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Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 127 records · Page 7Linked to original sources
PubMed1998

Gene and cDNA structures of flounder insulin-like growth factor-I (IGF-I): multiple mRNA species encode a single short mature IGF-I.

To understand the comprehensive mechanisms of gene expression and processing for insulin-like growth factor-I (IGF-I) in vertebrates, we have investigated the gene organization, promoter and transcriptional initiation sites, alternative splicing and polyadenylating sites, and the cDNA structures of this gene in the Japanese flounder, Paralichthys olivaceus. The flounder IGF-I gene was found to be composed of five exons and four introns spanning 17.5 kb. By Northern blot analysis, two major mRNA classes of 4.7 kb and 2.9 kb were found in the liver. cDNA cloning and reverse transcription polymerase chain reaction (RT-PCR) analysis indicated that these two mRNA classes result from two different-sized 3'-noncoding regions generated by alternative usage of two polyadenylating signals. Further analysis by RT-PCR and sequencing revealed that these mRNA classes both contain two subclasses of mRNA encoding two forms of IGF-I prepropeptide, preproIGF-I-1 and preproIGF-I-2. The two forms of preproIGF-I share the identical signal peptide and mature IGF-I domain but contain different E domains as a result of alternative splicing in exon 3. The mature form of flounder IGF-I was found to comprise 68 amino acid residues, showing a small molecular weight, 7486. In the 5'-flanking region, one major and four minor transcription start sites have been identified by ribonuclease protection assay between -230 and -130 from the translation initiation codon, but no canonical TATA box or GC box was detected in their upstream regions up to -724. The results suggest that some unknown transcription initiation factors are functioning in the promotion of IGF-I gene expression.

Amino Acid Sequence↗
PubMed1998

Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan.

OBJECTIVE: To compare the predictive powers of self-measurement of blood pressure at home (home blood pressure measurement) and casual (screening) blood pressure measurement for mortality. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: We obtained home and screening blood pressure measurements for 1789 subjects aged > or = 40 years who were followed up for a mean of 6.6 years. The prognostic significance of blood pressure for mortality was determined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, past history of cardiovascular disease, and the use of antihypertensive medication. RESULTS: When the home blood pressure values and the screening blood pressure values were simultaneously incorporated into the Cox model as continuous variables, only the average of multiple (taken more than three times) home systolic blood pressure values was significantly and strongly related to the cardiovascular mortality risk. The average of the two initial home blood pressure values was also better related to the mortality risk than were the screening blood pressure values. CONCLUSIONS: Home blood pressure measurement had a stronger predictive power for mortality than did screening blood pressure measurement for a general population. This appears to be the first study in which the prognostic significances of home and screening blood pressure measurements have been compared.

Adult↗
PubMed1998

Reference values for 24-hour ambulatory blood pressure monitoring based on a prognostic criterion: the Ohasama Study.

Although reference values for ambulatory blood pressure (ABP) monitoring have been investigated in several population studies, these values were derived from cross-sectional observations and were based merely on the statistical distribution of blood pressure values. Therefore, we conducted a prospective cohort study to identify reference values for 24-hour ABP in relation to prognosis. We obtained measurements of 24-hour ABP for 1542 subjects (565 men) aged 40 years and over in a general population of a rural Japanese community and then followed-up their survival status. There were 117 deaths during the follow-up period (mean, 6.2 years). The association between baseline 24-hour ABP values and mortality, examined by the Cox proportional hazards regression model adjusted for possible confounding factors, showed a better fit with a second-degree equation than with a first-degree equation. On the basis of the results of this analysis, we identified the following reference values as the optimal blood pressure ranges that predict the best prognosis: 120 to 133 mm Hg for systolic blood pressure and 65 to 78 mm Hg for diastolic blood pressure. 24-Hour ABP values >134/79 mm Hg and <119/64 mm Hg were related to increased risks for cardiovascular and noncardiovascular mortality, respectively. This is the first report to propose reference values for 24-hour ABP based on a prognostic criterion.

