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Biomedical subjects

Sachiko Ito

Publications and source records attributed to Sachiko Ito.

At least 19 recordsLinked to original sources

Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the microglia by amyloid-beta stimulation via the PI3K/Akt pathway.

Alzheimer's disease is characterized by the presence of senile plaques in the brain composed primarily of amyloid-beta peptide. Microglia have been reported to surround these Abeta plaques, which have opposite roles, provoking a microglia-mediated inflammatory response that contributes to neuronal cell loss or the removal of Abeta and damaged neurons. We herein analyzed the process of expression of Matrix metalloproteinases induced by Abeta stimulation. We found that Abeta1-42 induces a high level of MMP3, MMP12 and MMP13 in the microglia. The signal transduction pathway for the expression of these MMPs mRNA induced by Abeta1-42 depends on PI3K/Akt.

Alzheimer Disease↗

Atrial tachycardia arising from the right atrial inferoseptum masquerading as common atrial flutter.

Radiofrequency catheter ablation was performed in 2 patients with atrial tachycardia (AT). In both cases the AT originated from the inferoseptal portion of the right atrium, and the cycle length was 210 ms. The surface ECG demonstrated common counterclockwise atrial flutter, probably caused by functional block in the clockwise direction at the cavo-tricuspid isthmus and posterior right atrium with rapid activation of the origin. Although rare (2%), AT originating from the inferoseptum of the right atrium should be considered when the surface ECG exhibits common atrial flutter.

Adult↗

Idiopathic ventricular arrhythmias originating from the tricuspid annulus: Prevalence, electrocardiographic characteristics, and results of radiofrequency catheter ablation.

BACKGROUND: Idiopathic ventricular tachycardias (VTs) and premature ventricular contractions (PVCs) arising from the tricuspid annulus have been reported. OBJECTIVE: The purpose of this study was to clarify the prevalence and characteristics of VT/PVCs originating from the tricuspid annulus. METHODS: The ECG characteristics and results of radiofrequency (RF) catheter ablation were analyzed in 454 patients with idiopathic VT/PVCs. RESULTS: Thirty-eight (8%) patients had VT/PVCs arising from the tricuspid annulus: 28 VT/PVCs (74%) originated from the septal portion of the tricuspid annulus and the remaining 10 (26%) from the free wall of the tricuspid annulus. QRS duration and Q-wave amplitude in each of leads V1-V3 were greater in VT/PVCs arising from the free wall of the tricuspid annulus than those from the septum of the tricuspid annulus (all P < .01). "Notching" of the QRS complex was observed more often in VT/PVCs arising from the free wall of the tricuspid annulus than those from the septum of the tricuspid annulus (P < .01). A Q wave in lead V1 was observed more often in VT/PVCs arising from the septum of the tricuspid annulus than those from the free wall of the tricuspid annulus (P < .005). R-wave transition occurred beyond lead V3 more often in VT/PVCs arising from the free wall of the tricuspid annulus than those from the septum of the tricuspid annulus (P < .005). RF catheter ablation eliminated 90% of the VT/PVCs arising from the free wall of the tricuspid annulus but only 57% of the VT/PVCs arising from septum of the tricuspid annulus. CONCLUSION: Idiopathic VT/PVCs arising from tricuspid annulus are not rare, and the detailed origin can be determined by ECG analysis. The preferential site of origin was the septum but also could be the free wall of the tricuspid annulus.

Cardiac Catheterization↗

Amyloid-beta peptides induce several chemokine mRNA expressions in the primary microglia and Ra2 cell line via the PI3K/Akt and/or ERK pathway.

Alzheimer's disease (AD) is characterized by the presence of senile plaques composed primarily of amyloid-beta peptide (Abeta) in the brain. Microglia have been reported to surround these Abeta plaques, which have opposite roles, provoking a microglia-mediated inflammatory response that contributes to neuronal cell loss or the removal of Abeta and damaged neurons. To perform these tasks microglia migrate to the sites of Abeta secretion. We herein analyzed the process of chemokine expression induced by Abeta stimulation in primary murine microglia and Ra2 microglial cell line. We found that Abeta1-42 induced the expressions of CCL7, CCL2, CCL3, CCL4 and CXCL2 in the microglia. The signal transduction pathway for the expression of CCL2 and CCL7 mRNA induced by Abeta1-42 was found to depend on phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK), whereas the pathway for CCL4 depended only on PI3K/Akt. These inflammatory chemokine expressions by Abeta stimulation emphasize the contribution of neuroinflammatory mechanisms to the pathogenesis of AD.

