetylcholine in the control subjects. Plasma PDGF levels in aortic root remained unchanged in all three patient groups.'] |
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