Search PubMed⌕ Search

Biomedical subjects

T Kokubu

Publications and source records attributed to T Kokubu.

At least 55 records · Page 3Linked to original sources
PubMed1990

ES-8891, an orally active inhibitor of human renin.

A newly synthesized orally active renin inhibitor, N-morpholinoacetyl-(1-naphthyl)-L-alanyl-(4-thiazolyl)-L-alanyl (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoyl-n-hexylamide (ES-8891), was found to be a highly potent competitive inhibitor of human renin with an inhibition constant of 1.1 nM. This inhibitor was also active against monkey renin, although there was less inhibition of renin in pig, rabbit, and rat. ES-8891 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. A single oral administration of ES-8891 (10 or 30 mg/kg) to conscious, sodium-depleted marmosets caused a dose-related decrease in plasma renin activity and blood pressure. ES-8891 (30 mg/kg) produced an 80% inhibition of plasma renin activity, which lasted for more than 6 hours. Kidney renin messenger RNA was not significantly changed 6 hours after oral administration of ES-8891 (30 mg/kg). A single oral administration of 240 mg ES-8891 to healthy human volunteers (n = 6) produced a significant inhibition of plasma renin activity (75% inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) with a good correlation of plasma levels of ES-8891. There were no significant changes in blood pressure or heart rate, and no adverse effects were observed. These results suggest that ES-8891 is an orally active human renin inhibitor that may be clinically useful.

Administration, Oral↗
PubMed1990

10-year follow-up of young male patients with mild hypertension.

In 1977, 92 male patients with mild hypertension (persistent diastolic blood pressure between 90 and 104 mmHg) were found from among 1608 men aged between 18 and 40 years old who were employees of an industrial company. Of these, 81 patients were followed-up for 10 years. After that time, blood pressures (BP) of 44.4% of the mild hypertensive patients became normotensive (group N); BP of 22.2% remained mild hypertensive (group M); and BP of 33.4% increased to higher levels than the starting BP (group H). Higher levels of systolic and diastolic BP, a higher incidence of family history of hypertension, a higher voltage of SV1 + RV5 on ECG and a lower concentration of serum triglycerides at the starting point were risk factors for the progression to higher levels of hypertension. Body weights of patients in group H increased significantly during the follow-up period. These results indicate that male mild hypertensive patients with the above-mentioned risk factors should be followed carefully, especially with regard to increased body weights.

Adolescent↗
PubMed1990

Persistent elevation of cardiac enzymes in a patient with hypertrophic cardiomyopathy--with special reference to electrocardiographic, echocardiographic and 201-thallium myocardial scintigraphic findings.

A 17-year-old female patient with hypertrophic cardiomyopathy whose serum cardiac enzymes (creatine phosphokinase = CPK, lactic dehydrogenase = LDH) showed persistent elevation was presented. Percent of CPK-MB and LDH1 in 6-year-follow-up period ranged from 3.2% to 8.5%, and 58.0% to 63.2%, respectively. This finding strongly suggests the existence of a small amount of continuous myocardial necrosis for a long time. The influence of cardiac enzyme release on the heart was assessed by serial checks of electrocardiogram, echocardiogram and 201-thallium myocardial scintigram. In serial checks of electrocardiograms, markedly decreased R wave amplitude ranging between 31% and 47% was observed in II, III, aVF and V3-6. On echocardiograms, asymmetric septal hypertrophy and a narrow left ventricular cavity were observed in all echocardiograms through the follow-up period. But, in most recent apical two-dimensional echocardiograms, hourglass appearance of the left ventricle due to a distinct cavity-formation at the apex was observed. In 201-thallium single photon emission computed tomogram, hypoperfusion area markedly extended in anterior and lateral parts. These changes in electrocardiograms, echocardiograms and 201-thallium myocardial scintigrams seemed to reflect myocardial necrosis. Our case points to a mechanism for hypertrophic cardiomyopathy to change, over time, to dilated cardiomyopathy-like features.

Adolescent↗
PubMed1990

Elevated levels of soluble interleukin-2 receptors in tuberculous pleural effusions.