Amyloid beta-Peptides↗

PCR-mediated seamless gene deletion and marker recycling in Saccharomyces cerevisiae.

Repeated gene manipulations can be performed in yeast by excision of an introduced marker. Cassette modules containing a marker flanked by two direct repeat sequences of hisG or loxP have often been used for marker recycling, but these leave one copy of the repeats in the chromosome after excision. Genomic copies of a repeat can cause increased mistargeting of constructs containing the same repeats or unexpected chromosomal rearrangements via intra- or interchromosomal recombinations. Here, we describe a novel marker recycling procedure that leaves no scar in the genome, which we have designated seamless gene deletion. A 40 base sequence derived from an adjacent region to the targeted locus was placed in an integrating construct to generate direct repeats after integration. Seamless HIS3 deletion was achieved via a PCR fragment that consisted of a URA3 marker attached to a 40 base repeat-generating sequence flanked by HIS3 targeting sequences at both ends. Transformation of the designed construct resulted in his3 disruption and the generation of 40 base direct repeats on both sides of URA3 in the targeted locus. The resulting his3::URA3 disruptants were plated on 5-fluoroorotic acid medium to select for URA3 loss. All the selected colonies had lost URA3 precisely by recombination between the repeats, resulting in his3 deletion without any extraneous sequences left behind in the chromosome.

DNA, Fungal↗

Significance and utility of plasma brain natriuretic peptide concentrations in patients with idiopathic ventricular arrhythmias.

BACKGROUND: Secretion of B-type natriuretic peptide (BNP) appears to be regulated mainly by wall tension, and an increase in the plasma BNP concentration is considered to reflect ventricular structural and functional abnormalities. The aim of this study was to clarify the significance and utility of the measurement of the plasma BNP in the setting of idiopathic ventricular arrhythmias (I-VT/PVCs). METHODS: This study included 135 patients with symptomatic, monomorphic I-VT/PVCs (73 women; 53 +/- 17 years; 50 ventricular tachycardias [VTs], 85 premature ventricular contractions) who underwent radiofrequency catheter ablation. None had structural heart disease or renal dysfunction. RESULTS: The plasma BNP concentration exceeded the normal range (>18.4 pg/mL; high BNP concentration) in 79 patients (56%). The high BNP concentration was found more often in I-VT/PVCs originating from the left ventricle (LV; 74%) than the right ventricle (RV; 49%; P < 0.01). The plasma BNP concentration correlated with the age (P = 0.0001) and frequency of premature ventricular contractions (P < 0.0001), and left-sided I-VT/PVCs and the presence of controlled hypertension were independent predictors of a high BNP concentration (both P < 0.05). In patients with a successful ablation and high BNP concentration before the ablation, the BNP concentration decreased to the normal range in 61% of patients after ablation. In patients with a failed ablation, the BNP concentration did not decrease to the normal range after ablation in any of the patients (P < 0.0005). CONCLUSIONS: The plasma BNP concentration was elevated in about 60% of the patients with symptomatic I-VT/PVCs. Normalization of the high BNP concentration after ablation may indicate a successful ablation.

Adolescent↗

Cellular and systemic defense system against age-promoting stimuli.

Although much progress has been achieved in aging research using lower animals, especially yeast and C. elegans, aging in humans remains puzzling. Here I offer my hypothesis of host defense against age-promoting stimuli, which holds that the cell itself has a defense system and multi-organism, an even more sophisticated one against age-promoting stimuli. Here I review recent achievements in aging research and try to explain their findings in the light of my hypothesis. Age-promoting stimuli, including reactive oxygen species, telomere shortening or external stimuli such as UV or radiation induce stress responses in cells. The cellular defense system operates to overcome stimuli or repair damaged cellular components. Stress-induced damaged cells or infectious stimuli activate systemic defense systems, especially the innate immune system. Macrophages in the innate immune system are especially active not only in clearing damaged cells and repairing damaged tissue, but unfortunately, also in inducing age-related diseases.

Aging↗

Amyloid-beta peptides induce cell proliferation and macrophage colony-stimulating factor expression via the PI3-kinase/Akt pathway in cultured Ra2 microglial cells.

