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Selected AbstractsOn the transient phase of balanced SSFP sequencesMAGNETIC RESONANCE IN MEDICINE, Issue 4 2003Klaus Scheffler Abstract The signal intensity of balanced steady-state free precession (SSFP) imaging is a function of the proton density, T1, T2, flip angle (,), and repetition time (TR). The steady-state signal intensity that is established after about 5*T1/TR can be described analytically. The transient phase or the approach of the echo amplitudes to the steady state is an exponential decay from the initial amplitude after the first excitation pulse to the steady-state signal. An analytical expression of the decay rate of this transient phase is presented that is based on a simple analysis derived from the Bloch equations. The decay rate is a weighted average of the T1 and T2 relaxation times, where the weighting is determined by the flip angle of the excitation pulses. Thus, balanced SSFP imaging during the transient phase can provide various contrasts depending on the flip angle and the number of excitation pulses applied before the acquisition of the central k -space line. In addition, transient imaging of hyperpolarized nuclei, such as 3He, 129Xe, or 13C, can be optimized according to their T1 and T2 relaxation times. Magn Reson Med 49:781,783, 2003. © 2003 Wiley-Liss, Inc. [source] Comparison of relative forced expiratory volume of one second with dynamic magnetic resonance imaging parameters in healthy subjects and patients with lung cancer,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2005Christian Plathow MD Abstract Purpose To assess relative forced expiratory volume in one second (FEV1/vital capacity (VC)) in healthy subjects and patients with a lung tumor using dynamic magnetic resonance imaging (dMRI) parameters. Materials and Methods In 15 healthy volunteers and 31 patients with a non-small-cell lung carcinoma stage I (NSCLC I), diaphragmatic length change (LE1) and craniocaudal (CC) intrathoracic distance change within one second from maximal inspiration (DE1) were divided by total length change (LEtotal, DEtotal) as a surrogate of spirometric FEV1/VC using a true fast imaging with steady-state precession (trueFISP) sequence (TE/TR = 1.7/37.3 msec, temporal resolution = 3 images/second). Influence of tumor localization was examined. Results In healthy volunteers FEV1/VC showed a highly significant correlation with LE1/LEtotal and DE1/DEtotal (r > 0.9, P < 0.01). In stage IB tumor patients, comparing tumor-bearing with the non-tumor-bearing hemithorax, there was a significant difference in tumors of the middle (LE1/LEtotal = 0.63 ± 0.05 vs. 0.73 ± 0.04, DE1/DEtotal = 0.66 ± 0.05 vs. 0.72 ± 0.04; P < 0.05) and lower (P < 0.05) lung region. Stage IA tumor patients showed no significant differences with regard to healthy subjects. Conclusion dMRI is a simple noninvasive method to locally determine LE1/LEtotal and DE1/DEtotal as a surrogate of FEV1/VC in volunteers and patients. Tumors of the middle and lower lung regions have a significant influence on these MRI parameters. J. Magn. Reson. Imaging 2005;21:212,218. © 2005 Wiley-Liss, Inc. [source] Thyroid hormone receptor , can control action potential duration in mouse ventricular myocytes through the KCNE1 ion channel subunitACTA PHYSIOLOGICA, Issue 2 2010A. Mansén Abstract Aims:, The reduced heart rate and prolonged QTend duration in mice deficient in thyroid hormone receptor (TR) ,1 may involve aberrant expression of the K+ channel ,-subunit KCNQ1 and its regulatory ,-subunit KCNE1. Here we focus on KCNE1 and study whether increased KCNE1 expression can explain changes in cardiac function observed in TR,1-deficient mice. Methods:, TR-deficient, KCNE1-overexpressing and their respective wildtype (wt) mice were used. mRNA and protein expression were assessed with Northern and Western blot respectively. Telemetry was used to record electrocardiogram and temperature in freely moving mice. Patch-clamp was used to measure action potentials (APs) in isolated cardiomyocytes and ion currents in Chinese hamster ovary (CHO) cells. Results:, KCNE1 was four to 10-fold overexpressed in mice deficient in TR,1. Overexpression of KCNE1 with a heart-specific promoter in transgenic mice resulted in a cardiac phenotype similar to that in TR,1-deficient mice, including a lower heart rate and prolonged QTend time. Cardiomyocytes from KCNE1-overexpressing mice displayed increased AP duration. CHO cells transfected with expression plasmids for KCNQ1 and KCNE1 showed an outward rectifying current that was maximal at equimolar plasmids for KCNQ1-KCNE1 and decreased at higher KCNE1 levels. Conclusion:, The bradycardia and prolonged QTend time in hypothyroid states can be explained by altered K+ channel function due to decreased TR,1-dependent repression of KCNE1 expression. [source] Rotational and Vibrational Temperature Measurements in a High-Pressure Cylindrical Dielectric Barrier Discharge (C-DBD)CONTRIBUTIONS TO PLASMA PHYSICS, Issue 1 2005N. Masoud Abstract The rotational (TR) and vibrational (Tv) temperatures of N2 molecules were measured in a high-pressure cylindrical dielectric barrier discharge (C-DBD) source in Ne with trace amounts (0.02 %) of N2 and dry air excited by radio-frequency (rf) power. Both TR and Tv of the N2 molecules in the C 3,u state were determined from an emission spectroscopic analysis the 2nd positive system (C 3,u , B3,g). Gas temperatures were inferred from the measured rotational temperatures. As a function of pressure, the rotational temperature is essentially constant at about 360 K in the range from 200 Torr to 600 Torr (at 30W rf power) and increases slightly with increasing rf power at constant pressure. As one would expect, vibrational temperature measurements revealed significantly higher temperatures. The vibrational temperature decreases with pressure from 3030 K at 200 Torr to 2270 K at 600 Torr (at 30 W rf power). As a function of rf power, the vibrational temperature increases from 2520 K at 20 W to 2940 K at 60 W (at 400 Torr). Both TR and Tv also show a dependence on the excitation frequency at the two frequencies that we studied, 400 kHz and 13.56 MHz. Adding trace amounts of air instead of N2 to the Ne in the discharge resulted in higher TR and Tv values and in a different pressure dependence of the rotational and vibrational temperatures. