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Biomedical subjects

Takeshi Tomita

Publications and source records attributed to Takeshi Tomita.

At least 19 recordsLinked to original sources
PubMed2006

Endocardial impedance mapping during circumferential pulmonary vein ablation of atrial fibrillation differentiates between atrial and venous tissue.

BACKGROUND: Circumferential pulmonary vein ablation (CPVA) is an effective treatment for atrial fibrillation (AF). Accurate left atrial (LA) mapping is essential for creating lesions at the LA-pulmonary vein (PV) junction, avoiding PV stenosis. OBJECTIVES: The purpose of this study was to establish whether endocardial impedance varies within the LA and PVs and whether it is a useful tool for mapping and ablation. METHODS: Pilot Phase: Three-dimensional LA maps were created using CARTO. Impedance (Z) was measured using a radiofrequency generator at multiple points in the LA, PV ostia (PVO), and deep PVs in 79 patients undergoing their first AF ablation (group 1) and 29 patients undergoing repeat CPVA (group 2). Prospective Phase: In an additional 20 patients, using pilot phase data, one operator defined catheter tip location as either LA or PVO based on CARTO and fluoroscopy. A second operator blinded to CARTO simultaneously did the same based on impedance at 15 +/- 4 points per patient. RESULTS: Group 1: Z(LA) was 99.4 +/- 9.0 omega. Z(PVO) was higher (109.2 +/- 8.5 omega), rising further as the catheter advanced into deep PV (137 omega +/- 18). Z(PVO) differed from Z(LA) by 9 +/- 4 omega. Group 2 had a lower Z(LA) and Z(PVO) compared with group 1 (P <.05). Impedance monitoring differentiated between LA and PVO, with 91% specificity and sensitivity, 96% positive predictive value, and 81% negative predictive value. At 3-month follow-up, no patients had evidence of PV stenosis on magnetic resonance imaging. CONCLUSION: Impedance mapping reliably identifies the LA-PV transitional zone, facilitating AF ablation, and its use is associated with a low incidence of PV stenosis.

Atrial Fibrillation↗
PubMed2005

Experimental evaluation of a spherical aberration-corrected TEM and STEM.

We have successfully developed a spherical aberration (Cs)-corrected electron microscope for probe- and image-forming systems using hexapole correctors. The performance of the microscope has been evaluated experimentally. The point resolution attained using the image-forming Cs-corrector is better than 0.12 nm. For scanning transmission electron microscopy, the Ronchigram flat area was >40 mrad in half-angle using the probe-forming Cs-corrector.

Letter↗
PubMed2004

Roles of distal Asp in heme oxygenase from Corynebacterium diphtheriae, HmuO: A water-driven oxygen activation mechanism.

Heme oxygenases found in mammals, plants, and bacteria catalyze degradation of heme using the same mechanism. Roles of distal Asp (Asp-136) residue in HmuO, a heme oxygenase of Corynebacterium diphtheriae, have been investigated by site-directed mutagenesis, enzyme kinetics, resonance Raman spectroscopy, and x-ray crystallography. Replacements of the Asp-136 by Ala and Phe resulted in reduced heme degradation activity due to the formation of ferryl heme, showing that the distal Asp is critical in HmuO heme oxygenase activity. D136N HmuO catalyzed heme degradation at a similar efficiency to wild type and D136E HmuO, implying that the carboxylate moiety is not required for the heme catabolism by HmuO. Resonance Raman results suggest that the inactive ferryl heme formation in the HmuO mutants is induced by disruption of the interaction between a reactive Fe-OOH species and an adjacent distal pocket water molecule. Crystal structural analysis of the HmuO mutants confirms partial disappearance of this nearby water in D136A HmuO. Our results provide the first experimental evidence for the catalytic importance of the nearby water molecule that can be universally critical in heme oxygenase catalysis and propose that the distal Asp helps in positioning the key water molecule at a position suitable for efficient activation of the Fe-OOH species.

Aspartic Acid↗
PubMed2004

Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: electroanatomic characterization and treatment.

