ABSTRACT
Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The p16(Ink4a) and p19(Arf) knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27(Kip1) knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA.
Subject(s)
Animals , Mice , Cell Cycle , Codon, Nonsense , Cyclin-Dependent Kinase Inhibitor p16 , DNA , Exons , G1 Phase , Genome , Melanoma , Mice, Knockout , Mutagenesis, Insertional , Neurodegenerative Diseases , Phosphotransferases , Reading Frames , SarcomaABSTRACT
Cardiac papillary fibroelastomas (CPF) are benign cardiac tumors and usually discovered incidentally during echocardiography. This report describes the case of a 68-year-old man, referred to cardiology for multiple masses of the left ventricle and left atrium. The transthoracic echocardiography revealed multiple oscillating masses in the left ventricle and aortic valve, non-mobile mass in the left atrium with severe mitral stenosis and moderate aortic regurgitation. The patient underwent surgical resection of the masses with valve replacements. Histopathologic examination confirmed the diagnosis of CPF in the left ventricle and aortic valve, thrombus in the left atrium.
Subject(s)
Aged , Humans , Aortic Valve , Aortic Valve Insufficiency , Cardiology , Diagnosis , Echocardiography , Heart Atria , Heart Neoplasms , Heart Ventricles , Heart , Mitral Valve Stenosis , ThrombosisABSTRACT
Pulmonary tumor thrombotic microangiopathy [PTTM] is a rare condition causing pulmonary artery hypertension and acute right heart failure in patients with cancer. However, chest computer tomography shows negative finding of pulmonary thromboembolism. Serum D-dimer level may be elevated. Echocardiography reveals a dilated right ventricle and feature of pulmonary artery hypertension. Establishing this diagnosis can be very difficult, and most cases are diagnosed during autopsy, although a history of cancer may be a predictor. PTTM should be considered in all patients with apparent pulmonary artery hypertension and elevated D-dimer level, particularly when the patient is known to have an underlying malignancy, especially adenocarcinoma and most of all, the clinical manifestation is very rapidly progressive.
Subject(s)
Humans , Male , Female , Stomach Neoplasms , Fibrin Fibrinogen Degradation ProductsABSTRACT
During percutaneous coronary intervention, guidewire fractures are very exceptionally encountered in medical practice, but can cause fatal complications such as intracoronary thrombus formation, embolization and perforation. Removal of the remnant segments of guidewire is important for the prognosis. There are several methods being recommended for the treatment of fractured guidewire remnants. However, the best treatment of remnant guidewire filament is still unclear. Herein, we present a case where we did not completely remove remnant guidewire filaments that caused fatal coronary thrombosis.
Subject(s)
Coronary Thrombosis , Coronary Vessels , Methods , Percutaneous Coronary Intervention , Prognosis , Stents , ThrombosisABSTRACT
Pulmonary artery (PA) aneurysm is a rare finding in the thoracic cavity, accompanied by pulmonary hypertension. Clinical presentation of PA aneurysms is usually asymptomatic. The guideline for PA aneurysm treatment is unclear. We report an unusual case of low pressure PA aneurysm associated with atrial septal defect in a 69-year-old man.
Subject(s)
Aneurysm , Heart Septal Defects, Atrial , Hypertension, Pulmonary , Pulmonary Artery , Thoracic CavityABSTRACT
Acute myocarditis can be caused by viral, bacterial, or protozoal infection, or drug toxicity. Fulminant myocarditis progresses rapidly and frequently leads to cardiogenic shock, so patients should be supported by extracorporeal membrane oxygenation (ECMO), an intra-aortic balloon pump (IABP), mechanical ventilation, or a temporary pacemaker to maintain hemodynamic status. Most patients recover with supportive therapy. However, a few patients have persistent atrioventricular (AV) block. We report the case of a 34-year-old male with persistent complete atrioventricular block after the regression of acute myocarditis. Ultimately, a permanent pacemaker was implanted.
Subject(s)
Adult , Humans , Male , Atrioventricular Block , Drug-Related Side Effects and Adverse Reactions , Extracorporeal Membrane Oxygenation , Hemodynamics , Myocarditis , Respiration, Artificial , Shock, CardiogenicABSTRACT
Left ventricular free wall rupture (LVFWR) is a serious complication of myocardial infarction. It presents with a very high mortality rate and can be rescued by accurate diagnosis and emergency surgery. LVFWR can occur with sudden overt clinical symptoms or present insidiously. This report highlights the case of a man with no prior history of coronary artery disease, who presented with LVFWR and pericardial effusion that evolved to severe bacterial pericarditis.
Subject(s)
Coronary Artery Disease , Emergencies , Heart Rupture , Myocardial Infarction , Pericardial Effusion , Pericarditis , RuptureABSTRACT
The unicuspid aortic valve is an extremely rare congenital anomaly. It usually presents with aortic stenosis and/or aortic regurgitation. Other cardiovascular complications, such as aortic dilatation and left ventricular hypertrophy can accompany it. Herein, we present a case report of a 50-year-old asymptomatic male patient with unicuspid aortic valve, complicated by ascending aortic aneurysm.
Subject(s)
Adult , Humans , Male , Middle Aged , Aortic Aneurysm , Aortic Valve , Aortic Valve Insufficiency , Aortic Valve Stenosis , Dilatation , Hypertrophy, Left VentricularABSTRACT
Rupture of the interventricular septum is a serious complication of acute myocardial infarction, accounting for 5% of death due to acute myocardial infarction. The mortality with medical therapy alone exceeds 90%. Accurate diagnosis, urgent management, and early operative correction are necessary for survival. We report cases of 3 patients with ventricular septal rupture after acute myocardial infarction.
Subject(s)
Humans , Diagnosis , Mortality , Myocardial Infarction , Rupture , Ventricular Septal RuptureABSTRACT
Low-grade B cell mucosa-associated lymphoid tissue (MALT) lymphoma makes up 8% of non-Hodgkin's lymphomas. It has been characterized by a prolonged clinical course and persistent disease at the site of origin. Most patients with low-grade B cell MALT lymphoma occur in the stomach, orbit, intestine, lung, thyroid, salivary gland, skin, soft tissues, bladder, kidney, and central nervous system. The diagnosis of MALT lymphoma can be established by a characteristic finding of infiltration of small lymphocytes that are monoclonal B cell and CD5 negative. Bone marrow involvement seems uncommom but has been developed. Waldenstr m's macroglobulinemia (WM) is usually defined as bone marrow infiltration of lymphoplasmacytoid lymphocytes with a high level of circulating macroglobulin IgM. Lymphadenopathy and splenomegaly occurs in 20~40% of WM. It is very hard work to do differential diagnosis between disseminated low-grade B cell MALT lymphoma and WM with organ involvement by a bone marrow examination. We reprot one case of low grade mediastinal MALT lymphoma with bone marrow involvement and a high level of serum monoclonal IgM with clinical appearance of WM.