The levels of soluble IL-2R were measured in pleural fluid from patients with tuberculosis pleurisy. There were significantly elevated soluble IL-2R values in tuberculous pleural fluid as compared with pleural fluid of nontuberculous etiology including malignant, bacterial and transudative pleural effusions. In patients with tuberculous pleurisy, the level of soluble IL-2R in pleural fluid was markedly greater than that in serum. Furthermore, a significant positive correlation was observed between soluble IL-2R levels and adenosine deaminase levels in tuberculous pleural fluid. These findings suggest that elevated levels of pleural fluid soluble IL-2R in tuberculous pleurisy could reflect the local proliferation of activated T-cells and may be clinically useful in the diagnostic procedures for patients with pleural tuberculosis.

Adenosine Deaminase↗
PubMed1990

[Elevated soluble interleukin-2 receptor and interleukin-2 receptor positive cells in carcinomatous pleural effusions].

Soluble interleukin-2 receptor (IL-2R) level and IL-2R positive (IL-2R+) cells were studied in twenty patients with carcinomatous pleural effusions. The mean value of soluble IL-2R level in carcinomatous pleural effusions was 2930 +/- 1722 U/ml and that in sera was 965 +/- 610 U/ml. Soluble IL-2R level in carcinomatous pleural effusions was found to be significantly higher (p less than 0.001) than that in sera of patients with carcinomatous pleural effusions and that in transudates. Serum soluble IL-2R level in patients with carcinomatous pleural effusions was found, to be significantly higher (p less than 0.001) than that in normal controls (264 +/- 70 U/ml). We also studied IL-2R+ cells in pleural fluids and peripheral blood of patients with carcinomatous pleural effusions. The mean percentage of IL-2R+ cells in carcinomatous pleural fluid lymphocytes was 22.8 +/- 17.8%, as compared with 3.0 +/- 2.2% in peripheral blood lymphocytes of normal controls (p less than 0.001). No significant differences were observed among the cell types of lung cancer examined (adenocarcinoma, squamous, small cell and large cell carcinoma) and no correlation among levels of soluble IL-2R and IL-2R+ cell in either pleural fluid or blood. Our results suggest that in patients with carcinomatous pleural effusions, T cell-mediated active immune mechanisms (IL-2/IL-2R system) against cancer cells are more active in pleural fluid than in peripheral blood.

Adult↗
PubMed1989

Effect of oral potassium on urinary kallikrein excretion in essential hypertension.

Urinary kallikrein and potassium were excreted in parallel in not only static but also dynamic sodium states. Oral potassium load stimulated the release of urinary kallikrein in normotensive subjects and WHO stage I essential hypertensive patients. Stage II essential hypertensive patients had the lowest value of basal level of urinary kallikrein and showed no increase in urinary kallikrein by oral potassium load. These results suggest that the functional activity of renal kallikrein-kinin system decreases with the development of essential hypertension.

Administration, Oral↗
PubMed1989

Blood pressure elevation caused by inhibition of brain glutathione reductase.

The effect of brain glutathione reductase activity on blood pressure regulation was investigated. The intravenous administration of the glutathione reductase inhibitor, nitrofurantoin (0.1-0.3 mg/rat), to seven normotensive Wistar rats caused dose-dependent rises in blood pressure and the heart rate (delta mean blood pressure 17 +/- 1 mmHg; delta heart rate 89 +/- 7 beats/min for 0.3 mg). Rats treated with 0.3 mg nitrofurantoin showed a 50% decrease in glutathione reductase activity with a twofold increase in the ratio of glutathione disulphide to reduced glutathione in the hypothalamus and brainstem, and a 1.5-fold increase in plasma noradrenaline and plasma renin activity compared with controls. These nitrofurantoin-induced effects were totally abolished by pretreatment with a sympathetic ganglion blocker (4 mg pentolinium tartrate, administered subcutaneously) except for the increased ratio of glutathione disulphide to reduced glutathione and the decreased glutathione reductase activity in the brain. These results suggest that the blood pressure elevation caused by inhibition of brain glutathione reductase activity occurs through activation of the sympathetic nervous system and the renin-angiotensin system.

