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Biomedical subjects

T Kokubu

Publications and source records attributed to T Kokubu.

At least 109 records · Page 6Linked to original sources
PubMed1985

Physicochemical characteristics of human high molecular weight angiotensinogen.

A high molecular weight angiotensinogen (Mr. 332,000 daltons) was prepared from plasma of pregnant women by gel filtration on Sephacryl S-300. The molecular weight was reduced to 81,000 by treatment with dithiothreitol (DTT), but not by treatment with SDS. DTT-treated high molecular weight (HMW) angiotensinogen was very similar to low molecular weight (LMW) angiotensinogen with respect to molecular weight, pH profile for angiotensin formation by human kidney renin, thermostability, Km value and isoelectric point. The antibody against LMW-angiotensinogen completely cross-reacted with HMW-angiotensinogen. These results suggest that HMW-angiotensinogen is probably a complex of LMW-angiotensinogen and other protein(s) which might be bound by disulfide bond.

Angiotensinogen↗
PubMed1985

Angiotensin converting enzyme. A possible histologic indicator for human renal cell carcinoma.

Angiotensin converting enzyme (ACE) was studied in specimens of human renal cell carcinoma by indirect immunofluorescence using rabbit antibody to human kidney ACE and fluorescein-labeled goat antibody to rabbit immunoglobulin. ACE was demonstrated in the cells of all renal cell carcinomas from 10 patients and in the cultured cells set up from 4 of them, but not in any cells of 12 extrarenal carcinomas of prostate, lung, and alimentary tract. These results suggest that immunohistologic detection of ACE is of value in the histologic diagnosis of renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1985

Adverse effects of atrial fibrillation and syncope induced by calcium-channel blockers in hypertrophic cardiomyopathy.

Calcium-channel blockers are useful for the treatment of hypertrophic cardiomyopathy (HCM), but, their adverse effects, especially, those of diltiazem, have not been of much concern. Forty patients with HCM were treated with calcium-channel blockers such as nifedipine, diltiazem, and verapamil. Atrial fibrillation was induced by diltiazem in two patients and verapamil induced syncope in one patient. The clinical and hemodynamic characteristics of the patients were as follows. All of them had the obstructive type of HCM (HOCM). One of them had a high pressure gradient of the left ventricular outflow tract and the others had earlier onset. In these patients, the left atrial overload seemed to be severe. The vasodilating action of calcium-channel blockers decreases the systemic pressure and in turn, may increase the pressure gradient and the left ventricular end-diastolic pressure. The elevated left ventricular end-diastolic pressure causes the left atrial overload which could be at risk of atrial fibrillation in patients with HCM. Therefore, calcium-channel blockers should be used carefully in peculiar cases of HOCM.

Adult↗
PubMed1985

Clinical significance of measurements of serum apolipoprotein A-I, A-II and B in hypertriglyceridemic male patients with and without coronary artery disease.

To examine the relationship of hypertriglyceridemia to coronary artery disease (CAD), we measured serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo) A-I, A-II and B in 82 male patients with angiographically defined CAD and 140 age-matched healthy controls. The CAD patients had significantly lower apo A-I and A-II and HDL-C levels, but had higher apo B and triglyceride levels than the controls. After adjustments of apolipoproteins for serum triglyceride, CAD patients had significantly higher apo B and lower apo A-I and A-II levels than the controls. Discriminant analysis showed that apo B was the best discriminator and that apo A-I was next. In the normotriglyceridemic subgroup HDL-C also had a sufficient power for discrimination between CAD patients and the controls, but in the hypertriglyceridemic subgroup HDL-C had no discriminative power. Both apo A-I and B had significant discriminative power between CAD patients and the controls, independently of the serum triglyceride level. These results indicate that measurements of serum apo A-I and apo B are useful for the study of coronary risk factor in hypertriglyceridemic subjects. Finally, it is necessary to sub-classify dyslipoproteinemia by serum apolipoprotein levels for predicting the future occurrence of CAD in the general population.

Adult↗
PubMed1985

Effects of renal denervation on renin release induced by intracerebroventricular administration of biological active peptides in conscious rats.

Experiments were performed to determine whether the renal nerve mediates the renin release induced by intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT). In sham-operated rats, both ANG II and NT suppressed plasma renin activity (PRA), BK did not affect PRA, and Leu-ENK increased PRA. Renal denervation abolished the increase in PRA by Leu-ENK. Suppression of PRA by ANG II was attenuated in denervated rats. Renal denervation did not influence the renin release by BK or NT. These results suggest that the renal nerve plays an important role in elevating PRA after central stimulation by Leu-ENK. Although suppression of PRA is mainly mediated by mechanisms other than the renal nerve, the renal nerve partially participates in suppression of PRA by ANG II.

Angiotensin II↗
PubMed1985

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

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 the kindled rat brain there may be an increased release of SRIF but no down-regulation of SRIF receptors in the 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↗
PubMed1985

A radioimmunoassay for the measurement of aminopeptidase (microsomal) in human serum.

