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Biomedical subjects

T Kokubu

Publications and source records attributed to T Kokubu.

At least 73 records · Page 4Linked to original sources
PubMed1988

Vascular smooth muscle calponin. A novel troponin T-like protein.

In a search for additional Ca2+ regulatory components in vascular smooth muscle, a novel troponin T-like protein was purified from bovine aorta smooth muscle. The isolated protein was separated into several isoforms on isoelectric focusing. The major isoelectric variants were focused in the pH region of 8.4 to 9.1. The protein had slightly different molecular masses in the Mr range of 35,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its molar ratio relative to tropomyosin in the muscle extract was estimated to be 0.9:1.0. The novel protein bound to the immobilized calmodulin and exhibited a number of common physicochemical properties with gizzard (Mr = 34,000) calmodulin-binding and F-actin-binding protein. The aorta and gizzard proteins were immunologically cross-reactive. Both proteins shared a common antigenic determinant with COOH-terminal segments of rabbit skeletal and bovine cardiac troponin T and bound to the immobilized smooth muscle tropomyosin. Both proteins interacted with rabbit skeletal troponin C in the presence and absence of Ca2+, but they did not interact with troponin I. These results suggest that the novel protein, which is designated calponin, may be a specialized component of smooth muscle thin filament involved in the regulation of contractile apparatus.

Animals↗
PubMed1988

A highly potent and long-acting oral inhibitor of human renin.

An orally active renin inhibitor, ES 6864 (N-[(2R)-3-morpholinocarbonyl-2-(1-naphthylmethyl)propionyl]-(4- thiazolyl)-L-alanyl-cyclostatine-(2-morpholinoethyl)amide), was synthesized. ES 6864 was found to be a highly potent inhibitor of human renin with a Ki value of 7.3 x 10(-9) M. The compound competitively inhibited human renin. The inhibitor was also potent against monkey renin but was less effective against renins from pig, goat, dog, rabbit, and rat. ES 6864 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. ES 6864 was resistant to proteolytic actions of the enzymes in rat tissue homogenates (liver, kidney, pancreas, and small intestine). Oral administration of ES 6864 at 30 mg/kg to conscious, sodium-depleted marmosets produced a significant blood pressure reduction and almost complete inhibition of plasma renin activity, which persisted for 5 hours. Oral administration of ES 6864 also produced dose-related decreases of blood pressure in hog renin-infused rats, but the duration of action was much shorter than that in conscious marmosets. The parent compound in the blood following oral administration of ES 6864 to marmosets was confirmed directly by measuring the plasma concentration of ES 6864. These results enhance the possibility of developing renin inhibitors that can be used clinically.

Administration, Oral↗
PubMed1988

Dose-effect relationship of carvedilol in essential hypertension. An open study.

This study was performed to find the optimal dose of carvedilol, in terms of efficacy and safety, in Japanese patients with mild to moderate essential hypertension. 134 patients with blood pressure greater than 160/95 mm Hg after a 4-week placebo run-in period were initially given carvedilol 5mg once daily. The dose was increased to 10 and 20mg at 4-weekly intervals if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks' administration, the average blood pressure was significantly (p less than 0.001) reduced from 170/101 to 150/91 mm Hg. The hypotensive activity of carvedilol 5mg was mild, but sufficient hypotensive effect was observed in 65% of patients receiving up to 20 mg/day. No significant postural changes in blood pressure were observed. Although heart rate was significantly decreased (77 to 66 beats/min, p less than 0.001), no patient was judged to have bradycardia. Side effects occurred in 5.2% of patients. Carvedilol 10 to 20mg once daily is considered to be an effective and safe treatment for essential hypertension.

Adrenergic beta-Antagonists↗
PubMed1988

Cerebral and myocardial infarction induced by nonbacterial thrombotic endocarditis in a patient with ovarian cancer: report of a case.

