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Biomedical subjects

T Mitsuhashi

Publications and source records attributed to T Mitsuhashi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia.

We report a 76-year-old woman who developed TdP ventricular tachycardia induced by combined use of clarithromycin and disopyramide. She had a history of myocardial infarction 5 years earlier and has taken disopyramide for supraventricular arrhythmias. In addition, she had taken clarithromycin for upper respiratory tract infection. On admission, an ECG showed prolongation of QTc interval to 0.71 seconds and self-terminating TdP occurred several times. Disopyramide was metabolized by the cytochrome enzyme CYP3A4 and clarithromycin competitively inhibits this enzyme, probably resulting in an increase in plasma concentration of disopyramide. We should consider this possibility when prescribing clarithromycin in combination with antiarrhythmic agent disopyramide.

Aged↗
PubMed1999

Radiofrequency catheter ablation for sinoatrial node reentrant tachycardia: electrophysiologic features of ablation sites.

The aim of this study was to investigate catheter ablation of sino-atrial reentrant tachycardia (SART) and the electrophysiologic characteristics of the ablation sites. From January 1990 to October 1997, 651 patients with supraventricular tachycardia were referred and 11 patients were found to have SART. Ablation was successful in all cases with a mean number of 3.3 radiofrequency (RF) current pulses. SART terminated during 22 of 36 RF pulses. In spite of prompt termination, tachycardia could be re-induced in 3 of 11 patients with its earliest activation site shifted. At effective ablation sites, the electrograms during tachycardia were characterized as fractionated (75+/-17 ms), and 38+/-16 ms prior to surface P wave, and 42+/-18 ms prior to the high right atrium. Unipolar electrograms revealed a sharp negative unipolar deflection, so called QS pattern, in 15 of 20 sites during SART and 15 of 15 sites during sinus rhythm. During effective applications, atrial premature beats (APB) with activation sequences identical to sinus rhythm appeared in 14 of 22 cases. Effective ablation sites of SART showed fractionated electrograms during tachycardia and sinus rhythm. Unipolar electrogram with a QS pattern and APB during energy application could be an indicator of the optimal ablation sites.

Adenosine Triphosphate↗
PubMed1999

Atrial fibrillation and continuous hypotension induced by sildenafil in an intermittent WPW syndrome patient.

A 55-year-old Japanese man was hospitalized for palpitations and severe chest oppression one hour after he ingested about 1500 ml of beer and sildenafil (Viagra) 50 mg. At 43 years of age, he had been diagnosed with intermittent WPW syndrome following a paroxysmal supraventricular tachycardia (PSVT) attack. He took a 1 mg tablet of doxazosin daily for mild hypertension. On admission, his blood pressure was 90/54 mmHg and his heart beat was weak and irregular with a rate of about 220/min. Since atrial fibrillation (Af) was diagnosed on an electrocardiogram (minimum RR interval; 0.22 seconds), direct current shock was performed with 100 joules and 150 joules but conversion to sinus rhythm failed. Sinus rhythm returned spontaneously from Af four hours after taking sildenafil. Since blood pressure was 50/17 mmHg despite the return to sinus rhythm, blood pressure was maintained by dopamine for twelve hours after sinus rhythm returned. The patient underwent catheter ablation for curative therapy and thereafter has not had any further episodes of tachycardia.

Atrial Fibrillation↗
PubMed1999

Dietary glycotoxins: inhibition of reactive products by aminoguanidine facilitates renal clearance and reduces tissue sequestration.

Evidence indicates that the metabolic turnover of food-derived reactive orally absorbed advanced glycation end products (AGEs) or glycotoxins (GTs) is delayed, possibly contributing to the tissue damage induced by endogenous AGEs, especially in patients with diabetes and kidney disease. The aim of this study was to explore whether pharmacologic inhibition of dietary AGE bioreactivity by aminoguanidine (AG) can improve turnover and renal excretion of these substances. Normal Sprague-Dawley rats were fed single-labeled [14C]AGE-ovalbumin, double-labeled [14C-125I]AGE-ovalbumin, or control 125I-labeled ovalbumin diet plus free [14C]glucose, with or without AG (0.2% in water). [14C]AGE- and 125I-labeled peptide-associated radioactivity (RA) were compared with AGE immunoreactivity (by enzyme-linked immunosorbent assay) in tissues, serum, and 72-h urine samples. The effect of AG on dietary AGE bioreactivity was assessed by monitoring the inhibition of covalent complex formation between fibronectin (FN) peptide fragments and serum components, after a meal of labeled dietary AGE with or without AG. The radiolabeled AGE diet produced serum absorption and urinary excretion peaks kinetically distinct from those of free [14C]glucose or [125I]ovalbumin. Some 26% of the orally absorbed AGE-ovalbumin was excreted in the urine, whereas after AG treatment, urinary excre-tion of dietary AGEs increased markedly (to >50% of absorbed). More than 60% of tissue-bound RA was found covalently deposited in kidneys and liver, whereas after treatment with AG, tissue AGE deposits were reduced to <15% of the amount found in untreated AGE-fed controls. Sera enriched for dietary GTs formed covalently linked complexes with FN, a process completely inhibitable by AG cotreatment. Amelioration of dietary GT bioreactivity by AG improves renal elimination and prevents tissue deposition of food GTs. This may afford a novel and potentially protective use of AG against excessive tissue AGE toxicity in diabetic patients with renal disease.