OBJECTIVES: The purpose of this study was to evaluate the electroanatomic characteristics of left atrial tachycardia (AT) in a series of patients who underwent circumferential pulmonary vein ablation (CPVA) and to describe the ablation strategy and clinical outcome. BACKGROUND: Circumferential pulmonary vein ablation is an effective treatment for atrial fibrillation. A potential midterm complication is the development of left AT. There are only isolated reports describing mapping and ablation of such arrhythmias. METHODS: Thirteen patients (age 57.4 +/- 8.9 years, five female) underwent mapping and ablation of 14 left ATs via an electroanatomic mapping system a mean of 2.6 +/- 1.6 months after CPVA. RESULTS: Three patients were characterized as having focal AT (cycle length: 266 +/- 35.9 ms). Of 11 macro-re-entrant tachycardias studied in the remaining 10 patients (cycle length: 275 +/- 75 ms), 5 showed single-loop and 6 dual-loop circuits. Re-entrant circuits used the mitral isthmus, the posterior wall, or gaps on previous encircling lines. Such gaps and all three foci occurred anterior to the left superior pulmonary vein or at the septal aspect of the right pulmonary veins. Thirteen of 14 tachycardias (93%) were successfully ablated. CONCLUSIONS: Left AT after CPVA can be due to a macro-re-entrant or focal mechanism. Re-entry occurs most commonly across the mitral isthmus, the posterior wall, or gaps on previous ablation lines. Such gaps and foci occur most commonly at the anterior aspect of the left superior pulmonary vein and at the septal aspect of the right pulmonary veins. These arrhythmias can be successfully mapped and ablated with an electroanatomic mapping system.

Aged↗
PubMed2004

Regulation of Drosophila hypoxia-inducible factor (HIF) activity in SL2 cells: identification of a hypoxia-induced variant isoform of the HIFalpha homolog gene similar.

Although hypoxia-inducible factor-alpha (HIFalpha) subunit-specific hydroxylation and proteolytic breakdown explain the binary switch between the presence (hypoxia) and absence (normoxia) of HIFs, little is known of the mechanisms that fine-tune HIF activity under constant, rather than changing, oxygen tensions. Here, we report that the Drosophila HIFalpha homolog, the basic helix-loop-helix/PAS protein Sima (Similar), in hypoxic cultures of SL2 cells is expressed in full-length (fl) and splice variant (sv) isoforms. The following evidence supports the role of flSima as functional HIFalpha and the role of SL2 HIF as a transcriptional activator or suppressor. The pO(2) dependence of Sima abundance matched that of HIF activity. HIF-dependent changes in candidate target gene expression were detected through variously effective stimuli: hypoxia (strong) > iron chelation, e.g. desferrioxamine (moderate) >> transition metals, e.g. cobalt approximately normoxia (ineffective). Sima overexpression augmented hypoxic induction or suppression of different targets. In addition to the full-length exon 1-12 transcript yielding the 1510-amino acid HIFalpha homolog, the sima gene also expressed, specifically under hypoxia, an exon 1-7/12 splice variant, which translated into a 426-amino acid Sima truncation termed svSima. svSima contains basic helix-loop-helix and PAS sequences identical to those of flSima, but, because of deletion of exons 8-11, lacks the oxygen-dependent degradation domain and nuclear localization signals. Overexpressed svSima failed to transactivate reporter genes. However, it attenuated HIF (Sima.Tango)-stimulated reporter expression in a dose-dependent manner. Thus, svSima has the potential to regulate Drosophila HIF function under steady and hypoxic pO(2) by creating a cytosolic sink for the Sima partner protein Tango.

Amino Acid Sequence↗
PubMed2004

Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation.

BACKGROUND: There are no data to evaluate the relationship between autonomic nerve function modification and recurrent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA). This study assesses the incremental benefit of vagal denervation by radiofrequency in preventing recurrent AF in a large series of patients undergoing CPVA for paroxysmal AF. METHODS AND RESULTS: Data were collected on 297 patients undergoing CPVA for paroxysmal AF. Abolition of all evoked vagal reflexes around all pulmonary vein ostia was defined as complete vagal denervation (CVD) and was obtained in 34.3% of patients. Follow-up ended at 12 months. Heart rate variability attenuation, consistent with vagal withdrawal, was detectable for up to 3 months after CPVA, particularly in patients with reflexes and CVD, who were less likely to have recurrent AF than those without reflexes (P=0.0002, log-rank test). Only the percentage area of left atrial isolation and CVD were predictors of AF recurrence after CPVA (P<0.001 and P=0.025, respectively). CONCLUSIONS: This study suggests that adjunctive CVD during CPVA significantly reduces recurrence of AF at 12 months.

Atrial Fibrillation↗
PubMed2003

Spectroscopic characterization of five- and six-coordinate ferrous-NO heme complexes. Evidence for heme Fe-proximal cysteinate bond cleavage in the ferrous-NO adducts of the Trp-409Tyr/Phe proximal environment mutants of neuronal nitric oxide synthase.