A 40-year-old woman was admitted to our hospital because of left hemiplegia. She was affected with myocardial infarction and cerebral infarction. Echocardiogram revealed that the aortic and mitral valves had thick and uneven echoes suggesting vegetations. Judging from the finding that repeated blood cultures were negative, we had considered in her lifetime that myocardial and cerebral infarctions were due to embolization associated with nonbacterial thrombotic endocarditis (NBTE). At autopsy, histological diagnosis was made as ovarian cancer with disseminated intravascular coagulation. From the clinical course and the histological findings, we diagnosed this patient as NBTE.

Adult↗
PubMed1988

The role of hypothalamic glutathione in hypertensive animals.

The role of brain glutathione metabolism in hypertensive animals was studied. In spontaneously hypertensive rats (SHR) from prehypertension to established hypertension, the content of oxidized glutathione (GSSG) and the ratio of GSSG to GSH in the hypothalamus were significantly (p less than 0.05) higher than those in age-matched normotensive Wistar Kyoto rats (WKY). Hypothalamic glutathione reductase (GR) activities in prehypertensive and established hypertensive SHR were significantly (p less than 0.05) lower than those in WKY. DOCA-salt hypertensive rats (DSR) also had a significantly (p less than 0.05) higher content of GSSG and GSSG/GSH ratio and a significantly (p less than 0.05) lower GR activity in the hypothalamus than the normotensive control. There were no significant differences in these values in the brain stem between hypertensive and normotensive rats. These results suggest that the increased GSSG/GSH ratio due to reduced activity of GR in the hypothalamus may have an important role in the development of hypertension in SHR and DSR.

Animals↗
PubMed1988

[Left ventricular volume curve analysis using gated blood pool emission computed tomography].

Analysis of the left ventricular volume curve was performed using gated blood pool emission computed tomography (SPECT) in six patients with old myocardial infarction (MI), five with hypertrophic cardiomyopathy (HCM), three with dilated cardiomyopathy (DCM), and five normal controls (N). Image collection was synchronized with the QRS complex, and each cardiac cycle was divided into nine to 10 frames. In each frame, left ventricular volume was determined based on the number of voxels above the threshold level (50% cut-off level), and the volume curve was fitted to the third harmonics of Fourier analysis. From the fitted curve, the peak ejection rate (PER), the peak filling rate (PFR), end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated. 1. There were good correlations between SPECT and the conventional gated blood pool (MUGA) for PER (r = 0.694, p less than 0.005), PFR (r = 0.527, p less than 0.025) and EF (r = 0.682, p less than 0.005). 2. PER in MI (2.21 +/- 0.55, mean +/- SD) was lower than in N (3.68 +/- 0.80, p less than 0.05) and HCM (4.85 +/- 2.39, p less than 0.05), and EF in MI (36.6 +/- 6.4) was lower than in HCM (68.7 +/- 23.7, p less than 0.05). 3. There were good correlations between EDVs (y = 1.11x + 5.71, r = 0.877, p less than 0.01), and ESVs (y = 1.05x - 3.88, r = 0.876, p less than 0.01) estimated by MUGA and SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Significance of systolic time intervals in predicting prognosis of primary pulmonary hypertension.

To elucidate the characteristics of left ventricular (LV) function and LV shape in primary pulmonary hypertension (PPH), systolic time intervals (STIs) and two-dimensional echocardiograms in seven patients with PPH were studied and compared with those of 12 normal controls. Serial changes in STIs were also analyzed as to clinical outcomes. All patients were females and aged from 14 to 53 years. The follow-up period was 50 +/- 30 months, and five patients died of cardiac causes during the study period. The patients with PPH had a significantly prolonged pre-ejection period (PEP) and PEP index. Left ventricular ejection time (LVET) and the LVET index in the PPH group, at the time of diagnosis, showed no statistical differences compared with those of the controls, but three patients with PPH showed a marked shortening of LVET. A significant decrease in the LVET/PEP ratio was observed in patients with PPH. Left ventricular end-diastolic dimension (EDD) and end-systolic dimension (ESD) were significantly less in patients with PPH than in the controls. No difference in percent fractional shortening of the left ventricle and the mean velocity of circumferential fiber shortening was observed. The degree of LVET shortening correlated with the decrease in EDD (r = 0.97). During follow-up, marked shortening of the LVET index, below approximately 350 msec, was observed immediately before death or clinical deterioration. From these results, we conclude that in PPH, (1) left ventricular function is impaired due to reduced volume of the left ventricle during diastole, reflecting a shortening of LVET and the LVET index, and (2) analysis of serial LVET indexes is useful for predicting the prognosis.