Adult↗
PubMed1998

Successful treatment of anomalous origin of the left coronary artery from the pulmonary artery in a 5-week-old male infant.

A 5-week-old male infant who was referred to our hospital because of tachypnea and poor feeding. An electrocardiogram showed a deep Q wave in lead aVL, negative T waves in leads I, II, III, aVF and V6 and a positive T wave in VL. Echocardiography revealed severely impaired left ventricular function. Aortography confirmed with a diagnosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Takeuchi's procedure was performed and the patient maintained postoperatively on assisted circulation for 7 hours even though sternal closure delayed until 7 days post operatively. His left ventricular function showed and marked improvement gradually.

Assisted Circulation↗
PubMed1998

Discrepancy between screening blood pressure and ambulatory blood pressure: a community-based study in Ohasama.

We investigated factors underlying discrepancy between screening blood pressure and daytime ambulatory blood pressure (the difference) in a community-based population in northeastern Japan. Screening and ambulatory pressures were measured in 706 untreated subjects aged 20 yr or older. We analyzed the effects of age and blood pressure on the difference and then performed multivariate stepwise linear regression analysis using the difference as the dependent variable. The systolic difference positively correlated with age in men. Women in their 40s exhibited a large difference, disturbing the linear relationship between the difference and age. The difference positively correlated with the screening pressure in men and women. A positive difference (screening pressure > ambulatory pressure) was observed at screening pressures above 130/75 mmHg. The difference inversely correlated with the ambulatory pressure. Multivariate analysis demonstrated that body mass index and male sex were positively associated with the systolic and diastolic blood pressure differences. The daytime pulse rate was negatively associated with the systolic difference, and the standard deviation of daytime diastolic ambulatory blood pressure was positively associated with the diastolic difference. The diastolic difference in subjects with isolated systolic hypertension based on the screening pressure was significantly smaller than that in subjects with systolic/diastolic hypertension. The difference in subjects with isolated systolic hypertension based on ambulatory pressure was significantly higher than that in systolic/diastolic hypertension. When white-coal (isolated screening) hypertension was defined as a screening systolic pressure > or = 140 mmHg, a diastolic pressure > or = 90 mmHg, or both, and a 24-h ambulatory pressure < 136/87 mmHg in men and < 131/86 mmHg in women, white-coat (isolated screening) hypertension was present in 79 (56.8%) of 139 subjects with screening hypertension. The results confirm that the discrepancy between screening and ambulatory blood pressure is due to a variety of factors, including age, sex, blood pressure levels, and baroreflex function. Our results indicate that screening blood pressure in elderly hypertensive patients should be evaluated carefully.

Adult↗
PubMed1998

Experimental study of catheter ablation using ultrasound energy in canine and porcine hearts.

UNLABELLED: We examined the efficacy and safety of ultrasound energy in eliminating the arrhythmogenic substrates of atrial as well as ventricular tissue using a newly developed instrument in both in vivo and in vitro experiments. Ultrasound (US) applicators were tested on 79 lesions created on a beating heart in canine cardiac tissue, and on 64 lesions in porcine heart specimens. US lesions were created by using transducers with frequencies around 5-10 MHz. In the in vivo study, we observed a significant decrease in the amplitude of the electrograms recorded from the tip of the ablation catheter during the US application (p < 0.01). In some sites transmural lesions could be created which were well demarcated. Blood coagulum formation was observed on the tip of the ablation catheter on several occasions. In one dog ventricular fibrillation was provoked by the delivery of ultrasound energy to the left ventricle. In the in vitro study, lesion depth increased significantly with a longer duration of energy delivery when the temperature was maintained table (p < 0.001), and the lesion depth increased significantly with higher temperatures of energy delivery when the duration of US application was maintained (p < 0.05). In both cases, no significant change in surface area was observed. The maximum depth of the lesion was 10.3 mm. CONCLUSIONS: An ultrasound energy system is relatively safe and effective for creating lesions large enough to eliminate arrhythmogenic substrates deep in the ventricular myocardium. Although the US system is free from pop phenomenon, the problem of blood coagulation on the catheter tip remains to be settled.

