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Biomedical subjects

Yutaka Imai

Publications and source records attributed to Yutaka Imai.

At least 109 records · Page 6Linked to original sources

Insufficient duration of action of antihypertensive drugs mediates high blood pressure in the morning in hypertensive population: the Ohasama study.

Blood pressure (BP) usually peaks in the morning. The circadian variation of the onset of cardiovascular disease mimics this circadian BP variation. To examine the determinants of the BP difference between the self-recorded BP in the morning (home BP) and daytime average ambulatory BP a cross sectional study was done in the general population of Ohasama, Japan. 1207 subjects > or = 20 years measured both home (more than 14 times) and ambulatory BPs (326 treated for hypertension and 881 untreated subjects), The prevalence of subjects with the systolic BP difference (home BP in the morning - daytime ambulatory BP) of > or = 10 mmHg (high morning BP) was 5.6% in untreated normotensives, 2.9% in untreated hypertensives, and 25.8% in treated hypertensives. This trend was also observed for diastolic pressure. Multiple regression analysis demonstrated that age, male sex, and use of antihypertensive drugs were positively associated and day-night difference of BP was negatively associated with the high morning BP, respectively. These results suggest an insufficient duration of antihypertensive action of widely used antihypertensive drugs in Japan from the 1980s to 1990s. The amplitude of the day-night difference of ambulatory BP in subjects with a high morning BP was lower (non-dipping) than that without high morning BP. The high morning BP is not necessarily accompanied by hypertension but might be mediated, at least in part, by an insufficient duration of action of antihypertensive drugs. The high morning BP accompanies so-called non-dipper pattern of circadian BP variation. An insufficient duration of action of drugs may partly mediate non-dipping in subjects with antihypertensive medication.

Adult↗

Accuracy and reliability of wrist-cuff devices for self-measurement of blood pressure.

OBJECT: Self-measurement of blood pressure (BP) might offer some advantages in diagnosis and therapeutic evaluation and in patient management of hypertension. Recently, wrist-cuff devices for self-measurement of BP have gained more than one-third of the world market share. In the present study, we validated wrist-cuff devices and compared the results between wrist- and arm-cuff devices. The factors affecting the accuracy of wrist-cuff devices were also studied. METHOD: The research group to assess the validity of automated blood pressure measuring device consisted of 13 institutes in Japan, which validated two wrist-cuff devices (WC-1 and WC-2) and two arm-cuff devices (AC-1 and AC-2). They used a crossover method, where the comparison was done between auscultation, by two observers by means of a double stethoscope on one arm and the device on the opposite arm or wrist. RESULTS: There was good inter-observer agreement for the auscultation method in each institute (systolic blood pressure (SBP), -0.1 +/- 2.8 mmHg; diastolic blood pressure (DBP), -0.1 +/- 2.6 mmHg, n = 498). The mean difference between auscultation and the device was minimal both in arm-cuff devices (mean difference for AC-1, 2.2/1.9 mmHg, n = 97 and for AC-2, 5.1/2.9 mmHg, n = 136, SBP/DBP) and wrist-cuff devices (mean difference for WC-1, -2.1/1.2 mmHg, n = 173 mmHg and for WC-2, -2.3/-5.6 mmHg, n = 92). The standard deviation of the difference (SDD) in wrist-cuff devices, however (SDD for WC-1, 9.7/7.3 mmHg and for WC-2, 10.2/8.6 mmHg), was larger than that of the arm-cuff devices (SDD for AC-1, 5.6/6.6 mmHg and for AC-2, 6.3/5.1 mmHg). Grading of AC-1 and AC-2 based on criteria of British Hypertension Society was A/A and B/A, respectively, while that of WC-1 and WC-2 was C/B and D/B, respectively. Using the same validation protocol, the results of validation for one device were divergent in each institute. In wrist-cuff devices, the BP value obtained in palmar flexion was significantly higher and that obtained in palmar dorsiflexion was significantly lower than that in palmar extension. In some cases, finger plethysmogram did not disappear during maximum inflation of the wrist-cuff (congruent with 250 mmHg), even in palmar extension and especially in palmar flexion, suggesting incomplete obstruction of radial and/or ulnar arteries during inflation. CONCLUSION: The results suggest that wrist-cuff devices in the present form are inadequate for self-measurement of blood pressure and, thus, are inadequate for general use or clinical and practical use. However, there is much possibility in wrist-cuff device and the accuracy and reliability of wrist-cuff device are warranted by an improvement of technology.