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Transient expression of thyroid hormone nuclear receptor TR,2 sets S opsin patterning during cone photoreceptor genesisDEVELOPMENTAL DYNAMICS, Issue 5 2007M.L. Applebury Abstract Cone photoreceptors in the murine retina are patterned by dorsal repression and ventral activation of S opsin. TR,2, the nuclear thyroid hormone receptor , isoform 2, regulates dorsal repression. To determine the molecular mechanism by which TR,2 acts, we compared the spatiotemporal expression of TR,2 and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TR,2 and S opsin are expressed in cone photoreceptors only. Both are transcribed by E13, and their levels increase with cone genesis. TR,2 is expressed uniformly, but transiently, across the retina. mRNA levels are maximal by E17 at completion of cone genesis and again minimal before P5. S opsin is also transcribed by E13, but only in ventral cones. Repression in dorsal cones is established by E17, consistent with the occurrence of patterning during cone cell genesis. The uniform expression of TR,2 suggests that repression of S opsin requires other dorsal-specific factors in addition to TR,2. The mechanism by which TR,2 functions was probed in transgenic animals with TR,2 ablated, TR,2 that is DNA binding defective, and TR,2 that is ligand binding defective. These studies show that TR,2 is necessary for dorsal repression, but not ventral activation of S opsin. TR,2 must bind DNA and the ligand T3 (thyroid hormone) to repress S opsin. Once repression is established, T3 no longer regulates dorsal S opsin repression in adult animals. The transient, embryonic action of TR,2 is consistent with a role (direct and/or indirect) in chromatin remodeling that leads to permanent gene silencing in terminally differentiated, dorsal cone photoreceptors. Developmental Dynamics 236:1203,1212, 2007. © 2007 Wiley-Liss, Inc. [source] Genistein prevents thyroid hormone-dependent tail regression of Rana catesbeiana tadpoles by targetting protein kinase C and thyroid hormone receptor ,DEVELOPMENTAL DYNAMICS, Issue 3 2007L. Ji Abstract Thyroid hormone (TH)-regulated gene expression is mainly mediated by TH binding to nuclear thyroid hormone receptors (TRs). Despite extensive studies in mammalian cell lines that show that phosphorylation signaling pathways are important in TH action, little is known about their roles on TH signaling in vivo during development. Anuran metamorphosis is a postembryonic process that is absolutely dependent upon TH and tadpole tail resorption can be precociously induced by exogenous administration of 3,5,3,-triiodothyronine (T3). We demonstrate that genistein (a major isoflavone in soy products and tyrosine kinase inhibitor) and the PKC inhibitor (H7) prevent T3 -induced regression of the Rana catesbeiana tadpole tail. T3 -induced protein kinase C tyrosine phosphorylation and kinase activity are inhibited by genistein while T3 -induced up-regulation of TR, mRNA, but not TR, mRNA, is significantly attenuated, most likely through inhibition of T3 -dependent phosphorylation of the TR, protein. This phosphorylation may be modulated through PKC. These data demonstrate that T3 signaling in the context of normal cells in vivo includes phosphorylation as an important factor in establishing T3 -dependent tail regression during development. Developmental Dynamics 236:777,790, 2007. © 2007 Wiley-Liss, Inc. [source] Feuerwiderstandsfähigkeit von Metalldübeln , EOTA TECHNICAL REPORT TR 020 ,DIBT MITTEILUNGEN (FORMERLY-MITTEILUNGEN DEUT INST FUER BAUTECHNIK), Issue 6 2005Georg Feistel Dipl.-Ing. Mit der Veröffentlichung des Technical Report TR 020 liegt nun endlich eine einheitliche Beurteilung für die Ermittlung der Feuerwiderstandsfähigkeit von Verankerungen mit Metalldübel im Beton vor. Dieser in Europa abgestimmte Report erlaubt, die europäischen technischen Zulassungen für Metalldübel hinsichtlich ihrer Feuerwiderstandsfähigkeit zu ergänzen; es ist beabsichtigt, die ETAG 001 entsprechend anzupassen. Es wird somit künftig möglich sein, eine ingenieurmäßige Bemessung dieser Verankerungen unter Brandbeanspruchung (sog. heiße Bemessung) durchzuführen. [source] Tricuspid Regurgitation after Orthotopic Heart TransplantationECHOCARDIOGRAPHY, Issue 1 2010Nishant Kalra M.D. Background: Tricuspid regurgitation (TR) is a relatively common abnormality in normal adults as well as after orthotopic heart transplantation (OHT). A few studies have shown reduction in the incidence of TR after OHT by total bicaval surgical anastomosis technique. Other studies reported no significant difference in the rates of TR between the standard and bicaval techniques. Objective: Evaluate and compare the degree of TR after OHT by standard and bicaval anastomosis techniques. Method: Echocardiograms from the first 56 consecutive patients that had the total bicaval surgical technique performed were retrospectively reviewed and compared with the last 57 consecutive patients who had the standard biatrial technique performed. Patients with adequate two-dimensional and Doppler echocardiograms were included. Results: No statistical difference was observed for each grade of TR at both early and late time points. No significant difference was observed between the TR velocities of both biatrial and bicaval anastomosis patients at different periods. Conclusion: There appears to be no difference between the TR severity and TR velocity at early and late time points regardless of anastomotic technique. (Echocardiography 2010;27:1-4) [source] Right Ventricular Dimensions and Function in Isolated Left Bundle Branch Block: Is There Evidence of Biventricular Involvement?ECHOCARDIOGRAPHY, Issue 5 2008Jeroen Van Dijk M.D. Background: Isolated left bundle branch block (LBBB) may be an