Nitric oxide synthases (NOS) are a family of cysteine thiolate-ligated heme-containing monooxygenases that catalyze the NADPH-dependent two-step conversion of L-arginine to NO and L-citrulline. During the catalysis, a portion of the NOS heme forms an inhibitory complex with self-generated NO that is subsequently reverted back to NO-free active enzyme under aerobic conditions, suggesting a downstream regulator role of NO. Recent studies revealed that mutation of a conserved proximal tryptophan-409, which forms one of three hydrogen bonds to the heme-coordinated cysteine thiolate, to tyrosine or phenylalanine considerably increases the turnover number of neuronal NOS (nNOS). To further understand these properties of nNOS on its active site structural level, we have examined the oxygenase (heme-containing) domain of the two mutants in close comparison with that of wild-type nNOS with UV-visible absorption, magnetic circular dichroism, and electron paramagnetic resonance spectroscopy. Among several oxidation and ligation states examined, only the ferrous-NO adducts of the two mutants exhibit spectra that are markedly distinct from those of parallel derivatives of the wild-type protein. The spectra of the ferrous-NO mutants are broadly similar to those of known five-coordinate ferrous-NO heme complexes, suggesting that these mutants are predominantly five coordinate in their ferrous-NO states. The present results are indicative of cleavage of the Fe-S bond in the nNOS mutants in their ferrous-NO state and imply a significant role of the conserved tryptophan in stabilization of the Fe-S bond.

Circular Dichroism↗
PubMed2003

The influence of spontaneous termination of atrial fibrillation on P wave-triggered signal-averaged electrocardiogram.

BACKGROUND: Prolongation of total filtered P wave duration (Ad) and low root mean square voltages for the last 20 ms of the P wave (LP20) on a P wave-triggered signal-averaged electrocardiogram (PSAECG) are typically observed in paroxysmal atrial fibrillation (PAF) patients. A shortening of atrial refractoriness and intra-atrial conduction delay (atrial remodeling) have been shown to occur in response to PAF. We, therefore, investigated the effects of spontaneous termination of PAF on the parameters of PSAECG. METHODS: We measured the Ad, LP20 and left atrial (LA) diameter by ultrasonic echocardiography before, within 1 h after, and 3 and 12 months after PAF termination in patients with no structural heart disease (n=11). RESULTS: The PAF duration was 16+/-5 h. The Ads before, within 1 h after, and 3 and 12 months after PAF were 137+/-4, 148+/-4, 137+/-6, and 135+/-7 ms, respectively. The Ad within 1 h after PAF was significantly (P<0.01) longer than at the other three acquisition points. Although the LP20 within 1 h after PAF termination was not significantly different from the other three points, the change in LP20 (within 1 h after PAF-before PAF, -1.1+/-0.4 microV) in the long PAF duration group was significantly (P<0.05) greater than that of the short PAF duration group. LA diameter was unchanged at all points. CONCLUSION: These data suggest that PAF results in prolongation of Ad after termination of PAF.

Aged↗
PubMed2003

Role of autonomic tone in the initiation and termination of paroxysmal atrial fibrillation in patients without structural heart disease.

INTRODUCTION: Previous studies have suggested that paroxysmal atrial fibrillation (PAF) of vagal origin often occurs at night and PAF of sympathetic origin occurs during the daytime; however, autonomic tone after spontaneous termination of PAF has not been determined. The aim of this study was to evaluate by heart rate variability (HRV) analysis the relationship between the time of PAF onset and autonomic tone before and after PAF. METHODS AND RESULTS: Twenty-three patients (65 +/- 2 years) who underwent 24-hour ambulatory monitoring, had one or more episodes of PAF (>30 min), and had maintained normal sinus rhythm for >60 min before/after PAF were enrolled in this study. Mean duration of PAF was 6.2 +/- 1.2 hours. HRV parameters were analyzed in a 10-minutes section at 60 minutes, 20 minutes, and immediately before the onset of PAF and after its termination. PAF began at night in 14 patients (group N) and during the daytime in 9 patients (group D). In group N, the high-frequency (HF) component and low-frequency (LF) component showed a significant decrease after PAF; PAF was preceded by a gradual increase in HF and LF. Changes in the LF/HF ratio, however, did not occur before or after PAF. Conversely, group D showed a significant increase in the LF/HF ratio before PAF and a decrease in LF and the LF/HF ratio after PAF, but no changes in HF. These changes in HRV parameters were not influenced by the duration or termination time of PAF. CONCLUSION: This study suggests that the autonomic nervous system plays an important role in both the initiation and termination of PAF. Furthermore, the time of PAF onset influences the autonomic tone at the initiation and termination of PAF.

