Caspase cleaved presenilin-1 is part of active gamma-secretase complexes.

gamma-Secretase is a key enzyme involved in the processing of the beta-amyloid precursor protein into amyloid beta-peptides (Abeta). Abeta accumulates and forms plaques in Alzheimer's disease (AD) brains. A progressive neurodegeneration and cognitive decline occurs during the course of the disease, and Abeta is believed to be central for the molecular pathogenesis of AD.

The tachyarrhythmic cardiomyopathy--a rare entity in childhood.

Unlabelled: Persistent disturbances of rhythm with high heart rate may lead to reversible depression of left ventricular function and biventricular failure. This phenomenon may appear also in children with incessant supraventricular tachycardia. Because in most cases these patients are long time asymptomatic the diagnosis of these arrhythmias is very difficult and frequently is belated.

Progression of aortic valve sclerosis and aortic valve stenosis: what is the role of statin treatment?

Background: It has recently been suggested that statins could slow the progression of aortic stenosis, but this hypothesis has not been validated in large series. Moreover, there is little information about the role of statin treatment in patients with aortic valve sclerosis.

Methods: From our database 1988--2002, we retrospectively identified 1136 consecutive patients with aortic valve sclerosis (peak aortic velocity [Vmax] > 1.

Right ventricular functional recovery after acute myocardial infarction: relation with left ventricular function and interventricular septum motion. GISSI-3 echo substudy.

Objective: To evaluate the pattern of right ventricular (RV) functional recovery and its relation with left ventricular (LV) function and interventricular septal (IVS) motion in low risk patients after acute myocardial infarction (AMI).

Design And Setting: Multicentre clinical trial carried out in 47 Italian coronary care units.

Patients: 500 patients from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) -3 echo substudy, who underwent serial echocardiograms 24-48 hours after symptom onset and at discharge, six weeks, and six months after AMI.

Subaortic stenosis produced by an accessory mitral valve: the role of echocardiography.

Subaortic stenosis caused by an accessory mitral valve is an exceedingly rare finding. We report the case of an asymptomatic 14-year-old patient, in whom transthoracic echocardiography revealed an accessory mitral valve in the left ventricular outflow tract, producing mild subaortic stenosis. Except for an aneurysm of the interventricular septum, with no shunt, there were no other anomalies.

Association of left ventricular filling parameters assessed by pulsed wave Doppler and color M-mode Doppler echocardiography with left ventricular pathology, pulmonary congestion, and left ventricular end-diastolic pressure.

Among 90 consecutive patients with various degrees of left ventricular (LV) dysfunction (normal patients, LV hypertrophy, LV ejection fraction <50%, and <30%), the mitral valve pulse-wave E/A ratio showed a characteristic U-shaped curve with increasing severity of LV dysfunction. In contrast, there was a significant progressive decrease in flow propagation velocity of the E-wave (Vp) and a significant increase in E/Vp values with increasing severity of LV dysfunction. The E/Vp ratio was the best predictor of pulmonary congestion, and in a subgroup of patients who underwent cardiac catheterization, it was the only significant predictor of LV end-diastolic pressure.

Left atrium remodeling after acute myocardial infarction (results of the GISSI-3 Echo Substudy).

To evaluate the existence, timing, and determinants of post-infarction left atrial remodeling, we studied a subgroup of 514 patients from the Third Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Echo Substudy who underwent 4 serial 2-dimensional echocardiograms up to 6 months after acute myocardial infarction. This study is the first to demonstrate, in a large series of patients, the existence of early and late left atrial remodeling after low-risk acute myocardial infarction and the relation of left atrial remodeling to left ventricular remodeling.

Mechanisms of cell death in Alzheimer's disease: role of presenilins.

Presenilins are often mutated in familial forms of Alzheimer's disease (AD). Such mutations sensitize cells in culture to different apoptotic stimuli eg. staurosporine, calcium ionophore, growth factor withdrawal.

Effect of statins on the progression of bioprosthetic aortic valve degeneration.

To date, there is no proved medical therapy able to significantly reduce the degenerative process of biologic prosthetic aortic valves. It has recently been suggested that statins may reduce the progression of native aortic valve stenosis. We examined the effect of statin treatment on bioprosthetic aortic valve degeneration and found a beneficial effect of statins in slowing bioprosthetic degeneration.

Gamma-secretase activity of presenilin 1 regulates acetylcholine muscarinic receptor-mediated signal transduction.

Familial Alzheimer's disease (FAD) presenilin 1 (PS1) mutations give enhanced calcium responses upon different stimuli, attenuated capacitative calcium entry, an increased sensitivity of cells to undergo apoptosis, and increased gamma-secretase activity. We previously showed that the FAD mutation causing an exon 9 deletion in PS1 results in enhanced basal phospholipase C (PLC) activity (Cedazo-Minguez, A., Popescu, B.

Apolipoprotein E and beta-amyloid (1-42) regulation of glycogen synthase kinase-3beta.