expression of idiopathic cardiomyopathy affecting both ventricles. The present study was conducted to evaluate right ventricular (RV) dimensions and function in asymptomatic LBBB patients with mildly depressed left ventricular (LV) function. Methods: Fifteen patients with asymptomatic LBBB in whom coronary artery disease, hypertension, and valvular pathology was excluded were studied. Fifteen healthy volunteers and 15 idiopathic dilated cardiomyopathy LBBB patients served as controls. RV long axis and tricuspid annulus diameter were obtained, as were tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity (Sm) of the RV free wall annulus. Tricuspid regurgitation (TR) jets (peak TR jets) were used for RV pressure assessment. Results: RV dimensions were comparable between the asymptomatic LBBB patients and controls. RV functions of healthy volunteers and asymptomatic LBBB patients were similar (TAPSE: 24 ± 3 and 24 ± 4 mm, Sm: 13 ± 2 and 13 ± 3 cm/s, respectively), whereas functional parameters in idiopathic dilated cardiomyopathy patients were significantly reduced (TAPSE: 19 ± 5 mm, Sm: 9 ± 2 cm/s, both P < 0.01 by analysis of variance [ANOVA]). For the three groups combined, a significant inverse correlation between RV pressure (peak TR jets) and RV function (Sm) was observed (r =,0.52, P = 0.017). Conclusions: In patients with an asymptomatic LBBB, RV dimensions and function are within normal range. The present study suggests that screening of RV functional parameters in asymptomatic LBBB patients is not useful for identification of an early-stage cardiomyopathy, and RV dysfunction is merely a consequence of increased RV loading conditions caused by left-sided heart failure and does not indicate a generalized cardiomyopathy affecting both ventricles. [source] Tricuspid Valve Malfunction and Ventricular Pacemaker Lead: Case Report and Review of the LiteratureECHOCARDIOGRAPHY, Issue 8 2006Said B. Iskandar M.D. Pacemaker implantation can be associated with several complications, including myocardial perforation with or without pericardial effusion, venous thrombosis, vegetations of the tricuspid valve (TV) or pacing lead, and tricuspid regurgitation (TR). The TR is thought to be derived from deformity or perforation of the TV by the pacing lead or secondary to atrioventricular discordance with asynchronous ventricular pacing. Severe TR can be deleterious to the patient because it raises the central venous pressure by increasing the right sided preload. Chronically, the increase in right sided blood volume can result in an increase in the right atrial pressure leading to a decrease in venous return and low cardiac output. Severe TR from leaflet adhesion to the pacemaker lead has not been reported before. With the aging of the population and the expanding use of pacemakers and implantable cardioverter defibrillators (ICD) in clinical practice, this complication may be seen more frequently. We present a patient diagnosed with severe TR, years after his pacemaker implantation. His TR was thought to be caused by adhesion of the tricuspid valve to his pacemaker lead. [source] The Double Jeopardy of Blunt Chest Trauma: A Case Report and ReviewECHOCARDIOGRAPHY, Issue 3 2006Subha L. Varahan M.D. Cardiac injury, specifically valvular rupture, must be considered after blunt chest trauma even in previously healthy patients. Isolated mitral regurgitation (MR) and tricuspid regurgitation (TR) due to blunt chest trauma are rare phenomena. More unique is simultaneous complete papillary muscle rupture of the mitral valve (MV) and tricuspid valve (TV) with only four patients being previously reported in the literature. This case describes a patient with complete transection of the posteromedial papillary muscle of the MV with severe MR and a concomitant flail TV with severe TR following a motor vehicular accident. The importance of transthoracic and transesophageal echocardiography in the early evaluation of patients following blunt chest trauma is also highlighted by this case. [source] Effect of di(n -butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid ratsENVIRONMENTAL TOXICOLOGY, Issue 3 2007Ena Lee Abstract This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 ,g/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor ,-1 (TR,-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 245,255, 2007. [source] Exposure and effects assessment of resident mink (Mustela vison) exposed to polychlorinated dibenzofurans and other dioxin-like compounds in the Tittabawassee River basin, Midland, Michigan, USA,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2008Matthew J. Zwiernik Abstract Historically, sediments and floodplain soils of the Tittabawassee River (TR; MI, USA) have been contaminated with polychlorinated dibenzofurans (PCDFs), polychlorinated dibenzo- p -dioxins (PCDDs), and polychlorinatedbiphenyls (PCBs). Median concentrations of 2,3,7,8-tetrachlorodibenzo- p -dioxin equivalents (TEQs) based on 2006 World Health Organization tetrachloro-dibenzo- p -dioxin toxic equivalency factors (TEFs) in the diet of mink (Mustela vison) ranged from 6.8 × 10,1 ng TEQ/kg wet weight upstream of the primary source of PCDF to 3.1 × 101 ng TEQ/kg wet weight downstream. Estimates of toxicity reference values (TRVs) derived from laboratory studies with individual PCDDs/PCDFs and PCB congeners or mixtures of those congeners, as well as application of TEFs, were compared to site-specific measures of mink exposure. Hazard quotients based on exposures expressed as concentrations of TEQs in the 95th percentile of the mink diet or liver and the no-observable-adverse-effect TRVs were determined to be 1.7 and 8.6, respectively. The resident mink survey, however, including number of mink present, morphological measures, sex ratios, population age structure, and gross and histological tissue examination, indicated no observable adverse effects. This resulted for multiple reasons: First, the exposure estimate was conservative, and second, the predominantly PCDF congener mixture present in the TR appeared to be less potent than