Complete Revascularization of Simultaneous Acute Occlusion of Three Major Coronary Arteries.

Our case demonstrates that rapid and complete revascularization by PCI can save a patient with acute myocardial infarction caused by simultaneous acute occlusion of the three major coronary arteries.

Asymptomatic abdominal aortic stenosis detected by unenhanced computed tomography before angiography in acute myocardial infarction.

Although rapid treatment is important, unenhanced computed tomography before angiography is quick and can detect myocardial infarction induced by aortic dissection and also asymptomatic abdominal aortic stenosis in acute myocardial infarction cases.

A novel cardiac ryanodine receptor gene (RyR2) mutation in an athlete with aborted sudden cardiac death: a case of adult-onset catecholaminergic polymorphic ventricular tachycardia.

Sudden cardiac death (SCD) in athletes <35 years of age are mostly due to congenital or acquired cardiac malformations or hypertrophic cardiomyopathy. However, ion channelopathies such as catecholaminergic polymorphic ventricular tachycardia (CPVT) or long-QT syndromes, which are less frequently observed, are also potential pathogenesis of SCD in young athletes. CPVT is an inherited arrhythmia that is induced by physical or emotional stress and may lead to ventricular fibrillation syncope or SCD. Here, we report a case of athlete woman with adult-onset CPVT and aborted SCD who has a novel missense mutation (K4392R) in the cardiac RyR2 gene.

'Honeycomb appearance' on three-dimensional transthoracic echocardiography as the landmark of left ventricular non-compaction: two case reports.

INTRODUCTION: Left ventricular non-compaction is a rare congenital heart disease, and is most commonly diagnosed via two-dimensional echocardiography according to echocardiographic criteria. Recently, transthoracic three-dimensional echocardiography has become available in the clinical setting. CASE PRESENTATION: We present two isolated cases of left ventricular non-compaction from Japan (in an 84-year-old woman and 47-year-old man) that were confirmed by two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography and cardiac magnetic resonance imaging. In both cases, three-dimensional echocardiography successfully demonstrated the trabecular meshwork of the left ventricle, referred to as a 'honeycomb appearance'. CONCLUSIONS: Three-dimensional echocardiography has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible with two-dimensional echocardiography. We further emphasize the clinical utility of three-dimensional echocardiography, which is not limited to just the observation of the trabeculations and inter-trabecular recesses, but can also visualize the trabecular meshwork with a 'honeycomb appearance'.

Newly developed mobile mass superimposed on mitral annulus calcification in patient with cerebral infarction: Documentation of a unique embolic source.

Mitral annulus calcification (MAC) has been recognized as a potent risk factor to cause cerebral infarction. There has been suggested possible linkage between mass on MAC and systemic embolic events. We report a case of cerebral infarction with newly developed mobile mass superimposed on MAC.

GANP suppresses the arginine methyltransferase PRMT5 regulating IL-4-mediated STAT6-signaling to IgE production in B cells.

Antigen (Ag)-driven B cells undergo antibody (Ab) affinity maturation and class switching in germinal center (GC) B cells. GANP is one of the molecules required for Ab affinity maturation. We herein found an increase of IgE in B cell ganp-deficient mice and studied the signal transduction pathway regulated by GANP. GANP suppresses the STAT-mediated transcription activity in GC B cells with the regulation of arginine methyltransferase activity by the interaction with JAK-binding protein arginine methyltransferase (PRMT) 5 and JAK1/JAK3 that are responsible for STAT6 activation. The prmt5 mRNA was up-regulated in B cells after stimulation in vitro and in vivo in GC B cells. The loss of GANP caused up-regulation of phosphorylation and arginine dimethylation of STAT6 in B cells after stimulation with LPS and IL-4 in vitro. On the contrary, GANP over-expressed B cells in ganp gene-transgenic mice showed a low STAT6 phosphorylation after stimulation. The over-expression of PRMT5 caused the up-regulation of STAT6-mediated gene transcription, which was also suppressed by the co-transfection of GANP, in luciferase reporter assay. GANP down-regulates JAK1/JAK3 to STAT6-signaling with regulation of arginine methylation activity, which might be responsible for the B cell endogenous suppressive mechanism of hyper-IgE.

GANP suppresses DNA recombination, measured by direct-repeat beta-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cells.

