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K Hiwada

Publications and source records attributed to K Hiwada.

At least 91 records · Page 5Linked to original sources
PubMed1999

The unique 5-flanking region of the human basic calponin gene.

Calponin has been implicated in the regulation of smooth muscle contraction. Basic calponin, one of the calponin isoforms, is expressed exclusively in smooth muscle cell (SMC)-rich tissues, and is considered to be a phenotypic marker of differentiated SMC. To define the molecular mechanism of SMC-specific gene transcription in humans, we isolated and characterized the 5'-flanking region of this gene. Sequence analysis revealed that several putative cis-acting elements were clustered within a 500-bp sequence upstream of the transcription start site. However, the 1.9-kb promoter region obtained herein lacked a completely matched consensus sequence of the CArG box that is commonly identified in the promoter region of other SMC-specific genes. A luciferase assay demonstrated that the 1.9-kb promoter region was sufficient to drive a basal transcriptional activity not only in human vascular smooth muscle cells (VSMC) but also in HeLa cells. In particular, the sequence between positions -1,906 and -867 had a significantly higher transcriptional activity in VSMC than in HeLa cells. In contrast, the promoter activity was drastically decreased between positions -327 and -257 in both types of cells. These results indicate that the sequence spanning from position -327 to -257 contains an essential domain involved in the basal transcriptional activity of the human basic calponin gene, and that the distal region of the 1.9-kb 5'-flanking sequence presented herein may play a pivotal role in the phenotypic modulation of VSMC.

5' Untranslated Regions↗
PubMed1999

Difference in the incidence of cough induced by angiotensin converting enzyme inhibitors: a comparative study using imidapril hydrochloride and enalapril maleate.

To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12 wk (Period I) followed by enalapril for 12 wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p < 0.001). During Period I, decrease in blood pressure was observed in 63.9% (115/180) of Group IE and 64.6% (115/178) of Group EI patients. In approximately half of the patients in Group EI who developed cough during Period I and in whom the treatment was subsequently switched to imidapril, cough subsequently disappeared. It was concluded that the incidence of cough was significantly less under imidapril than under enalapril treatment, while there was no difference in the antihypertensive effects of the two ACE inhibitors.

Administration, Oral↗
PubMed1999

Low wall shear stress contributes to atherosclerosis of the carotid artery in hypertensive patients.

Numerous in vitro studies have indicated that low shear stress may contribute to intimal thickening and development of atherosclerosis. In the present study, we investigated wall shear stress in hypertensive patients and its relevance to atherosclerosis in the carotid arteries by means of a non-invasive technique. Fifty-five hypertensive patients and 23 normotensive controls were investigated. Intima-media thickness, number of plaques, internal dimension and blood flow velocity of the carotid artery were evaluated. Wall shear stress was calculated using the Poiseuillean parabolic model of velocity distribution as follows: shear stress = 4 X blood viscosity X central line flow velocity/internal dimension. Hypertensive patients showed increased intima-media thickness and dilated common carotid arterial dimension relative to normotensive controls. There was no difference in blood viscosity between the two groups. Both the mean shear stress and systolic peak shear stress were significantly lower in hypertensive patients than normotensive controls. Further, wall shear stress at both mean and peak velocity was significantly and negatively related to intima-media thickness and number of plaques in hypertensive patients, as well as in the total study population. These findings indicate that structural and functional alterations in the common carotid artery of hypertensive patients further precipitates atherosclerosis through low shear stress.

Aged↗
PubMed1999

Serum creatinine level underestimates hypertensive renal involvement in elderly patients with essential hypertension.