Animals↗
PubMed1998

A prospective cohort study on National Health Insurance beneficiaries in Ohsaki, Miyagi Prefecture, Japan: study design, profiles of the subjects and medical cost during the first year.

To examine the impact of health-related lifestyle upon medical care utilization and its costs, we conducted a cohort study among all National Health Insurance beneficiaries aged from 40 to 79 years living in the catchment area of Ohsaki Public Health Center, Miyagi, Japan. The baseline survey, using self-completed questionnaire regarding health-related lifestyle, was conducted between October and December 1994. Out of 54,996 eligible subjects, 52,029 (94.6%) responded and formed the cohort under study. Medical care utilization (number of outpatient visits and days of inpatient care) and the costs for each subject have been obtained from National Health Insurance Claim History files since January 1995. The baseline characteristics of health-related lifestyle and medical history at the study subjects were consistent with those at our another cohort subjects (so-called Miyagi cohort study; N = 47,605), which included all the residents aged from 40 to 64 years at 14 municipalities in Miyagi Prefecture, Japan conducted in 1990. The medical costs per capita in this cohort was quite compatible with the national average. This prospective cohort study would quantitatively demonstrate the economic impact of health-related lifestyle, thus would lead us to better provision of cost-effective preventive health services.

Adult↗
PubMed1998

Ambulatory blood pressure normality: experience in the Ohasama Study.

OBJECTIVE: To define the reference values of ambulatory blood pressure (APB) using results from the Ohasama study. RESULTS: The distribution criteria of 24 h ABP for the total population of Ohasama were 135/79 (mean + SD), 148/86 (mean + SD), and 146/85 mmHg (95th percentile), and those for normotensive subjects were 129/76 (mean + SD), 142/85 (mean + 2 SD) and 139/81 mmHg (95th percentile). The corresponding criteria [i.e. the 24 h ABP corresponding to 140/90 and 160/95 mmHg casual (clinical) blood pressure of the total population] were 125/76 and 132/76 mmHg. A long-term prospective study based on cardiovascular morbidity and mortality would provide the most meaningful values. For the prognostic criteria, based on nonparametric analysis, the hypertensive range of the 24 h ABP was postulated to be >/= 134/>/= 78 mmHg, whereas that based on parametric analysis was postulated to be >/= 134/ 79 mmHg. The lowest relative hazard was observed at 128/74 mmHg in parametric analysis. Thus, we tentatively propose reference values>/= 135/>/= 80 mmHg for hypertensive 24 ABP and < 125/< 75 mmHg for normotensive 24 h ABP.CONCLUSION:

Journal Article↗
PubMed1997

Silent myocardial ischemia in Kawasaki disease: evaluation of percutaneous transluminal coronary angioplasty by dobutamine stress testing.

BACKGROUND: Myocardial ischemia and myocardial infarction are the most serious complications of coronary artery lesions in children with Kawasaki disease (KD). Therefore, early detection and treatment of myocardial ischemia in patients with KD is essential. We studied the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) in patients with silent myocardial ischemia detected by dobutamine stress 99mTc myocardial scintigraphy (TMS), body surface mapping (BMS), and signal-averaged ECG late potentials (ELP). METHODS AND RESULTS: Eight of 76 asymptomatic patients with a coronary stenosis >25% and a positive dobutamine stress test were considered to have silent myocardial ischemia. All eight patients had >95% stenoses demonstrated by coronary angiography (CAG) just before PTCA. After PTCA, CAG showed that all of the coronary artery stenoses had been reduced to <50%. Additionally, intravascular ultrasonography (IVUS) performed in five patients before and after PTCA demonstrated adequate dilation of the coronary stenosis after PTCA. All eight patients underwent dobutamine stress TMS, BMS, and ELP 2 to 3 months after PTCA, which demonstrated no regions of myocardial ischemia. Approximately 6 months later, CAG was performed in all eight patients, and only one patient had developed restenosis. CONCLUSIONS: PTCA effectively dilates stenotic coronary arteries in children with KD. Moreover, dobutamine stress TMS, BMS, and ELP are useful for detecting silent myocardial ischemia and estimating the effectiveness of PTCA. Furthermore, IVUS is useful for evaluating the severity of coronary artery lesions before and after PTCA in patients with KD.