Animals↗
PubMed1999

[Accuracy, precision and clinically acceptable level of complete blood cell count by an automated multichannel hematology analyzer].

Measurement of complete blood cell count (CBC) is one of the essential laboratory tests. In this study, the accuracy of CBC was high, when measured by six different automated blood cell counters, including SE-9000/RAM-1, CELL-DYN 4000, ADVIA 120, VEGA RETIC-LC141 or GEN*S. The correlations of CBC counts among these instruments were also good. In contrast, the accuracy in abnormal samples depended on matching the instrument and type of clinical conditions. Internal quality control of automated multichannel hematology analyzers was recommended by the NCCLS H26-A in 1996. However, actual external quality control of the CBC count was poorly understood. We surveyed three samples from healthy volunteers for CBC values in 1997. Among six different instruments, the inter-assay of the red blood cell count (RBC), hemoglobin, hematocrit and MCV was fairly good, shown as < 4.2%, < 3.0%, < 4.4% and < 3.4%, respectively. In contrast, the inter-assay of the white blood cell count (WBC) and platelet (PLT) was not good, shown as < 11.4% and < 9.6%, respectively. The clinically acceptable levels for the blood cell count were reported to be 4% for RBC, 3% for hemoglobin, 4% for MCV, 5% for WBC and 7% for PLT, by JCCLS in 1994. The clinically acceptable CBC by hematologists at Keio University resembled those by councilors of The Japanese Society of Clinical Hematology, whereas, residents at Keio University and general physicians required more precise clinical CBC counts. These results indicate that a larger study is needed to clarify the accuracy, clinically acceptable level, and performance of different automated blood cell counters.

Blood Cell Count↗
PubMed1998

Reconstruction for the brilliance-upgrading project of the Photon Factory storage ring.

Reconstruction of the Photon Factory storage ring (PF ring; 2.5 GeV) is now in progress to provide very brilliant synchrotron radiation to users, i.e. the emittance is being reduced by a factor of five. Components, such as the quadrupole and sextupole magnets, vacuum chambers, beamlines and beam-position monitors, are being replaced by new ones in 16 normal-cell sections of the PF ring. The accelerating cavities, injection systems and control systems are also being replaced. Operation will commence when the improvements are completed on 1 October 1997.

Journal Article↗
PubMed1998

Activities of optical laboratories 1 and 2 at the Photon Factory.

Recent activities at optical laboratories 1 and 2 at the Photon Factory are presented. The activities are (i) construction of optical laboratory 1, (ii) reconstruction of optical laboratory 2, (iii) construction of a visible synchrotron radiation beam extraction mirror made of beryllium, (iv) small-beam-profile measurement by means of the image restoration method, (v) application of the adaptive optical system for correction of distorted wavefronts caused by deformation of the extraction mirror, (vi) construction of a synchrotron radiation interferometer for investigation of the spatial coherency of the visible synchrotron radiation beam and its application to the measurement of vertical beam profile and size.

Journal Article↗
PubMed1998

Single-pass BPM system of the Photon Factory storage ring.

At the 2.5 GeV ring of the Photon Factory, a single-pass beam-position monitor (BPM) system is being prepared for the storage ring and the beam transport line. In the storage ring, the injected beam position during the first several turns can be measured with a single injection pulse. The BPM system has an adequate performance, useful for the commissioning of the new low-emittance lattice. Several stripline BPMs are being installed in the beam transport line. The continuous monitoring of the orbit in the beam transport line will be useful for the stabilization of the injection energy as well as the injection beam orbit.

Journal Article↗
PubMed1998

Left ventricular function and coagulation activity in healed myocardial infarction.

We investigated the plasma levels of molecular markers for the thrombotic and fibrinolytic status in patients with healed myocardial infarction to determine the relation between left ventricular (LV) function and coagulation activity. Our findings demonstrated that the coagulation activity was increased in patients with healed myocardial infarction along with LV dysfunction, suggesting that anticoagulant therapy is considered in patients with severe LV dysfunction to prevent systemic thromboembolism.

Blood Coagulation Factors↗
PubMed1998

Mitral regurgitation reduces the risk of stroke in patients with nonrheumatic atrial fibrillation.