Alzheimer's disease is characterized by numerous amyloid-beta peptide (Abeta) plaques surrounded by microglia. Here we report that Abeta induces the proliferation of the mouse microglial cell line Ra2 by increasing the expression of macrophage colony-stimulating factor (M-CSF). We examined signal cascades for Abeta-induced M-CSF mRNA expression. The induction of M-CSF was blocked by a phosphatidylinositol 3 kinase (PI3-kinase) inhibitor (LY294002), a Src family tyrosine kinase inhibitor (PP1) and an Akt inhibitor. Electrophoretic mobility shift assays showed that Abeta enhanced NF-kappaB binding activity to the NF-kappaB site of the mouse M-CSF promoter, which was blocked by LY294002. These results indicate that Abeta induces M-CSF mRNA expression via the PI3-kinase/Akt/NF-kappaB pathway.

Amyloid beta-Peptides↗

Idiopathic ventricular arrhythmia arising from the mitral annulus: a distinct subgroup of idiopathic ventricular arrhythmias.

OBJECTIVES: We sought to clarify the prevalence and characteristics of idiopathic ventricular tachycardia or premature ventricular contraction originating from the mitral annulus (MAVT/PVC). BACKGROUND: Recent case reports have presented patients with MAVT/PVC. METHODS: Electrocardiographic (ECG) characteristics and the results of electrophysiologic investigation and radiofrequency catheter ablation (RFCA) were analyzed in 352 patients with symptomatic idiopathic ventricular tachycardia (IVT)/premature ventricular contraction (PVC). RESULTS: Nineteen cases of IVT/PVC (5%) represented MAVT/PVC. Of these, 11 (58%) originated from the anterolateral portion of the mitral annulus (AL-MAVT/PVC), and 2 (11%) arose from the posterior portion (Pos-MAVT/PVC). The remaining six cases of MAVT/PVC (31%) had posteroseptal origin (PS-MAVT/PVC). In all patients, an S-wave was present in lead V(6). The QRS polarity in inferior leads and leads I and aVL was useful for differentiating AL-MAVT/PVC from Pos-MAVT/PVC or PS-MAVT/PVC. The Pos-MAVT/PVC had an Rs pattern in lead I and an R pattern in lead V(1), whereas PS-MAVT/PVC invariably had an R pattern in lead I and a negative QRS component in lead V(1). The AL-MAVT/PVC and Pos-MAVT/PVC showed a longer QRS duration than the PS-MAVT/PVC (p < 0.001), and all had late-phase "notching" of the QRS complex in inferior leads. In all patients, RFCA eliminated MAVT/PVC, with no recurrences during follow-up for 21 +/- 15 months. CONCLUSIONS: Mitral annular VT/PVC is a rare but distinct subgroup of IVT/PVC. MAVT/PVC origin could be determined by ECG analysis. The AL and PS sites of the MA were preferential.

Adult↗

Tissue tracking imaging as a new modality for identifying the origin of idiopathic ventricular arrhythmias.

Tissue tracking imaging was performed in 33 patients with idiopathic ventricular arrhythmias before radiofrequency catheter ablation. The site of the arrhythmia origin, defined as the site where the earliest color-coded signal appeared on the myocardium at the onset of the arrhythmia, corresponded to the site of origin as determined on fluoroscopy during activation mapping in all patients. Catheter ablation at that site abolished the arrhythmia in 29 patients (88%).

Catheter Ablation↗

Long-term results of cryoablation with a new cryoprobe to eliminate chronic atrial fibrillation associated with mitral valve disease.

The purpose of this study was to examine the performance of a new cryoprobe in the treatment of chronic atrial fibrillation (AF) associated with mitral valve disease. The study included 66 patients undergoing mitral valve replacement. The mean AF duration was 9.0 +/- 9.0 years and mean left atrial (LA) was diameter 57 +/- 10 mm. Cryoablation (-60 degrees C) was applied to four pulmonary vein (PV) orifices over 2-3 minute. The spherical tip (2-cm in diameter) of the cryoprobe is capable of ablating the left atrium near the PV, as well as the PV ostium with a single cryoablation. After cryoablation, mitral valve surgery or a combined surgical procedure were performed in 66 patients. There were no intraoperative complications. Sinus rhythm was restored in 60 patients (91%) immediately after the operation. Recurrent AF was treated with antiarrhythmic drugs and/or direct current cardioversion in 43 patients (72%). At discharge, 48 patients (72%) were in sinus rhythm. During a mean follow-up period of 31 +/- 16 months, 40 patients (61%) were in sinus rhythm with (29) or without antiarrhythmic drugs (11). In patients in sinus rhythm at the end of the follow-up period, the duration of preoperative AF duration was significantly shorter (P < 0.05) and the preoperative LA diameter and cardiothoracic ratio were significantly smaller than in patients who were in AF (both for P < 0.005). Using this new cryoprobe, sinus rhythm was restored and maintained in 61% of patients with chronic AF and mitral valve disease with a 12-15 minute cryoablation procedure.

