Biomedical subjects

T Ikeda

Publications and source records attributed to T Ikeda.

At least 127 records · Page 7Linked to original sources

PubMed2001

Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification.

OBJECTIVES: The aim of this study was to compare the use of various noninvasive markers for detecting risk of life-threatening arrhythmic events in patients with Brugada syndrome. BACKGROUND: The role of conduction disturbance in arrhythmogenesis of the syndrome is controversial, whereas it is well established that repolarization abnormalities are responsible for arrhythmias. The value of noninvasive markers reflecting conduction or repolarization abnormalities in identifying patients at risk for significant arrhythmias has not been shown. METHODS: We assessed late potentials (LP) using signal-averaged electrocardiography (ECG), microvolt T-wave alternans (TWA), and corrected QT-interval dispersion (QTD) in 44 consecutive patients who had ECGs showing a pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 but structurally normal hearts. The patients were compared with 30 normal individuals. RESULTS: Eleven patients were excluded from data analysis because of an absence of ECG manifestations of Brugada syndrome at the time of the tests. A history of life-threatening events defined as syncope and aborted sudden death was present in 19 of 33 patients (58%); in 15 of the 19 patients, stimulation induced ventricular fibrillation or polymorphic ventricular tachycardia. The LP were present in 24 of 33 patients (73%); TWA were present in 5 of 31 patients (16%); and a QTD >50 ms was present in 9 of 33 patients (27%). The incidence of LP in Brugada patients was significantly (p < 0.0001) higher than in the controls, whereas incidences of TWA and QTD were not significantly different. Multivariate logistic regression analysis revealed that the presence of LP had the most significant correlation to the occurrence of life-threatening events (p = 0.006). CONCLUSIONS: Late potentials are a noninvasive risk stratifier in patients with Brugada syndrome. These results may support the idea that conduction disturbance per se is arrhythmogenic.

Action Potentials↗

PubMed2001

Demonstration of downregulation of alpha-smooth muscle actin in interferon-gamma-treated myofibroblast by a novel cell-capture enzyme immunoassay.

We developed a simple method for determining the relative amount of alpha-smooth muscle actin (alphaSMA) produced in fibroblasts. The principle of the method is based on an enzyme immunoassay (EIA) for alphaSMA in microcultured fibroblasts. The optimized protocol of the assay is as follows. Human fibroblasts were cultured with transforming growth factor beta1 (TGFbeta1) in a microtiter plate and directly immobilized on the plate. The alphaSMA produced was labeled and subjected to indirect enzyme immunoassay using alkaline phosphatase, and optical density was measured. Semiquantitativeness was confirmed using various numbers of cells in which alphaSMA production was induced by treatment with TGFbeta1. The assay simply demonstrated that interferon-gamma (INF-gamma) inhibited the production of alphaSMA in an established cell line and that in primary cultured cells originated from the contractile nodule. Since the assay is simple and semi-quantitative, it is useful for elucidating the mechanism of contractile diseases and screening a large number of substances that have an inhibitory effect on the change in activity of myofibroblasts.

Actins↗

PubMed2001

Phylogenetic diversity and similarity of active sites of Shiga toxin (stx) in Shiga toxin-producing Escherichia coli (STEC) isolates from humans and animals.

Nucleotide sequences of Shiga toxin (Stx) genes in STEC from various origins were determined and characterized by phylogenetic analysis based on Shiga toxin (Stx) with those deposited in GenBank. The phylogenetic trees placed Stx1 and Stx2 into two and five groups respectively, and indicated that Stx1 in sheep-origin STEC were placed into a different group from those in other STEC, and that Stx2 of deer-origin STEC also belonged to the unique group and appeared to be distantly related to human-origin STEC. On the other hand, Stx of STEC isolated from cattle, seagulls and flies were closely related to those of human-origin STEC. Such a diversity of Stx suggested that STEC might be widely disseminated in many animal species, and be dependent on their host species or their habitat. In addition, the active sites in both toxins were compared; the active sites in both subunits of Stx in all the animal-origin STEC were identical to those in human-origin STEC, suggesting that all the toxin of STEC from animals might be also cytotoxic, and therefore, such animal-origin STEC might have potential pathogenicity for humans.

Amino Acid Sequence↗

PubMed2001

Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions.