Adolescent↗

Angiotensin-converting enzyme I/D polymorphism and hypertension: the Ohasama study.

OBJECTIVE: Angiotensin-converting enzyme (ACE) I/D polymorphism in intron 16 of the ACE gene was analyzed in a general Japanese population in relation to self-blood pressure (BP) measurement at home (home BP) and ambulatory BP monitoring (ABPM) to determine the association between genetic variants of this polymorphism and hypertension. DESIGN: A cross-sectional study. METHODS AND RESULTS: We genotyped the ACE I/D polymorphism in 1245 subjects with home BP and 803 subjects with ABPM in Ohasama, a rural community in Japan. All the subjects were 40 years of age and over, and gave written informed consent for the present genetic analysis. Hypertensive subjects were defined as those receiving antihypertensive drugs and those who had a home BP higher than 135 mmHg in systole and/or higher than 85 mmHg in diastole. The frequencies of the II, ID, and DD genotypes in these Japanese subjects were 0.45, 0.45, and 0.10, indicating a lower frequency of the D allele (0.33) than in Caucasians. There was no significant difference of BP level, prevalence of hypertension or nocturnal decline in BP among the genotypes. There were no differences in the prevalence of previous cardiovascular disease, age, body mass index, male gender, smoking, or biochemical and hormonal parameters among the three genotypes. CONCLUSION: The present results indicate the absence of direct effects of the ACE D-allele on BP level, prevalence of hypertension, prevalence of cardiovascular disease, and circadian BP variation. We conclude there is little association between ACE I/D polymorphism and hypertension in the general Japanese population.

Adult↗

alpha-Adducin Gly460Trp polymorphism is associated with low renin hypertension in younger subjects in the Ohasama study.

BACKGROUND: The Gly460Trp polymorphism of the alpha-adducin gene (ADD-1 ) has been examined as a candidate gene for essential hypertension with salt sensitivity in the Caucasian population. However, we failed to detect a positive association between the Gly460Trp polymorphism of ADD-1 and hypertension in a small series of Japanese subjects. OBJECTIVE: To examine the precise association between the Gly460Trp polymorphism of ADD-1 and blood pressure (BP), we carried out an association study using a Japanese population: the Ohasama Study. DESIGN: Subjects (n = 1490) were recruited from participants in the Ohasama Study, which is a cohort in a rural community of northern Japan. METHODS: DNA was extracted from the buffy coat of the participants who gave informed consent for genetic analysis, and the Gly460Trp polymorphism of ADD-1 was determined by the TaqMan polymerase chain reaction method. Various BP values (casual BP, ambulatory BP and home BP) were measured in the Ohasama study. We used the mean values of these BP measurements for analysis. RESULTS: The frequencies of genotypes in the Ohasama population were 23% Gly/Gly, 49% Gly/Trp, and 28% Trp/Trp. In the baseline characteristics, age, sex, body mass index, frequency of diabetes and hyperlipidemia were significantly different between hypertensive or normotensive subjects. In total subjects, all BP values were not different among genotypes. In the younger subjects ( 60 years old) with low plasma renin activity (< 1.0 ng/ml per h), however, ambulatory BP and home BP were significantly higher in the subjects with the Gly/Trp or Trp/Trp genotypes of ADD-1 polymorphism than in those with the Gly/Gly genotype. In the same population, the frequency of the Gly/Trp or Trp/Trp genotypes of was significantly higher in hypertensives than in normotensives (83 versus 72%, chi1(2) = 4.04, P<0.05; odds ratio, 2.12; 95% confidence interval, 1.02-4.68). CONCLUSIONS: These findings suggest the possibility that the Gly460Trp polymorphism of ADD-1 is associated with low renin hypertension.

Blood Pressure↗

Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study.