Atrial Fibrillation↗

Simultaneous mapping in the left sinus of valsalva and coronary venous system predicts successful catheter ablation from the left sinus of valsalva.

Idiopathic ventricular tachycardia originating from the left epicardium (Epi-VT) can be ablated from the left sinus of Valsalva (LSV) in selected patients. We hypothesized that the analysis of electrograms at the LSV and transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV) could predict the efficacy of radiofrequency catheter ablation (RFCA) from the LSV. Simultaneous mapping in the LSV and coronary venous system was performed in 25 patients (12 VTs and 13 premature ventricular contractions). The earliest ventricular activation (VA) during the arrhythmias was found at the LSV or GCV-AIV in all patients. RF applications from the LSV were successful in 17 patients success group (S-Gr) and failed in 8 failure group (F-Gr). The earliness of the VA recorded in the LSV (VA[LSV]) and in GCV-AIV (VA[GCV-AIV]) was compared between the two groups. (1) The VA[LSV] preceded the QRS onset by 28 +/- 11 ms in S-Gr and 14 +/- 10 ms in F-Gr (P < 0.01). (2) In S-Gr, the VA[GCV-AIV] was earlier than the VA[LSV] in 5 five patients (35%). However, in F-Gr, the VA[GCV-AIV] was earlier than the VA[LSV] in all patients. (3) In patients in whom the earliest VA was found at the LSV or GCV-AIV, a VA [GCV-AIV] preceding the VA[LSV] by less than 10 ms identified successful RFCA from the LSV with a sensitivity of 88 %, specificity of 100%, and high predictive value. With a detailed analysis of the electrograms recorded from the GCV-AIV and LSV, it was possible to identify the successful catheter ablation of Epi-VT from the LSV.

Catheter Ablation↗

Pulmonary vein morphology before and after segmental isolation in patients with atrial fibrillation.

BACKGROUND: The morphology of the pulmonary veins (PVs) before and after segmental isolation of the PVs has not been sufficiently characterized. METHODS AND RESULTS: Multi-slice computed tomography was performed before and 3 +/- 1 months after ablation in 30 patients with atrial fibrillation who underwent PV isolation. Before ablation, PV narrowing (> or =25% luminal reduction) was found in nine (8%) PVs. After ablation, de novo PV narrowing was found in 24 PVs (26%) and was detected only in the supero-inferior direction in 14 PVs (58%). The diameter reduction inside the PVs after ablation was greater in the supero-inferior direction (14 +/- 12%) than in the antero-posterior direction (9 +/- 13%; P < 0.0001). In the ablated PVs, the PV trunk was shorter than before ablation (P < 0.0001). The reduction in the diameters of both the PV ostium and the ablation site in the ablated PVs, as well as the diameter of the PV ostium in the nonablated PVs, correlated with the decrease in the left atrial diameter. Shortening of the PV trunk correlated with the severity of PV narrowing, but it was not related to the percent diameter reduction of the left atrium. PV narrowing before or after ablation did not result in any clinical consequences. CONCLUSIONS: PV narrowing is present in about 10% of PVs before ablation. Asymmetric luminal reduction and longitudinal shrinkage of the PV trunk occur after ablation. Reverse remodeling of the PV and contraction of the PV wall may contribute to the reduction in the PV diameter. PV morphology should be assessed with multi-directional views to avoid missing heterogeneous legions.

Analysis of Variance↗

Left atrial and pulmonary vein ostial ablation as a new treatment for curing persistent atrial fibrillation.

BACKGROUND: Segmental pulmonary vein (PV) isolation has been performed to eliminate paroxysmal atrial fibrillation (AF). However, this technique is not effective in most patients with persistent AF. METHODS AND RESULTS: Left atrial catheter ablation (LACA) was performed by encircling the left- and right-sided PV 1-2 cm from the ostia, guided by an electroanatomical mapping system in 16 patients with persistent AF (>1 month). Twelve patients (75%) had a history of unsuccessful transthoracic cardioversion and prophylactic antiarrhythmic drugs. Ablation lines were also created in the mitral isthmus and posterior LA. PV isolation was also performed for each PV if there were residual PV potentials after the LACA. After LACA, 38 PV (59%) were completely isolated, and complete PV isolation was achieved with only a few radiofrequency energy applications (2.7+/-2.0 min) on a narrow area of the PV ostium (24+/-15%) in the remaining PV. The mean procedure time was 200+/-38 min. During the follow-up period (17+/-3 months), 12 patients (75%) had normal sinus rhythm and were free of symptomatic AF with (n = 10) or without antiarrhythmic drugs (n = 2). One patient had a stroke just after the procedure. No other complications including PV narrowing (>50%) occurred. CONCLUSION: This approach was effective in persistent AF, however, concomitant use of antiarrhythmic drugs was often required.