It is well recognized that serum creatinine level provides a quick general assessment of renal function. However, we frequently encounter elderly hypertensive patients with renal involvement whose serum creatinine levels are within normal limits. The aim of this study was thus to determine whether serum creatinine level is a sensitive indicator of renal function in elderly hypertensive patients. Study groups were classified according to age: 82 elderly patients (aged 65 yr or older) and 98 middle-aged patients (aged 40-65 yr) with essential hypertension. To assess hypertensive renal involvement, serum creatinine and serum uric acid levels were measured. We also measured the left ventricular mass (LVM) index by using echocardiography as a marker of hypertensive target organ damage. There was no age-related difference in the LVM index, but the serum creatinine level in elderly hypertensive patients was significantly lower than that in middle-aged hypertensive patients. There was no significant difference in serum uric acid level between the two groups. In addition, the LVM index was correlated with the serum uric acid level (r = 0.46, p = 0.0001) but not with the serum creatinine level in elderly hypertensive patients. In middle-aged hypertensive patients, the LVM index was related to both serum uric acid level (r = 0.41, p = 0.007) and serum creatinine level (r = 0.43, p = 0.003). In conclusion, serum creatinine level may underestimate hypertensive renal involvement in elderly hypertensive patients. In contrast, serum uric acid level may be a sensitive indicator of hypertensive target organ damage irrespective of age.

Adult↗
PubMed1999

[Multicenter prospective survey of prognosis of hypertensive elderly outpatient under antihypertensive treatment--morbidity and mortality of cardiovascular diseases and cancer].

Although calcium-channel blockers and angiotensin-I-converting enzyme inhibitors are often used for treatment of hypertension in the elderly in Japan compared to those in the United States and in European countries, there have been few investigations on the prognosis of the elderly receiving these antihypertensive treatments. The Research Group for "Guidelines on the Treatment of Hypertension in the Elderly" collaborated with the Comprehensive Research Projects on Aging and Health group of the Ministry of Health and Welfare of Japan in performing a 3-year survey on the outcome of 700 hypertensive elderly outpatients (> or = 60 years) receiving treatment of antihypertensive drugs. Antihypertensive drugs including dihydropyridine-type calcium channel blockers, beta blockers, angiotensin-I-converting enzyme inhibitors, diltiazem, diuretics and old-type antihypertensives (hydralazine, budralazine, and centrally acting drugs such as clonidine, methyldopa and guanabenz) were administered to 71.3%, 30.4%, 26.2%, 14.0%, 8.6%, and 6.4% of the 642 elderly patients surveyed for three years, at the time of registration, respectively. Morbidity and mortality rates of total cerebro-cardiovascular diseases, stroke, and heart diseases, were 27.6 and 7.81/1,000 patient-years, 15.1 and 3.6/1,000 patient-years, 10.4 and 4.2/1,000 patient-years, respectively. These results were similar or even better than those of megatrials of antihypertensive treatments for elderly patients in Europe and United States. After adjustment for potential confounding factors, multiple logistic analysis revealed that a past history of ischemic heart disease, use of the old-type antihypertensive drugs, male gender, and diastolic high blood pressure were independent risk factors for the morbidity of cerebro-cardiovascular diseases taking the group of non-cerebro-cardiovascular disease as the reference group. We also identified 22 cases of newly occurred malignancies including 7 fatal cases. However, none of the antihypertensives was significantly related to the occurrence of malignancies. These results lead support to the tendencies in the use of antihypertensive drugs in Japan.

Aged↗
PubMed1999

Adriamycin activates E-cadherin-mediated cell-cell adhesion in human breast cancer cells.

