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Biomedical subjects

K Kohara

Publications and source records attributed to K Kohara.

At least 55 records · Page 3Linked to original sources
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

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↗
PubMed1998

Activity-dependent survival and enhanced turnover of calcium in cultured rat cerebellar granule neurons.

Neurons survive when their activity is maintained. An influential hypothesis on the cellular mechanism underlying this phenomenon is that there is an appropriate range of intracellular Ca2+ concentration ([Ca2+]i) for survival. The rat cerebellar granule neuron in culture serves as the most often used model system for the analysis of activity-dependent survival, since it does not survive unless an excitant (KCl or glutamate) is added to the culture medium. Against the above-mentioned hypothesis, we found in our previous examination no difference between steady-state [Ca2+]i in granule neurons cultured under high KCl (i.e., survival) and low KCl (i.e., death) conditions. In this report, we present the quantitative background of unchanged [Ca2+]i between the two culture conditions. Influx of Ca2+ due predominantly to L-type voltage-dependent calcium channels was higher in high KCl cultures than in low KCl cultures. At the same time, efflux of Ca2+ due to the activity of Ca2+/Na+ antiport was also higher in high KCl cultures. Additionally, we found that the endocytotic activity was greater in high KCl cultures than in low KCl cultures, as monitored by the rate of uptake of horseradish peroxidase added to medium. Since the uptake was blocked by an internal Ca2+ chelator, the increased endocytotic activity in high KCl cultures might be a consequence of the enhanced Ca2+ turnover.

Animals↗
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

Postprandial hypotension: evaluation by ambulatory blood pressure monitoring.

To elucidate whether postprandial hypotension (PPH) is associated with any diurnal change of blood pressure, ambulatory blood pressure monitoring was performed on 121 hospitalized essential hypertensive patients who received standardized meals. Postprandial change in blood pressure was defined as the difference between mean systolic blood pressure (SBP) 1 h before and 2 h after each meal. The postprandial decline of SBP showed age-dependent augmentation. The degree of PPH was significantly related to the level of preprandial blood pressure for each meal. Patients were divided into the following three groups according to the mean PPH of three meals: Normal group (n = 79); mean postprandial decline of SBP <5 mm Hg, PPH-1 group (n = 24); 5 mm Hg ' mean PPH < 10 mm Hg, and PPH-2 group (n = 18); PPH 2 > or = 10 mm Hg. There was no difference in 24-h, nighttime, or daytime blood pressure among the three groups. The prevalence of dipper and nondipper patients was not different among the three groups. However, patients in PPH-2 showed significantly greater daytime and 24-h blood pressure variability. Furthermore, there was a significant positive relationship between the morning surge of SBP and PPH after breakfast (r = 0.36, P < .001). These findings indicate that PPH increases blood pressure variability independently of nocturnal change in blood pressure.

Adult↗
PubMed1998

Alteration of carotid circulation in essential hypertensive patients with left ventricular hypertrophy.

To investigate carotid haemodynamic characteristics in essential hypertensive patients with left ventricular hypertrophy, we evaluated the structure and function as well as blood flow of the common carotid artery by using a combination of B-mode ultrasound and pulsed-Doppler in control subjects (n = 38), and hypertensive patients with (n = 40) and without (n = 27) left ventricular hypertrophy. Hypertensive patients had a higher intima-medial thickness compared with control subjects. Diastolic/systolic flow velocity ratio as well as flow volume ratio was significantly decreased in hypertensive patients with left ventricular hypertrophy in association with decline of distensibility of the common carotid artery. In the hypertensive patients with left ventricular hypertrophy, diastolic/systolic flow velocity ratio as well as flow volume ratio had significant correlation with diastolic blood pressure, pulse pressure and carotid arterial distensibility. These findings indicate that diastolic blood flow in the common carotid artery is impaired in hypertensive patients with left ventricular hypertrophy. Decreased distensibility and low diastolic perfusion pressure may be the underlying mechanisms.

Carotid Arteries↗
PubMed1998

Molecular structure and function of rat platelet-derived growth factor beta-receptor gene promoter.

OBJECTIVE: To understand the regulatory mechanism of platelet-derived growth factor beta-receptor gene expression. METHODS: A 1.7 kb genomic fragment was obtained from a rat genomic library. After we had determined an entire sequence of this fragment, transcription start sites were determined both by primer extension analysis and by riboprobe mapping. We performed a functional promoter assay by using a dual-luciferase reporter system. Progressive 5'-deletions of the fragment and site-directed mutagenesis for the CCAAT motif located at -67 or -94 were used for the assay, and their promoter activities in vascular smooth muscle cells were assessed. Gel-mobility shift analysis was also performed for the CCAAT motif at -67. Effects of the upstream sequence spanning -310 through -120 on heterologous gene promoters were also investigated. RESULTS: Multiple transcription start sites were observed in the 5'-flanking region, and the 1.7 kb sequence was actually active as a functional promoter in vascular smooth muscle cells. Two important sequences responsible for the basal transcriptional activity were identified by the functional promoter assay. One was the CCAAT motif at -67 which acts as a promoter itself, and the other was the upstream region spanning -310 through -210 which positively regulates the basal promoter activity. CONCLUSION: The basal promoter activity of the rat platelet-derived growth factor beta-receptor gene is mainly regulated by the interaction or coordination of two sequences, the CCAAT motif and the upstream control element.

