39 research outputs found
OneG: A Computational Tool for Predicting Cryptic Intermediates in the Unfolding Kinetics of Proteins under Native Conditions
Understanding the relationships between conformations of proteins and their stabilities is one key to address the protein folding paradigm. The free energy change (ΔG) of unfolding reactions of proteins is measured by traditional denaturation methods and native hydrogen-deuterium (H/D) exchange methods. However, the free energy of unfolding (ΔGU) and the free energy of exchange (ΔGHX) of proteins are not in good agreement, though the experimental conditions of both methods are well matching to each other. The anomaly is due to any one or combinations of the following reasons: (i) effects of cis-trans proline isomerisation under equilibrium unfolding reactions of proteins (ii) inappropriateness in accounting the baselines of melting curves (iii) presence of cryptic intermediates, which may elude the melting curve analysis and (iv) existence of higher energy metastable states in the H/D exchange reactions of proteins. Herein, we have developed a novel computational tool, OneG, which accounts the discrepancy between ΔGU and ΔGHX of proteins by systematically accounting all the four factors mentioned above. The program is fully automated and requires four inputs: three-dimensional structures of proteins, ΔGU, ΔGU* and residue-specific ΔGHX determined under EX2-exchange conditions in the absence of denaturants. The robustness of the program has been validated using experimental data available for proteins such as cytochrome c and apocytochrome b562 and the data analyses revealed that cryptic intermediates of the proteins detected by the experimental methods and the cryptic intermediates predicted by the OneG for those proteins were in good agreement. Furthermore, using OneG, we have shown possible existence of cryptic intermediates and metastable states in the unfolding pathways of cardiotoxin III and cobrotoxin, respectively, which are homologous proteins. The unique application of the program to map the unfolding pathways of proteins under native conditions have been brought into fore and the program is publicly available at http://sblab.sastra.edu/oneg.htm
Repeated successful surgical rescues of early and delayed multiple ruptures of ventricular septum, right ventricle and aneurysmal left ventricle following massive biventricular infarction
A 58 year old man underwent 6 surgical interventions for various complications of massive biventricular myocardial infarction over a period of 2 years following acute occlusion of a possibly "hyperdominant" left anterior descending coronary artery. These included concomitant repair of apicoanterior post-infarction VSD and right ventricular free wall rupture, repeat repair of recurrent VSD following inferoposterior extension of VSD in the infarcted septum 5 weeks later, repair of delayed right ventricular free wall rupture 4 weeks subsequently, repair of a bleeding left ventricular aneurysm eroding through left chest wall 16 months thereafter, repair of right upper lobe lung tear causing massive anterior mediastinal haemorrhage, mimicking yet another cardiac rupture, 2 months later, followed, at the same admission, 2 weeks later, by sternal reconstruction for dehisced and infected sternum using pedicled myocutaneous latissimus dorsi flap. 5 years after the latissimus myoplasty, the patient remains in NYHA class 1 and is leading a normal life
The unhappy triad of the knee re-revisited
Aim of the study: To describe the surgical findings of the anterolateral complex in patients with the “unhappy triad” lesion of the knee. Method: One hundred and twenty-five consecutive patients presenting with acute anterior cruciate ligament (ACL) tears were selected for this study. Only cases, evaluated with a valgus stress test under fluoroscopy, with a medial opening more than 5 mm of the medial collateral ligament (MCL) were included in the study (11 patients). For the included cases, open MCL surgical repair was performed only in cases with a valgus stress test more than 10 mm as revealed by fluoroscopy (3 patients). All included cases (11 patients) underwent ACL reconstruction and exploration of the anterolateral complex that was then assessed, photographed, classified, and eventually repaired. Results: At clinical evaluation under anaesthesia, all patients presented a positive Lachman test and a pivot shift test graded as ++ in four cases and +++ in five cases, not valuable in two cases. At surgical exploration, the anterolateral complex was involved in all cases (11 patients): one case demonstrated a type I injury, eight cases a type II injury, two cases a type III injury, and no patient with a type IV injury (Segond’s fracture). All anterolateral complex lesions were repaired by direct suture and re-tensioning. Discussion: On the basis of a recent analysis performed by other authors, we could speculate that injuries of ACL and anterolateral compartment occur in the very early phase of the injury when the knee is forced into internal rotation. The MRI evidence of bone bruising in the lateral compartment in most cases of the present series support the hypothesis of an internal rotation torque. Conclusions: The unhappy triad of injuries to the knee is actually a tetrad involving not just the ACL, MCL, and medial/lateral meniscus but also involved the anterolateral complex