E-cadherin-mediated cell-cell adhesion plays a crucial role in intercellular communication, which is related to the regulation of cell proliferation, differentiation, and apoptosis. Our previous study showed that decreased expression of MUC1 can induce E-cadherin-mediated cell-cell adhesion in human breast cancer cell lines proliferating in suspension without aggregation. Using such a cell line (YMB-S), we observed the effects of an anticancer agent, adriamycin, on cell-cell adhesion and expression of E-cadherin-catenin complex and MUC1. The cells showed E-cadherin-mediated cell-cell adhesion after 48 h exposure to 0.4 micromol/l adriamycin. And in these cells, expression of E-cadherin and beta-catenin mRNA obviously began to increase, while expression of MUC1 mRNA decreased, as demonstrated by Northern blot analysis. Such change in mRNA levels were followed by increases in E-cadherin and beta-catenin protein levels and a decrease in MUC1 protein level. Though expression of alpha-catenin mRNA began to increase on day 2, its protein level did not change. In immunohistochemical analysis, beta-catenin protein in untreated cells showed diffuse cytoplasmic localization, whereas beta-catenin in treated cells was present in cytoplasm with a clear submembranous localization, indicating that increased beta-catenin mainly bound with E-cadherin, participating in cell-cell adhesion. These findings show for the first time that adriamycin can induce E-cadherin-mediated cell-cell adhesion by increasing expression of E-cadherin and beta-catenin and decreasing expression of MUC1 during breast cancer cell apoptosis induced by this drug.

Antineoplastic Agents↗
PubMed1999

Serial changes in sarcoplasmic reticulum gene expression in volume-overloaded cardiac hypertrophy in the rat: effect of an angiotensin II receptor antagonist.

This study was designed to clarify whether gene expression in the cardiac sarcoplasmic reticulum [sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, ryanodine receptor and calsequestrin] changes in accordance with left ventricular functional alterations in the volume-overloaded heart. Further, the effect of the angiotensin II type 1 receptor antagonist, TCV-116, on the expression of these genes was also evaluated. Left ventricular fractional shortening was significantly increased at 7 days, had returned to control levels at 21 days, and had significantly decreased at 35 days after the shunt operation, compared with sham-operated rats. The level of SERCA mRNA was significantly decreased at both 21 days and 35 days after the shunt operation. The levels of ryanodine receptor and phospholamban mRNAs were significantly decreased at 35 days in shunt-operated rats. The decrease in the SERCA mRNA level preceded the development of cardiac dysfunction. The levels of SERCA and ryanodine receptor mRNAs were correlated positively with left ventricular fractional shortening (r=0.73, P<0.0001 and r=0.61, P<0.01 respectively). Attenuation of the decrease in left ventricular fractional shortening occurred on treatment with TCV-116. After the treatment with TCV-116, the levels of SERCA and phospholamban mRNAs were restored to the respective values in sham-operated rats. Ryanodine receptor mRNA levels remained unchanged after treatment with TCV-116. These results indicate that the down-regulation of SERCA and ryanodine receptor mRNA levels may be related to cardiac dysfunction in the volume-overloaded heart. In addition, treatment with an angiotensin II receptor antagonist may restore the altered sarcoplasmic reticulum mRNA levels to control levels, and this may result in attenuation of the functional impairment in the volume-overloaded heart.

Angiotensin II↗
PubMed1999

Effects of benidipine hydrochloride on 24-hour blood pressure and blood pressure response to mental stress in elderly patients with essential hypertension.

OBJECTIVE: The effects of a new dihydropyridine calcium antagonist, benidipine hydrochloride, on 24-hour blood pressure and blood pressure response to mental arithmetic test were investigated. SUBJECTS: Ten elderly patients with essential hypertension (mean age: 65+/-4 years; 7 male and 3 female). METHOD: After a control period of 4 weeks, 4 mg benidipine was administered once daily in the morning for 12 weeks. Ambulatory blood pressure was monitored using a non-invasive automatic portable device with the cuff-oscillometric method at the end of both the control and treatment periods. RESULTS: Benidipine administration significantly decreased 24-hour blood pressure, while little change was noted in heart rate. Daytime blood pressure decreased significantly, from 148.2+/-11.5/90.8+/-8.8 to 133.8+/-9.2/82.5+/-10.8 mmHg. However, no significant decrease in nighttime diastolic blood pressure was noted, and the decrease in nighttime systolic blood pressure was small (from 129.8+/-9.9/77.1+/-7.6 to 121.8+/-10.1/74.7+/-9.1 mmHg). No significant changes were observed in diurnal variability of blood pressure and heart rate. The decrease in systolic blood pressure by benidipine administration showed a significant positive correlation with systolic blood pressure before treatment in the 24-hour and daytime periods. Single cosinor analysis showed that benidipine administration significantly decreased MESOR of both systolic and diastolic blood pressure, without an increase in amplitude. Both systolic and diastolic blood pressure during mental arithmetic test were significantly decreased after treatment with benidipine, and the increase in systolic blood pressure induced by mental arithmetic test was also significantly attenuated. CONCLUSIONS: These findings indicate that administration of benidipine once daily in the morning effectively decreases blood pressure and attenuates blood pressure response to mental stress. Neither reflex tachycardia, deterioration of diurnal blood pressure change, nor excessive lowering of nighttime blood pressure was observed after benidipine administration. It is suggested that benidipine is a potent and long-lasting calcium antagonist which may be useful for the treatment of elderly hypertensive patients with cardiovascular disease.