Aged↗
PubMed2003

A spherical aberration-corrected 200 kV TEM.

A spherical aberration (Cs)-corrected 200 kV TEM was newly developed. The column of the microscope was extended by 25 cm and the inner yoke of the objective lens was modified to insert some parts of the corrector elements. The corrector has two hexapole elements that play a main role in Cs correction and they are placed at a position equivalent to the coma-free point of the objective lens by using two transfer doublet lenses. The Cs correction was successfully carried out by means of the third-order aberration that was generated in the two extended hexapoles. The Cs can be corrected to the desired value and also can be overcompensated in order to produce a negative Cs, as with the corrected Cs of -23 microm shown in this work. The optical system of the corrector does not produce second- and fourth-order aberrations, and can correct residual aberrations up to the third order. All of the corrector elements are computer-controlled and the third-order aberrations are quite stable after they are properly corrected. The resolution of 0.135 nm was experimentally confirmed by the Young's fringe method. Image simulations of a silicon [110] single crystal were made with various Cs and defocus values to demonstrate the effectiveness of arbitral control of Cs.

Journal Article↗
PubMed2003

T-wave alternans in patients with right ventricular tachycardia.

Microvolt T-wave alternans has been proposed as a new risk marker for ventricular arrhythmias. However, the clinical significance of T-wave alternans in patients with ventricular tachycardia (VT) originating from the right ventricle has been unknown. The study population consisted of 20 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic VT. T-wave alternans was measured during bicycle exercise testing using the CH 2000 system. Of the 7 patients with ARVC, 6 (86%) were positive for T-wave alternans. On the other hand, only 1 (8%) of 13 patients with idiopathic VT originating from the right-ventricular outflow tract was positive for T-wave alternans.

Adipocytes↗
PubMed2002

Resonance Raman studies on xanthine oxidase: observation of Mo(VI)-ligand vibrations.

Resonance Raman spectra were investigated for the sulfo and desulfo forms of cow's milk xanthine oxidase, with various visible excitation lines between 400 and 650 nm, and Mo(VI)-ligand vibrations were observed for the first time. The Mo(VI)=S stretch was identified at 474 and 462 cm(-1 )for the (32)S- and (34)S-sulfo forms, respectively, but was absent in the reduced state and in the desulfo form. The Mo(VI)=O stretch was weakly observed at 899 cm(-1 )for the sulfo form and shifted to 892 cm(-1) with very weak intensity for the dioxo desulfo form. In measurements of an excitation profile, the two bands at 474 and 899 cm(-1) showed maximum intensity at similar excitation wavelengths, suggesting that the Raman intensity of the metal-ligand modes is due to the Mo(VI)<--S charge transfer transition, and that this is the origin of the intrinsically weak features of the Mo(VI)-ligand Raman bands. When the sulfo form was regenerated from the desulfo form, the 899 cm(-1) band reappeared. However, the band at 899 cm(-1) showed no frequency shift when regeneration was conducted in H(2)(18)O, or after several turnovers in the presence of xanthine in H(2)(18)O. When the sulfo form was reduced and reoxidized in H(2)(18)O buffer, the 899 cm(-1) band reappeared without any frequency shift. These observations suggest that the oxo oxygen in the Mo center of xanthine oxidase is not labile. Low-frequency vibrations of the Mo center were observed together with those of the Fe(2)S(2) center with some overlaps, while FAD modes were observed clearly. The absence of dithiolene modes in XO is in contrast to the Mo(VI) centers of DMSO reductase and sulfite oxidase.

Animals↗
PubMed2002

Nature of the displaceable heme-axial residue in the EcDos protein, a heme-based sensor from Escherichia coli.