OBJECTIVE: To examine the relationship between the normal nocturnal decline in blood pressure and the risk of cardiovascular mortality in individuals with and without high 24-h blood pressure values. METHODS: We obtained 24-h ambulatory blood pressure readings from 1542 residents of Ohasama, Japan, who were aged 40 years or more and were representative of the Japanese general population. We then followed up their survival for a mean of 9.2 years. The relationship was analysed using a Cox proportional hazards model adjusted for possible confounding factors. RESULTS: There was a linear relationship between the nocturnal decline in blood pressure and cardiovascular mortality. On average, each 5% decrease in the decline in nocturnal systolic/diastolic blood pressure was associated with an approximately 20% greater risk of cardiovascular mortality. There were no significant interactions for the risk between 24-h systolic/diastolic blood pressure values and continuous values for the nocturnal decline in blood pressure ( for interaction 0.6). Even when 24-h blood pressure values were within the normal range ( 135/80 mmHg, average 118/69 mmHg), diminished nocturnal decreases in systolic/diastolic blood pressure were associated with an increased risk of cardiovascular mortality. CONCLUSIONS: This is the first study to demonstrate that a diminished nocturnal decline in blood pressure is a risk factor for cardiovascular mortality, independent of the overall blood pressure load during a 24-h period, in the general population.

Aged↗

Pulse wave velocity and the second derivative of the finger photoplethysmogram in treated hypertensive patients: their relationship and associating factors.

OBJECTIVES: To clarify the factors influencing two measures of arterial stiffness, pulse wave velocity (PWV) and the second derivative of the finger photoplethysmogram (SDPTG), and to evaluate their relationship in treated hypertensive subjects. SUBJECTS AND METHODS: The subjects were 294 hypertensive patients aged 32-91 years (mean, 61.4 +/- 10.5 years). After blood pressure (BP) was measured, carotid-femoral PWV and SDPTG were recorded with the subjects in the supine position, with the aid of an automatic device. For assessing SDPTG, we focused mainly on the ratios of the absolute value of the height of the early negative 'b' wave (B) and that of the late re-decreasing 'd' wave (D) to that of the initial positive 'a' wave (A), namely the B : A and D : A ratios, and the aging index (AGI). Factors influencing PWV and SDPTG indices, and the relationship between PWV and SDPTG indices were evaluated by bivariate and multivariate analyses. RESULTS: According to multiple linear regression analysis, age, systolic blood pressure (SBP), and heart rate (HR) were variables independently and positively correlated with PWV. The age and BP were significantly and independently related to SDPTG indices; there were positive correlations with the D : A ratio and AGI, and negative correlations with the B : A ratio. HR was correlated negatively with the D : A ratio and AGI, and positively with the B : A ratio. According to multiple logistic regression analysis, adjusted-odds ratios of high PWV, low B : A ratio, high D : A ratio, and high AGI were significantly elevated among the elderly and among the subjects with uncontrolled BP. Although PWV and the SDPTG indices were associated with common factors, including age and BP, bivariate analysis revealed that they were only weakly correlated with each other. CONCLUSIONS: The results suggest that in hypertensive patients, PWV and SDPTG provide different information about arterial properties at central and peripheral sites.

Aged↗

Rationale and design of HOMED-BP Study: hypertension objective treatment based on measurement by electrical devices of blood pressure study.

BACKGROUND: How far should blood pressure (BP) be lowered to achieve the greatest reduction in the risk of cardiovascular disease? Although a few trials have tried to answer this question, they failed to convincingly establish an optimal target BP level, in part because of poor reproducibility and the wide variability of conventional casual BP measurement they used. At the same time, in Japan, calcium antagonist (Ca-A) and angiotensin-converting enzyme inhibitor (ACE-I) have been two major medications in initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also now used widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medications can give the greatest benefit in reducing the risk of cardiovascular disease in the Japanese hypertensive patient. OBJECTIVE: The objectives of the study are, first, to determine an optimal target BP level, based on BP values self-measured at home (home BP). This way of measurement provides more reproducible and less variable BP values than conventional casual measurements. Secondly, we seek to determine the optimal initial antihypertensive medication for the Japanese hypertensive population. METHOD: The study is a 2 x 3 factorial randomized controlled trial conducted with a prospective randomized open-blinded endpoint design. The study will include a total of 9000 untreated essential hypertensive patients aged 40 to 78 years with home BP values > or = 135/85 mmHg. Eligible patients are randomized to one of the two home BP target groups (systolic/diastolic home BP within the range of 134-125/84-80 mmHg, or > or = 125/80 mmHg), and to regimens based on one of three initial antihypertensive drugs (Ca-A or ACE-I or ARB). These randomizations, performed by our host computer, are transmitted to terminals at the outpatient clinic through the Internet. The patient measures BP at home with newly developed equipment (HEM-7471C-N; Omron, Japan) that records BP values, the date, and the time of each measurement. The data are downloaded to the outpatient terminal at every clinic visit then transmitted to the host computer via the Internet. Based on these home BP values, the host computer determines the necessity of additional therapy or dose increments in four further steps to reach the randomized target BP, and then transmits the information to the terminal at the outpatient clinic. The primary study outcome is a composite of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death. The scheduled average post-randomization duration of follow-up is 7 years. CONCLUSION: This is the first large-scale home BP-based and Internet-connected intervention trial on antihypertensive treatment. The HOMED-BP study (Hypertension Objective treatment based on Measurement by Electrical Devices of BP) will improve the recruitment of general practitioners and participants and will supply unbiased BP data, providing reliable information on optimal target BP levels and the optimal initial antihypertensive medication.

