Computational analysis of the CB1 carboxyl-terminus in the receptor-G protein complex: Computational Analysis of the CB1 Carboxyl-Terminus

Despite the important role of the carboxyl-terminus (Ct) of the activated brain cannabinoid receptor one (CB1) in the regulation of G protein signaling, a structural understanding of interactions with G proteins is lacking. This is largely due to the highly flexible nature of the CB1 Ct that dynamically adapts its conformation to the presence of G proteins. In the present study, we explored how the CB1 Ct can interact with the G protein by building on our prior modeling of the CB1-Gi complex (Shim J-Y, Ahn KH, Kendall DA. The Journal of Biological Chemistry 2013;288:32449-32465) to incorporate a complete CB1 Ct (Glu416Ct–Leu472Ct). Based upon the structural constraints from NMR studies, we employed ROSETTA to predict tertiary folds, ZDOCK to predict docking orientation, and molecular dynamics (MD) simulations to obtain two distinct plausible models of CB1 Ct in the CB1-Gi complex. The resulting models were consistent with the NMR-determined helical structure (H9) in the middle region of the CB1 Ct. The CB1 Ct directly interacted with both Gα and Gβ and stabilized the receptor at the Gi interface. The results of site-directed mutagenesis studies of Glu416Ct, Asp423Ct, Asp428Ct, and Arg444Ct of CB1 Ct suggested that the CB1 Ct can influence receptor-G protein coupling by stabilizing the receptor at the Gi interface. This research provided, for the first time, models of the CB1 Ct in contact with the G protein

Isolated Left Ventricular Noncompaction Cardiomyopathy Accompanied by Severe Mitral Regurgitation

Isolated left ventricular noncompaction cardiomyopathy (IVNC) is a cardiomyopathy thought to be caused by arrest of normal embryogenesis of the endocardium and myocardium. This abnormality is often associated with other congenital cardiac defects. A 21-year-old man presented to the emergency department with worsening exertional dyspnea during the previous 2 months. Two-dimensional and Doppler echocardiography revealed an enlarged left atrium (LA) and a markedly dilated left ventricle (LV) with preserved LV systolic function, severe mitral valve regurgitation, and prolapse due to chordae rupture. The myocardium of the LV and right ventricle (RV) had excessively prominent trabeculations and deep intertrabecular recesses. He is the first patient in Korea who has undergone mitral valve replacement surgery because of severe mitral valve regurgitation and prolapse due to chordae rupture accompanied by IVNC

The Utility of Multi-detector Row Spiral CT for Detection of Coronary Artery Stenoses

Contrast-enhanced multi-detector row spiral computed tomography (MDCT) was introduced as a promising noninvasive method for vascular imaging. This study examined the accuracy of this technique for detecting significant coronary artery stenoses. Both MDCT(Sensation 16, Siemens, Germany, 12 × 0.75 mm collimation and 0.42 sec rotation speed, 120 kV, 500 effective mA, and 2.7 mm/rotation table-feed) and invasive coronary angiography (CAG) were performed on 61 patients (mean age 59.2 ± 10, 44 men) who were suspected of having coronary artery disease. All patients were treated with atenolol (25 - 50 mg) prior to imaging and the heart rate was maintained below 65 beats per minutes during image acquisition. The images were reconstructed in the diastole around TI - 400 ms with a 0.5 mm increment and a 1.0 mm thickness. All coronary arteries with a diameter of 2.0 mm or more were assessed for the presence of a stenosis (> 50% luminal narrowing). Two independent radiologists who were unaware of the results of the invasive CAG evaluated the MDCT data, and the results were compared with those from the invasive CAG (interval 1- 27, mean 11 days). An evaluation of the CT coronary angiogram (CTCA) was possible in 58 of the 61 patients (95%). Image acquisition of the major coronary arteries including the left main trunk was available in 229 out of 244 arteries. Invasive CAG showed that 35 out of 58 patients had significant coronary artery stenoses by. patient analysis of those who could be evaluated showed that CT coronary angiography correctly classified 30 out of 35 patients as having at least 1 coronary stenosis (sensitivity 85.7%, specificity 91.3%, positive predictive value 93.8%, negative predictive value 80.8%). By analyzing each coronary artery, CAG found 62 stenotic coronary arteries in the 229 coronary arteries that could be evaluated. MDCT correctly detected 50 out of 62 stenotic coronary arteries and an absence of stenosis was correctly identified in 156 out of 167 normal coronary arteries (sensitivity 80.6%, specificity 93.4%, positive predictive value 81.9%, negative predictive value 92.8%). The non-invasive technique of MDCT for examining the coronary artery appears to be a useful method for detecting coronary artery stenoses with a high accuracy particularly with the proximal portion and large arteries

Takayasu's Arteritis Treated by Percutaneous Transluminal Angioplasty with Stenting in the Descending Aorta

A 17-yr-old young woman was referred to our hospital with a 2-yr history of claudication of the lower extremities and severe arterial hypertension. Physical examination revealed significantly different blood pressures between both arms (160/92 and 180/95 mmHg) and legs (92/61 and 82/57 mmHg). The hematological and biochemical values were within their normal ranges, except for the increased erythrocyte sedimentation rate (83 mm/hr) and C-reactive protein (6.19 mg/L). On 3-dimensional computed tomographic angiography, the ascending aorta, the aortic arch and its branches, and the thoracic and, descending aorta, but not the renal artery, were shown to be stenotic. The diagnosis of type IIb Takayasu's arteritis was made according to the new angiographic classification of Takayasu's arteritis, Takyasu conference 1994. Percutaneous transluminal angioplasty with stenting was performed on the thoracic and abdominal aorta. After the interventional procedures, the upper extremity blood pressure improved from 162/101 mmHg to 132/85 mmHg, respectively. She has been free of claudication and there have been no cardiac events during 2-yr of clinical follow-up