Association of QRS-T angle and Late Gadolinium Enhancement in patients with a Clinical Suspicion of Myocarditis.

Objective: To investigate the association of a wide QRS-T angle on the surface ECG and late gadolinium enhancement on contrast-enhanced cardiovascular magnetic (CMR) imaging in patients with clinically suspected myocarditis. Background: Diagnosis and risk stratification in patients with suspected myocarditis is particularly challenging due to a great spectrum of clinical presentations. Late gadolinium enhancement (LGE) visualizes myocardial necrosis and fibrosis in patients with biopsy-proven myocarditis. The presence or absence of late gadolinium enhancements in these patients is prognostically meaningful. The QRS-T angle from the surface ECG, on the other hand, may serve as a simple and easily available risk marker in suspected myocarditis. Methods: We enrolled 97 consecutive patients that were referred to CMR imaging for a clinical suspicion of myocarditis. All patients obtained a standardized digital 12-lead ECG for the calculation of the QRS-T angle and underwent contrast-enhanced CMR imaging. Patients were divided into two groups according to the absence or presence of LGE on CMR. Results: 78 of 97 patients with suspected myocarditis had LGE on CMR. Patients with LGE had wider QRS-T angles as compared to the patient group without LGE (53.95-47.5 vs. 26.2-21.2; p<0.001). The sensivity, specificity, negative predictive value and positive predictive value for a QRS-T angle above 90 degrees for LGE positive myocarditis were 16.5%, 100%, 24.7%, and 100%, respectively. Conclusion: A wide QRS-T angle of 90 degrees or more is linked to myocardial fibrosis or necrosis (late gadolinium enhancement) in patients with suspected myocarditis.

QRS-T-angle in Patients with ST-Segment Elevation Myocardial Infarction (STEMI) - a Comparison with Cardiac Magnetic Resonance Imaging.

Background: The QRS-T angle from the surface EKG is a promising prognostic marker in patients with coronary artery disease. Cardiovascular magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) offers high resolution imaging of myocardial damage. We investigated the association of the QRS-T angle and the extent of myocardial damage as assessed by LGE in patients with acute ST-segment myocardial infarction (STEMI) Methods: 169 patients with STEMI obtained a standardized digital 12-lead EKG on admission for the calculation of the QRS-T angle and underwent CMR imaging for analysis of infarct size by LGE within the first week. Patients were divided into groups: (1) abnormal QRS-T angle ≥ 90 degree and (2) QRS-T angle < 90 degree. Results: Patients with a QRS-T angle of 90 degree or more had larger infarcts (36.5±12.4 vs. 13.3±9.5; p<0.001) and lower ejection fraction (42.9±12.1% vs. 50.6±10.6%; p<0.001). Conclusion: The extent of myocardial damage as measured by the gold standard LGE is associated with a larger QRS-T angle calculated from the surface EKG.

Health promotion: the impact of beliefs of health benefits, social relations and enjoyment on exercise continuation.

The aim of this study was to explore how and why participants in structured exercise intervention programs continue or stop exercising after the program is finished. We conducted four focus group interviews with four groups of middle-aged and elderly men (total n = 28) who had participated in exercise interventions involving playing either a team sport (football) or a more individually focused activity (spinning and crossfit). Our results show that different social, organizational and material structures inherent in the different activities shape the subjects' enjoyment of exercise participation, as well as their intention and ability to continue being active. In conclusion, team sport activities seem to be intrinsically motivating to the participants through positive social interaction and play. They are therefore more likely to result in exercise continuation than activities that rely primarily on extrinsic motivation such as the expectation of improved health and well-being.

Echocardiography versus intracardiac electrocardiography-based optimization for cardiac resynchronization therapy : a comparative clinical long-term trial.