A radioimmunoassay for the measurement of aminopeptidase (microsomal) (AP) in human serum was developed by using antiserum to human kidney AP. AP purified from kidney and AP present in normal serum and in serum from a patient with obstructive jaundice gave parallel logit-log transformation lines, suggesting immunological identity. The mean concentration of AP in normal serum (n = 104) was 1.33 +/- 0.30 (mean +/- SD) micrograms/ml. Men had significantly higher serum AP levels (1.41 +/- 0.30 micrograms/ml) (p less than 0.005) than women (1.24 +/- 0.28 micrograms/ml). Serum AP levels of patients with hepatoma (2.26 +/- 0.87 micrograms/ml) and cancer of the pancreas or the biliary tract (2.90 +/- 0.67 micrograms/ml) were significantly higher (p less than 0.005) than those of normal subjects. Patients with acute and chronic hepatitis (2.06 +/- 0.66 micrograms/ml) also had significantly higher serum AP levels (p less than 0.005) than normal subjects. In pregnant women, however, the increase in AP activity without the increase in AP concentration showed that the increased AP activity was due to an enzyme other than AP. The enzyme levels and activities in normal serum as well as in patients' sera were significantly correlated (normal, r = 0.77; patients, r = 0.95). Based on the specific activity of AP purified from human plasma, the enzyme activity splitting L-alanyl-beta-naphthylamide is due almost completely to AP in normal subjects and in patients with hepatobiliary diseases.

Adult↗
PubMed1985

Difference in myocardial characteristics between hypertrophic cardiomyopathy and myocardial hypertrophy due to essential hypertension.

To investigate the qualitative difference in myocardial hypertrophy that exists between hypertrophic cardiomyopathy (HCM) and essential hypertension (HT), we measured the mean wall thickness (MWT), the early diastolic time intervals (IIA-MVO time: from the second heart sound to the point of mitral valve opening, MVO-O time: from MVO to the O point of apexcardiogram) and the MVO-O/IIA-MVO ratio. The MWT in HCM and HT was measured by biventriculogram and echocardiogram, respectively. The MWT showed no significant difference between HT (13.1 +/- 3.0 mm) and non-obstructive type of HCM (14.8 +/- 3.7), but the MWT in obstructive type (1.08 +/- 0.24) was significantly thinner than that in HT. As the MWT increased, both IIA-MVO and MVO-O time were prolonged in both groups. But the mode of prolongation was quite different. In HT, the prolongation of the IIA-MVO time was almost always greater than that of the MVO-O time. In HCM, the prolongation of the latter was greater than that of the former. The MVO-O/IIA-MVO ratio in HT was significantly less than that in normal subjects, but those in HCM were significantly greater. These findings suggest that the differences in the early diastolic time intervals between HCM and HT are not due to the magnitude of the left ventricular hypertrophy, but due to myocardial characteristics.

Adult↗
PubMed1985

Changes of plasma renin activity following intracerebroventricular administration of biologically active peptides in two-kidney, one clip hypertensive rats.

We studied the effects of intracerebroventricular (ICV) 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 acute (less than 4 weeks) and chronic (more than 12 weeks) two-kidney, one clip (2K-1C) hypertensive rats. These four peptides all produced pressor responses. The pressor responses caused by ICV injection of ANG II, BK, Leu-ENK and NT in hypertensive rats did not differ significantly from the response in normal rats. In both acute and chronic 2K-1C hypertensive rats, ANG II and BK significantly suppressed PRA, NT did not affect PRA, and Leu-ENK produced a significant increase in PRA followed by a significant decrease in PRA. As compared to normal rats, suppression of PRA by ANG II and NT was attenuated or abolished but BK and Leu-ENK produced significant reductions in PRA in 2K-1C hypertensive rats. The results indicate that the effects of these four centrally administered peptides on blood pressure, heart rate and PRA in acute and chronic 2K-1C hypertensive rats were not essentially different from those in normal rats.

Angiotensin II↗
PubMed1985

The analysis of systolic and diastolic time intervals: a more sensitive non-invasive method in the assessment of left ventricular dysfunction in the patients with essential hypertension.

Time indices and volumetric parameters were investigated in patients with essential hypertension subdivided into three groups according to the WHO stage classification. The ratio of ejection time (ET) and pre-ejection period (PEP), ET/PEP remained within normal range in WHO-I but decreased significantly in WHO-II and reached extremely low values in WHO-III. ET did not change in WHO-I and WHO-II but became significantly reduced in WHO-III. Prolongation of PEP in WHO-II and WHO-III increased with progression of hypertensive stage. Isovolumic relaxation time (IRT) showed the same pattern as the prolongation of PEP; positive correlation between PEP and IRT was observed (r=0.55). On the other hand, significant changes of volumetric parameters were only observed in WHO-III. These results indicated that the time indices were a more sensitive parameter than the volumetric ones in the assessment of left ventricular dysfunction in the patients with essential hypertension.

Adult↗
PubMed1984

Highly potent and specific inhibitors of human renin.

We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.

Aldehydes↗