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Yutaka Imai

Publications and source records attributed to Yutaka Imai.

At least 73 records · Page 4Linked to original sources
PubMed2004

Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations.

OX40/OX40 ligand (OX40L) interactions are implicated in costimulation for both CD4(+) T and B cells in a bidirectional manner. To determine the role of OX40/OX40L interactions in recipient antidonor responses after multiple allogeneic transfusions, we examined alloreactive cytotoxic T lymphocyte (allo-CTL) activity and alloantibody production in repeatedly alloimmunized OX40L-deficient mice. After the fifth alloimmunization, whereas OX40L-deficient mice showed allo-CTL activity with levels comparable to those of wild-type mice, alloantibody production in OX40L-deficient mice was significantly reduced, accompanied by fewer memory B and CD4(+) T cells with reduced function. Furthermore, nu/nu mice that received OX40L-deficient T cells still exhibited impaired alloantibody production with fewer memory CD4(+) T and B cells. In contrast, RAG-2-deficient mice that received both wild-type T cells and OX40L-deficient B cells produced scant alloantibodies with fewer memory B cells, but sufficient memory CD4(+) T cells. Thus, OX40L on B cells, rather than on T cells, is apparently required for adequate and persistent production of alloantibodies after repeated alloimmunizations.

Animals↗
PubMed2004

Progress report on the HOMED-BP Study: hypertension objective treatment based on measurement by electrical devices of blood pressure study.

Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure Study (HOMED BP Study) is the first large-scale intervention trial in Japan using a Prospective Randomized Open Blinded Endpoint (PROBE) design to determine an optimal target blood pressure (BP) level on the basis of self-measured BP at home, and an optimal initial course of antihypertensive medication. The registered patients are randomized to either a more intensive BP-lowering group (home systolic BP < 125 mmHg and diastolic < 80 mmHg) or a less intensive group (home systolic/diastolic BP within the range 134-125/84-80 mmHg) by host computer via the Internet. The differential effect of three classes of initial antihypertensive regimens on the prognosis, i.e., calcium antagonist (Ca-A), angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor antagonist (ARB), which are used most frequently in Japan, are examined. Three regimens are also randomly assigned to the host computer via the Internet. A pilot study was started in May 2001. In March 2002, the number of participating doctors was 461. At the end of March 2002, 546 patients were recruited. Of these, 412 (202 men and 210 women, aged 58.4 +/- 10.2 y) were randomized. Patients will be recruited until February, 2006 and followed for 7 years.

Adult↗
PubMed2004

The effects of physical activity and autonomic nerve tone on the daily fluctuation of blood pressure.

The effects of daily activity and autonomic nerve tone on the fluctuation of ambulatory blood pressure were studied in hypertensive patients. The autonomic nerve tone was measured by frequency domain analysis of the RR interval. Physical activity was evaluated by a walk count, converted to a walk rate (WR), recorded using a digital Holter ECG fitted with an accelerometer, with simultaneous monitoring of blood pressure (Bp). Average values of the WR, H and L/H components were calculated for the 15 min. period just prior to Bp monitoring. The relationship between the average WR, H and L/H values and the Bp was determined by a linear regression analysis. Hypertension was classified into three types, autonomic nerve dominant (AN), exercise dominant (EX), and irregular (IR), based on a high correlation coefficient between Bp and either H or L/H (AN type), between Bp and WR (EX type), or no significant correlation between Bp and any of the parameters (IR type). Of the thirty hypertensive patients studied 11 were classified as AN, 12 as EX, and 7 as IR. Patients of the EX type had significantly lower Bp than patients in the other two classes. Furthermore, all of the IR type patients showed non-dipper type hypertension, suggesting that the Bp regulation mechanisms were impaired. The results suggest the significance of simultaneous monitoring of physical activity and autonomic nerve function at the time of Bp monitoring.

Aged↗
PubMed2004

How many times should blood pressure be measured at home for better prediction of stroke risk? Ten-year follow-up results from the Ohasama study.