BACKGROUND: Optimization of AV and VV delay programming has been shown to be essential for the success of cardiac resynchronization therapy (CRT). Acute hemodynamic improvement can be obtained by intracardiac electrocardiogram (IEGM)-based optimization. The aim of the present study was to evaluate whether this IEGM-based algorithm is comparable to the current gold standard of echocardiography. METHODS: After device implantation patients with standard criteria for CRT, AV and VV delay programming was either optimized by an IEGM-based algorithm (IEGM group, n = 24) or by echocardiography (echo group, n = 24). Cardiopulmonary exercise capacity was assessed after 3 and 12 months on the basis of NYHA class and the 6-min-walk test. Left ventricular ejection fraction was evaluated by echocardiography. RESULTS: In both groups there was a significant decrease in NYHA class and a significant increase in 6-min-walk distance and ejection fraction after 3 and 12 months. After 12 months there was no significant difference in the proportion of responders, NYHA class and 6-min-walk distance between the IEGM the echo group. CONCLUSION: The present data show that a sustained improvement of cardiopulmonary exercise capacity can be obtained by optimizing CRT patients on the basis of an IEGM algorithm. The comparable results for cardiopulmonary exercise parameters suggest that this new method might become an important tool for adjusting CRT programming in daily practice.

Coronary artery calcium score: influence of the reconstruction interval on cardiac risk stratification in asymptomatic patients using dual-source computed tomography.

PURPOSE: To evaluate the impact of the reconstruction interval on coronary calcium score and cardiac risk stratification using dual-source computed tomography (DSCT). MATERIALS AND METHODS: DSCT coronary calcium scoring was performed in 61 consecutive patients, and five data sets per patient were reconstructed within diastole (50 - 70 % of the R-R interval). The Agatston score, volumetric score and the relative variability were assessed for all reconstructions. To assess the individual cardiovascular risk, patients were assigned to risk groups based on age and gender-matched percentile ranks. RESULTS: The mean Agatston score was 184.8 ± 377.9 (relative variability 47 % ± 52 %). The mean volumetric score was 164.4 ± 310.1 (relative variability 49 % ± 58 %). There was a negative correlation between the total Agatston score and the relative variability (r = -0.37; p < 0.01). Depending on the reconstruction interval used, 18 predominantly young patients were assigned to more than one risk group. CONCLUSION: Despite the increased temporal resolution of DSCT examinations, the Agatston and volumetric scores depend on the reconstruction time within the cardiac cycle. The fact that the greatest relative variability for both the Agatston score and the volumetric score was found in young patients with small amounts of coronary calcium may result in different treatment strategies for young patients depending on the reconstruction used. Therefore, more accurate risk stratification may require the analysis of multiple reconstruction intervals.

A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing, clinical outcomes and adverse effects in pediatric kidney transplant patients.

There is paucity in the data examining the differences in mycophenolate mofetil (MMF) dosing and outcomes among pediatric kidney transplant recipients (PKTX) between races. The aims of this study were as follows (i) to assess whether higher doses of MMF are being utilized in African American (AA) PKTX (ii) to determine whether there is a correlation between MMF dose and outcomes between races, and (iii) to assess the adverse effects of MMF between races. This study analyzed 109 PKTX who received MMF between 7/99 and 5/08. Demographics were similar between groups. Fewer AAs received kidneys from living donors (18% vs. 44%), spent more time on dialysis (1.0 vs. 0.5 yr), and had more human leukocyte antigen mismatches (4 vs. 3). MMF doses among AA patients were higher throughout the study, with statistical differences at week 4, month 3, and month 18. AA patients had significantly higher acute rejection rates and trended toward poorer graft survival; infections, adverse events from MMF and post-transplant lymphoproliferative disease tended to be lower in the AA patients. AA PKTX received higher MMF doses within the first three yr post-transplant compared to their non-AA counterparts, yet demonstrate significantly more acute rejection episodes. Importantly, MMF caused fewer adverse events in AA patients, despite these patients receiving higher doses.

SNP mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians.