Adolescent↗
PubMed1997

Enantioselective high-performance liquid chromatographic determination of nicardipine in human plasma.

A sensitive method for the enantioselective high-performance liquid chromatography (HPLC) determination of nicardipine in human plasma is described. (+)-Nicardipine, (-)-nicardipine and (+)-barnidipine as an internal standard are detected by an ultraviolet detector at 254 nm. Racemic nicardipine in human plasma was extracted by a rapid and simple procedure based on C18 bonded-phase extraction. The extraction samples were purified and concentrated on a pre-column using a C1 stationary phase and the enantiomers of nicardipine are quantitatively separated by HPLC on a Sumichiral OA-4500 column, containing a chemically modified Pirkle-type stationary phase. Determination of (+)- and (-)-nicardipine was possible in a concentration range of 5-100 ng ml(-1) and the limit of detection in plasma was 2.5 ng ml(-1). The recoveries of (+)- and (-)-nicardipine added to plasma were 91.4-98.4% and 93.3-96.7%, respectively, with coefficients of variation of less than 9.0 and 9.4% respectively. The method was applied to low level monitoring of (+)- and (-)-nicardipine in plasma from healthy volunteers.

Calcium Channel Blockers↗
PubMed1997

Synthesis and cataleptic effects of optically active dihydrohaloperidols and dihydrobromoperidols.

Optically active dihydrohaloperidols and dihydrobromoperidols, the major metabolites of haloperidol and bromoperidol, clinically used as neuroleptic drugs in humans, were asymmetrically synthesized by Jaen's method. The motor effects of all the reduced haloperidol and bromoperidol metabolites were evaluated by the mouse catalepsy test. The results indicate that administration of the optically active dihydrohaloperidols and dihydrobromoperidols as well as haloperidol and bromoperidol can cause significant motor deficits in mice.

Animals↗
PubMed1997

Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

The relationship between the cytochrome P450 (CYP) 2D6 genotype and the steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depressed Japanese patients receiving trazodone 150 mg at bedtime. By use of allele-specific PCR analysis, the wild type allele, three mutated alleles causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and one mutated allele causing decreased enzyme activity (CYPZD6 Ch) were identified. The means (ranges) of the Css of trazodone, corrected to the median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (281-1115), 643 (302-1362) and 671 (234-1418) ng/ml, respectively, while the values of mCPP were 60 (35-121), 65 (33-99) and 58 (38-112) ng/ml, respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the three groups. The present study thus suggests that the CYP2D6 genotype cannot predict the Css of these compounds.

Adult↗
PubMed1997

Predictors of sinus rhythm restoration after Cox maze procedure concomitant with other cardiac operations.

BACKGROUND: There have been sporadic cases of persistent atrial fibrillation and sick sinus syndrome after the maze procedure. The purpose of this study was to identify the predictors of sinus rhythm restoration after operation. METHODS: Between March 1993 and June 1995, we evaluated retrospectively 96 consecutive patients who underwent the maze procedure (maze III) in combination with another type of cardiac operation. Four patients who died and 6 patients who required permanent pacemaker implantation because of sick sinus syndrome were excluded. Ambulatory electrocardiographic monitoring was evaluated 1 year after operation. Multiple logistic regression analysis was applied to identify the predictors of sinus rhythm restoration. RESULTS: The final population comprised 86 patients (mean age, 59.8 years; 67 patients with mitral valve disease). Overall, sinus rhythm was restored in 68 of 86 patients (79.1%). The magnitude of the atrial fibrillatory wave positively predicted postoperative sinus rhythm restoration. Conversely, left atrial diameter was inversely related to postoperative sinus rhythm restoration. The odds ratio of having both a fine atrial fibrillatory wave (< 1.0 mm) and enlarged left atrial diameter (> or = 65 mm) for patients with sinus rhythm restoration was 0.04 (95% confidence interval, 0.01 to 0.28). CONCLUSIONS: Atrial fibrillatory wave and left atrial diameter were independent predictors of sinus rhythm restoration after the maze procedure in patients with chronic atrial fibrillation and organic heart disease.