predicted from TEQs based on dose,response comparisons. Given this, there appears to be great uncertainty in comparing the measured concentrations of TEQs at this site to TRVs derived from different congeners or congener mixtures. Based on the lack of negative outcomes for any measurement endpoints examined, including jaw lesions, a sentinel indicator of possible adverse effects, and direct measures of effects on individual mink and their population, it was concluded that current concentrations of PCDDs/PCDFs were not causing adverse effects on resident mink of the TR. [source] Course and outcome of childhood epilepsy: A 15-year follow-up of the Dutch Study of Epilepsy in ChildhoodEPILEPSIA, Issue 7 2010Ada Geerts Summary Purpose:, To study the course and outcome of childhood-onset epilepsy during 15-year follow-up (FU). Methods:, We extended FU in 413 of 494 children with new-onset epilepsy recruited in a previously described prospective hospital-based study by questionnaire. Results:, Mean FU was 14.8 years (range 11.6,17.5 years). Five-year terminal remission (TR) was reached by 71% of the cohort. Course during FU was favorable in 50%, improving in 29%, and poor or deteriorating in 16%. Mean duration of seizure activity was 6.0 years (range 0,21.5 years), strongly depending on etiology and epilepsy type. Duration was <1 year in 25% of the cohort and exceeded 12 years in another 25%. Antiepileptic drugs (AEDs) were used by 86% during a mean of 7.4 years: one-third had their last seizure within 1 year of treatment, and one-third continued treatment at the end, although some had a 5-year TR. At last contact, 9% of the cohort was intractable. In multivariate analysis, predictors were nonidiopathic etiology, febrile seizures, no 3-month remission, and early intractability. Eighteen patients died; 17 had remote symptomatic etiology. Standardized mortality ratio for remote symptomatic etiology was 31.6 [95% confidence interval (CI) 18.4,50.6], versus 0.8 [95% CI 0.02,4.2] for idiopathic/cryptogenic etiology. Discussion:, In most children with newly diagnosed epilepsy, the long-term prognosis of epilepsy is favorable, and in particular, patients with idiopathic etiology will eventually reach remission. In contrast, epilepsy remains active in ,30% and becomes intractable in ,10%. AEDs probably do not influence epilepsy course; they merely suppress seizures. Mortality is significantly higher only in those with remote symptomatic etiology. [source] Upregulation of Brain Expression of P-Glycoprotein in MRP2-deficient TR - Rats Resembles Seizure-induced Up-regulation of This Drug Efflux Transporter in Normal RatsEPILEPSIA, Issue 4 2007Katrin Hoffmann Summary:,Purpose: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood,brain barrier (BBB). MRP2 is absent in the transport-deficient (TR,) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR, rats compared with nonmutant (wild-type) Wistar rats. Methods: The expression of MRP2 and Pgp in brain and liver sections of TR, rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. Results: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR, rats. TR, rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR, rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. Conclusions: The data on TR, rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR, rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose. [source] Nonsymptomatic Generalized Epilepsy in Children Younger than Six Years: Excellent Prognosis, but Classification Should Be Reconsidered after Follow-up: The Dutch Study of Epilepsy in ChildhoodEPILEPSIA, Issue 7 2002C. M. Middeldorp Summary: ,Purpose: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy. Methods: Of the cohort of the Dutch Study of Epilepsy in Childhood (n = 466), all children younger than 6 years with a diagnosis of idiopathic (IGE) or cryptogenic (CGE) generalized epilepsy either at intake (n = 108) and/or after 2 years of follow-up (n = 102) were included. The number of reclassifications after 2 years was determined, and the reasons for reclassification were analyzed. All children receiving a diagnosis of IGE or CGE at 2 years were followed up for 5 years to study their outcome in terms of terminal remission (TR). Data on their level of intellectual functioning were collected at the start of this analysis. Results: The epilepsy syndrome was reclassified in 17 children. In 14 of them, the seizure type also was reclassified, and in three, the course of the epilepsy determined the new epilepsy type. Two other children had a reclassification of their seizure types without a change of the epilepsy type. Many children were categorized as having IGE not otherwise specified. In all probability, this is a heterogeneous group, containing patients with various epilepsy syndromes, with generalized tonic,clonic seizures as a common hallmark. Of the 102 children with IGE or CGE at 2 years of follow-up, 75% had a TR of >6 months after 2 years, and 85% a TR of ,1 year after 5 years. Conclusions: In a fair proportion of children with nonsymptomatic generalized epilepsy in this age group, it is not possible to classify firmly the epilepsy and/or the seizures immediately after the intake. Instead, they are reclassified during the course of the disease. This and the apparent heterogeneity of the category IGE not otherwise specified point to inherent drawbacks of the current International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The prognosis of IGE at this young age is generally excellent. [source] An echocardiographic and auscultation study of right heart responses to training in young National Hunt Thoroughbred horsesEQUINE VETERINARY JOURNAL, Issue S36 2006G. LIGHTFOOT Summary Reasons for performing study: There are few data available to determine the effect of training on cardiac valve function. Objectives: To investigate the effect of commercial race training on right ventricular (RV) and tricuspid valve function in an untrained group of National Hunt Thoroughbreds (TB). Material and methods: Cardiac auscultation, guided M-mode echocardiography