This study is an extension to previously published work that has linked variation in the human leukocyte antigen (HLA) class I region with susceptibility to multiple sclerosis (MS) in Australians from the Island State of Tasmania. Single nucleotide polymorphism (SNP) mapping was performed on an 865-kb candidate region (D6S1683-D6S265) in 166 Tasmanian MS families, and seven candidate genes [ubiquitin D (UBD), olfactory receptor 2H3 (OR2H3), gamma-aminobutyric acid B receptor 1 (GABBR1), myelin oligodendrocyte glycoprotein (MOG), HLA-F, HLA complex group 4 (HCG4) and HLA-G] were resequenced. SNPs tagging the extended MS susceptibility haplotype were genotyped in an independent sample of 356 Australian MS trios and SNPs in the MOG gene were significantly over-transmitted to MS cases. We identified significant effects on MS susceptibility of HLA-A*2 (OR: 0.51; P = 0.05) and A*3 (OR: 2.85; P = 0.005), and two coding polymorphisms in the MOG gene (V145I: P = 0.01, OR: 2.2; V142L: P = 0.04, OR: 0.45) after full conditioning on HLA-DRB1. We have therefore identified plausible candidates for the causal MS susceptibility allele, and although not conclusive at this stage, our data provide suggestive evidence for multiple class I MS susceptibility genes.

Noni as an anxiolytic and sedative: a mechanism involving its gamma-aminobutyric acidergic effects.

Noni (Morinda citrifolia) is increasing in worldwide popularity as a food or dietary supplement with versatile health benefits. The aim of this study was to investigate the effects of Noni fruit on anxiety symptoms in vitro. To this end, a competitive GABAa receptor-binding assay was developed. Our preliminary study indicates that the methanol crude extract of Noni fruit showed significant affinity to the gamma-aminobutyric acid A (GABAa) inhibitory neurotransmitter receptors, and displayed 75% binding inhibition of the agonist radioligand [3H] muscimol at a concentration of 100 microg/ml. Further experiments demonstrated that the MeOH extract, and its BuOH and H2O partitions, exhibited IC50 values of 22.8, 27.2, and 17.1 microg/ml, respectively, in the GABAa-binding assay. Experimental results with Noni fruit indicate the presence of competitive ligand(s), which may bind to the GABAa receptor as an agonist, and thus induce its anxiolytic and sedative effects. The study provides an in vitro rationale for one of Noni's versatile and traditional uses. In addition, an HPLC fingerprint profile of the methanolic extract of Noni fruit has been established for quality control purpose.

The isolation and properties of the dimeric subunit of concanavalin A.

Concanavalin A (Con A) was dissociated into dimeric and monomeric subunits by incubation at 37 degrees C in acetate buffer of pH 3.8 containing 0.5% sodium dodecyl sulfate. The dimer was isolated in pure form by a density gradient ultracentrifugation method. Several properties of the dimer were determined including the formation of a precipitin with anti-Con A antibodies, the molecular weight, the lack of a binding site for glycogen, the lack of mitogenic activity for spleen lymphocytes, and the lack of inhibition by alpha-methyl D-glucoside. The latter findings differ from results reported by other investigators.

A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1.

The 90 kDa ribosomal S6 kinase-2 (RSK2) is a growth factor-stimulated protein kinase with two kinase domains. The C-terminal kinase of RSK2 is activated by ERK-type MAP kinases, leading to autophosphorylation of RSK2 at Ser386 in a hydrophobic motif. The N-terminal kinase is activated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) through phosphorylation of Ser227, and phosphorylates the substrates of RSK. Here, we identify Ser386 in the hydrophobic motif of RSK2 as a phosphorylation-dependent docking site and activator of PDK1. Treatment of cells with growth factor induced recruitment of PDK1 to the Ser386-phosphorylated hydrophobic motif and phosphorylation of RSK2 at Ser227. A RSK2-S386K mutant showed no interaction with PDK1 or phosphorylation at Ser227. Interaction with Ser386-phosphorylated RSK2 induced autophosphorylation of PDK1. Addition of a synthetic phosphoSer386 peptide (RSK2(373-396)) increased PDK1 activity 6-fold in vitro. Finally, mutants of RSK2 and MSK1, a RSK-related kinase, with increased affinity for PDK1, were constitutively active in vivo and phosphorylated histone H3. Our results suggest a novel regulatory mechanism based on phosphoserine-mediated recruitment of PDK1 to RSK2, leading to coordinated phosphorylation and activation of PDK1 and RSK2.

