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Biomedical subjects

Yutaka Imai

Publications and source records attributed to Yutaka Imai.

At least 91 records · Page 5Linked to original sources

Diffuse cavernous hemangioma of the rectum: report of a case.

Cavernous hemangioma of the rectum (CHR) is an uncommon benign vascular lesion, which mainly affects young adults. The rectosigmoid area is the most common site of cavernous hemangioma in the gastrointestinal tract. CHR is often misdiagnosed due to a lack of knowledge of the clinical features. We report a case of CHR, focusing on the clinical features, diagnostic procedures used, and treatments given. This patient was finally treated effectively with abdominoperineal resection. Thorough preoperative imaging is necessary to confirm the diagnosis and evaluate both the site and extent of the hemangioma. Magnetic resonance imaging (MRI) provides information about the dimensions of the tumor and involvement of the adjacent structures with its high resolution and multiplanar capability, without the use of contrast medium. Moreover, endorectal surface coil MRI depicts the five separate layers of the bowel wall and internal and external sphincter more clearly than the conventional body coil MRI.

Female↗

Vasopressin-independent renal urinary concentration: increased rBSC1 and enhanced countercurrent multiplication.

BACKGROUND: A close association between the expression of the sodium transporter, rat bumetanide sensitive cotransporter (rBSC), in thick ascending limb of Henle and urinary concentration has been reported. However, direct evidence for this association and the mechanism of rBSC1 expression are still to be elucidated. METHODS: Brattleboro (BB) rats weighing approximately 200 g were dehydrated by water restriction for 4 hours, which induced around a 5% body weight reduction. Although plasma arginine vasopressin (AVP) was undetectable even after the water restriction, BB rats concentrated urine from 182 +/- 23 (mean +/- SD) at baseline to 404 +/- 65 mOsm/kg. H2O. RESULTS: Urinary volume was reduced from 5.8 +/- 1.8 to 1.4 +/- 0.6 mL/h. This treatment significantly increased sodium and urea accumulation in the renal medulla and reduced urinary sodium excretion. rBSC1 signals for both mRNA and protein were increased in dehydrated rats, although aquaporin type 2 (AQP2) expression was not enhanced in dehydrated BB rats. Subcutaneous infusion of desmopressin acetate (DDAVP) intensified rBSC1 signals of BB rats more than those in dehydrated condition. CONCLUSION: Dehydration increased rBSC1 expression and enhanced countercurrent multiplication even in AVP deficiency. These results supply strong evidence for the association between rBSC1 expression and urinary concentration, and indicate the presence of an AVP-independent mechanism for urine concentration.

Animals↗

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy.

BACKGROUND: Renal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated. METHODS: Li nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined. RESULTS: Rats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 +/- 11 (mean +/- SD) at baseline to 450 +/- 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved. CONCLUSIONS: Our results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function.

Animals↗

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

The issue of how far blood pressure (BP) should be lowered to achieve the greatest reduction in the risk of cardiovascular disease has been a matter of scientific debate. Although a few trials tried to answer this question, they failed to convincingly show the optimal target BP level, in part because of poor reproducibility and wide variability of conventional casual BP measurement used in these trials. On the other hand, in Japan, calcium antagonist (Ca-A) and angiotensin converting enzyme inhibitor (ACE-I) have been two major medications of initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also used now widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medication can give the greatest benefit in terms of reduced cardiovascular disease risk in the Japanese hypertensive patients.

Adult↗

The influence of one-year treatment by angiotensin converting enzyme inhibitor on baroreflex sensitivity and flow-mediated vasodilation of the brachial artery in essential hypertension--comparison with calcium channel blockers.