OBJECTIVE: To determine the optimum number of blood pressure self-measurements taken at home (home blood pressure) in relation to their predictive value for stroke risk. METHODS: We obtained more than 14 measurements of home blood pressure from 1491 people aged >or=40 years without a history of stroke in the general population in Japan, and followed them up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. RESULTS: The predictive value of home blood pressure increased progressively with the number of measurements, showing the highest predictive value with the average of whole measurements (mean = 25 measurements, 35% increase in the risk of stroke per 10 mmHg elevation in blood pressure). The initial home blood pressure values (one measurement) showed a significantly greater relation with stroke risk than conventional blood pressure values (mean of two measurements) (19/8% increase in the risk of stroke per 10 mmHg elevation in initial home/conventional systolic blood pressure values, respectively). CONCLUSIONS: There was no threshold for the number of home blood pressure measurements within the range of 1-14 measurements for increasing the predictive power of stroke risk, suggesting that as many measurements as possible, preferably more than 14 measurements, is recommended for better prediction of stroke risk. It should be emphasized that home blood pressure has a stronger predictive power than does conventional blood pressure, even for a lower number of measurements.

Adult↗
PubMed2004

Patient characteristics and factors associated with inter-arm difference of blood pressure measurements in a general population in Ohasama, Japan.

OBJECTIVES: To assess whether there is a natural difference in blood pressure (BP) measurements between the right and left arms, and to identify what factors are associated with this difference in a general population. METHODS: The study subjects were 1090 individuals who participated in a medical check-up in Ohasama, Japan. The BP was measured simultaneously in both arms, using an automated device. The inter-arm BP difference was expressed as the relative difference [right-arm BP (R) minus left-arm BP (L): R - L] and the absolute difference (|R - L|). The relationship between inter-arm difference and various factors was analyzed using univariate analysis. The characteristics of subjects in whom the absolute systolic BP (SBP) difference was greater than 10 mmHg were analyzed using multivariate logistic analysis. RESULTS: The relative differences in SBP and diastolic BP (DBP) were -0.6 +/- 6.6 (mean +/- SD) and 1.1 +/- 4.7 mmHg, while the absolute differences were 4.9 +/- 4.4 and 3.7 +/- 3.0 mmHg. The absolute SBP difference was found to correlate significantly with age, body mass index, ankle-brachial index (ABI), and hypertension. Subjects with hypertension, hypercholesterolemia, obesity, elevated hemoglobin A1c (HbA1c) and low ABI had a significant and independent increase in the risk of an absolute SBP difference greater than 10 mmHg. CONCLUSIONS: The results suggest that there is considerable difference in the measured BP in the right and left arms and that large differences in the absolute SBP are associated with risk factors for arteriosclerosis such as hypertension, hypercholesterolemia, obesity, metabolic abnormalities and low ABI.

Adult↗
PubMed2004

The second progress report on the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study.

BACKGROUND: The Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study is a large-scale intervention trial to determine both optimal target blood pressure (BP) on the basis of self-measured BP at home, and optimal initial antihypertensive medication. OBJECTIVE: To investigate the quality of randomization at the end of March 2003, and BP-controlled conditions during initial 6 months. METHODS: We evaluated the number of patients randomized by the end of March 2003, and BP changes during the initial 6 months based on intention-to-treat analysis. RESULTS: By the end of March 2003, a total of 1086 patients (12% of a planned randomization of 9000 patients) had been randomized. Among 653 patients who had been followed for > or =6 months after randomization, mean systolic/diastolic BPs at randomization in the calcium antagonist, angiotensin-converting enzyme and angiotensin II receptor blocker groups were 149/89, 150/89 and 149/88 mmHg, respectively. Blood pressures were reduced after 3 months (137/83, 139/82 and 136/82 mmHg, respectively), and further reduced after 6 months (134/81, 135/80 and 133/80 mmHg, respectively), with no significant differences identified between groups. In more- and less-intensive BP-lowering groups, mean systolic/diastolic BPs at randomization were 149/88 and 150/89 mmHg, respectively. Although BPs were reduced after treatment for 3 months (137/83 and 137/82 mmHg, respectively) and 6 months (134/80 and 135/80 mmHg, respectively) in each target group, significant differences were still not observed between groups. CONCLUSIONS: Good quality of randomization was observed at the end of March 2003, but rate of achievement for target BPs was insufficient.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Prediction of ischaemic and haemorrhagic stroke by self-measured blood pressure at home: the Ohasama study.