Animals↗
PubMed1989

Effects of renin inhibitors on the expression of kidney renin gene and tissue renin-like activity.

The effect of renin inhibitor ES-1005 on renin gene expression was investigated in sodium-depleted marmosets. The kidneys were removed after continuous infusion of ES-1005 (12 mg/kg per h) for 2 h. The relative amount of kidney renin messenger (m)RNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin complementary (c)DNA fragment as a hybridization probe. Plasma renin activity was completely inhibited by ES-1005. The level of kidney renin mRNA decreased significantly to about one-third of the normal control value. We also investigated the inhibitory potency of the renin inhibitor ES-6864 on the renin-like activity in dog tissues (adrenal glands, aorta and brainstem). ES-6864 inhibited the tissue renin-like activity with an IC50 of 10(-7) to 10(-8) mol/l in vitro. Renin inhibitors not only inhibit the activity of plasma and tissue renin, but also suppress the synthesis of renin in the kidney.

Animals↗
PubMed1989

Impact of a family history of hypertension on blood pressure levels during early and late adolescence.

The aim of this study was to examine the impact of a family history of hypertension (FHH) on blood pressure levels in Japanese rural adolescents. The study population consisted of 458 and 553 subjects, aged 13 and 16 years, respectively. Particular attention was focussed on subjects with a FHH (13 years old, n = 38; 16 years old, n = 46) and those without a FHH (13 years old, n = 83; 16 years old, n = 97). Significant associations were found between FHH and systolic blood pressure for boys and girls at 16 years old and diastolic blood pressure for girls at 16 years old. The impact of a FHH on blood pressure mainly affected systolic blood pressure in late adolescence (16 years of age). In early adolescence (13 years of age), different physical maturation status may have masked the real impact of a FHH on blood pressure.

Adolescent↗
PubMed1989

Blood pressure distribution and determinants of higher levels of blood pressure in Japanese rural adolescents.

The blood pressures (BP) and anthropometric values of 1,014 Japanese rural school children aged 12-17 years old were measured at one-year interval. The strongest correlation for systolic BP (SBP) was weight and for diastolic BP (DBP) it was age. Larger values of weight, body mass index, triceps skinfold thickness and smaller increment of height showed significant discriminative powers in differentiating the subjects who had been above the age-sex specific 80th percentile value (H-H group) from those who had been below the 20th percentile value (L-L group) for both SBP and DBP. Subjects with a family history of hypertension (FHH) had higher SBP than those without a FHH, and were more prevalent in H-H group for SBP. These results indicate that larger body size and more mature stature are determinants of higher levels of BP during adolescence, and that FHH affects SBP only in this period.

Adolescent↗
PubMed1989

[Molecular forms of plasma atrial natriuretic peptide (ANP) after three kinds of ANP releasing stimulation].

This study analyzed by high performance gel permeation chromatography (HPGC) molecular forms of atrial natriuretic peptide (ANP) in plasma from anesthetized dogs stimulated by balloon inflation at the main pulmonary artery (Group A, n = 4), right atrial pacing (Group B, n = 4) and low-molecular dextran injection to right atrium (Group C, n = 4). Mean pulmonary arterial (PA) pressure, mean right atrial (RA) pressure, mean arterial pressure, heart rate and ECG were monitored by polygraph system Mean PA pressure in Group A, heart rate in Group B and mean RA pressure in Group C increased significantly by the stimulation (p less than 0.01, p less than 0.001 and p less than 0.05 respectively). Other parameters were not changed significantly in the three groups. There were significant increases in ANP concentration after the three stimulations (Group A: 52.4 +/- 5.4 (SD) pg/ml----86.4 +/- 12.2 (SD) pg/ml, Group B: 43.8 +/- 6.7 (SD) pg/ml----72.0 +/- 14.1 (SD) pg/ml, Group C: 42.7 +/- 8.8 (SD) pg/ml----69.3 +/- 10.0 (SD) pg/ml; each p less than 0.01). Gel filtration profiles showed that the increased form of plasma ANP in the three groups was alpha-ANP. These results suggest that alpha-ANP may be a main molecular form in plasma from dogs stimulated by the stretch of pulmonary arterial wall and right atrial wall, and atrial pacing.