BACKGROUND: Both baroreflex sensitivity and flow-mediated vasodilator function have been recognized to have prognostic significance in cardiovascular diseases. Long-term antihypertensive treatment effects on these parameters, however, remain unclear. SUBJECTS AND METHODS: We examined the effects of long-term treatment by angiotensin converting enzyme inhibitors (ACEI) orcalcium channel blockers (CCB) on baroreflex and flow-mediated vasodilator function in patients with essential hypertension (EH). We recruited 36 patients aged 56 +/- 11 years, with systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg. Patients were assigned either to treatment by long-acting ACEI (n = 12) or CCB (n = 24). All patients were followed for 12 months. Optimal BP was achieved by two optional increases in treatment: dose-doubling of the primary drug during the first three months and the addition of diuretics or beta-blockers thereafter. Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg. Baroreflex sensitivity was examined by spectral analysis of blood pressure and RR interval variabilities before treatment and after 3 and 12 months of treatment. The flow-mediated vasodilator function was determined before and 12 months after treatment by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. RESULTS: Baseline blood pressures were similar between the ACEI and CCB groups (172 +/- 5/103 +/- 2 vs. 172 +/- 4/101 +/- 3 mmHg). Blood pressures after 3 and 12 months of treatment also did not differ between the ACEI and CCB groups (149 +/- 4/91 +/- 2 vs. 145 +/- 2/85 +/- 2 mmHg, and 133 +/- 5/84 +/- 2 vs. 133 +/- 2/81 +/- 2 mmHg, respectively). Baseline baroreflex sensitivity was similar between the groups (6.7 +/- 0.8 vs. 5.9 +/- 0.6 msec/mmHg). This parameter remained unchanged at three months but increased after 12 months of treatment in both the ACEI (9.5 +/- 1.6 msec/mmHg, p = 0.05) and CCB (9.1 +/- 1.2 msec/mmHg, p = 0.006) groups. Percent increases in brachial arterial diameter and flow during reactive hyperemia increased in the group treated with ACEI (12.4 +/- 3.5 vs. 25.8 +/- 6.3% and 618 +/- 72 vs. 953 +/- 166, p < 0.05 for both) but both parameters remained unchanged in the group treated with CCB. CONCLUSION: These data suggest that long-term blood pressure control with modem antihypertensive drugs improves baroreflex function. Treatment with ACEI may be more favorable for flow-mediated vasodilator function than treatment with CCB.

Aged↗

Therapeutic effects of evening administration of guanabenz and clonidine on morning hypertension: evaluation using home-based blood pressure measurements.

OBJECTIVE: To clarify the effects of bedtime administration of the centrally acting alpha(2)-agonists, guanabenz and clonidine, on morning hypertension. METHODS: Patients with morning hypertension were assigned to receive once-daily evening administration of guanabenz (2 mg/day, n = 81; 4 mg/day, n = 2) or clonidine (75 microg/day, n = 40; 150 microg/day, n = 10) for 4 weeks, and the blood pressure (BP)-lowering effects of these drugs in the morning and evening were evaluated by assessing self-monitored BP in the home environment. The subjects were then subdivided into different groups according to their evening BP, and the effects of guanabenz and clonidine on evening BP were evaluated further for each group. In addition, as a substitute for the trough/peak ratio, the evening/morning (E/M) ratio was calculated to assess the duration of action of the two alpha(2)-agonists. RESULTS: Evening dosing with guanabenz or clonidine lowered morning BP significantly. Both drugs decreased evening BP in the subgroup of subjects with a high evening BP, but not in those with a normal evening BP. The individual E/M ratios for guanabenz, but not for clonidine, were significantly greater in those with a high evening BP than in those with a normal evening BP. In the early treatment period, treatment with guanabenz resulted in a higher diastolic E/M ratio in those subjects with a high evening diastolic BP than did treatment with clonidine. CONCLUSION: The results suggest that evening administration of the central alpha(2)-agonists guanabenz and clonidine effectively suppresses the morning BP elevation in treated hypertensive patients.

Aged↗

Heart rate measurement and outcome.

Previous studies on the predictive value of heart rate and heart rate variability for the risk of cardiovascular disease remains controversial. Since heart rate is known to be variable with several physical and mental stresses, the inconclusive nature of previous studies might reflect the difference in accuracy and reproducibility of the heart rate measurement. In the Ohasama study, which has been conducted since 1985 in the northern part of Japan, home measurements and ambulatory monitoring of heart rate as well as blood pressure were examined with special reference to cardiovascular mortality. Heart rate measured at home and averaged for 21 days was shown to be linearly associated with cardiovascular mortality, while heart rate variability (standard deviation of daytime ambulatory heart rate measured every 30 min) inversely correlated with cardiovascular mortality. In conclusion, heart rate and heart rate variability must not be overlooked when evaluating hypertension.

Blood Pressure↗

An international database of prospective ambulatory blood pressure monitoring studies.

An international database of prospective studies of ambulatory blood pressure monitoring was set up in 2001, and will include at least eight individual studies. The goals are to enable analyses that cannot be made reliably from the individual studies, such as the predictive value of different measures of blood pressure, for example the morning surge and blood pressure variability, the ability to look at the prediction of specific endpoints, for example stroke versus myocardial infarction, and also to look at differences in different populations.

Blood Chemical Analysis↗

Urinary concentration defect and limited expression of sodium cotransporter, rBSC1, in a rat model of chronic renal failure.