PURPOSE: To evaluate an interaction between simvastatin and itraconazole in in vitro studies and to attempt a quantitative prediction of in vivo interaction in humans. METHODS: The inhibitory effect of itraconazole on simvastatin metabolism was evaluated using human liver microsomes and the Ki values were calculated for the unbound drug in the reaction mixture. A physiologically-based pharmacokinetic model was used to predict the maximum in vivo drug-drug interaction. RESULTS: Itraconazole competitively inhibited the metabolism of simvastatin to M-1 and M-2 with Ki values in the nM range. The area under the curve (AUC) of simvastatin after concomitant dosing with itraconazole was predicted to increase ca. 84-101-fold compared with that without administration of itraconazole. Taking into consideration the fact that this method predicts the maximum interaction, this agrees well with the clinical observation of a 19-fold increase. A similar prediction, based on the Ki value without taking into account the drug adsorption to microsomes, led to an underevaluation of the interaction. CONCLUSIONS: It was demonstrated that the competitive inhibition of CYP3A4-mediated simvastatin metabolism by itraconazole is the main cause of the drug interaction and that a Ki value corrected for drug adsorption to microsomes is the key factor in quantitatively predicting the maximum in vivo drug interactions.

Anticholesteremic Agents↗

PubMed2001

Macular star associated with posterior hyaloid detachment.

PURPOSE: To report a patient with a Leber's idiopathic stellate neuroretinitis-like lesion that was caused by vitreous traction accompanying a posterior hyaloid detachment. METHODS: We present a 49-year-old woman who showed segmental optic disc edema, peripapillary retinal detachment, and a macular star. RESULTS: An incomplete posterior hyaloid detachment was present, and the posterior hyaloid membrane was attached to the nasal margin of the optic disc. Fluorescein angiography revealed a bent retinal artery on the upper margin of the optic disc, and leakage of fluorescein was observed from this area. CONCLUSION: Vascular damage to the optic disc due to vitreous traction should also be considered as a mechanism for the ophthalmoscopic appearance of the fundus when lesions suggestive of Leber's idiopathic stellate neuroretinitis are present in an adult.

Capillary Permeability↗

PubMed2001

Expression of p27(Kip1) protein in transitional cell carcinoma of the upper urinary tract.

The expression of p27(Kip1), a negative regulator of the cell cycle, has been reported to correlate with the biological behavior and prognosis of several tumors. However, its prognostic importance in transitional cell carcinoma of the upper urinary tract (TCC-UUT) has not previously been investigated. We investigated p27(Kip1) protein expression using immunohistochemistry in 132 cases of TCC-UUT and also its relation to proliferating cell nuclear antigen (PCNA) immunoreactivity, p53 oncoprotein immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of p27(Kip1) protein was recognized in 94.7% of the samples and was apparent within tumor nuclei. In the normal urothelium, its expression was identified in all cell layers. A positive expression of p53 oncoprotein was recognized in 27.2% of the patients. The PCNA index was 7.4 to 93.1% (mean, 66.4%). Examination of the relationships between the expression of p27(Kip1) protein and clinicopathologic findings, PCNA index, and the expression of p53 oncoprotein revealed that the expression of p27(Kip1) protein decreased significantly with stage and grade. In a univariate analysis of disease-free and overall survival rates, no correlation was found between the expression of p27(Kip1) protein and prognosis. The expression of p27(Kip1) protein appears to be of little or no value in informing the prognosis in TCC-UUT.

Adult↗

PubMed2001

Expression of telomerase catalytic subunit (hTERT) mRNA does not predict survival in patients with transitional cell carcinoma of the upper urinary tract.

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric repeats onto chromosomal ends using a segment of its RNA component as a template. Its activity has become an established indicator of the diagnosis, biological behavior, and prognosis of several tumors. However, few studies have investigated the diagnostic and prognostic importance of the expression of telomerase catalytic subunit (hTERT) mRNA in transitional cell carcinoma of the upper urinary tract (TCC-UUT). We investigated the expression of hTERT mRNA using in situ hybridization in 125 cases of TCC-UUT, and also its relation with the expression of telomerase RNA component (hTERC), proliferating cell nuclear antigen (PCNA) immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of hTERT mRNA was recognized in 93.6% of the samples and was apparent within the cytoplasm of tumor cells. In the normal urothelium examined in a few cases, its expression was barely detected. hTERT mRNA scores showed a significant association with hTERC score. However, no relationship was found between the expression of hTERT mRNA and clinicopathologic findings, PCNA index, or prognosis. These results suggest that the expression of hTERT mRNA does not predict prognosis in TCC-UUT.

Adult↗

PubMed2001

Burkitt's acute lymphoblastic leukaemia transformation after myelodysplastic syndrome.