Animals↗
PubMed1998

Beneficial hemodynamic effects of oral prostacyclin (PGI2) analogue, beraprost sodium, on a patient with primary pulmonary hypertension--a case report.

A 65-year-old woman was admitted to our hospital because of exertional dyspnea in 1987. A diagnosis of primary pulmonary hypertension was confirmed by right heart catheterization. She had received conventional therapy in the outpatient clinic. She was readmitted with the deterioration of exertional dyspnea in 1995. Stabilization of pulmonary hemodynamics, while not achieved with conventional therapy, was achieved with additive administration of an oral prostacyclin (PGI2) analogue, beraprost sodium.

Administration, Oral↗
PubMed1998

[An elderly patient with bleeding from the alimentary tract caused by aberrant pancreas of the small intestine].

A 71-year-old woman was admitted to hospital because of malaise and bloody stool. Laboratory findings consistently showed anemia (Hb 9.2 g/dl) and occult blood in the stool. Although barium series and endoscopy of the upper and lower intestinal tructs were carried out, there was no evidence of bleeding from the gastrointestinal tract 99mTcO4- scintigraphy, which was performed to exclude bleeding from Meckel's diverticulum, also did not locate a significant lesion. Angiographic imaging of the superior mesenteric arteries (SMA) was performed to exclude lesions such as small intestine tumors with extraluminal growth and vascular abnormalities such as A-V malformation and it revealed the round encasement of arteries in the peripheral SMA region, strongly suggestive of a small intestine tumor. Surgery was performed and an extraluminally protruding tumor was found in the small intestine. The excised tumor was 4 x 3 x 3.5 cm in size, are was diagnosed histologically as aberrant pancreas. The postoperative laboratory findings showed that the anemia had improved and occult blood was not detected in the stools. Although aberrant pancreas of the small intestine is a common benign tumor, it is a very unusual cause of bleeding from the alimentary tract.

Aged↗
PubMed1997

Activity-dependent survival of rat cerebellar granule neurons is not associated with sustained elevation of intracellular Ca2+.

Ca2+ plays a pivotal role for the activity-dependent survival of neurons. In primary culture of cerebellar granule neurons, we found that there is no significant difference in intracellular Ca2+ level in the survival-promoting condition (cultures in the presence of 25 mM KCl) and that in the apoptosis-inducing condition (cultures in the presence of 5 mM KCl). This was not due to the inactivation of voltage-dependent L-type Ca2+ channels in the survival-promoting condition, but due to the enhanced rate of the influx and the efflux of Ca2+ in the survival-promoting condition compared to that in the apoptosis-inducing condition. These results suggest that the activity-dependent survival of the granule neurons is not associated with sustained rise of intracellular Ca2+ but associated with the enhanced turnover rate of Ca2+.

Animals↗
PubMed1997

Molecular structure and function of rat CCAAT-enhancer binding protein-delta gene promoter.

CCAAT-enhancer binding protein-delta (C/EBP delta) is a transcriptional nuclear factor, and belongs to basic region-leucine zipper class DNA binding proteins. One genomic clone containing a 12-kb sequence of the C/EBP delta gene was isolated from a rat genomic library, and a 2,056-bp fragment containing the 5'-flanking region was characterized. Sequence analysis of this fragment revealed that there were a TATA-like sequence (TAGAAAA) and many transcriptional regulatory elements. The transcription start site of the gene was determined by both primer extension analysis and riboprobe mapping. Both analyses indicated that the transcription start site was located at 31-bp downstream of the TATA-like sequence. Transient transfection experiments showed that the fragment cloned in this study was able to act as a functional promoter in rat vascular smooth muscle cells. The 5'-deletion analysis of this fragment revealed that the sequence spanning -235 through -82, which was designated as an upstream control element (UCE), remarkably increased a basal promoter activity of the C/EBP delta gene, and was also able to act as a promoter by itself. In addition, we also studied effects of the UCE on the heterologous gene promoter including rat alpha-actin gene promoter or SV40 virus promoter. Interestingly, the UCE specifically increased the promoter activity of the rat alpha-actin gene suggesting that the C/EBP delta gene may be positively controlled by the UCE via a cell-type or promoter-type specific manner.

Actins↗
PubMed1997

Asymptomatic cerebrovascular damages in essential hypertension in the elderly.