BACKGROUND: Renal urinary concentration is associated with enhanced expression of sodium cotransporter (rBSC1) in thick ascending limb of Henle. Overexpression of rBSC1 was reported recently in hypertrophied nephrons after unilateral nephrectomy (UNX) and in kidney isografts. Since urinary concentration defect and hypertrophy of residual nephrons are major manifestations of chronic renal failure (CRF), we investigated the rBSC1 signals for RNA and protein in a rat model of CRF. METHODS: Rats underwent 5/6 nephrectomy and examined 8 weeks after operation. rBSC1 mRNA was examined by competitive PCR and in situ hybridization, and rBSC1 protein signals by western blotting and immunohistochemistry. Rats that underwent sham-operation, UNX, or 5/6 nephrectomy followed by a 3-week recovery period (acute renal failure), were used as control. Water intake was restricted for 24 h in subgroups of control and CRF rats. RESULTS: Microscopic examination showed hypertrophy of residual nephrons in both UNX and CRF rats. Signals for rBSC1 mRNA and protein were enhanced at basal condition only in rats with UNX. Under basal conditions, CRF rats demonstrated low urinary osmolality in spite of high plasma arginine vasopressin levels. Water restriction resulted in increased signals for rBSC1 mRNA and protein and concentration of urine in sham-operated rats, but such increases were absent and urinary concentration was incomplete in CRF rats. CONCLUSIONS: Compensatory overexpression and upregulation of rBSC1 expression in response to dehydration are both absent in CRF rats. These limitations are thought to be the underlying mechanisms of urinary concentrating defect seen in CRF.

Animals↗

A/C1166 gene polymorphism of the angiotensin II type 1 receptor (AT1) and ambulatory blood pressure: the Ohasama Study.

We previously investigated the relation between hypertension and each of three major genetic polymorphisms in the renin-angiotensin (AGT)-aldosterone system (R-A-A), AGT M235T, angiotensin convert enzyme (ACE) I/D, and CYP11B2 -344C/T, by means of ambulatory blood pressure (ABP) monitoring in a general Japanese population (the Ohasama Study). A/C1166 gene polymorphism in the 3' untranslated region of the angiotensin II type 1 receptor (AT1) gene is the final remaining major target in R-A-A to be examined in the Ohasama Study population. In the present study, the AT1 A/C1166 polymorphism was genotyped by the TaqMan polymerase chain reaction (PCR) method or restriction fragment length polymorphism (RFLP) in 802 Japanese subjects aged 40 and over, who were previously genotyped for the AGT M235T, ACE D/I, CYP11B2 -344C/T polymorphisms. The AA genotype, AC genotype, and CC genotype were present in 678 (84.5%), 121 (15.1%), and 3 (0.4%) of subjects, respectively. Since the frequency of the C allele was quite low (0.079), the genotypes were classified according to the presence or absence of the C allele. Although daytime blood pressure (BP) was higher in subjects with the C allele, the difference was not statistically significant after adjusting for age, gender, body mass index, and smoking status. No significant difference was noted in the prevalence of cardiovascular diseases or nocturnal BP decline between the two groups. These results indicated that AT1 A/C1166 polymorphism was not associated with any clinical parameters associated with hypertension or atherosclerosis in the Japanese population.

Aged↗

T+31C polymorphism (M235T) of the angiotensinogen gene and home blood pressure in the Japanese general population: the Ohasama Study.

The angiotensinogen (AGT) gene polymorphism M235T (a methionine to threonine amino acid substitution) has been investigated in association with essential hypertension (EHT) based on conventional measurement of blood pressure (BP); however, the results have been inconsistent. Recently, we have been conducting lines of genetic analysis on a general population of Ohasama Town in Iwate Prefecture, Japan, who measured their BP at home (Ohasama genetic analysis and home BP project). We here assessed the association between AGT M235T polymorphism and hypertension within the same population (1,245 subjects aged 40 years and over). AGT M235T polymorphism was determined by genotyping the AGT T+31C polymorphism, which has complete disequilibrium with the AGT M235T polymorphism. We defined subjects as hypertensive if they were being treated with antihypertensive medication and/or had home BP values of more than 135 mmHg in systole and/or 85 mmHg in diastole. The genotype frequencies were similar to those in previous Japanese studies. There was no significant difference among the genotypes in home BP values (p = 0.63/0.74 for systolic/diastolic blood pressure) or in prevalence of hypertension (MM: 44.7%; MT: 42.3%; TT: 39.6%; p = 0.61). No difference was noted in the frequency of familial history of hypertension. Pulse pressure, however, was significantly different among the genotypes (p = 0.049), and this association was prominent in the older (age260) population (p = 0.0018), but not noted in the younger population (60 > age > or = 40). In conclusion, the present analysis confirmed the lack of a significant effect of AGT M235T polymorphism on blood pressure level, but the difference in pulse pressure in the older population suggests that further investigations of this polymorphism should be made in the Japanese population.

Aged↗

Japanese society of hypertension (JSH) guidelines for self-monitoring of blood pressure at home.

