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Biomedical subjects

T Kokubu

Publications and source records attributed to T Kokubu.

At least 127 records · Page 7Linked to original sources
PubMed1984

Two different types of inactive renin in human plasma: molecular and kinetic properties.

We separated inactive renin in human plasma into two types, adsorbed and non-adsorbed, by chromatography on a concanavalin A-Sepharose column. About 75% of fresh plasma inactive renin was adsorbed to the column, and the rest passed through it. Non-adsorbed and adsorbed inactive renins were partially purified. Non-adsorbed inactive renin had a molecular weight of 48000 and an isoelectric point of 5.44. Adsorbed inactive renin had a molecular weight of 46000 and isoelectric points of 5.56 and 5.80. After activation with trypsin, both activated inactive renins were similar with respect to molecular weight (45000), thermostability, Km value (0.56 mumol/l) and pH profile. But pI values of both activated inactive renins differed. These results indicate that there exist in human plasma two different types of inactive renin which differ in carbohydrate composition.

Chemical Phenomena↗
PubMed1984

A study of somatostatin receptors in amygdaloid-kindled rat brain.

Kindling is an animal model of epilepsy. Previously somatostatin (SRIF) was implicated in seizure activity in the brain. Recently we reported a significant increase in brain SRIF content in the temporal cortices and cortices of kindled rats. Since the interaction between the neurotransmitter and the receptor eventually is responsible for the biological response, the present study was undertaken to examine evidence for the participation of SRIF receptor in the kindled state. In this study we present a procedure for detection of SRIF receptors using radiolabeled (D-Tyr8)-SRIF as a tracer. The present study indicates that in kindled rats there are no differences in the total number or affinity of the binding sites in the temporal cortex and a slight increase in the total number of binding sites in the cortex when compared with controls. These results, in view of our other observations, suggest that in kindled rat brain there may be an increased release of SRIF but no down-regulation of SRIF receptors in temporal cortex and cortex. There appears to be a significant decrease in the number of SRIF receptors in kindled hippocampus. The mechanism by which this occurs remains unclear.

Amygdala↗
PubMed1984

Purification and characterization of aminopeptidase N from human plasma.

Human plasma aminopeptidase N (EC 3.4.11.2) was homogeneously purified from outdated bank plasma. Purification procedures included ammonium sulfate fractionation, immunoaffinity chromatography, DEAE-cellulose column chromatography, hydroxyapatite column chromatography and Sephadex G-200 gel filtration. The final recovery of the enzyme was 18% and its specific activity was 71.6 mumol/min/mg protein. SDS-polyacrylamide gel disc electrophoresis and analytical ultracentrifugation showed the homogeneity of the enzyme. Equilibrium ultracentrifugation showed a molecular weight of 210,800. SDS-polyacrylamide gel disc electrophoresis indicated that the enzyme was a dimer consisting of two identical subunits. The isoelectric point of the enzyme was 3.9 at 4 degrees C. The amino acid composition of the enzyme was very similar to those of aminopeptidase N from human kidney, small intestine, and placenta which we have reported previously. Neutral sugar accounted for 11.6%. The Km, Vmax and Kcat values and hydrolytic coefficient (Kcat/Km) of the enzyme with L-alanyl-beta-naphthylamide as substrate were 8.7 X 10(-5) mol/l, 85.9 mumol/min/mg protein, 303/s and 3,483/mmol/l/s, respectively. The enzyme was activated by cobalt ions and markedly inhibited by amastatin. Plasma aminopeptidase N was immunologically indistinguishable from kidney aminopeptidase N.

Amino Acids↗
PubMed1984

Direct radioimmunoassay for human renin substrate and its measurement in plasma from essential hypertensive patients, diabetic patients and pregnant women.