Adult↗

Blood pressure measurement in research.

OBJECTIVE: The aim of this paper is to summarize the issues raised during a consensus conference on the role of different blood pressure (BP) monitoring techniques in research, including pathophysiological studies, clinical outcome trials and clinical pharmacology trials. METHODS: This review includes the contribution of the participants in a task force at the Eighth Consensus Conference on Ambulatory BP Monitoring (October 28-31, 2001, Sendai, Japan) and the results of a discussion open to all conference participants. Individual contributions have been summarized together with the points raised during the subsequent discussion, and the main statements are also presented in a table format. POINTS OF CONSENSUS: (1) BP monitoring in pathophysiological studies. The essential role played by continuous BP monitoring in this field had been acknowledged, and further development of non-invasive beat-by-beat monitoring techniques has been advocated. (2) BP monitoring in clinical trials. In clinical trials automated ambulatory BP monitoring (ABPM) and self BP measurements (SBPM) at home share similar advantages, with specific features that make these approaches not alternative solutions but rather approaches able to complement each other. A few examples of application of ABPM and SBPM in clinical trials include the Treatment of Hypertension according to Home or Office Blood Pressure (THOP) trial and the Trial of Preventing Hypertension (TROPHY). (3) Use of ABPM in clinical pharmacology studies. Use of ABPM is now an established routine, aimed at describing the 24-h effect of new antihypertensive drugs. An example of these applications that was discussed in the conference is the use of ABPM in the evaluation of a new long-acting calcium channel blocker (Barnidipine) (J-MUBA study). (4) Specific models for the analysis of BP fluctuations. The features characterizing the chronobiological approach to description of 24-h BP profiles and its limitations (mainly consisting of the high risk of data over-modelling) are discussed. Also the possible occurrence of a circaseptan (approximately with a 7-day period) rhythm in BP has been addressed, although repeated performance of 24-h ABPM over a week obviously faces a number of practical problems. (5) Progress in technology: BP monitoring and telemedicine. The possibility to implement an interactive telemonitoring system of home SBPM values and the perspectives for a clinical application of this technology in the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) trial is discussed.

Biomedical Research↗

Superparamagnetic iron oxide-mediated hepatic signal intensity change in patients with and without cirrhosis: pulse sequence effects and Kupffer cell function.

PURPOSE: To analyze superparamagnetic iron oxide (SPIO)-mediated hepatic signal intensity change in cirrhotic and noncirrhotic liver and to investigate the relationship between pulse sequence effects in SPIO-enhanced magnetic resonance (MR) imaging for hepatic cirrhosis. MATERIALS AND METHODS: Twelve patients with and 12 patients without cirrhosis underwent T2-weighted fast spin-echo, T2*-weighted gradient-echo (GRE), and T1-weighted GRE MR imaging before and twice (early and late phase) after SPIO administration. To assess the effect of SPIO, postcontrast relative signal-to-noise ratio (SNR) changes were statistically analyzed with repeated measurements analysis of variance for each pulse sequence. RESULTS: No interaction was shown between groups and data time points for any pulse sequence. There was no significant difference in mean hepatic relative SNR change on T2-weighted fast spin-echo images between the cirrhotic group and noncirrhotic group (-38.6% and -40.7%, early phase; -42.2% and -49.6%, late phase, respectively). For GRE images, statistically significant differences in mean hepatic relative SNR change were found between the cirrhotic group and noncirrhotic group (-14.2% and -44.5%, early phase; -28.5% and -56.4%, late phase on T2*-weighted GRE images (P <.001); 31.8% and 12.9%, early phase; 23.8% and 2.2%, late phase on T1-weighted GRE images (P <.05), respectively. CONCLUSION: Decreased overall phagocytic activity in cirrhotic liver is more likely due to Kupffer cell dysfunction than to Kupffer cell depletion, since magnetic susceptibility effects on T2*-weighted GRE images depend on intracellular SPIO cluster size.