UNLABELLED: Home blood pressure (BP) measurements are indispensable for the improvement of hypertension management in medical practice as well as for the recognition of hypertension in the population. The Working Group for Establishment of Guidelines for Measurement Procedures of Self-Monitoring of Blood Pressure at Home of the Japanese Society of Hypertension has established standards for all techniques and procedures of home BP measurements. The recommendations are as follows. RECOMMENDATION: 1) Arm-cuff devices based on the cuff-oscillometric method that have been validated officially, and the accuracy of which has been confirmed in each individual, should be used for home BP measurement. 2) The BP should be measured at the upper arm. Finger-cuff devices and wrist-cuff devices should not be used for home BP measurements. 3) Devices for home BP measurement should be adapted to the American Association for Medical Instrumentation (AAMI) standards and the British Hypertension Society (BHS) guidelines. In addition, the difference between the BP measured by the auscultatory method and that measured using the device should be within 5 mmHg in each individual. The home measurement device should be validated before use, and at regular intervals during use. 4) Home BP should be monitored under the following conditions. The morning measurement should be made within 1 h after waking, after micturition, sitting after 1 to 2 min of rest, before drug ingestion, and before breakfast. The evening measurement should be made just before going to bed, sitting after 1 to 2 min of rest. 5) Home BP should be measured at least once in the morning and once in the evening. 6) All home BP measurements should be documented without selection, together with the date, time, and pulse rate. Use of devices with a printer or an integrated circuit memory is useful to avoid selection bias. 7) The home BP in the morning and that in the evening should be averaged separately for a certain period. The first measurement on each occasion should be used for totaling. 8) Home BP values averaged for a certain period indicate hypertension when 135/80 mmHg and over and definite hypertension when 135/85 mmHg and over. Normotension is defined as less than 125/80 mmHg and definite normotension as less than 125/75 mmHg. Home BP measurements based on these guidelines can be considered an appropriate tool for clinical decision-making, and it is hoped that these guidelines will serve to reduce confusion and confirm the place of home BP measurement in clinical practice.

Blood Pressure↗

Genotypes of the betaENaC gene have little influence on blood pressure level in the Japanese population.

The gene for the beta-subunit of the epithelial sodium channel (betaENaC) is one of the most prominent candidate genes being analyzed for an association with human essential hypertension. It is known that a deletion or alteration of PY motif in exon 12 of betaENaC is responsible for Liddle's syndrome. Although the localization of genetic polymorphisms of betaENaC is unique to each population, intensive analysis of individuals of white and African ancestry has demonstrated that genetic variants are localized in exons 8 and 12, with two frequent polymorphisms, G442V in exon 8 and T594M in exon 12. These two mutations are both found in individuals of African ancestry, and might be associated with elevated blood pressure (BP). Previously, we have screened the last two-thirds of exon 12 in the Japanese population, and demonstrated the absence of the T594M mutation and the presence of a novel P592S mutation. In the present study, we further examined the rest of exon 12 and exon 8 in a general population from Ohasama, Japan (the Ohasama Study), using single-strand conformational polymorphism (SSCP) analysis. We screened 803 subjects randomly selected from the representative participants, who measured their home and casual BP. The PCR products presenting a shift in SSCP gels, as well as controls, were directly sequenced by autoanalyzer to identify the mutation. A novel gel shift was noted in exon 12 (n = 8) and sequencing identified a polymorphism at codon Ser 520, leading to no change in amino acid sequence (G77576C TCG-->TCC). In exon 8, all three SSCP variants were heterogynous for V434M (GTG-->ATG), which is coincident with a rare polymorphism in whites. The G442V mutation, however, was absent from the Japanese population. A novel mutation of exon 12 was not associated with a significant difference in clinical features. These results indicate that Japanese people possess three polymorphisms in exon 12, all of which are unique, and one in exon 8. These genetic variants of betaENaC may not influence the BP level of Japanese people.

Aged↗

T+31C polymorphism of angiotensinogen gene and nocturnal blood pressure decline: the Ohasama study.

BACKGROUND: We assessed the association between several polymorphisms of angiotensinogen gene (AGT) and essential hypertension using ambulatory blood pressure (BP). METHODS: We recruited 802 subjects in a rural Japanese community who were aged >40 years and who gave written informed consent for monitoring of their ambulatory BP and genetic analysis (the Ohasama Study). As a polymorphism of AGT, T+31C, which is in complete linkage disequilibrium with M235T, was determined using the TaqMan polymerase chain reaction method. RESULTS: The genotype distribution of AGT/T-+31C in the Ohasama Study was similar to that in another large Japanese population. Although there was no significant difference in 24-h and daytime ambulatory BP values, the nighttime BP was significantly lower in the subjects with TT, resulting in greater decline of nocturnal systolic (P = .090) and diastolic (P = .025) BP in subjects with TT. CONCLUSIONS: AGT/T+31C is associated with the circadian BP variation but not with BP level in the Japanese general population.

Angiotensinogen↗