OBJECTIVE: To examine the predictive value of self-measured blood pressure values taken at home (home blood pressure) for risk of stroke and subtypes. METHODS: We obtained home blood pressure measurements from 1702 people, aged > or =40 years, without a history of stroke, in the general population in Japan, and continued follow-up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. RESULTS: There was a linear relationship between home blood pressure and risk of stroke and subtypes. On average, each 10/5 mmHg elevation in home systolic/diastolic blood pressure respectively, was associated with an approximately 30/20% respectively, higher risk of total stroke. A similar relationship was observed for the risk of haemorrhagic stroke (intracerebral and subarachnoid haemorrhage), and the risk of ischaemic stroke [cerebral infarction and transient ischaemic attack (TIA)]. The risk of stroke and subtypes showed a significantly greater relation with home blood pressure values compared to conventional blood pressure values. CONCLUSIONS: This is the first study to demonstrate that home blood pressure is an independent predictor for haemorrhagic and ischaemic stroke, in the general population.

Adult↗
PubMed2004

CYP11B2 polymorphisms and home blood pressure in a population-based cohort in Japanese: the Ohasama study.

Genetic polymorphisms of the aldosterone synthase gene (CYP11B2) have been major targets of studies into the genetic factors involved in hypertension. We have identified three genetic variants of CYP11B2, -344C/T at the promoter region, a conversion in intron 2 from the CYP11B2 sequence to the CYP11B1 sequence, and R173K in exon 3, in the Japanese population. -344C/T and R173K were in complete linkage disequilibrium in CYP11B2, and -344C/T was in strong, but not complete, linkage disequilibrium with the polymorphism in intron 2. Thus, two genetic polymorphisms, -344C/T and the gene conversion in intron 2, were investigated in association with home blood pressure (BP) values and clinical parameters in 1,242 subjects aged 40 and over in Ohasama, a rural Japanese community. Hypertension was defined as being treated with antihypertensive medication and/or having home BP values of more than 135 mmHg in systole and/or 85 mmHg in diastole. The results demonstrated that the -344T allele was significantly associated with increased prevalence of hypertension (p=0.015 in multiple logistic regression analysis, adjusted by age, gender, BMI, and smoking status), though BP level was unaltered. This allele was also significantly related to the prevalence of cardiovascular diseases in the older population (60 < or = age, p=0.014). The resting polymorphism, a gene conversion in CYP11B2 intron 2, was not associated with any clinical parameters. Therefore, -344C/T polymorphism in CYP11B2 was considered an independent genetic factor possibly associated with hypertension or atherosclerotic diseases in the Japanese population.

Aged↗
PubMed2004

Association between angiotensin II type 1 receptor gene polymorphism and essential hypertension: the Ohasama Study.

Gene targeting approaches have suggested that the angiotensin II type 1 receptor (AT1R) is involved in blood pressure (BP) regulation and modulation of the effect of angiotensin II. The A1166C polymorphism of the AT1 receptor gene (AT1R/A1166C) is associated with hypertension in Caucasians, but not in Japanese. The goal of this study, the Ohasama Study, was to examine the association between AT1R/A1166C and hypertension, especially home BP, in the Japanese general population. The Ohasama Study was a cohort study based on Japanese rural residents of Ohasama Town in the northern part of Japan. Subjects who gave informed consent to the study protocol and genetic analysis were recruited. Home BP was measured twice in the morning within 1 h of waking up and in the evening just before going to bed. The TaqMan polimerase chain reaction (PCR) method clearly determined AT1R/A1166C genotypes (n =1,207). The genotype distribution of AT1R/A1166C was as follows: AA 84%; AC 15%; CC 1%. There was almost no difference in baseline characteristics among the AT1R genotypes (AA, AC, CC). In the subjects not receiving antihypertensive medication (n =817), both casual BP and home BP were not different among the AT1R genotypes after adjusting for confounding factors (age, sex, body mass index, current smoking habit and current alcohol consumption). The frequency of hypertension showed no difference among AT1R genotypes after adjusting for confounding factors, though the AC and CC genotypes were more frequent in hypertensives than in normotensives. Our data suggested that the AT1R/A1166C polymorphism is not a major genetic predisposing factor for hypertension in Japanese.