Animals↗
PubMed1989

[A patient with olivopontocerebellar atrophy combined with sleep apnea syndrome].

A 52-year-old man with olivopontocerebellar atrophy was admitted to Ehime University Hospital for examination of sleep apnea. Overnight polysomnographic study revealed that his sleep apnea was predominantly the central type. With progress of the disease, the dominance of apnea pattern changed from the central type to the obstructive type. After tracheostomy, the apnea index decreased from 15 per hour to 12.4 per hour. However, the apnea index of the central type increased from 1.5 per hour to 12.4 per hour. These findings suggest that the effect of tracheostomy is not always beneficial in sleep apnea, and that the frequency and the pattern of apnea are not always indicators of tracheostomy.

Humans↗
PubMed1989

Kidney renin gene expression in spontaneously hypertensive rats.

We studied the expression of kidney renin gene in hypertensive animals by measuring the kidney renin messenger (m) RNA. The kidney renin mRNA was quantified by densitometric Northern blot analysis using a 32P-labelled rat renin genomic DNA fragment as a hybridization probe. Spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) were treated with a low-sodium diet plus furosemide, captopril or propranolol for a week. Plasma renin activity (PRA) in SHR and WKY was increased similarly by sodium depletion and by treatment with captopril. PRA in both strains was not decreased significantly by treatment with propranolol. Both sodium depletion and captopril treatment caused significant increases in the kidney renin mRNA in SHR and WKY. However, the increases in the kidney renin mRNA of SHR were greater than those in the corresponding WKY (SHR, 10.0- and 22.1-fold increases; WKY, 6.2- and 7.8-fold increases, respectively). Propranolol had no effect on the kidney renin gene expression in either WKY or SHR. These results indicate that SHR show an enhanced expression of the renin gene in the kidney compared with WKY in response to stimuli that increase renin release.

Animals↗
PubMed1988

A novel troponin T-like protein (calponin) in vascular smooth muscle: interaction with tropomyosin paracrystals.

Calponin is a smooth muscle tropomyosin-binding protein which is antigenically related to troponin T. The fine localization of calponin and troponin T on the polar paracrystals of smooth muscle tropomyosin were studied by electron microscopy. Both calponin and troponin T bound to the filamentous tropomyosin at a site about 17 nm away from the C-terminal end of tropomyosin molecule. This calponin-binding site corresponds to the domain which is highly conserved in the amino-acid sequences among the tropomyosin isoforms from skeletal muscle and smooth muscle. The result suggests that calponin, in collaboration with tropomyosin, may play an important role in regulating contractile apparatus.

Animals↗
PubMed1988

Disparate difference in preload reserve between myocardial hypertrophy due to essential hypertension and hypertrophic cardiomyopathy.

To investigate the left ventricular preload reserve in essential hypertensives, the legs-up procedure was performed and the data were compared with those in patients with non-obstructive hypertrophic cardiomyopathy and in normal subjects. Stroke volume index and the following systolic time intervals were measured before and after the legs-up procedure: left ventricular ejection time, pre-ejection period and the ratio of pre-ejection period to left ventricular ejection time (PEP/ET). No changes in blood pressure, heart rate or plasma catecholamine levels were noted before and after the legs-up procedure in all groups. A shortening in the pre-ejection period, a prolongation of ejection time, a decrease in the PEP/ET ratio and an increase in the stroke volume index were observed in essential hypertensives and in normal subjects. However, the changes in these parameters were not observed in patient with hypertrophic cardiomyopathy. The legs-up procedure is known to increase left ventricular end-diastolic volume. These results suggest that myocardial hypertrophy due to essential hypertension preserves the same preload reserve as in normals, but hypertrophic cardiomyopathy does not.

Blood Pressure↗