Adult↗
PubMed1997

Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype.

OBJECTIVES: To assess the possible relationship between the metabolic disposition of pantoprazole and genetically determined S-mephenytoin 4'-hydroxylation phenotype and genotype. METHODS: The pharmacokinetic disposition of pantoprazole was investigated in 14 Japanese male volunteers (seven extensive and seven poor metabolizers of S-mephenytoin). All subjects received a single 40 mg oral dose of pantoprazole as the enteric-coated formulation. RESULTS: An interphenotypic difference in the metabolic disposition of pantoprazole was observed: the mean values for area under the concentration-time curve (AUC), elimination half-life (t1/2), and apparent oral clearance were significantly (p < 0.01) greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean AUC of pantoprazole sulfone was greater (p < 0.01) in the poor metabolizers than in the extensive metabolizers, whereas the mean AUC of the main demethylated metabolite (M2) was lower (p < 0.01) in the poor metabolizers than in the extensive metabolizers. A significant negative correlation was observed between the individual values for log10% urinary excretion of 4'-hydroxymephenytoin and AUC of pantoprazole (rs = -0.816; p < 0.005). The CYP2C19 genotyping test results were found to be in a complete accordance with the phenotypes. CONCLUSION: These data indicated that the metabolic disposition of pantoprazole is under the pharmacogenetic control of S-mephenytoin 4'-hydroxylase (CYP2C19).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Plasma concentrations of trazodone and m-chlorophenylpiperazine at steady state can be predicted from those after an initial dose of trazodone.

1. The authors studied the correlations between plasma concentrations of trazodone and mCPP at steady state and those after an initial dose of trazodone. 2. Fifteen depressed patients received trazodone 150 mg at bedtime for 3 weeks, and blood samplings were taken 12 h after the initial dose and 12 h after the last dose at each week. Plasma concentrations of trazodone and mCPP were measured by high-performance liquid chromatography. 3. Plasma concentration of mCPP, but not trazodone, was significantly higher at each week than after initial dosing. 4. For both trazodone and mCPP, significant linear relationships were found between plasma concentration after initial dosing and the average of 3 weeks' plasma concentrations. 5. The present study thus suggests that plasma concentrations of trazodone and mCPP at steady state can be predicted from those after an initial dose of trazodone.

Adult↗
PubMed1997

Effects of genetically determined S-mephenytoin 4-hydroxylation status and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam.

This study examines the effects of genetically determined S-mephenytoin 4-hydroxylation capacity and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam in 12 healthy male volunteers. Six subjects each were extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Seven subjects were smokers (> 10 cigarettes/day), and five were nonsmokers, according to their self-reports. Each subject took a single oral dose of 0.8 mg of alprazolam, and blood samples were collected up to 48 hours postdose. Psychomotor function was assessed at times of blood samplings using the Digit Symbol Substitution Test (DSST), Visual Analog Scale (VAS), and UKU Side Effect Rating Scale. Plasma alprazolam concentrations were measured by a high-performance liquid chromatography assay. None of the mean pharmacokinetic parameters was significantly different between the EM and PM phenotype groups. Although the mean elimination half-life was significantly shorter in the smoker group (p < .01) than in the nonsmoker group (13.1 +/- 2.9 vs. 20.0 +/- 2.7 hours, mean +/- SD), other pharmacokinetic parameters did not differ significantly between the two groups. Psychomotor function parameters did not differ significantly either between the EM and PM groups or between the nonsmoker and smoker groups. The present study thus suggests that neither S-mephenytoin 4-hydroxylation status nor self-reports of extensive cigarette smoking has a major impact on the metabolism of alprazolam in humans.

Adult↗