We homogeneously purified human renin substrate from outdated bank plasma and raised antibody against it. The antibody did not cross-react with angiotensin I, angiotensin II or synthetic tetradecapeptide at concentrations of up to 160 nmol, nor did it cross-react with up to 0.2 ml of plasma from rat, rabbit or sheep. It did, however, completely cross-react with human des-angiotensin I renin substrate. A direct radioimmunoassay for human renin substrate was developed using the antibody, and the minimum detectable value of renin substrate found to be 70 pg of protein. Plasma renin substrate concentrations of normal subjects, essential hypertensive patients, diabetic patients and pregnant women were measured by direct and indirect assays. Hypertensive patients had similar concentrations of plasma renin substrate to normal subjects, whereas diabetic patients had significantly lower plasma renin substrate concentrations (p less than 0.01). The direct assay always gave a higher value than the indirect assay, and the ratios of the two assays (direct assay/indirect assay) were similar in normal subjects, hypertensive patients, diabetic patients and pregnant women.

Angiotensinogen↗
PubMed1984

Noninvasive evaluation of left ventricular function by systolic time intervals in essential hypertension with angina pectoris.

In order to clarify the hemodynamic characteristics in essential hypertension (HT) with angina pectoris (AP), systolic time intervals (STIs) were measured in 13 normal subjects (N), 23 patients with AP, 43 HT (WHO stage I: 13, WHO stage II: 23, WHO stage III: 7) and 19 HT with AP (WHO I: 9, WHO II: 10). The ET/PEP ratio was 2.41 +/- 0.24 in N, 2.70 +/- 0.34 in AP (p less than 0.02, vs N), 2.25 +/- 0.29 in WHO I, 2.13 +/- 0.25 in WHO II (p less than 0.01, vs N), 1.54 +/- 0.37 in WHO III (p less than 0.001, vs N), 2.68 +/- 0.32 in WHO I with AP (p less than 0.05, vs N: p less than 0.005, vs HT) and 2.71 +/- 0.30 in WHO II with AP (p less than 0.02, vs N: p less than 0.001, vs HT). Ejection time index (ETI) was 385 +/- 15 msec in N, 399 +/- 16 in AP (p less than 0.05, vs N), 387 +/- 13 in WHO I, 385 +/- 15 in WHO II, 363 +/- 25 in WHO III (p less than 0.05, vs N), 393 +/- 16 in WHO I with AP and 402 +/- 15 in WHO II with AP (p less than 0.05, vs N: p less than 0.01, vs HT). Pre-ejection period index (PEPI) was 142 +/- 10 msec in N, 135 +/- 11 in AP, 148 +/- 12 in WHO I, 156 +/- 13 in WHO II (p less than 0.005, vs N), 192 +/- 24 in WHO III (p less than 0.001, vs N), 134 +/- 13 in WHO I with AP (p less than 0.05, vs HT) and 136 +/- 9 in WHO II with AP (p less than 0.001, vs HT). These results showed that the ET/PEP ratio in HT with AP was significantly higher than that in HT alone, and this increase in ET/PEP ratio was mainly due to the shortening of PEP interval in WHO stage I and the lengthening of ET in addition to it in WHO stage II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Activation of prokallikrein in the rat kidney by proteases.

Prokallikrein was activated by trypsin and by alpha-chymotrypsin, but not by proteases, such as plasmin, thrombin, urokinase, carboxypeptidase B, papain, elastase, pepsin, and cathepsin D. Moreover, rat fresh serum did not activate prokallikrein. Maximum activation of prokallikrein by trypsin was obtained at the concentration of 10 micrograms to 1 mg per ml in PBS and that by alpha-chymotrypsin was at the concentration of 5 mg per ml. The enzymic properties of trypsin-activated and alpha-chymotrypsin-activated kallikreins were identical with those of active kallikrein in the kidney.

Animals↗
PubMed1984

An exaggerated natriuretic response to hypertonic saline infusion in the stage II (who stage classification) essential hypertensive patients.

We examined the natriuretic response to a hypertonic saline infusion in essential hypertensive patients who were subgrouped according to WHO stage classification. We studied 36 essential hypertensive patients and 17 normal subjects matched for age under the precise state of sodium balance (120 mEq sodium per day). The stage II essential hypertensive patients had exaggerated diuretic and natriuretic responses following the infusion of 525 ml of saline containing 120 mEq sodium for 1 hour. Our results suggest that development of essential hypertension induces a functional state that resembles expansion of extracellular fluid volume.