Female↗
PubMed2004

valsartan in elderly isolated systolic hypertension (VALISH) study: rationale and design.

Although antihypertensive therapy has been proven to reduce cardiovascular morbidity and mortality, it is unclear how much blood pressure should be decreased in elderly patients with hypertension. The Valsartan in Elderly Isolated Systolic Hypertension (VALISH) study is a multicenter parallel-group study comparing the incidence of cardiovascular events between two target systolic blood pressure levels, below 140 mmHg and below 150 mmHg, under treatment with valsartan, an angiotensin II receptor blocker, as an initial antihypertensive drug in elderly patients with isolated systolic hypertension. The number of patients to be recruited is 3,000 and the duration of follow-up is at least 2 years. This 3,000-patient trial was designed with a two-sided alpha level of 0.05 and 80% power to detect the difference in incidence of cardiovascular events between the target blood pressure levels based on estimation of the cardiovascular events ratio as 21.5/1,000 patient-years and 29.1/1,000 patient-years for the two blood pressure levels. The VALISH study, a large-scale investigator-initiated trial in Japan, will determine whether age should be considered in setting target blood pressure in treatment of isolated systolic hypertension in elderly patients.

Aged↗
PubMed2004

Control of blood pressure as measured at home and office, and comparison with physicians' assessment of control among treated hypertensive patients in Japan: First Report of the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

The Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study was conducted to measure the control of blood pressure (BP) as evaluated by home BP measurement among 3,400 patients with essential hypertension (mean age: 66 years; females: 55%) receiving antihypertensive treatment in primary care settings in Japan. The purpose of this first report was to compare characteristics of BP control as measured at home and in the clinic (office) and define their association with BP control as evaluated by physicians. Mean systolic/diastolic BP (SBP/DBP) values were 140/82 mmHg for home BP and 143/81 mmHg for office BP. BP levels were not adequately controlled among approximately 60% of the patients, according to reference values described in the national guidelines (office BP: <140/90 mmHg; home BP: <135/85 mmHg). Even among patients evaluated by physicians as having excellent or fairly good BP control, office and home SBP values were insufficiently controlled in approximately 50%. Although the tendency was more remarkable among older patients, whose recommended target BP levels are higher than those of middle-aged patients in the Japanese Hypertension Society 2000 criteria, office and home BP values were not adequately controlled in approximately 50% of the middle-aged patients whose BP control was evaluated as good. Our findings suggest that an important reason why home and office BP values are not adequately controlled is that physicians approve relatively higher BP levels under treatment, even among middle-aged patients.

Aged↗
PubMed2004

Practical aspect of monitoring hypertension based on self-measured blood pressure at home.

Devices for home blood pressure (BP) measurement are produced worldwide at a rate of more than 10 million a year and 30 million such devices have already been distributed in Japan. The clinical significance of home BP measurement is obvious; patients can recognize the effects of antihypertensive treatment. Home BP measurements encourage medication compliance, follow-up clinic visits, and active participation in the medical treatment, thus resulting in improved management of hypertension. Home BP measurements more accurately reflect damage to target organs and the prognosis of cardiovascular diseases. The purpose of home BP measurements is to obtain information on the patient's inherent BP pattern using longterm, repetitive measurement under controlled conditions. Since home BP is measured under controlled condition, values are reproducible, and thus, useful in the diagnosis and treatment of hypertension. Blood pressures measured under standardized condition are indispensable when comparing data among individuals, among groups and among institutes. Working Group of Japanese Society of Hypertension (JSH) established JSH Guidelines for Self-Monitoring of Blood Pressure at Home in 2003. Standardization of the measurement procedure may elevate the position of home BP measurements for the purpose of diagnosing and treating hypertension. As a result, home BP measurements may improve the accuracy of screening for hypertension and assessment of BP control during treatment and encourage drug compliance. Home BP measurements, under such controlled conditions, should have a beneficial effect on the economics of diagnosing and treating hypertension.