Adolescent↗
PubMed1987

Occurrence of anti-gizzard P34K antibody cross-reactive components in bovine smooth muscles and non-smooth muscle tissues.

In our previous paper (Biochem. Biophys. Res. Commun. 141, 20-26 (1986) we reported the isolation of a 34000-dalton protein (p34K) which binds to calmodulin and F-actin from chicken gizzard smooth muscle. We examined the distribution of the immunoreactive component of gizzard p34K in bovine tissues by immunoblot analysis using a rabbit polyclonal antibody raised against gizzard p34K. The immunoreactive components with molecular weights of 33000-35000 were detected in all smooth muscles from aorta, esophagus, stomach, trachea and uterus. In non-smooth muscle tissues, a 36000-dalton cross-reactive protein was present in adrenal medulla and cortex. The immunoreactive form of gizzard p34K occurred in large amounts in smooth muscles from various bovine tissues.

Animals↗
PubMed1987

Radioimmunoassay of glandular kallikrein in human plasma after partial purification by immunoaffinity column.

Glandular kallikrein in human plasma was partially purified by immunoaffinity column (1.0 X 2.0 cm) and was measured by a radioimmunoassay (RIA). Plasma (5-10 ml) was diluted with an equal volume of 10 mmol/l sodium phosphate buffer, pH 7.4, containing 0.9% NaCl (PBS) and was applied to an immunoaffinity column from which glandular kallikrein was eluted with 3 mol/l NaSCN (20 ml). The enzymic fraction was concentrated with an Amicon PM 10 filter and dialyzed against PBS. The final recovery of the enzyme was 51.6 +/- 1.6% (mean +/- SD), determined by using [125I]kallikrein. The usable range of the standard curve covered 2.5-100 ng/tube. The coefficient of variation within the series was 5.9%, and the coefficient of variation between the series was 7.6%. In healthy controls (n = 25), the plasma content of glandular kallikrein was 1.36 +/- 0.39 ng/ml. In patients with acute pancreatitis (n = 6), the plasma concentration was 8.02 +/- 6.15 ng/ml, significantly different from the control group (p less than 0.01).

Acute Disease↗
PubMed1987

Comparative effects of calcium-channel blockers and beta-adrenergic blocker on early diastolic time intervals and A-wave ratio in patients with hypertrophic cardiomyopathy.

To compare the effects of calcium-channel blockers with those of beta-adrenergic blockers in patients with hypertrophic cardiomyopathy (HCM), diastolic time intervals (IIA-O time, from the second heart sound to the O point of apexcardiogram, IIA-MVO time, from IIA to the mitral valve opening, and MVO-O time, from the MVO to the O point of apexcardiogram), and A-wave ratio measured from apexcardiogram were evaluated before and after more than three months of treatment. In both groups, heart rate significantly decreased after treatment. The IIA-MVO time was not affected by either drug. The IIA-O and the MVO-O times were significantly shortened by calcium-channel blockers (from 234.6 +/- 77.4 ms to 204.6 +/- 39.2 ms; p less than 0.01, and from 133.1 +/- 66.4 ms to 100.3 +/- 34.0 ms; p less than 0.01, respectively). However, they were not affected by beta-adrenergic blocker. A-wave ratio significantly decreased after calcium-channel blockers (from 18.0 +/- 9.8% to 13.7 +/- 7.3%; p less than 0.01) and beta-adrenergic blocker (from 21.7 +/- 12.6% to 17.2 +/- 8.0%; p less than 0.01). From these observations, it is suggested tht calcium-channel blockers improved the early diastolic filling rate, whereas beta-adrenergic blocker did not affect it. It is concluded that the effects of calcium-channel blockers and beta-adrengergic blocker on early diastolic time intervals were different in patients with HCM.