Adult↗
PubMed1984

Changes of plasma renin activity by intracerebroventricular administration of biological active peptides in conscious rats.

We studied the effects of intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT) on plasma renin activity (PRA), blood pressure and heart rate in conscious and unrestrained rats. Five microliters of each peptide solution was injected into the lateral cerebral ventricle. These four peptides all produced pressor effects after intracerebroventricular injection. ANG II and NT significantly suppressed PRA, BK did not affect PRA, and Leu-ENK significantly increased PRA. The central peptidergic stimulation caused by these four peptides increased blood pressures in conscious rats but showed different effects on PRA.

Angiotensin II↗
PubMed1984

A family with a high serum aminopeptidase (microsomal) activity: properties of the enzyme from serum of the propositus.

We found a family with a high activity for hydrolyzing L-alanyl-beta-naphthylamide in their serum. This enzyme was confirmed to be aminopeptidase (microsomal) (EC 3.4.11.2) by means of immunological experiments involving anti-human kidney aminopeptidase (microsomal) antibody. We could not find the cause of the increased activity from the results of clinical and laboratory examinations. The enzyme from the propositus resembled that from the serum of normal subjects in molecular mass (240 000 Da), Km value (87 mumol/L), and degree of inhibition by antiserum to human kidney aminopeptidase (microsomal). It differed from the normal enzyme with respect to electrophoretic mobility (R1 value, 0.58; normal, 0.51), isoelectric point (pI, pH 3.4; normal, pH 3.8), and heat stability (more labile than normal). From information on this family and another one reported in the Japanese literature, we suggest that the mode of inheritance of a high activity of serum aminopeptidase (microsomal) may be autosomal dominant.

Adolescent↗
PubMed1984

Orthostatic hypertension with nephroptosis and aortitis disease.

A 53-year-old woman with nephroptosis and aortitis disease was found also to have orthostatic hypertension. When standing, she had high renin levels and normal catecholamine values, with a reduced baroreflex sensitivity. This orthostatic hypertension largely may be due to an activation of the renin system caused by nephroptosis and partly due to a reduced baroreflex sensitivity caused by aortitis. Captopril and propranolol hydrochloride were effective for the treatment of hypertension.

Aortitis↗
PubMed1984

A catheter-induced syncopal attack in a case of hypertrophic obstructive cardiomyopathy.

A 48-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) was studied by serial cardiac catheterization during incidentally induced syncope. His hospital admission was for repeated syncopal attacks and chest pain. His electrocardiogram showed giant negative T waves (greater than 10 mm) in V3, V4 and V5 leads, and his M-mode echocardiogram disclosed typical asymmetric septal hypertrophy, systolic anterior movement of the mitral valve, and a midsystolic semiclosure of the aortic valve. During cardiac catheterization, we incidentally induced syncope and recorded the serial pressure changes. During syncope, systemic blood pressure dropped without appreciable changes in pulmonary arterial and right ventricular pressures. Although blood pressure was maintained by administering etilefrine and hydrocortisone, syncope persisted. After administration of propranolol, he recovered from syncope. He was on sinus rhythm throughout the examinations. The ejection time (ET) obtained from the aortic pressure curve was extremely short (160 msec) during syncope and prolonged (300 msec) after recovery without significant change in the heart rate. We believe that the prompt intravenous administration of propranolol was very effective in relieving myocardial spasm as a possible cause of syncope.

Cardiac Catheterization↗
PubMed1983

Activation and molecular weight changes of human plasma inactive renin by proteolytic enzymes.

By treating human plasma with trypsin (1 mg/ml), 3 different peaks of renin activity were detected by a gel filtration on Ultrogel AcA 44. The molecular weights of these activated renins were estimated to be 47,000, 45,000 and 43,000 daltons, respectively. 2) The molecular weight of human plasma active renin partially purified was 43,000 daltons. After treatment with neuraminidase, the molecular weight decreased to 38,000 daltons. 3) When the partially purified plasma inactive renin, which was completely separated from active renin, was activated by trypsin, chymotrypsin, plasmin, pepsin and renin, the activated renins had different molecular weights. The highest molecular weight form (47,000-48,000) was trypsin-activated or plasmin-activated renin and the lowest molecular weight form (38,000) was renin-activated renin. 4) These results suggest that cleavage of the specific site in peptide bond of plasma inactive renin by various proteolytic enzymes results in different molecular weights of activated renins. Plasma active renin free from sialic acid is very similar to kidney renin.