Blood Glucose Self-Monitoring↗
PubMed2004

[New preparation method for barium enema: efficacy and administration of oral intestinal lavage solution with gastrointestinal prokinetic agent].

The modified Brown's method is commonly used in Japan as preparation for barium enema; however, in a few cases, its cleansing effect is not satisfactory even with the use of adequate diet. To develop a new method of preparation for barium enema, we examined the use of an oral intestinal lavage solution (PEG-ELS) with mosapride and compared it with the modified Brown's method. We administered mosapride and PEG-ELS by four different methods. These methods were assessed by the amount of remaining feces and the adequacy of barium coating. Methods in which mosapride was taken separately before and after the intake of PEG-ELS were more effective than the method using mosapride and the modified Brown's method. Lesion detection was almost the same as that with the modified Brown's method. In conclusion, preparation for barium enema using mosapride before and after PEG-ELS intake is more effective than the modified Brown's method.

Administration, Oral↗
PubMed2003

Protection of dopaminergic neurons with a novel astrocyte modulating agent (R)-(-)-2-propyloctanoic acid (ONO-2506) in an MPTP-mouse model of Parkinson's disease.

We examined the neuroprotective effects of a novel astrocyte-modulating agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), in a mouse model of Parkinson's disease. Male C57BL/6 mice received four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (10 mg/kg) at 1-h intervals. Dopamine content in the striatum, measured with HPLC 3 days after MPTP injection, was reduced to 23% of control. But this dopamine depletion was dose-dependently prevented by repeated treatments with ONO-2506 (3, 10 and 30 mg/kg, i.p.) administered 1, 6, 24 and 48 h after MPTP injection (51% of control in 30 mg/kg group, p<0.01). ONO-2506 treatment (30 mg/kg) started after 6 h, followed by treatments at 24 and 48 h, also prevented the reduction of dopamine content (42% of control vs. 11% of control in the saline-treated group, p<0.01). We also performed immunohistochemistry for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). The MPTP injection resulted in a loss of TH-positive dopaminergic neurons (42% of control, p<0.01) in the substantia nigra after 7 days, but ONO-2506 treatment prevented this neuronal loss (70% of control, p<0.01). The MPTP injection led to reactive astrocytosis in the striatum after 7 days, but ONO-2506 induced earlier, moderate astrocytic activation after 3-7 days. These findings show that ONO-2506 protects dopaminergic neurons against MPTP neurotoxicity probably through facilitating astrocytic support for neuronal recovery from injury. Pharmacological modulation of astrocytes may offer a novel therapeutic strategy for Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Expression of S-100 protein is related to neuronal damage in MPTP-treated mice.

S-100beta is a calcium-binding protein expressed at high levels in brain and is known as a marker of brain damage. However, little is known about the role of S-100beta protein during neuronal damage caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To determine whether S-100beta protein is induced in glial cells after MPTP treatment, we investigated the expression of S-100 protein immunohistochemically, using MPTP-treated mice. We also examined the change of neurons and glial cells in mice after MPTP treatment. The present study shows that tyrosine hydroxylase (TH) immunoreactivity decreased gradually in the striatum and substantia nigra from 1 day after MPTP treatment. Thereafter, TH-immunopositive cells and fibers decreased in the striatum and substantia nigra at 3 days after MPTP treatment. In contrast, S-100-immunopositive cells and glial fibrillary acidic protein (GFAP)-immunopositive cells increased markedly in the striatum and substantia nigra at 3 days after MPTP treatment. Seven days after MPTP treatment, S-100-immunopositive cells decreased in the striatum and substantia nigra. However, the number of GFAP-immunopositive cells increased in these regions. In double-labeled immunostaining with anti-S-100 and anti-GFAP antibodies, S-100 immunoreactivity was observed only in the GFAP-positive astrocytes. These results provide evidence that astrocytic activation may play a role in the pathogenesis of MPTP-induced degeneration of dopaminergic neurons. Furthermore, the present study demonstrates that S-100 protein is expressed selectively by astrocytes, but not by microglia, after MPTP treatment. These results provide valuable information for the pathogenesis of the acute stage of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