BACKGROUND: Significant mitral regurgitation (MR) is protective against left atrial (LA) spontaneous echo contrast formation that is associated with an increased thromboembolic risk. However, the effects of MR on the risk of stroke in patients with nonrheumatic atrial fibrillation (AF) have been unknown. We studied whether or not MR was associated with a decreased risk of stroke in patients with nonrheumatic AF. METHODS: We performed an observational analysis of retrospectively collected data on 290 patients with nonrheumatic AF. Left atrial diameter (LAD) and the degree of MR were estimated by transthoracic echocardiography. Risk factors for stroke were assessed by univariate and multivariate analyses. The mean follow-up was 7.4 years. RESULTS: Among these patients, 68 had a stroke during the follow-up (rate of stroke per year of follow-up 3.2%). In 95 patients with LAD of > or =48 mm, the incidence of stroke (9%) in the severe MR group (moderate or severe, n=43) was significantly lower than that (25%) of the mild MR group (none, trivial, or mild; n=52) (chi-square=3.95, p=0.047). The relative risk of stroke for increase in MR from mild to severe groups, for every 10 mm increment in LA size, for sex, and for every increase of 10 years of age was 0.45 (95% CI, 0.20 to 0.97), 1.06 (95% CI, 0.75 to 1.49), 0.98 (95% CI, 0.55 to 1.72), and 1.33 (95% CI, 1.04 to 1.71), respectively. CONCLUSIONS: In patients with nonrheumatic AF, age was an independent predictor of an increased risk of stroke, and MR may be protective against stroke, especially in those patients with LA enlargement.

Adult↗
PubMed1998

Plasma levels of natriuretic peptides and adrenomedullin in elderly hypertensive patients: relationships to 24 h blood pressure.

OBJECTIVE: The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives. DESIGN AND METHODS: We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects. RESULTS: Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups. CONCLUSIONS: Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.

Adrenomedullin↗
PubMed1998

Interocular suppression of a half-occluded region of stereoscopic images.

We assessed the detectability d' of a monocular small gray dot target presented on a half-occluded region of stereoscopic three-dimensional background images by comparing it with that on a two-dimensional (2D) region. For our experiments we used a typical two-alternative temporal forced-choice procedure, in which the target was presented in one of two temporal intervals for approximately 67 ms, and observers selected the interval they believed to have contained the target by pressing the corresponding key. To vary target signal intensity, we changed the target contrast against the background. According to signal-detection theory, we converted the percent-correct data to detectability d' and found that the relationship between d' and the contrast of the target followed Legge's equation. We used Legge's equation to calculate the contrast threshold and found that the contrast threshold of the target on the half-occluded region was higher than that on the 2D region. This elevation of contrast threshold indicates that interocular suppression of the half-occluded region occurs more frequently than that of the 2D region. We also refer to the monocular performance of the human visual system.

Adult↗
PubMed1998

Induction of torsades de pointes by dobutamine infusion in a patient with idiopathic long QT syndrome.

We used a provocative test with dobutamine infusion to diagnose long QT syndrome (LQTS) in a girl with a history of syncope. When dobutamine was infused at a rate of 10 microg/kg/min, the QT interval corrected for heart rate (QTc) was prolonged from 460 ms to 620 ms with abnormal TU complexes and torsades de pointes developed. In 5 control subjects the QTc did not change significantly during low-dose dobutamine infusion. Low-dose dobutamine, in addition to isoproterenol, may be useful for evaluation of prolongation of the QT interval and abnormal TU complexes in patients in whom LQTS is suspected.

Adolescent↗
PubMed1998

[Structure-function relationship of thyroid hormone receptor and analysis of its physiological role by gene targeting].

Thyroid hormone plays important role in growth, development and maintenance of homeostasis through regulation of the expression of its target genes. The receptor of thyroid hormone belongs to the superfamily of nuclear hormone receptors, and there are two isotype receptors, alpha and beta, encoded by two distinct homologous genes. Molecular dissection and crystalographical analysis clarified the detailed structure-function relationship of the receptor such as DNA binding, dimerization, hormone binding, and interaction with transcription factors, leading to the understanding of the mechanism of regulation of transcription by thyroid hormone receptor. Furthermore, gene targeting revealed the physiological functions of the alpha and beta thyroid hormone receptor isotypes.

Animals↗
PubMed1998

Endothelial cell damage and angiotensin-converting enzyme insertion/deletion genotype in elderly hypertensive patients.