We describe a patient with myelodysplastic syndrome (MDS) that transformed to Burkitt's acute lymphoblastic leukaemia (ALL). The leukaemic blasts were negative for peroxidase staining, and expressed CD10, CD19, CD22, CD38, human leucocyte antigen (HLA)-DR and surface immunoglobulin (sIg) M, but neither sIgD nor sIgG were expressed. Chromosomal study during the ALL phase showed t(8;22)(q24;q11) in addition to the karyotypes determined during the MDS phase. Furthermore, overexpression of c-myc mRNA was confirmed in ALL blasts. These findings indicate that MDS transformed to Burkitt's ALL through multiple cytogenetic evolutions, the final event of which seems to be overexpression of the c-myc gene.

Acute Disease↗

PubMed2001

Establishment of a tetraploid Meth-A cell line through polyploidization by demecolcine but not by staurosporine, K-252A and paclitaxel.

Polyploid cells are made by DNA reduplication without cell division, however, it is not easy to establish polyploid mammalian cell lines. It is worth studying the difference in cell character between hyperploid and parent cell lines. Meth-A cells were polyploidized by demecolcine, K-252a, staurosporine and paclitaxel. The cell-cycle responses of highly polyploid Meth-A cells after the removal of the drugs were examined by flow cytometry (FCM). Meth-A cells were highly polyploidized by these drugs. The polyploid Meth-A cells gradually decreased in ploidy after the drug release. A tetraploid Meth-A cell line was established only from the demecolcine-induced polyploid Meth-A cells. The duration of G1, S and G2/M phases of the tetraploid cell line were mostly the same as those of the parent diploid cells, except that the G2/M phase was 1.5 h longer. The chromosome number of tetraploid Meth-A cell line was about twice of the diploidy. A tetraploid Meth-A cell line was established.

Animals↗

PubMed2001

New pathway of amine oxidation respiratory chain of Paracoccus denitrificans IFO 12442.

The physiological electron acceptor of quinohemoprotein amine dehydrogenase (QH-AmDH) from Paracoccus denitrificans IFO 12442 was identified by biochemical and electrochemical methods. Of three types of heme c-containing proteins purified together with QH-AmDH from the periplasm of n-butylamine-grown cells, only constitutive cytochrome c-550 was reduced by the addition of QH-AmDH and n-butylamine. Reconstitution of the respiratory chain revealed that cytochrome c-550 mediates the electron transfer from QH-AmDH to the terminal oxidase. This is a new pathway of the amine oxidation respiratory chain of P. denitrificans.

Amines↗

PubMed2001

Adrenocorticotropin-independent unilateral adrenocortical hyperplasia with Cushing's syndrome: Immunohistochemical studies of steroidogenic enzymes, ultrastructural examination and a review of the literature.

A 60-year-old woman presented with a history of palpitations, headaches and severe hypertension, which was resistant to hypotensive agents. She had a 2-year history of obesity and a moon face. Her plasma adrenocorticotropic hormone level was below the limits of detection and did not respond to corticotropin-releasing hormone. Urinary-free cortisol was elevated and the circadian rhythm of serum cortisol level had completely disappeared. Imaging analysis demonstrated a unilaterally functioning mass in the left adrenal gland. Serum cortisol level in the left adrenal vein was elevated. The resected adrenal mass measured 4 x 3.5 x 2.5 cm, and ranged from yellow to tan in color. The adrenal cortex adjacent to the nodule did not demonstrate cortical atrophy. The mass was well circumscribed but not encapsulated, and consisted of multiple cortical nodules. These nodules were composed predominantly of clear cortical cells, and partly of compact cortical cells. Immunoreactivity of steroidogenic enzymes including cholesterol side-chain-cleavage P450, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase cytochrome P450, 11beta-hydroxylase cytochrome P450 and 17alpha-hydroxylase cytochrome P450 was marked in cortical nodules, but minimal in non-nodular cortex. Ultrastructural examination of nodular cortical cells also demonstrated well-developed mitochondria and smooth endoplasmic reticulum, consistent with elevated steroidogenesis in these cells.

3-Hydroxysteroid Dehydrogenases↗

PubMed2001

Changes of cytokines in direct endotoxin adsorption treatment on postoperative multiple organ failure.