Adult↗

Detection of mRNA for alpha-3 chain of type IV collagen in the glomerular epithelium, and the effect of perfused elastase on its expression.

BACKGROUND: The type IV collagen is a complex of trimetric molecule composed of six genetically distinct polypeptide chains; alpha1-6(IV). Since alpha3(IV) distribute specifically in the glomerular basement membrane (GBM) of glomerular capillary, we tried to develop the detection methods for the transcripts of alpha3(IV) in glomerular epithelial cells (GEC) which produce most of the components for GBM. Then, using these molecular techniques, the influence of elastase, one of the proteases released from activated polymorphonuclear leukocytes at the site of inflammation, on GEC was determined as manifested by expressional alteration of alpha3(IV) mRNA. METHODS: DIG-labeled oligo-DNA probe designating non-collagenous region of alpha3(IV) was used for in situ hybridization. Semiquantitative measurement of alpha3(IV) in the renal cortex was performed by PCR reactions, each reaction being normalized by that for GAPDH. Then, the femoral artery of each of 18 Sprague-Dawley rats was catheterized and the left kidney was perfused with saline alone (0.5 ml) or saline containing 100 microg/ml elastase. After collection of urine for 24 h, the left kidney was harvested for analysis of mRNA (4 for in situ hybridization and 5 kidneys for PCR analysis). RESULTS: Antisense cDNA probe and PCR reaction well identified alpha3(IV) mRNA in the cytoplasm of GEC and in the renal cortex, respectively. Urinary protein excreted by rats with elastase perfusion was 47.2 +/- 3.8 mg/24 h but this was only 13.9 +/- 1.1 mg/24 h in control rats (mean +/- SEM, p < 0.05). In situ hybridization demonstrated that expression of alpha3(IV) mRNA in GEC was focally or diffusely reduced in the glomeruli of rats with elastase perfusion, whereas the transcripts were well stained in GEC of controls. PCR analysis showed about 25% decrease in transcripts of alpha3(IV) in the renal cortex of rats with elastase perfusion compared to those of control rats. CONCLUSIONS: alpha3(IV) mRNA was identified specifically in the GEC in the glomeruli. Co-incidence of proteinuria and reduced alpha3(IV) expression by elastase suggests adverse effects of elastase on GEC and close association between proteinuria and GEC injury.

Animals↗

Association of a mast cell chymase gene variant with HDL cholesterol, but not with blood pressure in the Ohasama study.

Two enzymes, chymase and angiotensin converting enzyme (ACE), are involved in the production of angiotensin II. Our previous study revealed the male-specific effect of the ACE DD genotype on the risk for hypertension, but the genetic role of chymase remains unclear. In the present study, we report the results of an association study involving 1,046 subjects recruited from a general population in Ohasama, a rural community in the northern part of Japan. In addition to casual blood pressure (casual BP) measurement, home BP measurements were obtained from all participants. There were no differences in either home or casual BP values according to G3255A polymorphism of the mast cell chymase gene (MCC). HDL cholesterol level was significantly higher among carriers of the A3255 allele (p<0.04). After adjustment for confounding factors, the A3255 allele was still shown to have an effect on HDL cholesterol metabolism (p<0.03). Multiple regression analysis showed that MCC polymorphism was significantly and independently related to serum HDL cholesterol level. In conclusion, G3255A polymorphism of MCC is not directly associated with blood pressure but may modulate the prevalence of hypertensive complications via alteration of lipid metabolism.

Alleles↗

Blood pressure control assessed by home, ambulatory and conventional blood pressure measurements in the Japanese general population: the Ohasama study.