The EcDos protein belongs to a group of heme-based sensors that detect their ligands with a heme-binding PAS domain. Among these various heme-PAS proteins, EcDos is unique in having its heme iron coordinated at both axial positions to residues of the protein. To achieve its high affinities for ligands, one of the axial heme-iron residues in EcDos must be readily displaceable. Here we present evidence from mutagenesis, ligand-binding measurements, and magnetic circular dichroism, resonance Raman, and electron paramagnetic resonance spectroscopies about the nature of the displaceable residue in the heme-PAS domain of EcDos, i.e., EcDosH. The magnetic circular dichroism spectra in the near-infrared region establish histidine-methionine coordination in met-EcDos. To determine whether in deoxy-EcDos coordination of the sixth axial position is also to methionine, methionine 95 was substituted with isoleucine. This substitution caused the ferrous heme iron to change from an exclusively hexacoordinate low-spin form (EcDosH) to an exclusively pentacoordinate high-spin form (M95I EcDosH). This was accompanied by a modest acceleration of the dissociation rates of ligands but a dramatic increase (60-1300-fold) in the association rate constants for binding of O(2), CO, and NO. As a result, the affinity for O(2) was enhanced 10-fold in M95I EcDosH, but the partition constant M = [K(d)(O(2))/K(d)(CO)] between CO and O(2) was raised to about 30 from the extraordinarily low EcDosH value of 1. Thus a major consequence of the increased O(2) affinity of this sensor was the loss of its unusually strong ligand discrimination.

Amino Acid Sequence↗
PubMed2002

A comparative resonance Raman analysis of heme-binding PAS domains: heme iron coordination structures of the BjFixL, AxPDEA1, EcDos, and MtDos proteins.

The heme-PAS is a specialized domain with which a broad class of signal-transducing heme proteins detect physiological heme ligands. Such domains exhibit a wide range of ligand binding parameters, yet they are all expected to feature an alpha-beta heme binding fold and a predominantly hydrophobic heme distal pocket without a distal histidine. We have compared, for the first time, the resonance Raman spectra of several heme-PASs: the heme-binding domains of Bradyrhizobium japonicum FixL, Escherichia coli Dos, Acetobacter xylinum PDEA1, and Methanobacterium thermoautotrophicum Dos. In all cases, the nu(Fe)-(CO) and nu(C-O) values of the carbonmonoxy forms were consistent with coordination of the heme iron to histidine on the proximal side and binding of the CO without electrostatic interaction with the heme distal pocket. EcDos was unusual in having predominantly hexacoordinate heme iron in the deoxy and met forms. Despite an evident lack of CO interaction with the EcDos heme pocket, relatively low Fe-O(2) (562 cm(-1)) and N-O (1576 cm(-1)) stretching frequencies indicated that strong polar interactions with that heme distal pocket are possible for highly bent ligands such as O(2) or NO. None of the newly studied NO adducts exhibited evidence of the Fe-His rupture and pentacoordination previously noted for Sinorhizobium meliloti FixL. A low Fe-His stretching frequency, formerly interpreted as a strained Fe-His bond, and the slow association of O(2) with S. meliloti FixL failed to correlate with the newly studied proteins having low association rate or low equilibrium association constants for binding of O(2). We conclude that although heme-PASs share some features, they represent distinct signal transduction mechanisms.

Acetobacter↗
PubMed2002

Balloon coronary angioplasty and long-term survival of non-diabetic patients with isolated severe left anterior descending coronary artery disease.

Although long-term survival of diabetic patients with multivessel coronary disease has been reported to be better in those treated with bypass surgery than with coronary angioplasty, it is unclear if diabetic patients who undergo coronary angioplasty show better long-term survival than those treated medically. Between 1985 and 1994, 667 consecutive patients with isolated severe (> or = 90% diameter stenosis) proximal left anterior descending (LAD) coronary artery disease were divided into 4 groups according to the initial therapeutic choice and their diabetic status: of 225 diabetic patients, 104 were treated medically and 121 underwent coronary angioplasty; of 442 non-diabetic patients, 215 were treated medically and 227 underwent coronary angioplasty. The primary end-point of follow-up was death from any cause, and the secondary end-point was cardiac death. Cox's proportional hazard model was used to assess the relative risk of baseline variables. The mean follow-up interval was 6.5+/-3.0 years. The relative distribution of baseline parameters of medically treated patients to those treated with coronary angioplasty was identical in diabetic and non-diabetic patients. Although non-diabetic patients who underwent coronary angioplasty showed better long-term survival than those treated medically, this survival advantage was not observed in diabetic patients. After adjustment of parameters using Cox's proportional hazard model, age over 65 years, coronary angioplasty and low left ventricular ejection fraction were independent determinants of total death. Long-term survival in non-diabetic patients with severe LAD coronary artery disease is more favorable in patients treated with coronary angioplasty than those treated medically, but this advantage is overridden when the patients are diabetic.

Age Factors↗