Multiple organ failure (MOF) is a serious condition that involves simultaneous or consecutive functional failure of several important organs. Furthermore, sepsis is known to play an important role in the occurrence of MOF. Hemoadsorption therapy with the endotoxin adsorption column containing polymyxin B immobilized fibers by direct hemoperfusion (PMX-DHP) is reportedly effective in the treatment of septic shock. This study examined the changes induced on cytokines upon PMX-DHP treatment in 25 patients who underwent emergency abdominal surgery and were immediately started on a postoperative regimen of continuous hemodiafiltration (CHDF) and PMX-DHP. Postoperative MOF was observed in these patients with a mean APACHE II SCORE of 25.5. Eighty percent of patients survived for more than 1 month. We were able to reduce the necessary dose of dopamine in 85.7% of patients because hemodynamic stability improved after administration of PMX-DHP. Interleukin 6 blood levels did not change significantly before or after PMX-DHP treatment in either the surviving or nonsurviving patients. Blood interleukin 1 receptor antagonist levels decreased in both groups. Intercellular adhesion molecular-1, NOx, and thrombomodulin did not change significantly during the course of treatment in either group. Decreased blood levels of PAI-1 levels were found in the surviving patients whereas increased levels of PAI-1 were found in the non-surviving patients. In conclusion, PMX-DHP treatment may be limited clinically in its ability to remove inflammatory cytokines and humoral mediators. However, PMX-DHP treatment is useful for hemodynamic stabilization, which prevents development of MOF.

APACHE↗

PubMed2001

Role of structural complexities of septal tissue in maintaining ventricular fibrillation in isolated, perfused canine ventricle.

INTRODUCTION: It is unclear how the patterns of wavelet propagation during ventricular fibrillation (VF) vary between structurally different tissues. We hypothesized that the structural complexities of septal tissue influence the maintenance of reentrant wavelets in the ventricle. METHODS AND RESULTS: Endocardial activation patterns during VF were analyzed in the isolated, perfused canine right ventricular (RV) free wall (n = 9), interventricular septum (n = 5), and left ventricular (LV) free wall (n = 6) using a computerized mapping system (2-mm resolution) with 120-msec consecutive windows. Each tissue sample was cut progressively to reduce the tissue mass until the VF was terminated. More wavelets were seen in the septa than in the RV and LV free walls at baseline (P = 0.004), and VF in the septa displayed a shorter cycle length than in the RV and LV free walls (P = 0.017). As the tissue mass decreased, VF became successively more organized in all regions: the number of wavelets decreased and the cycle length of VF lengthened. Single and "figure-of-eight" stationary, reentrant wavelets often were mapped after tissue mass reduction in the RV free walls and rarely in the LV free walls, but they were not observed in the septa. Less critical mass was required to maintain VF in the septa than in the RV and LV free walls (P = 0.0006). Gross anatomic and histologic examinations indicated that the tissue structure of the septa is more complex than that of the RV and LV free walls. CONCLUSION: VF activation patterns with progressive reduction of tissue mass differ for the septum and the ventricular free walls. The structural complexities of the septal tissue influence the maintenance of fibrillation in the ventricle.

Animals↗

PubMed2001

Breakthrough waves during ventricular fibrillation depend on the degree of rotational anisotropy and the boundary conditions: a simulation study.

INTRODUCTION: The left ventricle (LV) and right ventricle (RV) are characterized by specific fiber orientation known as "rotational anisotropy." However, it remains unclear whether the LV and RV are different with regard to the effect of rotational anisotropy on the dynamics of scroll waves during ventricular fibrillation (VF). To resolve this issue, we used a computation-based model to study scroll wave behavior. METHODS AND RESULTS: We composed an environment of simulated three-dimensional ventricular wall slabs, with optional ratios of fiber rotation to wall thickness (0 degrees, 6 degrees, and 12 degrees/mm thickness; LV 10 mm, RV 5 mm), using Luo-Rudy phase I equations. When rotational anisotropy was not incorporated into the LV wall slab (theta endo to approximately theta epi = 0 degrees), most scroll waves rotated around the filaments perpendicular to the tissue surface, with only a few accompanying breakthrough waves. In a twisted LV model (theta endo to approximately theta epi = 60 degrees and 120 degrees), the scroll waves were demonstrated as multiple wavelets scattered spatiotemporally, frequently accompanied by breakthrough waves that were promoted by rotational anisotropy. In a twisted RV model (theta endo to approximately theta epi = 30 degrees and 60 degrees), single scroll waves and/or figure-of-eight reentrant waves appeared, with comparatively few breakthrough waves, regardless of the degree of fiber twist. CONCLUSION: The proportion of electrical effects of rotational anisotropy and tissue boundaries plays an important role in the genesis of breakthrough waves during VF, and the difference in wave propagating patterns and frequency spectrum of the ventricles may arise, in part, from the number of breakthrough waves promoted by rotational anisotropy.

Anisotropy↗

PubMed2001

Electroporation in a model of cardiac defibrillation.