Glycogen synthase kinase-3beta (GSK-3beta) is implicated in regulating apoptosis and tau protein hyperphosphorylation in Alzheimer's disease (AD). We investigated the effects of two key AD molecules, namely apoE (E3 and E4 isoforms) and beta-amyloid (Abeta) 1-42 on GSK-3beta and its major upstream regulators, intracellular calcium and protein kinases C and B (PKC and PKB) in human SH-SY5Y neuroblastoma cells. ApoE3 induced a mild, transient, Ca2+-independent and early activation of GSK-3beta.

The contribution of non-invasive imaging modalities to the diagnosis of left ventricular pseudoaneurysm.

Background: Left ventricular pseudoaneurysm (LVPA) is a rare entity characterized by a tendency to spontaneous rupture due to its morphology, a lack of myocardial fibers and fibrous tissue delineating the cavity. An early diagnosis is essential in order to guide appropriate therapy.

Purpose: To determine the diagnostic accuracy of different imaging techniques, treatment results, and prognosis of patients (pts) with LVPA.

Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo.

Apoptotic cell death induced by kainic acid (KA) in cultures of rat cerebellar granule cells (CGC) and in different brain regions of Wistar rat pups on postnatal day 21 (P21) was studied. In vitro, KA (100-500 microM) induced a concentration-dependent loss of cell viability in MTT assay and cell death had apoptotic morphology as studied by chromatin staining with propidium iodide (PI). In vivo, twenty-four hours after induction of status epilepticus (SE) by an intraperitoneal KA injection (5 mg/kg) we quantified apoptotic cells in hippocampus (CA1 and CA3), parietal cortex and cerebellum using PI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique.

Selective protection by phosphatidic acid against staurosporine-induced neuronal apoptosis.

Phosphatidic acid, the main product of lipid breakdown through phospholipase D activation, has been implicated in important signal transduction pathways able to influence cell fate in many ways. The purpose of this work was to determine possible effects of phosphatidic acid on neuronal cell death pathways. Here we used cerebellar granular cell cultures and cell death was triggered with either staurosporine or H(2)O(2).

Early electrocortical changes consistent with ischemic preconditioning in rat.

Ischemic preconditioning (IPC) of the brain describes the neuroprotection induced by a short, conditioning ischemic episode (CIE) to a subsequent severe (test) ischemic episode (TIE). Most of the supporting evidence for IPC is based on histological assessment, several days after TIE. The aim of this study is to investigate if changes induced by IPC can be detected within 30 min of reperfusion following the ischemic episode.

The presenilin 1 deltaE9 mutation gives enhanced basal phospholipase C activity and a resultant increase in intracellular calcium concentrations.

We studied effects of the familial Alzheimer's disease presenilin 1 (PS1) exon 9 deletion (PS1-DeltaE9) mutation on basal and carbachol-stimulated phosphoinositide (PI) hydrolysis and intracellular Ca(2+) concentrations ([Ca(2+)](i)) in human SH-SY5Y neuroblastoma cells. We demonstrate that PS1-DeltaE9 cells have an enhanced basal PI hydrolysis and [Ca(2+)](i) as compared with both wild type PS1 (PS1-WT) and nontransfected (NT) cells. Both were reversed by the phospholipase C (PLC) inhibitor neomycin.

Caspase cleavage of exon 9 deleted presenilin-1 is an early event in apoptosis induced by calcium ionophore A 23187 in SH-SY5Y neuroblastoma cells.

Presenilins (PSs) are mutated in a majority of familial Alzheimer disease (FAD) cases. Mutated PSs may cause FAD by a number of pro-apoptotic mechanisms, or by regulating gamma-secretase activity, a protease involved in beta-amyloid precursor protein processing to the neurotoxic beta-amyloid peptide. Besides their normal endoproteolytic processing, PSs are substrates for caspases, being cleaved to alternative N-terminal and C-terminal fragments.

Assessment of pseudohypertrophy as a measure of left-ventricular compression in patients with cardiac tamponade.

Background: Left-ventricular pseudohypertrophy reflecting left-ventricular compression was reported in a selected group of patients with cardiac tamponade.

Hypothesis: Criteria for the presence of pseudohypertrophy can be established to guide its use as a sign of left-ventricular compression in patients with cardiac tamponade.

Methods: Left-ventricular wall thickness, diameters, relative diastolic wall thickness (%) = (posterior wall thickness/end diastolic radius) x 100 and estimated left-ventricular mass were measured in patients with small, moderate and large pericardial effusion, in patients with cardiac tamponade before and after pericardiocentesis (16 patients in each group) and in 30 control subjects with normal echocardiograms.

Noninvasive assessment of left ventricular end-diastolic pressure by the response of the transmitral a-wave velocity to a standardized Valsalva maneuver.

Impaired relaxation is frequently masked by elevated filling pressures, resulting in a pseudonormal flow pattern (E/A >1.0). Because the E/A wave ratio increases as filling pressures rise, it is generally assumed that patients with an E/A ratio of <1.