90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1.

90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth factor-activated serine/threonine kinases composed of two kinase domains connected by a regulatory linker region. The N-terminal kinase of RSK2 is involved in substrate phosphorylation. Its activation requires phosphorylation of the linker region at Ser(369), catalyzed by extracellular signal-regulated kinase (ERK), and at Ser(386), catalyzed by the C-terminal kinase, after its activation by ERK. In addition, the N-terminal kinase must be phosphorylated at Ser(227) in the activation loop by an as yet unidentified kinase. Here, we show that the isolated N-terminal kinase of RSK2 (amino acids 1-360) is phosphorylated at Ser(227) by PDK1, a constitutively active kinase, leading to 100-fold stimulation of kinase activity. In COS7 cells, ectopic PDK1 induced the phosphorylation of full-length RSK2 at Ser(227) and Ser(386), without involvement of ERK, leading to partial activation of RSK2. Similarly, two other members of the RSK family, RSK1 and RSK3, were partially activated by PDK1 in COS7 cells. Finally, our data indicate that full activation of RSK2 by growth factor requires the cooperation of ERK and PDK1 through phosphorylation of Ser(227), Ser(369), and Ser(386). Our study extend recent findings which implicate PDK1 in the activation of protein kinases B and C and p70(S6K), suggesting that PDK1 controls several major growth factor-activated signal transduction pathways.

The species selectivity of chemically distinct tachykinin nonpeptide antagonists is dependent on common divergent residues of the rat and human neurokinin-1 receptors.

During evolution mutations have occurred in peptide receptors that are neutral with respect to binding of the natural peptide ligand but frequently affect the binding of nonpeptide antagonists. By systematically introducing the nonconserved residues from the human neurokinin (NK)-1 receptor into the corresponding rat receptor we have attempted to localize the structural elements that are responsible for 15-76-fold higher affinity of three tachykinin nonpeptide antagonists for the human receptor, compared with the corresponding rat receptor. Surprisingly, exchange of the four divergent residues located around the previously located apparent binding site for CP 96,345 and FK 888 at the top of transmembrane segment (TM) V and VI, either alone or as a group, did not affect the binding of these nonpeptide compounds. However, substitution of Ser290 in TM VII of the rat receptor with isoleucine present in the human receptor increased the affinity for FK 888 20-fold and that for CP 96345 6-fold, corresponding to an affinity that was only about 4-fold less than the affinity for the human NK-1 receptor. Full human-like affinity for FK 888 and CP 96,345 could be conveyed to the rat receptor by the combined substitution of Ser290 in TM VII to isoleucine and Leu116 in TM III to valine. The NK-2 receptor-selective compound SR 48,968 was found to bind with low affinity to the human NK-1 receptor but with 15-fold even lower affinity to the rat receptor. Substitution of residue 290, which is situated within the previously located binding site for this compound, could completely account for this difference. These data demonstrate that the species selectivities of the nonpeptide antagonists CP 96345, FK 888, and SR 48,968, independently of clear differences in their chemical structures and modes of discovery, have a similar structural basis, being dependent on two divergent residues that apparently are not involved in peptide agonist binding.

Biotin carboxyl carrier protein in barley chloroplast membranes.

Biotin localized in barley chloroplast lamellae is covalently bound to a single protein with an approximate molecular weight of 21 000. It contains one mole of biotin per mole of protein and functions as a carboxyl carrier in the acetyl-CoA carboxylase reaction. The protein was obtained by solubilization of the lamellae in phenol/acetic acid/8 M urea. Feeding barley seedlings with [14C]-biotin revealed that the vitamin is not degraded into respiratory substrates by the plant, but is specifically incorporated into biotin carboxyl carrier protein.