Aged↗

Percutaneous transvenous mitral commissurotomy and radiofrequency catheter ablation in patients with mitral stenosis.

BACKGROUND: The purpose of this study was to evaluate the short- and long-term results of radiofrequency catheter ablation (RFCA) for the treatment of atrial fibrillation (AF) in patients with mitral stenosis (MS) following percutaneous transvenous mitral commissurotomy (PTMC). METHODS AND RESULTS: Four patients (2 males, age 59+/-6 years) underwent simultaneous PTMC and pulmonary vein (PV) ablation. All patient had AF and MS (2 had persistent AF >1 month, 2 had paroxysmal AF), and the mean duration of AF was 3.4+/-3.3 years. The mean left atrial dimension was 47+/-7 mm and the mean ejection fraction was 58+/-4%. After PTMC, RFCA was performed in all patients (3 underwent PV isolation and 1 had PV focal ablation). The mitral valve area increased from 1.11 +/-0.19 to 1.90+/-0.20 cm(2) (p < 0.01). The frequency of AF episodes was dramatically reduced in the 2 patients with paroxysmal AF, and the 1 with persistent AF maintained sinus rhythm, but 1 patient with persistent AF developed recurrent AF. No complications or cardiac events occurred in any of the patients. CONCLUSION: The combination of RFCA and PTMC was safe and feasible, and may be useful in patients with MS and AF.

Catheter Ablation↗

Three-dimensional visualization of the coronary venous system using multidetector row computed tomography.

BACKGROUND: This study was undertaken to investigate the applicability and image quality of contrast-enhanced visualization of the coronary venous system (CVS) by multidetector row computed tomography (MDCT). METHODS AND RESULTS: A total of 70 patients underwent MDCT and for each patient, 6 data sets were created throughout the cardiac cycle. The number and location of coronary veins were evaluated in 3-dimensional images using the 6 data sets. The quality of all images reconstructed from the 6 data sets was too poor to evaluate the CVS in 6 patients (9%). In the remaining 64 patients (91%), the diameter of the CVS was usually greater in the images reconstructed from data acquired during systole than in those reconstructed from data acquired during diastole. However, artifacts were observed more often in images from systole than from diastole. The coronary sinus and middle cardiac vein were visible in all 64 patients. The left marginal and posterior veins also were identified in 54 (84%) and 60 patients (94%), respectively. CONCLUSIONS: MDCT can be used as a non-invasive modality for evaluating the CVS anatomy in most patients.

Adult↗

Tissue Doppler imaging and strain Doppler imaging as modalities for predicting clinical improvement in patients receiving biventricular pacing.

BACKGROUND: The purpose of this study was to determine the utility and efficacy of tissue Doppler imaging (TDI) and strain Doppler imaging (SDI) for evaluating ventricular synchrony and function, and for predicting the long-term clinical improvement in patients undergoing biventricular pacing (BVP). METHODS AND RESULTS: TDI and SDI were performed before and <1 month after initiating BVP in 17 patients with advanced heart failure. An intraventricular conduction delay between the left ventricular (LV) septal and lateral walls was measured by TDI. The average LV strain (LV-strain) was calculated from data obtained at the center of 6 regions of the LV (base and mid-point between the basal and apical portions, and the mid-point between these 2 points on the septal and lateral walls). During a 23+/-7 month follow-up period, 12 patients improved clinically and did not require re-hospitalization for heart failure (responder group), but the remaining 5 did not improve (nonresponder group). Before BVP, the intraventricular conduction delay was greater in the responder group than in the nonresponder group (p<0.01), but after BVP, it did not differ between the 2 groups. LV-strain improved after BVP in the responder group but not in the nonresponder group (p<0.05). CONCLUSION: A high intraventricular conduction delay before BVP and decreased strain shortly after BVP may predict long-term clinical improvement in patients undergoing this treatment.

Aged↗