To investigate the underlying mechanisms of asymptomatic cerebrovascular damage, the diurnal change in blood pressure was evaluated in hypertensive patients with silent cerebral infarction (SCI). Sixty elderly hypertensive patients (age > or = 60 years) were matched with 40 middle-aged patients (age < or = 59 years) for sex and left ventricular mass index (LVMi). Lacunar lesions were evaluated by magnetic resonance imaging as SCI. The presence and the severity of SCI increased with age. In the middle-aged group, the presence of SCI was significantly related to 24-h blood pressure and LVMi evaluated by echocardiography. In elderly patients, the presence of SCI had no relationship with 24-h blood pressure or LVMi. The lowest level of nocturnal diastolic blood pressure showed a J-shaped relationship with the incidence of SCI in the elderly patients. These findings indicate that the hemodynamic characteristics underlying the development of SCI differ between middle-aged and elderly hypertensive patients. A different approach to the treatment of hypertension in the elderly appears necessary.

Aged↗
PubMed1997

Left ventricular hypertrophy precedes other target-organ damage in primary aldosteronism.

To elucidate whether there is a difference in the progression of target-organ damage between primary aldosteronism and essential hypertension, we compared left ventricular hypertrophy and extracardiac target-organ damage in 23 patients with primary aldosteronism and 116 patients with essential hypertension. The severity of hypertensive retinopathy and the renal involvement in primary aldosteronism were subclinical and similar to those in essential hypertension without left ventricular hypertrophy but significantly milder than those in essential hypertension with left ventricular hypertrophy. There was a strongly significant correlation between the degree of left ventricular mass index and the severity of hypertensive retinopathy and renal involvement independent of office blood pressure in essential hypertension. In contrast, left ventricular hypertrophy markedly progressed despite the mild extracardiac target-organ damage in primary aldosteronism. Left ventricular end-diastolic dimension index in primary aldosteronism (3.16+/-0.50 cm/m2) was significantly larger than in essential hypertension without (2.87+/-0.23) and with (2.88+/-0.22) left ventricular hypertrophy. On the other hand, there was no difference in extracardiac target-organ damage between 13 primary aldosteronism patients with eccentric left ventricular hypertrophy and the 26 essential hypertensive patients with eccentric left ventricular hypertrophy. The results suggest that predominantly volume load, be it due to aldosteronism or other mechanisms, resulting in eccentric left ventricular hypertrophy is less likely to cause extracardiac target-organ damage than hemodynamic or nonhemodynamic mechanisms resulting in concentric left ventricular hypertrophy.

Adult↗
PubMed1997

[Evaluation by specialists of the Guidelines on Treatment of Hypertension in the Elderly--the second questionnaire survey].

The Guidelines on Treatment of Hypertension in the Elderly, 1995 was published by the Research Group for Guidelines on Treatment of Hypertension in the Elderly Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare. To assess the guidelines, and to further investigate the changes in the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 133 Japanese hypertension specialists who had replied to the first mailed questionnaire in 1993. We received 102 replies (77%). Overall, the guidelines were scored 4.3/5.0. More than 95% of the specialists agreed with levels of blood pressure (BP) indicative for treatment, as well as the goal of BP control. The guidelines propose that the rate of increase of the drug dose should be very slow, at least every four weeks, and that the target BP be reached after two months. The majority of the specialists agreed with this. However, 10% of them preferred to follow patients every two weeks. The guidelines propose long-acting Ca antagonists and ACE inhibitors as the first choice of drug for the treatment of uncomplicated hypertension in the elderly. Two-thirds of the specialists agreed. However, 17% of specialists proposed adding diuretics or beta-blockers to the first line therapy. Ten specialists (10%) expressed concerns about Ca antagonists and three (3%) insisted on withdrowing them from the first line of drugs. In the guidelines, alpha and beta blockers are designated as relatively contraindicated in elderly patients with hypertension, but half the specialists answered that these drugs can be used safely in elderly patients. These findings indicate that the therapeutic policy of Japanese specialists in hypertension in the elderly has not changed substantially for three years.

Aged↗
PubMed1997

[Mollaret meningitis associated with a high level of cytokines in cerebrospinal fluid].

A 70-year-old man was admitted to our hospital for further evaluation of recurrent fever, which had begun in October 1994. The patient had 5 to 7 days without fever, and then 2 to 3 days of fever. He had headaches during the febrile periods. On admission, he had abnormal pyramidal, extrapyramidal, and celebellar signs, and nuchal rigidity during the febrile period. However, these neurological abnormalities were completely absent during the afebrile period. Examination of cerebrospinal fluid revealed pleocytosis of mononuclear cells. During the febrile period, pleocytosis was associated with high levels of IgG, IL-6, TNF-alpha, and PGE2 in the cerebrospinal fluid. Administration of indomethacin prevented the fever, which suggests that abnormal production of cytokines in the cerebrospinal fluid contributes to fever in Mollaret meningitis.

Aged↗