OBJECTIVES: The purpose of this study was to investigate the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotype and endothelial cell dysfunction or hypercoagulable state in elderly hypertensive patients. BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) polymorphism was recently reported to be associated with various cardiovascular diseases. However, the precise mechanism of this association remains unknown, and some confounding factors might also affect the association. Endothelial cell dysfunction and coagulation activation play important roles in both the atherosclerotic process and the onset of cardiovascular events. METHODS: We identified the ACE I/D genotype and measured the plasma levels of markers of endothelial cell damage (von Willebrand factor [vWF] and thrombomodulin) and of coagulation activation (prothrombin fragment F1 + 2 [F1 + 2]) in 318 asymptomatic elderly patients with hypertension, aged 59-93 years. RESULTS: The vWF level was significantly higher in those with the DD genotype (n = 54) than in those with the II genotype (n = 131, p < 0.0001) or with the ID genotype (n = 133, p < 0.0001). The TM levels were also higher in patients with the ID genotype (p < 0.005) and the DD genotype (p < 0.01) than in those with the II genotype. There were no differences in F1 + 2 level among the groups. Positive correlations of systolic blood pressure with levels of both vWF and thrombomodulin were found predominantly in patients with the II genotype (both p < 0.001), but no correlation was noted in those with the DD genotype. CONCLUSIONS: Considering the increased plasma levels of both endothelial cell-derived markers in the hypertensive patients with ACE DD genotype, we speculate that the ACE D allele is a risk factor for the development of hypertensive cardiovascular disease associated with endothelial cell damage.

Aged↗
PubMed1997

Tobacco smoke is a source of toxic reactive glycation products.

Smokers have a significantly higher risk for developing coronary and cerebrovascular disease than nonsmokers. Advanced glycation end products (AGEs) are reactive, cross-linking moieties that form from the reaction of reducing sugars and the amino groups of proteins, lipids, and nucleic acids. AGEs circulate in high concentrations in the plasma of patients with diabetes or renal insufficiency and have been linked to the accelerated vasculopathy seen in patients with these diseases. Because the curing of tobacco takes place under conditions that could lead to the formation of glycation products, we examined whether tobacco and tobacco smoke could generate these reactive species that would increase AGE formation in vivo. Our findings show that reactive glycation products are present in aqueous extracts of tobacco and in tobacco smoke in a form that can rapidly react with proteins to form AGEs. This reaction can be inhibited by aminoguanidine, a known inhibitor of AGE formation. We have named these glycation products "glycotoxins." Like other known reducing sugars and reactive glycation products, glycotoxins form smoke, react with protein, exhibit a specific fluorescence when cross-linked to proteins, and are mutagenic. Glycotoxins are transferred to the serum proteins of human smokers. AGE-apolipoprotein B and serum AGE levels in cigarette smokers were significantly higher than those in nonsmokers. These results suggest that increased glycotoxin exposure may contribute to the increased incidence of atherosclerosis and high prevalence of cancer in smokers.

Animals↗
PubMed1997

Standardizing the immunological measurement of advanced glycation endproducts using normal human serum.

Advanced glycation endproducts (AGEs) have been linked to many sequelae of diabetes, renal disease and aging. To detect AGE levels in human tissues and blood samples, a competitive enzyme-linked immunosorbent assay (ELISA) has been widely used. As no consensus or standard research method for the quantitation of AGEs currently exists, nor a universally defined AGE unit available, the comparative quantitation of AGEs between research laboratories is problematic and restricts the usefulness of interlaboratory clinical data. By comparing the cross-reactivities of five different anti-AGE antisera with five different in vitro AGE-modified proteins, we found that the immunological recognition of AGEs by competitive ELISA is both AGE-carrier protein- and anti-AGE antibody-dependent. This suggests that in vitro AGE-modified proteins might not be appropriate standards for AGEs that occur naturally in vivo. Based on our observation that serum AGE levels in the normal human population are consistently within a narrow range and several folds lower than in diabetics, we propose a method to standardize AGE units against normal human serum (NHS). In this new method, one AGE unit is defined as the inhibition that results from 1:5 diluted NHS in the competitive AGE-ELISA; thus the AGE value in NHS is 5 units/ml. This NHS method requires a competitive AGE-ELISA with reasonable sensitivity such that 1:5 NHS produces a 25 to 40% inhibition of anti-AGE antibody binding to immobilized AGE-proteins. By using this standardized method we found that the AGE levels in normal human serum (5.0 +/- 2.2 units/ml; mean +/- SD, n = 34) fit a normal distribution (chi 2-test, p < 0.01), and the serum AGE levels in diabetic patients (20.3 +/- 3.8 units/ml, n = 7) are significantly higher than that of the normal population (p < 0.0001). Since AGE units can now be defined against a universally available standard, NHS, the results of quantitative AGE measurements using this method should be comparable between assays and between different laboratories. Taken together, standardizing the AGE-ELISA protocol as described here provides a simple and quantitative method that should facilitate the expanded application of clinical AGE data.

Adult↗