Administration, Oral↗
PubMed1999

Apoptosis and Bcl-xs in the intimal thickening of balloon-injured carotid arteries.

We performed balloon injury in the rat carotid artery and identified intimal thickening after injury. Balloon-injured carotid arteries showed maximum thickness of the neointima on the 14th day before complete endothelial cell regeneration. In this lesion we identified apoptosis of vascular smooth muscle cells (VSMCs) by in situ DNA labelling and electron microscopy in the neointima on the 14th day after injury. mRNA expression levels of bcl-2, bax, bcl-x, p53 and caspase-1 were determined by the reverse transcriptase-polymerase chain reaction method both in injured and uninjured carotid arteries. Neither bcl-2 nor bcl-xl mRNA expression was detected in either injured or uninjured arteries, whereas bax and p53 mRNA expression was identified and their mRNA levels were not altered after balloon injury. In contrast, both bcl-xs and caspase-1 mRNA was detected and was markedly induced only in the injured carotid artery. Positive staining for immunoreactive Bcl-x was observed specifically in the injured arterial wall and co-localized with positive staining of nuclei identified by in situ DNA labelling. We conclude that two opposite cellular responses, VSMC proliferation and apoptosis, exist together in the neointima of the rat carotid artery after balloon injury, and selective induction of Bcl-xs expression is a key regulator of VSMC apoptosis in the process of vascular remodelling.

Angioplasty, Balloon↗
PubMed1999

[Comparison with other antihypertensive drugs, especially with ACEI].

In this review angiotensin II receptor antagonists (Angiotensin antagonists are discussed on the efficacy and safety in the treatment of essential hypertension. Angiotensin antagonists are more complete renin angiotensin system blockade, and are potent as ACE inhibitors, but they have rarely troublesome dry cough specific to ACE inhibitors. Angiotensin antagonists have demonstrated an excellent tolerability profile. Angiotensin antagonists will have potentially greater protection from end-organ damage, since they have provided end-organ protection in animal experiments. These agents will be considered for first-line therapies in very near future.

Angiotensin Receptor Antagonists↗
PubMed1999

Contribution of non-cardiomyocyte apoptosis to cardiac remodelling that occurs in the transition from compensated hypertrophy to heart failure in spontaneously hypertensive rats.