To assess blood pressure control in the Japanese population, we analyzed previously obtained measurements of conventional, home and ambulatory blood pressures in 1,174 subjects aged > or =40 in a Japanese community. On the basis of conventional blood pressure values and the use of antihypertensive medication, participants were classified as normotensive, untreated hypertensive and treated hypertensive subjects. When 140/90, 135/85 and 135/85 mmHg were used as the hypertension criteria for conventional, home and ambulatory blood pressure measurements, respectively, all three blood pressure values were higher in untreated and treated hypertensive subjects than in normotensive subjects. Among the treated hypertensive subjects, approximately half were classified as hypertensive not only by conventional blood pressure, but also by home or ambulatory measurements. Approximately 10% of the subjects defined as normotensive by conventional blood pressure measurement were classified as hypertensive by home or ambulatory measurements, whereas 60% of the untreated hypertensive subjects as defined by conventional blood pressure measurement had normal home or ambulatory blood pressure values. Therefore, we concluded that 1) the poor blood pressure control in treated hypertensive subjects was attributable not only to the white coat effect but also to inadequate control of blood pressure; and 2) a certain percentage of subjects were misclassified as hypertensive or normotensive by conventional blood pressure measurement.

Adult↗

Genetic aberration on chromosome 10 in human oral squamous cell carcinoma.

Recently a tumor suppressor gene, a deleted in malignant brain tumor gene (DMBT1), was detected on chromosome 10. In some types of tumors, the frequent deletion of DMBT1 locus have been reported as well as loss of heterozygosity (LOH) on chromosome 10. However, little is known relating to human oral squamous cell carcinoma (OSCC). To study the genetic aberrations on chromosome 10 in OSCC, we performed polymerase chain reaction (PCR) analysis of microsatellite polymorphisms corresponding to 16 loci, containing 2 DMBT1 loci. We examined 38 oral primary squamous cell carcinoma (SCC) tissues and corresponding normal tissues. Microsatellite instability (MI) was detected at least on 1 of the 16 loci in 15 (39.5%) of 38 cases, and loss of heterozygosity (LOH) at least 1 of the 16 loci was also observed in 28 (73.7%) of 38 cases. LOH was accumulated at D10S202 (34.6%) and D10S217 (28.6%), suggesting the presence of two putative tumor suppressor genes associated with OSCC. The 2 DMBT1 loci, D10S209 and D10S587, had comparatively high frequent LOH (20.0 and 22.7%, respectively), maybe indicating the important role of DMBT1 in OSCC. No significant correlation between histological differentiation and LOH was found. These results suggest that genetic aberrations on chromosome 10 play important roles in the oncogenesis of OSCC.

Carcinoma, Squamous Cell↗

[The autonomic nervous activity of hypertension].

Autonomic nervous function was evaluated by means of power spectral analysis of heart rate variability in hospitalized patients with different circadian blood pressure(BP) variation, i.e., dipper(n = 33), non-dipper(n = 37), extreme dipper(n = 26) and riser(n = 20). Ambulatory BP monitoring was performed by A & D TM2425 based on a cuff-oscillometric method. Circadian BP variation was defined in these subjects. The non-dipper, extreme dipper and riser subjects were defined as those whose nocturnal decrease in systolic BP was less than 10%, more than 20% and elevation of BP, as compared to the daytime BP, respectively. Power spectral analysis of hourly R-R intervals for 24 hours was done to obtain the low frequency power(LF, 0.04 to 0.15 Hz) and high frequency power(HF, 0.15 to 0.40 Hz). LF/HF ratio was considered to be an index of sympathetic nervous activity, and HF parasympathetic nervous activity, respectively. LF/HF was significantly lower in both riser and non-dipper than that in dipper subjects throughout the day. In non-dipper day-night difference of HF was smaller than in dipper and extreme dipper groups. These findings indicated that riser and non-dipper hypertensives were characterized by decreased physiological circadian fluctuation of autonomic functions when compared to dipper subjects. The circadian variation of BP may be mediated at least in part by circadian variation of autonomic nervous system activity.

Adult↗

Effects of Ca2+ antagonists on motor activity and the dopaminergic system in aged mice.