INTRODUCTION: It is known that high-strength shock disrupts the lipid matrix of the myocardial cell membrane and forms reversible aqueous pores across the membrane. This process is known as "electroporation." However, it remains unclear whether electroporation contributes to the mechanism of ventricular defibrillation. The aim of this computer simulation study was to examine the possible role of electroporation in the success of defibrillation shock. METHODS AND RESULTS: Using a modified Luo-Rudy-1 model, we simulated two-dimensional myocardial tissue with a homogeneous bidomain nature and unequal anisotropy ratios. Spiral waves were induced by the S1-S2 method. Next, monophasic defibrillation shocks were delivered externally via two line electrodes. For nonelectroporating tissue, termination of ongoing fibrillation succeeded; however, new spiral waves were initiated, even with high-strength shock (24 V/cm). For electroporating tissue, high-strength shock (24 V/cm) was sufficient to extinguish ongoing fibrillation and did not initiate any new spiral waves. Weak shock (16 to 20 V/cm) also extinguished ongoing fibrillation; however, in contrast to the high-strength shock, new spiral waves were initiated. Success in defibrillation depended on the occurrence of electroporation-mediated anodal-break excitation from the physical anode and the virtual anode. Some excitation wavefronts following electrical shock used a deexcited area with recovered excitability as a pass-through point; therefore, electroporation-mediated anodal-break excitation is necessary to block out the pass-through point, resulting in successful defibrillation. CONCLUSION: The electroporation-mediated anodal-break excitation mechanism may play an important role in electrical defibrillation.

Action Potentials↗

PubMed2001

Effect of insulin, proinsulin, and amylin on renin release from perfused rat kidney.

To evaluate the possible role of insulin, proinsulin, and amylin in the renin-angiotensin system, the direct effect of these peptides on renin release was examined using perfused kidney of rats. Renin release was significantly increased from a basal value of 6.1 +/- 1.8 to a peak value of 10.1 +/- 2.3 ng angiotensin I (Ang I)/mL/h by 0.5 nmol insulin, from 6.0 +/- 1.7 to 16.7 +/- 4.5 ng Ang I/mL/h by 1 nmol insulin, and from 6.1 +/- 1.8 to 18.0 +/- 5.5 ng Ang I/mL/h by 8 nmol insulin. Renin release was not significantly changed by perfusion of 0.05 nmol proinsulin or amylin but significantly increased from a basal value of 6.1 +/- 1.7 to a peak value of 8.1 +/- 3.6 ng Ang I/mL/h by 1 nmol proinsulin, from 5.6 +/- 1.7 to 12.1 +/- 3.8 ng Ang I/mL/h by 8 nmol proinsulin, from 5.7 +/- 1.9 to 8.2 +/- 3.5 ng Ang I/mL/h by 1 nmol amylin, and from 5.2 +/- 2.0 to 12.4 +/- 3.3 ng Ang I/mL/h by 8 nmol amylin. The concentration of cyclic adenosine monophosphate in the effluent was significantly increased from a basal value of 5.1 +/- 1.6 to a peak value of 10.6 +/- 2.5 mmol/min by 8 nmol amylin but not altered by perfusion of insulin or proinsulin. The addition of 0.05 nmol proinsulin and 0.05 nmol of amylin on 0.5 nmol insulin significantly enhanced renin release. These results indicate that insulin may play an important physiologic role in the renin-angiotensin system and suggest that proinsulin and amylin may be involved in the genesis and development of hypertension through enhancement of insulin-stimulated renin release.

Amyloid↗

PubMed2001

Lack of noninvasive markers of ventricular repolarization inhomogeneity in patients with idiopathic ventricular tachyarrhythmia.

Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.

Adult↗

PubMed2001

A piezoelectric film-based intrasplint detection method for bruxism.

STATEMENT OF PROBLEM: An accurate, easy-to-use, long-term method other than EMG is needed to monitor bruxism. PURPOSE: This article presents pilot data on the reproducibility, validity, and utility of an intrasplint piezoelectric film method. MATERIAL AND METHODS: Simulated bruxism behaviors (steady-state and rhythmic clenching, grinding, and tapping) in 5 subjects were recorded with the use of both masseter EMG and an intrasplint piezoelectric film method. RESULTS: Correlation coefficients calculated for simulated bruxism event duration with the use of a masseter EMG or an intrasplint piezoelectric film method were 0.99 for tapping and steady-state clenching, 0.96 for rhythmic clenching, and 0.79 for grinding. CONCLUSION: Piezoelectric film has its limitations and does not faithfully capture sustained force magnitudes. However, for the target behaviors associated with bruxism (tooth grinding, clenching, and tapping), it appears to faithfully reproduce above-baseline events with durations statistically indistinguishable from those recorded with masseter EMG. Masseter EMG was poorest at detecting a simulated side-to-side grinding behavior.

Adult↗