of the RV, and colour flow Doppler (CFD) tricuspid valve and right atrium were performed in 90 TB horses (age 2,7 years) 1998,2003. Forty horses were examined at least once and 48 horses were examined on at least 2 occasions. Examinations were then classified as: i) before commencement of race training, ii) after cantering exercise had been sustained for a period of 8,12 weeks and iii) at full race fitness. Tricuspid valve regurgitation (TR) murmurs were graded on a 1,6 scale and CFD echocardiography TR signals were graded on a 1,9 scale. Right ventricular internal diameter (RVID) in diastole and systole (RVIDd and RVIDs) was measured by guided M-mode. Associations between continuous RVID and TR measures and explanatory covariates of weight, age, heart rate, yard and stage of training were examined using general linear mixed models with horse-level random effects. Results: On average, RVIDd and RVIDs increased by 0.08 and 0.1 cm, respectively, per year increase in age (P=0.1 and 0.02) and by 0.3 and 0.4 cm, respectively between pre-training and race fitness (P = 0.07 and 0.005). Tricuspid regurgitation score by colour flow Doppler increased by 0.6/year with age (P<0.0001) and by 1.8 between pre-training and race fitness (P< 0.0001). No significant associations were found between any outcomes and weight, heart rate and training yard. Due to the high level of co-linearity between age and training, multivariable models including both terms were not interpretable. Conclusions and clinical relevance: Athletic training of horses exerts independent effects on both severity and prevalence of tricuspid valve incompetence. This effect should therefore be taken into account when examinations are performed. Dimensions of RV increase with age and training in TB horses in a manner that appears to be similar to that of the LV. [source] Effects of short-term training on insulin sensitivity and skeletal muscle glucose metabolism in Standardbred horsesEQUINE VETERINARY JOURNAL, Issue S36 2006L. STEWART-HUNT Summary Reasons for performing study: Increased insulin sensitivity occurs after a period of exercise training, but the mechanisms underlying this training-associated increase in insulin action have not been investigated. Objective: To examine the effects of short-term endurance training (7 consecutive days) and a subsequent period of inactivity (5 days) on whole body insulin sensitivity and GLUT-4 protein and the activities of glycogen synthase (GS) and hexokinase (HK) in skeletal muscle. It was hypothesised that training would increase insulin sensitivity in association with increased GLUT-4 protein and activities of GS and HK, but that these changes would be transient, returning to baseline after 5 days of inactivity. Methods: Seven mature Standardbred horses completed training consisting of 7 consecutive days of 45 min of treadmill exercise at a speed that elicited 55% of pretraining maximal aerobic capacity (VO2peak). Insulin sensitivity was determined by rate of glucose disposal (M) during the last 60 min of a 120 min euglycaemic-hyperinsulinaemic clamp (EHC) performed before (-2 days) and at 1 and 6 days following training. VO2peak was measured before (UT) and after (TR) training and the period of inactivity (IA). Results: Training resulted in a 9% increase in mean VO2peak (P<0.05) that was maintained following inactivity (IA). Mean M values were more than 2-fold higher (P<0.05) in TR than in UT. Mean M was also higher (P<0.05) in IA when compared to UT. GLUT-4 protien abundancewas more than 10-fold higher in TR and IA (P<0.001) than in UT. Pre-EHC GS activity and GS fractional velocity were increased (P<0.05) in TR when compared to UT and IA. Pre-EHC HK activity was increased (P<0.05) in IA when compared to UT and TR. Muscle glycogen was 66% lower (P<0.05) in TR than in UT and IA. Conclusions: Short-term training resulted in increases in whole body insulin sensitivity, and GLUT-4 protein content and glycogen synthase activity in skeletal muscle. The enhancements in insulin sensitivity, GLUT-4 protein and glycogen synthase activity were still evident after 5 days of inactivity. Potential relevance: Insulin resistance in equids has been associated with obesity and predisposition to laminitis. Regular physical activity may mitigate risk of these conditions via enhancement of insulin sensitivity and/or control of bodyweight. [source] ICER/CREM-mediated transcriptional attenuation of IL-2 and its role in suppression by regulatory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Josef Bodor Dr. Abstract Here, we report that inducible cAMP early repressor/cAMP response element modulator (ICER/CREM) is induced early in CD25+CD4+ regulatory T cell (TR) assays mainly in activated Foxp3, effector T cells and this induction correlates with sharp decrease in number of IL-2-expressing T cells. Importantly, RNAi targeting of ICER/CREM in responder CD25,CD4+ T cells antagonizes TR -mediated suppression. Moreover, forced expression of Foxp3 in naive CD25, T cells induces constitutive expression of ICER/CREM in T cells with a regulatory phenotype. Foxp3 facilitates expression of ICER/CREM both in Foxp3 transductants as well as CD25, responder T cells suggesting that induction of TR function in suppression assays may utilize contact-dependent interaction. Indeed, CTLA-4 blockade or use of B7-deficient CD25, responder T cells prevents ICER/CREM accumulation and leads to the rescue of IL-2 expression. Therefore, we propose that CTLA-4 binding to B7 ligands expressed on activated ligand-bearing Foxp3, effector T cells results in ICER/CREM-mediated transcriptional attenuation of IL-2. Collectively, these data suggest that Foxp3 expression in TR cells imposes suppression in contact-dependent fashion by induction of constitutive ICER/CREM expression in activated CD25+ Foxp3, T cell effectors thus preventing them from producing IL-2. [source] SHORT COMMUNICATION Learning-induced reduction in post-burst after-hyperpolarization (AHP) is mediated by activation of PKCEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2002Yaron