Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase

Aromatic interactions are well-known players in molecular recognition but their catalytic role in biological systems is less documented. Here, we report that a conserved aromatic stacking interaction between dUTPase and its nucleotide substrate largely contributes to the stabilization of the associative type transition state of the nucleotide hydrolysis reaction. The effect of the aromatic stacking on catalysis is peculiar in that uracil, the aromatic moiety influenced by the aromatic interaction is relatively distant from the site of hydrolysis at the alpha-phosphate group. Using crystallographic, kinetics, optical spectroscopy and thermodynamics calculation approaches we delineate a possible mechanism by which rate acceleration is achieved through the remote π–π interaction. The abundance of similarly positioned aromatic interactions in various nucleotide hydrolyzing enzymes (e.g. most families of ATPases) raises the possibility of the reported phenomenon being a general component of the enzymatic catalysis of phosphate ester hydrolysis

Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours

BACKGROUND: A solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour. CASE PRESENTATION: A 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray. The echocardiographic examination revealed pericardial effusion and an inhomogeneous mobile mass located in the pericardial sac around the left ventricle. Cardiac magnetic resonance (MRI) examination showed an intrapericardial, semilunar-shaped mass attached to the pulmonary trunk with an intermediate signal intensity on proton density-weighted images and high signal intensity on T2-weighted spectral fat saturation inversion recovery images. First-pass perfusion and early and late gadolinium-enhanced images showed a vascularized mass with septated, patchy, inhomogeneous late enhancement. Coronary computed tomography angiography revealed no invasion of the coronaries. Based on the retrospectively analysed screening chest X-rays, the mass had started to form at least 7 years earlier. Complete resection of the tumour with partial resection of the pulmonary trunk was performed. Histological evaluation of the septated, cystic mass revealed tumour cells forming an irregular patternless pattern; immunohistochemically, the cells tested positive for vimentin, CD34, CD99 and STAT6 but negative for keratin (AE1-AE3), CD31 and S100. Thus, the diagnosis of an intrapericardial solitary fibrous tumour was established. There has been no recurrence for 3 years based on the regular MRI follow-up. CONCLUSION: Intrapericardial SFTs, showing slow growth dynamics, can present with massive extent even in completely asymptomatic patients. MRI is exceedingly useful for characterizing intrapericardial masses, allowing precise surgical planning, and is reliable for long-term follow up

raw database

Raw data regarding the paper entitled "The Demanding Grey Zone: Sport Indices by Cardiac Magnetic Resonance Imaging Differentiate Hypertrophic Cardiomyopathy from Athlete’s Heart" is presented in the current file. Codes applied in the database are presented in a separate spreadsheet. Abbreviations are listed in the manuscript

Data from: The demanding grey zone: sport indices by cardiac magnetic resonance imaging differentiate hypertrophic cardiomyopathy from athlete's heart

Background: We aimed to characterize gender specific left ventricular hypertrophy using a novel, accurate and less time demanding cardiac magnetic resonance (CMR) quantification method to differentiate physiological hypertrophy and hypertrophic cardiomyopathy based on a large population of highly trained athletes and hypertrophic cardiomyopathy patients. Methods and Results: Elite athletes (n=150,>18 training hours/week), HCM patients (n=194) and athletes with hypertrophic cardiomyopathy (n=10) were examined by CMR. CMR based sport indices such as maximal end-diastolic wall thickness to left ventricular end-diastolic volume index ratio (EDWT/LVEDVi) and left ventricular mass to left ventricular end-diastolic volume ratio (LVM/LVEDV) were calculated, established using both conventional and threshold-based quantification method. Whereas 47.5% of male athletes, only 4.1% of female athletes were in the grey zone of hypertrophy (EDWT 13-16mm). EDWT/LVEDVi discriminated between physiological and pathological left ventricular hypertrophy with excellent diagnostic accuracy (AUCCQ:0.998, AUCTQ:0.999). Cut-off value for LVM/LVEDVCQ<0.82 mm×m2/ml and for EDWT/LVEDViTQ<1.27 discriminated between physiological and pathological left ventricular hypertrophy with a sensitivity of 77.8% and 89.2%, a specificity of 86.7% and 91.3%, respectively. LVM/LVEDV evaluated using threshold-based quantification performed significantly better than conventional quantification even in the male subgroup with EDWT between 13-16mm (p<0.001). Conclusions: Almost 50% of male highly trained athletes can reach EDWT of 13 mm. CMR based sport indices provide an important tool to distinguish hypertrophic cardiomyopathy from athlete’s heart, especially in highly trained athletes in the grey zone of hypertrophy

How are ECG parameters related to cardiac magnetic resonance images? Electrocardiographic predictors of left ventricular hypertrophy and myocardial fibrosis in hypertrophic cardiomyopathy

Abstract Background Structural myocardial changes in hypertrophic cardiomyopathy (HCM) are associated with different abnormalities on electrocardiographs (ECGs). The diagnostic value of the ECG voltage criteria used to screen for left ventricular hypertrophy (LVH) may depend on the presence and degree of myocardial fibrosis. Fibrosis can cause other changes in ECG parameters, such as pathological Q waves, fragmented QRS (fQRS), or repolarization abnormalities. Methods We investigated 146 patients with HCM and 35 healthy individuals who underwent cardiac magnetic resonance imaging (CMR; with late gadolinium enhancement [LGE] in HCM patients) and standard 12‐lead ECGs. On the ECG, depolarization and repolarization abnormalities, the Sokolow–Lyon index, the Cornell index, and the Romhilt–Estes score were evaluated. The left ventricular ejection fraction, volumes, and myocardial mass (LVM) were quantified. Myocardial fibrosis was quantified on LGE images. Results The sensitivity of the Romhilt–Estes score was the highest (75%), and this hypertrophy criterion had the strongest correlation with the LVM index (p < .0001; r = .41). The amount of fibrosis was negatively correlated with the Cornell index (p = .015; r = −.201) and the Sokolow–Lyon index (p = .005; r = −.23), and the Romhilt–Estes score was independent of fibrosis (p = .757; r = 0.026). fQRS and strain pattern predicted more fibrosis, while the Cornell index was a negative predictor of myocardial fibrosis (p < .0001). Among others, the strain pattern was an independent predictor of the LVM (p < .0001). Conclusion The Romhilt–Estes score is the most sensitive ECG criterion for detecting LVH in HCM patients, as myocardial fibrosis does not affect this criterion. The presence of fQRS and strain pattern predicts myocardial fibrosis

Additional file 3: of Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours

The patient’s clinical history organized as a timeline. (PDF 287 kb