Various alterations in molecular and cellular events have been considered as possibly contributing to the cardiac remodelling that occurs during the transition from compensated hypertrophy to heart failure. The aim of the present study is to clarify (1) whether cardiac apoptosis occurs during the transition from compensated hypertrophy to decompensated heart failure, and (2) whether expression of the genes encoding Bax (an apoptosis inducer) and Bcl-xL and Bcl-2 (apoptosis inhibitors) is altered during this transition. We used 12-month-old and 20-month-old male spontaneously hypertensive rats (SHR(12) and SHR(20) respectively) and age-matched Wistar-Kyoto rats (WKY(12) and WKY(20) respectively). These rats were killed after measurement of haemodynamic parameters by transthoracic echocardiography and use of a tipmanometer via the right carotid artery. The expression of bcl-2, bcl-xL and bax was analysed by Northern blotting. Samples were also fixed in 4% paraformaldehyde for in situ nick end-labelling (TUNEL) methods and immunohistochemistry. SHR(12) had well compensated left ventricular hypertrophy with normal fractional shortening and normal end-systolic wall stress. In contrast, the hearts of SHR(20) developed decompensated dilatation, with a decrease in fractional shortening and an increase in end-systolic wall stress. TUNEL-positive cells were seen exclusively in the hearts of SHR(20). The major cell types that showed TUNEL-positive nuclei were non-cardiomyocytes. The expression of bax remained unchanged during the transition to heart failure. However, there was increased expression of bcl-xL in the failing stage, whereas the expression of bcl-2 remained unchanged. Immunohistochemical studies revealed that Bcl-xL protein was up-regulated in the hearts of SHR(20). In conclusion, non-cardiomyocyte apoptosis may play a contributory role in the remodelling that occurs in the transition from compensatory hypertrophy to decompensated heart failure. In addition, it is suggested that enhanced expression of bcl-xL plays an important role in the preservation of cardiomyocytes during this transition.

Animals↗
PubMed1999

Hypertrophic cardiomyopathy with mid-ventricular obstruction and splenic infarction associated with paroxysmal atrial fibrillation: a case report.

A 54-year-old woman had been treated for hypertrophic cardiomyopathy and paroxysmal atrial fibrillation since 1992. She was admitted with paroxysmal atrial fibrillation which was resolved by medical treatment. However, on the next day, left lateral chest pain appeared. Computed tomography disclosed a low density area in the spleen. She received anticoagulant therapy under a diagnosis of splenic infarction, and the pain disappeared. Echocardiography showed hypertrophic cardiomyopathy with mid-ventricular obstruction. She was treated with cibenzoline to prevent paroxysmal atrial fibrillation attack and attenuate the hemodynamic load. After treatment, the pressure gradient decreased from 41 to 7 mmHg. This patient with hypertrophic cardiomyopathy suffered a rare isolated splenic infarction associated with paroxysmal atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed1998

Platelet-derived growth factor induces apoptosis in vascular smooth muscle cells: roles of the Bcl-2 family.

Apoptosis (programmed cell death) is observed in vascular smooth muscle cells (VSMC) in atherosclerotic lesions and stenotic lesions after injury, and modulates the cellularity of these lesions. It is recognized that cell growth and apoptosis are two linked processes. Platelet-derived growth factor (PDGF) induces VSMC proliferation and migration in vitro. We studied the effect of PDGF on apoptosis in VSMC. Cultured rat VSMC were treated with PDGF-AA or PDGF-BB. PDGF-BB induced cell death in cultured VSMC in a time- and dose-dependent manner, but PDGF-AA did not. Gel electrophoresis of genomic DNA and in situ DNA labeling confirmed that the cell death induced by PDGF-BB is apoptosis. PDGF-BB treatment reduced bcl-2 mRNA and bcl-xl mRNA expression, in contrast, induced bcl-xs mRNA expression, linked with the induction of apoptosis in cultured VSMC.

Animals↗
PubMed1998

Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines.

Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our laboratory. They proliferated in suspension culture without aggregation in a complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced cell-cell and cell-surface adhesion. In this study, we explored the mechanism of this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting a role for E-cadherin. However, there were no changes in the expression of E-cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1 than did untreated cells. To examine the possibility that the adhesion of these cells might be induced by decreased MUC1 expression, the level of MUCI expression was directly reduced using an antisense oligonucleotide. The MUC1 antisense oligonucleotide induced cell-cell and cell-surface adhesion of these breast cancer cells, just as NaB did. Our observations indicate that E-cadherin can be functionally suppressed by overexpression of MUC1 but resumes its activity after suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy for cancer therapy.

Blotting, Northern↗