Chromatography, Gel↗
PubMed1983

Diagnostic significance of early diastolic time intervals in patients with hypertrophic cardiomyopathy and myocardial hypertrophy due to essential hypertension.

In order to differentiate hypertrophic cardiomyopathy (HCM) from myocardial hypertrophy due to essential hypertension (HT), echocardiogram, apexcardiogram and phonocardiogram were simultaneously recorded in patients with HCM (n = 22), HT (n = 34) and normal subjects (N) (n = 22). The following early diastolic time intervals were measured: 1) IIA-O time, 2) IIA-MVO time (IRT) and 3) MVO-O time. The IIA-O time was 119 +/- 9 msec in N, 159 +/- 31 in HT (p less than 0.001, vs N) and 228 +/- 57 in HCM (p less than 0.001, vs N and HT, respectively). The IIA-MVO time was 66 +/- 11 msec in N, 95 +/- 18 in HT (p less than 0.001, vs N) and 102 +/- 24 in HCM (p less than 0.001, vs N). The MVO-O time was 53 +/- 9 msec in N, 66 +/- 21 in HT and 126 +/- 48 in HCM (p less than 0.001, vs N and HT, respectively). These results showed that among the early diastolic time intervals HT was abnormal only in the IIA-MVO time. On the other hand, HCM had abnormalities not only in the IIA-MVO time but also in the MVO-O time. Both the IIA-MVO and the MVO-O times in hypertrophic non-obstructive cardiomyopathy were prolonged significantly as compared to those in obstructive one. Analysis of early diastolic time intervals may be very useful to differentiate HCM, especially of the non-obstructive type, from HT.

Cardiomegaly↗
PubMed1983

Effect of clonidine on blood pressure in chronic one-kidney, one-clip and two-kidney, one-clip hypertensive rats.

Oral administration of clonidine lowered the high blood pressure in two-kidney, one-clip hypertensive rats in chronic stage (three to four months), but not in one-kidney, one-clip hypertensive rats. This reduction of blood pressure was well correlated with decrease in plasma renin concentration, but not with decrease in urinary noradrenaline excretion. These results suggest that the reduction of blood pressure in two-kidney, one-clip hypertensive rats may be due to reduced renin release through the action of clonidine, while in one-kidney, one-clip hypertensive rats the sympathetic nervous activity may play little or no role in the maintenance of high blood pressure.

Animals↗
PubMed1983

Different mechanisms maintaining high blood pressure in chronic one-kidney, one-clip, and two-kidney, one-clip hypertensive rats.

To evaluate the difference of the blood pressure regulating mechanisms of chronic (12-14 weeks) one-kidney, one-clip (1K-1C) and chronic two-kidney, one-clip (2K-1C) hypertensive rats, we administered captopril, captopril plus indomethacin, and indomethacin to the rats. Pretreatment values of plasma renin concentration, plasma aldosterone concentration and urinary kallikrein excretion were significantly higher in 2K-1C than in 1K-1C hypertensive rats. Captopril-induced blood pressure reduction was greater in 2K-1C than in 1K-1C hypertensive rats. When captopril was administered to the rats treated with indomethacin, captopril-induced blood pressure reduction was attenuated only in 2K-1C hypertensive rats. Indomethacin produced renal impairment and further raised the blood pressure in 1K-1C hypertensive rats, but did not in 2K-1C hypertensive rats. These results suggest that the renin-angiotensin system functions to maintain high blood pressure more predominantly in chronic 2K-1C than in 1K-1C hypertensive rats. The renal kallikrein-kinin system is suppressed in chronic 1K-1C hypertensive rats but not in 2K-1C hypertensive rats. The renal prostaglandin system is more important for regulating the renal circulation in chronic 1K-1C than in 2K-1C hypertensive rats.

Aldosterone↗