Seroussi Abstract We studied the role of protein kinase C (PKC) and protein kinase A (PKA) in mediating learning-related long lasting reduction of the post-burst after-hyperpolarization (AHP) in cortical pyramidal neurons. We have shown previously that pyramidal neurons in the rat piriform (olfactory) cortex from trained (TR) rats have reduced post-burst AHP for 3 days after odour-discrimination learning, and that this reduction is due to decreased conductance of calcium-dependent potassium current. In the present study, we examined whether this long-lasting reduction in AHP is mediated by second messenger systems. The broad-spectrum kinase inhibitor, H7, increased the AHP in neurons from TR rats, but not in neurons from pseudo-trained (pseudo-TR) and naive rats. Consequently, the difference in AHP amplitude between neurons from TR and control animals was diminished. This effect was also obtained by application of the specific PKC inhibitor, GF-109203x. The PKC activator, 1-Oleoyl-2-acetyl- sn -glycerol (OAG), significantly reduced the AHP in neurons from naive and pseudo-TR rats, but not in neurons from TR rats, so that the difference between the groups was abolished. The PKA-specific inhibitor, H-89, increased the AHP in neurons from all groups to a similar extent, and the difference in AHP amplitude between neurons from TR rats and neurons from controls was maintained. We suggest that while the post-burst AHP in piriform cortex pyramidal neurons is modulated by both PKC and PKA, a PKC-dependent process maintains the learning-related reduction of the AHP in these cells. [source] Adhesive bonding of titanium,aluminum,niobium alloy with nine surface preparations and three self-curing resinsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2003Hiroaki Yanagida The purpose of the current study was to evaluate the adhesive performance of metal conditioners when used for bonding between auto-polymerizing methacrylic resins and a titanium alloy. Disk specimens were cast from a titanium,aluminum,niobium (Ti,6Al,7Nb) alloy, air-abraded with alumina, and bonded with 24 combinations of eight metal conditioners (Acryl Bond, ACB; All-Bond 2 Primer B, ABB; Alloy Primer, ALP; Cesead II Opaque Primer, COP; Metafast Bonding Liner, MBL; Metal Primer II, MPII; MR Bond, MRB; Super-Bond liquid, SBL) and three autopolymerizing methacrylic resins (Repairsin, RE; Super-Bond C & B, SB; Tokuso Rebase; TR). Unprimed specimens were used as controls. Shear bond strengths were determined both before and after thermocycling (4,60°C, 20, 000 cycles). The ALP-SB group recorded the greatest post-thermocycling bond strength (21.8 MPa) followed by the COP-SB group (17.8 MPa) and the MPII-SB group. The post-thermocycling bond strengths of the unprimed-SB group and the ALP-RE group were statistically comparable. No significant differences were found among the nine TR resin groups, and these groups showed the lowest bond strength. In conclusion, the use of one of the three conditioners (ALP, COP, and MPII) in combination with the SB resin is recommended for bonding the Ti,6Al,7Nb alloy. [source] Novel regulation of yolk utilization by thyroid hormone in embryos of the direct developing frog Eleutherodactylus coquiEVOLUTION AND DEVELOPMENT, Issue 5 2010Srikanth Singamsetty SUMMARY Thyroid hormone (TH) is required for metamorphosis of the long, coiled tadpole gut into the short frog gut. Eleutherodactylus coqui, a direct developing frog, lacks a tadpole. Its embryonic gut is a miniature adult form with a mass of yolky cells, called nutritional endoderm, attached to the small intestine. We tested the TH requirement for gut development in E. coqui. Inhibition of TH synthesis with methimazole arrested gut development in its embryonic form. Embryos treated with methimazole failed to utilize the yolk in their nutritional endoderm, and survived for weeks without further development. Conversely, methimazole and 3,3,,5-tri-iodo- l -thyronine, the active form of TH, stimulated gut development and utilization and disappearance of the nutritional endoderm. In Xenopus laevis, the receptor for TH, TR,, is upregulated in response to TH. Similarly, EcTR,, the E. coqui ortholog, was upregulated by TH in the gut. EcTR, expression was high in the nutritional endoderm, suggesting a direct role for TH in yolk utilization by these cells. An initial step in the breakdown of yolk in X. laevis is acidification of the yolk platelet. E. coqui embryos in methimazole failed to acidify their yolk platelets, but acidification was stimulated by TH indicating its role in an early step of yolk utilization. In addition to a conserved TH role in gut development, a novel regulatory role for TH in yolk utilization has evolved in these direct developers. [source] Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor-dependent mannerFEBS JOURNAL, Issue 14 2003Toshiko Yamada-Okabe Thyroid hormone has various effects on cell proliferation, growth and apoptosis. To gain more insight into the molecular dynamics caused by thyroid hormone, gene expression in HeLaTR cells that constitutively overexpressed the thyroid hormone receptor (TR) was analyzed. Gene expression profiling of the HeLaTR cells with an oligonucleotide microarray yielded 229 genes whose expression was significantly altered by T3. Among these genes, the expression of 4-1BB, which is known to initiate a signal cascade activating NF-,B, was significantly up-regulated by T3. Although treatment of the HeLaTR cells with T3 did not induce expression of NF-,B reporter luciferase, even in the presence of the 4-1BB-Ligand, it increased the caspase activities. An increase in the caspase activities was also observed in the HeLaTR cells transfected with 4-1BB cDNA, and the 4-1BB-Ligand further increased the caspase activities of the HeLaTR cells overexpressing the 4-1BB. Furthermore, up-regulation of 4-1BB and an increase in caspase activities also occurred in the rat FRTL cells that expressed only authentic TR. These results demonstrate that the expression of 4-1BB serves as the mediator of signals from T3 to activate