Adrenergic beta-Antagonists↗
PubMed1987

Clinical significance of early diastolic time intervals for the differentiation of idiopathic dilative cardiomyopathy from ischemic cardiomyopathy.

In order to differentiate idiopathic dilative cardiomyopathy from ischemic cardiomyopathy noninvasively, systolic time intervals (STIs) and early diastolic time intervals were investigated in patients with idiopathic dilative cardiomyopathy (n = 11), patients with ischemic cardiomyopathy (n = 8), and normal controls (n = 17). Minimal left ventricular pressure and pulmonary capillary wedge pressure (PCWP) were also measured to clarify the relationship between early diastolic time intervals and early diastolic hemodynamics. Cardiac function estimated by STIs was markedly depressed both in idiopathic dilative cardiomyopathy and ischemic cardiomyopathy, and there was no difference between the two diseases. In early diastolic time intervals, IIA-O time (the interval from the aortic component of the second heart sound to the O point of apexcardiogram) was significantly prolonged both in idiopathic dilative cardiomyopathy (144 +/- 31 (SD); p less than 0.01) and ischemic cardiomyopathy (153 +/- 15; p less than 0.01) compared to normal controls (126 +/- 11). IIA-MVO time (the interval from IIA to the mitral valve opening) in idiopathic dilative cardiomyopathy (49 +/- 23) was significantly shorter than that in normal controls (70 +/- 8; p less than 0.05). On the contrary, IIA-MVO time in ischemic cardiomyopathy (126 +/- 11) was markedly prolonged compared with normal controls (p less than 0.01) and idiopathic dilative cardiomyopathy (p less than 0.01). MVO-O time was significantly prolonged in idiopathic dilative cardiomyopathy (94 +/- 18; p less than 0.01). However, it was conversely shortened in ischemic cardiomyopathy (25 +/- 15) compared with normal controls (54 +/- 7; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

SEM-EPMA observation of three types of apatite-containing glass-ceramics implanted in bone: the variance of a Ca-P-rich layer.

The progressive changes of a Ca-P-rich layer between bone and three types of apatite-containing glass-ceramics of the same chemical composition: MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF2 0.5 (in weight ratio) were examined. Plates (15 mm X 10 mm X 2 mm, mirror surface) containing apatite (35 wt%) (designated A-GC), apatite (35 wt%) and wollastonite (40 wt%) (designated A.W-GC), and apatite (20 wt%), wollastonite (55 wt%), and whitlockite (15 wt%) (designated A.W.CP-GC) were prepared. They were implanted into the tibia of mature male rabbits for 5 days, 10 days, 20 days, 30 days, 60 days, 6 months, and 12 months. All three types of glass-ceramics showed direct bonding to the bone 30 days after implantation. It was observed by SEM-EPMA 30 days after implantation that Si and Mg content decreased, P content increased, and Ca content did not change across the reactive zone from the glass-ceramics to bone. The level of P and Si in the A.W.CP-GC changed five days after implantation. In A.W-GC and A-GC, a little change in P and Si levels was observed between 10 and 20 days after implantation. The width of reactive zone was narrowest with A-GC, wider with A.W-GC, and widest with A.W.CP-GC. The dissolution of glass-ceramics stopped 6 months after implantation. This phenomenon shows that the glass-ceramics may be suitable for clinical use.

Animals↗