I n a 77-year-old man with apical hypertrophic cardiomyopathy and nonsustained ventricular tachycardia, a pulmonary nodule in the right middle lobe was incidentally detected on a chest computed tomography (CT), which was performed for screening purposes of the interstitial pneumonia as a side effect of amiodarone. To establish the diagnosis of lung cancer, the patient was admitted to undergo a CT-guided transthoratic needle biopsy of the lung.The procedure was performed by an experienced pulmonologist using the 18-gauge outer coaxial needle of a disposable core biopsy instrument under CT guidance. The patient was placed in a supine position for the procedure. The biopsy needle was advanced into the lesion, and a specimen was successfully obtained ( Figure 1A). Immediately after removing the biopsy needle followed by a postprocedure CT, the patient coughed, discharged a small amount of bloody phlegm, and developed chest pain. Then, he lost consciousness and developed shock with severe hypotension and decreased oxygen saturation. After he was administered 100% oxygen through a mask and received a large quantity of hydration, a chest CT was obtained again for suspected pulmonary hemorrhage or pneumothorax. The CT imaging revealed a small pulmonary hemorrhage and a small pneumothorax in the right lung ( Figure 1B). At that time, an electrocardiogram (ECG) showed bradycardia with STsegment elevation. Therefore, a 12-lead ECG was obtained and showed complete atrioventricular block and ST-segment elevation in leads II, III, and aVF (Figure 2). On closer examination, both the first and second CT scans showed a massive air embolism extending from the ostium to the midportion of the right coronary artery (RCA), as well as the existence of air in the ascending aorta and the left ventricular apex (Figure 3).The patient underwent coronary angiography for the diagnosis of a coronary air embolism with temporary pacing and also received intravenous catecholamine support. Angiography showed that the main RCA vessel had already recanalized with slow flow, but the coronary flow in the right ventricular branch and in the posterior descending branch was still interrupted ( Figure 4A; Movie I in the online-only Data Supplement). Coronary aspiration and the selective injection of vasodilators via an aspiration catheter into the occluded branches were performed. After these procedures, angiography demonstrated the recovery of coronary flow (Movie II in the online-only Data Supplement); his ECG recovered to sinus rhythm, and the ST-segment elevation resolved
Colorectal cancer (CRC), a common malignant tumour of the gastrointestinal tract, is a life-threatening cancer worldwide. Mutations in KRAS and BRAF, the major driver mutation subtypes in CRC, activate the...
The sensitivity of phosphorylation site identification by mass spectrometry has improved markedly. However, the lack of kinase–substrate relationship (KSR) data hinders the improvement of the range and accuracy of kinase activity prediction. In this study, we aimed to develop a method for acquiring systematic KSR data on anaplastic lymphoma kinase (ALK) using mass spectrometry and to apply this method to the prediction of kinase activity. Thirty-seven ALK substrate candidates, including 34 phosphorylation sites not annotated in the PhosphoSitePlus database, were identified by integrated analysis of the phosphoproteome and crosslinking interactome of HEK 293 cells with doxycycline-induced ALK overexpression. Furthermore, KSRs of ALK were validated by an in vitro kinase assay. Finally, using phosphoproteomic data from ALK mutant cell lines and patient-derived cells treated with ALK inhibitors, we found that the prediction of ALK activity was improved when the KSRs identified in this study were used instead of the public KSR dataset. Our approach is applicable to other kinases, and future identification of KSRs will facilitate more accurate estimations of kinase activity and elucidation of phosphorylation signals.
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