caspases. [source] Analysis of single-locus tests to detect gene/disease associations,GENETIC EPIDEMIOLOGY, Issue 3 2005Kathryn Roeder Abstract A goal of association analysis is to determine whether variation in a particular candidate region or gene is associated with liability to complex disease. To evaluate such candidates, ubiquitous Single Nucleotide Polymorphisms (SNPs) are useful. It is critical, however, to select a set of SNPs that are in substantial linkage disequilibrium (LD) with all other polymorphisms in the region. Whether there is an ideal statistical framework to test such a set of ,tag SNPs' for association is unknown. Compared to tests for association based on frequencies of haplotypes, recent evidence suggests tests for association based on linear combinations of the tag SNPs (Hotelling T2 test) are more powerful. Following this logical progression, we wondered if single-locus tests would prove generally more powerful than the regression-based tests? We answer this question by investigating four inferential procedures: the maximum of a series of test statistics corrected for multiple testing by the Bonferroni procedure, TB, or by permutation of case-control status, TP; a procedure that tests the maximum of a smoothed curve fitted to the series of of test statistics, TS; and the Hotelling T2 procedure, which we call TR. These procedures are evaluated by simulating data like that from human populations, including realistic levels of LD and realistic effects of alleles conferring liability to disease. We find that power depends on the correlation structure of SNPs within a gene, the density of tag SNPs, and the placement of the liability allele. The clearest pattern emerges between power and the number of SNPs selected. When a large fraction of the SNPs within a gene are tested, and multiple SNPs are highly correlated with the liability allele, TS has better power. Using a SNP selection scheme that optimizes power but also requires a substantial number of SNPs to be genotyped (roughly 10,20 SNPs per gene), power of TP is generally superior to that for the other procedures, including TR. Finally, when a SNP selection procedure that targets a minimal number of SNPs per gene is applied, the average performances of TP and TR are indistinguishable. Genet. Epidemiol. © 2005 Wiley-Liss, Inc. [source] Effect of reline material and denture base surface treatment on the impact strength of a denture base acrylic resinGERODONTOLOGY, Issue 1 2010Luciano Elias Da Cruz Perez doi:10.1111/j.1741-2358.2009.00292.x Effect of reline material and denture base surface treatment on the impact strength of a denture base acrylic resin Objective:, In this study, the effect of relining and surface treatment on the impact strength (IS) of a heat-polymerising denture base acrylic resin (Lucitone 550-L) was evaluated. Materials and methods:, Rectangular bars of L were made (60 × 6 × 2 mm) and relined (2 mm) with the relining resins Ufi Gel Hard (UH) and Tokuso Rebase Fast (TR). Specimens relined with L and intact L, TR and UH specimens were also made (60 × 6 × 4 mm), for comparison. Before relining, the L surface was left untreated or wetted with methyl methacrylate monomer and/or the bonding agents (BA) supplied by manufacturers of the reline resins. V-notches were machined at the midpoint of the length of all specimens. The notches were made either across the width (Nw) or across the thickness of the specimens (Nth). The Charpy impact test was performed using a 0.5-J pendulum, which had been specially designed and constructed. Data were analysed separately for each notch position using one-way analysis of variance and Tukey honestly significant difference post - hoc test (p = 0.05). Results:, The IS of L was similar to that of L/L. For the Nw notch, treating the denture base L with TR BA and relining with TR reline material produced the highest IS. Conclusion:, The IS of specimens made from heat polymerising acrylic resin Lucitone 550 was increased after relining using the hard chairside reline resin TR with its proprietary BA. [source] The occurrence of porosity in reline acrylic resins.GERODONTOLOGY, Issue 1 2009Effect of microwave disinfection Background:, Microwave energy has proved to be an effective method for disinfecting acrylic dentures. However, the effect of microwave heating on the porosity of autopolymerising denture reline resins has not been investigated. Objective:, The purpose of the study was to determine the effect of microwave disinfection on the porosity of autopolymerised denture reline materials (Kooliner-K, New Truliner-NT, Tokuso Rebase Fast-TR and Ufi Gel Hard-UGH) and a conventional heat-polymerised denture base resin (Lucitone 550-L). Material and methods:, Specimens (10 mm × 20 mm × 1 mm) were obtained from the impression surface of the palatal mucosa in a single person and divided into four groups (n = 5). The porosity was evaluated after polymerisation (C1), after two cycles of microwave disinfection (MW2), after seven cycles of microwave disinfection (MW7) and after 7 days storage in water at 37°C (C2). Specimens from group MW7 were exposed to microwave disinfection daily being stored in water at 37°C between exposures. All the replicas were sputter coated with gold and micrographs/digital images were taken of each replica using scanning electron microscopy at magnification × 100. The SEM micrographs were then examined using an image analyser to determine the number of pores. Comparison between materials and groups were made using Kruskal,Wallis tests. Results:, MW7 resulted in a significant increase in the number from the pores of material K, but decreased in number in reline material TR and UGH reline resin. The number of pores in materials NT and L remained unaffected following microwave disinfection. Conclusion:, Differences in the porosity amongst the materials and for different experimental conditions were observed following microwave disinfection. [source] Mrp2 modulates the activity of chloride channels in isolated hepatocytesHEPATOLOGY, Issue 1 2002Xinhua Li Adenosine