We investigated the effects of the Ca(2+) antagonist nilvadipine on the dopaminergic system and motor activity in aged mice, in comparison with an other Ca(2+) antagonist, amlodipine. Furthermore, we examined the close correlation between the dopaminergic system and motor activity during the aging process. Striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents were measured in 2-, 4-, 8-, 18- and 36-week-old mice. Behavioral tests (pole and catalepsy test) were performed with 4- and 36-week-old mice. Nilvadipine or amlodipine was administered intraperitoneally twice a day for 3 consecutive days to 30-36-week-old mice. The striatal dopamine, DOPAC and HVA contents were examined and behavioral tests were performed 1h after the last injection of each Ca(2+) antagonist. The dopamine, DOPAC and HVA contents in 2-week-old mice were significantly decreased in the striatum, as compared with 4-week-old animals. Thereafter, age-related increases in the dopamine, DOPAC and HVA contents were observed from 4 to 18 weeks old. However, in 36-week-old mice, the dopamine and DOPAC contents were reduced in the striatum, as compared with 18-week-old animals. Age-related decreases in motor function between 5- and 36-week-old mice were observed in both pole test and catalepsy tests. On the other hand, nilvalipine treatment produced a significant and dose-dependent increase in the striatal dopamine and DOPAC contents in 30-36-week-old mice. In contrast, no significant changes were observed in the striatal dopamine content in amlodipine-treated mice, although this drug showed a significant and dose-dependent increase in the striatal DOPAC and HVA content. In our behavioral study, nilvadipine also showed a significant and dose-dependent inhibition against motor deficits in 30-36-week-old mice. In contrast, amlodipine showed no significant effect on motor deficits in 30-36-week-old mice. The present study demonstrated that nilvadipine has a protective effect against the deficits in both the striatal dopaminergic system and motor activity in aged mice. Our study also suggested that the beneficial effect of nilvadipine against motor abnormalities may be mediated by a protective effect against the reduced activity of the dopaminergic system in aged mice. These results suggested that nilvadipine may offer a new approach for the treatment of hypobulia in aged humans.

3,4-Dihydroxyphenylacetic Acid↗

Relationship between personality and self-measured blood pressure value at home: the Ohasama study.

We conducted a cross-sectional community survey in northern Japan to assess the relationship between personality and home blood pressure value. The Japanese version of the short-form Eysenck personality questionnaire was used to assess personality. A total of 999 people selected from the general population participated. We showed that the personality extroversion score positively affected the systolic blood pressure value, whereas no significant relationship was observed between personality psychoticism or neuroticism and blood pressure value. This study is the first to clarify the relationship between personality assessed by the Eysenck personality questionnaire and blood pressure measured in a non-medical setting. When physicians investigate the pathogenesis of essential hypertension, they should take psychological factors into consideration, as well as the many environmental and genetic factors.

Blood Pressure↗

RT-PCR amplification of RNA extracted from formalin-fixed, paraffin-embedded oral cancer sections: analysis of p53 pathway.

We present a new approach towards the detection of the mRNAs in formalin-fixed, paraffin-embedded samples using a reverse transcriptase (RT)-polymerase chain reaction (PCR). The total RNAs were extracted from 10-micron-thick sections and were reverse-transcribed, then the RT-products were subjected to PCR amplification of GAPDH mRNA for screening the mRNA degradation. Next, nested PCR was performed for examining the expression of p53-related genes, p21WAF1, MDM2, p33ING1 and p14ARF. GAPDH mRNA expression was detectable in 12 out of 21 oral squamous cell carcinoma (SCC) samples. p21WAF1 mRNA expression was detectable in 5 out of 12 SCC samples, MDM2 mRNA expression was detectable in 5 our of 12 SCC samples and p33ING1 mRNA expression was detectable in 6 out of 12 SCC samples. However, the expression of p14ARF mRNA was not detectable in any of the samples. Seven out of 12 oral SCC samples showed abnormal nuclear accumulation of p53 protein by immunohistochemical staining, whereas 5 out of 12 oral SCCs showed negative staining for p53 protein. Of of p33ING1 mRNA. One of these was a verrucous carcinoma in which the p53 gene products might be inactivated by the oncoprotein E6 of human papilloma virus. Thus, the p53 tumor suppressor pathway was disrupted in most oral SCCs at the cellular levels, due to either an abnormality in p53 itself or loss of expression of p53 regulatory factors. This method would assist in making diagnosis, determining therapeutic strategy and predicting the prognosis of various cancers including oral SCCs.

Animals↗