Immunoglobulin V-region somatic hypermutation and C-region class-switch recombination are initiated by activation-induced cytidine deaminase (AID) in B-cells. AID-induced DNA damage at the immunoglobulin S-region is known to be repaired by non-homologous end-joining, but repair mechanisms at the V-region remain to be elucidated. In Saccharomyces cerevisiae, DNA homologous recombination is regulated by the expression of Sac3, involved in actin assembly, cell cycle transition and mRNA metabolism. Here, we demonstrate that the Sac3-homologue GANP suppresses DNA recombination in a direct-repeat beta-galactosidase gene construct in mammalian cells. Homozygous ganp gene knockout is embryonic lethal in mice. Embryonic fibroblasts immortalized from hetero-deficient ganp(+/-) mice showed more DNA recombination than wild-type. In contrast, over-expression of GANP suppressed either spontaneous DNA recombination or that caused by the introduction of aid cDNA into NIH3T3 cells (susceptible to I-sceI restriction enzyme cleavage but not to RAG-mediated immunoglobulin gene recombination). GANP suppresses the DNA recombination not only on the extrachromosomal DNA construct but also on the integrated DNA. The Sac3-homology portion is necessary for the suppressive activity, but the truncated carboxyl terminal MCM3-binding/acetylating region adversely augmented DNA recombination, acting as a dominant negative form. Expression of full-length GANP is critical for suppression of DNA hyper-recombination in mammalian cells.

Left ventricular hypertrophy in mice with a cardiac-specific overexpression of interleukin-1.

Recent studies have identified the importance of proinflammatory cytokines in the development of left ventricular (LV) hypertrophy. However, the precise role of interleukin-1 (IL-1), one of the major proinflammatory cytokines, in the myocardium is not fully understood. In this study, we investigated the pathophysiological consequences of cardiac expression of IL-1 in vivo. We generated mice with a cardiac-specific overexpression of human IL-1alpha. We then analyzed their heart morphology and functions. Histological and echocardiographic analyses revealed concentric LV hypertrophy with preserved LV systolic function in the mice. Our results suggest that myocardial expression of IL-1 is sufficient to cause LV hypertrophy.

The Sac3 homologue shd1 is involved in mitotic progression in mammalian cells.

Saccharomyces Sac3 required for actin assembly was shown to be involved in DNA replication. Here, we studied the function of a mammalian homologue SHD1 in cell cycle progression. SHD1 is localized on centrosomes at interphase and at spindle poles and mitotic spindles, similar to alpha-tubulin, at M phase. RNA interference suppression of endogenous shd1 caused defects in centrosome duplication and spindle formation displaying cells with a single apparent centrosome and down-regulated Mad2 expression, generating increased micronuclei. Conversely, increased expression of SHD1 by DNA transfection with shd1-green fluorescent protein (gfp) vector for a fusion protein of SHD1 and GFP caused abnormalities in centrosome duplication displaying cells with multiple centrosomes and deregulated spindle assembly with up-regulated Mad2 expression until anaphase, generating polyploidy cells. These results demonstrated that shd1 is involved in cell cycle progression, in particular centrosome duplication and a spindle assembly checkpoint function.

Osteopontin plays an important role in the development of medial thickening and neointimal formation.

Osteopontin (OPN) is a soluble secreted phosphoprotein that binds with high affinity to several integrins and it has been found at the site of atherosclerotic lesions. However, the role of OPN expression in vivo is still poorly understood. To investigate the physiological role of OPN in detail, we generated transgenic mice (Tg) overexpressing the OPN gene under control of the cytomegalovirus enhancer/chicken beta-actin promoter. We detected OPN mRNAs in almost all tissues of 3 lines of Tg mice by Northern blotting. The serum levels of OPN were significantly higher in Tg than in non-Tg mice (782+/-107 versus 182+/-44 ng/mL; P<0.001). Compared with non-Tg mice, a 73% (88+/-6 versus 51+/-7 microm; P<0.001) and 94% (126+/-15 versus 73+/-11 microm; P<0.0001) increase in the medial thickness of the aorta was determined in Tg mice at 16 and 32 weeks after birth. However, we found no evidence of inflammatory cells adhering to endothelial cells, intimal hyperplasia, or calcification in any region of Tg mice without artery injury. We then investigated the effect of cuff-induced injury to the femoral artery. The intimal thickening in Tg mice increased 2.9-fold more than that in non-Tg mice (4.9+/-1.9 versus 1.7+/-0.4 microm; P=0.022). The expression of OPN induces both medial thickening without injury and neointimal formation after injury, thus suggesting that OPN plays a role in the development of atherosclerosis, vascular remodeling, and restenosis after angioplasty in vivo.