triphosphate binding cassette family transport proteins are important organic ion transporters in hepatocytes but these molecules may also exhibit other functions. In the present study we have measured the effects of substrates of the canalicular organic ion transporter multidrug resistance associated protein 2 (Mrp2) on chloride channel activation and cell volume regulation. We found that substrates such as leukotriene D4, 17-,-estradiol glucuronide, and the leukotriene inhibitor MK-571 accelerated the activation of chloride channels by cell swelling and activated chloride channels in cytokine-pretreated hepatocytes. Two conjugated estrogens that are not Mrp2 substrates did not produce this effect. Hepatocytes derived from a strain of transport-deficient rats (TR,), which lack Mrp2 expression, showed none of these substrate effects. Coincident with their ability to activate channels, the Mrp2 substrates increased the rate of volume regulatory decrease by approximately 50% (P < .01), confirming that enhanced channel activation under this condition stimulated volume regulation. In TR-hepatocytes the Mrp2 substrate had no effect on volume regulation. In conclusion, Mrp2 plays a role in regulation of chloride channel function by reducing the lag time necessary for channel activation and consequently accelerating the process of cell volume regulation. Substrates of Mrp2 affect the ability of the protein to interact with chloride channels. These findings represent an alternative function of Mrp2 in hepatocytes. [source] Effect of interferon ,-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitisHEPATOLOGY RESEARCH, Issue 5 2009Mika Kurokawa Aim:, The objective of this study was to elucidate the long-term effects of interferon (IFN),-2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Methods:, A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN-,-2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis. Results:, A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non-SVR patients (P = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years (P = 0.006), advanced histological staging (P = 0.033), non-SVR to IFN therapy (P = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of , 40 IU/L after the combination therapy (P = 0.021). Conclusions:, These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development. [source] Assessing the influence of scanner background noise on auditory processing.HUMAN BRAIN MAPPING, Issue 8 2007Abstract We compared two experimental designs aimed at minimizing the influence of scanner background noise (SBN) on functional MRI (fMRI) of auditory processes with one conventional fMRI design. Ten subjects listened to a series of four one-syllable words and had to decide whether two of the words were identical. This was contrasted with a no-stimulus control condition. All three experimental designs had a duration of ,17 min: 1) a behavior interleaved gradients (BIG; Eden et al. [1999] J Magn Reson Imaging 41:13,20) design (repetition time, TR, = 6 s), where stimuli were presented during the SBN-free periods between clustered volume acquisitions (CVA); 2) a sparse temporal sampling technique (STsamp; e.g., Gaab et al., [2003] Neuroimage 19:1417,1426) acquiring only one set of slices following each of the stimulations with a 16-s TR and jittered delay times between stimulus offset and image acquisition; and 3) an event-related design with continuous scanning (ERcont) using the stimulation design of STsamp but with a 2-s TR. The results demonstrated increased signal within Heschl's gyrus for the STsamp and BIG-CVA design in comparison to ERcont as well as differences in the overall functional anatomy among the designs. The possibility to obtain a time course of activation as well as the full recovery of the stimulus- and SBN-induced hemodynamic response function signal and lack of signal suppression from SBN during the STsamp design makes this technique a powerful approach for conducting auditory experiments using fMRI. Practical strengths and limitations of the three auditory acquisition paradigms are discussed. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [source] Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis,INFLAMMATORY BOWEL DISEASES, Issue 2 2007Qi T. Yu BS Abstract Background: CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental murine colitis but little is known about their potential role in human inflammatory bowel disease (IBD). FOXP3 is a transcription factor that plays a critical role in the development and function of CD4+CD25+ TR. The aim of this study was to examine the presence and functional characteristics of TR cells in colonic lymphoid tissues in patients with ulcerative colitis (UC). Methods: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, and reverse-transcriptase polymerase chain reaction (RT-PCR). Functional characterization of CD4+CD25+ cells was analyzed by suppression of proliferation and secretion of cytokines by cocultured effector CD4+CD25, T cells. Results: FOXP3+CD4+ T cells are increased in the lamina propria (LP) of inflamed and noninflamed areas of UC colon compared to normal colon. CD4+CD25+ T cells in UC mesenteric lymph nodes (MLN) express FOXP3 mRNA and protein and suppress the proliferation of autologous MLN CD4+CD25, T cells. The suppressor activity of MLN CD4+CD25+ T cells is cell contact-dependent but cytokine-independent. In addition, CD4+CD25+ T cells potently suppress the production of both Th1 (IFN-,, IL-2) and Th2 (IL-5, IL-13) cytokines by cocultured CD4+CD25, T cells. FOXP3+ cells localized in the T-cell-rich areas of MLN and occasionally present in the follicles. Conclusions: There is an expansion of FOXP3+CD4+ T cells in mucosal lymphoid tissues in UC. CD4+CD25+ isolated from UC MLN express FOXP3 and display features of TR cells in spite of active mucosal inflammation. These data suggest that their suppressor activity may be abrogated in vivo or they are unable to counterbalance the chronic mucosal inflammation in UC. (Inflamm Bowel Dis 2007) [source] | |||||||||||||||||||||||||||||||||||||||||||