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Biomedical subjects

O Iimura

Publications and source records attributed to O Iimura.

At least 235 records · Page 13Linked to original sources

Urinary excretions of kininase I and kininase II activities in essential hypertension. A sensitive and simple method for its kinin-destroying capacity.

To further clarify the role of the renal kallikrein-kinin system in essential hypertension, a sensitive and simple method for the determination of both human urinary kininase I and kininase II was established, and the system components were determined in patients. In the measurement of kininase activity, desalted urine samples were incubated with synthetic bradykinin, and the reaction was terminated with kininase inhibitors, ethylene diamine tetraacetic acid and phenanthroline. Thus, kininase activity was determined as the kinin-destroying capacity. Moreover, the specific inhibitor for kininase II, SQ14225, was applied for the separation of kininase I and kininase II activities. Daily urinary excretions of total kininase and kininase I activities were significantly higher in essential hypertensive patients than those in normotensive subjects, whereas no difference was observed in kininase II activity. As reported previously, daily excretions of urinary kallikrein and kinin simultaneously determined in these patients were significantly lower than excretions in normotensive subjects. From these results, it was suggested that not only decreased renal kallikrein, but also increased kininase activity, may play an important role in the suppression of the renal kallikrein-kinin system through the reduction of active kinin level in essential hypertension.

Adolescent↗

Studies on experimental coronary insufficiency. Effect of L-carnitine on myocardial ischemia produced by sympathetic-nerve stimulation with high plasma fatty acids.

Our previous studies revealed that sympathetic-nerve stimulation (SNSt) plays an important role in the precipitation and the augmentation of myocardial ischemia in dogs with coronary constriction. To clarify the underlying mechanism of the detrimental effect of free fatty acids (FFA) at a high plasma concentration and the beneficial effect of L-carnitine on myocardial ischemia, ischemic changes following SNSt were compared among three groups of dogs with mild or moderate coronary constriction: a saline control group, an intralipid [(IL) 0.1 ml/kg per min + heparin 5 mg/kg] group, and an IL + L-carnitine (200 mg/kg) group. High plasma concentration of FFA aggravated the ischemic changes induced by SNSt in dogs with coronary constriction, in which no signs of increase in myocardial oxygen consumption were seen. L-Carnitine clearly alleviated the mechanical dysfunction, acceleration of anaerobic metabolism, depletion of myocardial contents of high-energy phosphates, myocardial accumulation of lactate, and ECG ischemic changes that were augmented by high plasma FFA in the coronary-constricted dogs with SNSt. From these findings, it was suggested that an increased plasma FFA might aggravate myocardial ischemia, at least, produced by SNSt in dogs with mild or moderate coronary constriction and that L-carnitine might improve the ischemia augmented by FFA, presumably by reducing myocardial accumulation of FFA intermediates.

Animals↗

A very sensitive direct radioimmunoassay system for plasma angiotensin II and its clinical application in various hypertensive diseases.

A very sensitive and simplified direct radioimmunoassay system for plasma angiotensin II was developed using the antiserum against synthetic angiotensin II (final dilution = 1: 1,500,000) in combination with 125I-labeled angiotensin II (specific activity = 1,600 microCi/micrograms). In this assay system, it was possible to carry out a direct assay using 100 microliter of plasma without any extraction procedure. This conclusion was supported by 100% recovery, parallelism of plasma samples against the standard curve, and no difference in hormone levels, there was also a high positive correlation between the plasma angiotensin II levels measured by this direct assay and the dowex column extraction method. The sensitivity of this assay system was 0.1 pg/tube, which is the highest sensitivity in studies reported to date. The cross-reactivities of angiotensin III and I against this antiserum were 100% and less than 0.1%, respectively, suggesting that the antiserum was very specific for the C-terminal of angiotensin II. Plasma angiotensin II levels in normal subjects after overnight fasting ranged from 3.0 to 21.3 pg/ml (12.0 +/- 2.1 pg/ml, mean +/- SE). By comparison, plasma angiotensin II levels of patients with essential hypertension were similar to those in the normal renin group, lower than those in low renin group and higher than those in high renin group. In patients with secondary hypertension, levels were lower in those with primary aldosteronism and higher in those with renovascular hypertension when compared to normal subjects.

Angiotensin II↗

Plasma noradrenaline concentration and pressor response to infused noradrenaline in patients with borderline hypertension, and mild or moderate essential hypertension.

In order to evaluate the significance of sympathetic nerve activity in the pathophysiology and pathogenesis of borderline hypertension or mild or moderate essential hypertension, plasma noradrenaline concentration (PNA) at supine rest and pressor response to infused noradrenaline (NA-R) were evaluated in these in-patients. A significantly positive correlation (r = 0.395, p less than 0.001) between PNA and age was found in normotensive subjects (NT), but not in essential hypertensives (EHT). In the young (below 40 years of age) group, the mean value of PNA in EHT was significantly higher (p less than 0.05) than that in NT. However no significant difference in PNA between NT and EHT was observed in the middle-age (40-59 years) and old-age (above 60 years) groups. PNA was highest in borderline hypertensives (BHT), second highest in EHT with WHO stage I (WHO-I), third in EHT with WHO stage II (WHO-II), and lowest in NT. Among these age-matched four groups, significant differences in the mean value of PNA were found between NT and BHT (p less than 0.001) or WHO-I (p less than 0.05), and between BHT and WHO-II (p less than 0.05). In a comparison of the age-matched NT, normal renin EHT (NRH) and low renin EHT (LRH), the mean value of PNA in NRH was significantly higher than that in NT (p less than 0.001) and LRH (p less than 0.001). Similar differences were observed in the peak value of PNA during 20 minutes when the head was tilted up. A close positive correlation between PNA and simultaneously measured mean arterial pressure (MAP) in the young EHT (r = 0.698, p less than 0.001) and WHO-I (r = 0.631, p less than 0.001), and a weak correlation in the middle-age EHT (r = 0.435, p less than 0.05) and NRH (r = 0.311, p less than 0.05) were demonstrated immediately after hospital admission. In the old-age EHT, WHO-II and LRH, however, no significant correlation was found between PNA and MAP. The mean value of NA-R in young (p less than 0.005) and middle-aged EHT (p less than 0.001) was significantly greater than that in respectively age-matched NT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A case of normotensive primary aldosteronism--comparison with 13 previously experienced cases with hypertension.

A 47-year-old woman with normotensive primary aldosteronism is reported. In this case, hypopotassemia was found, but the patient's blood pressure was within the normal range. Her condition was diagnosed as primary aldosteronism without hypertension, which is very rare, based on an increased level of plasma aldosterone concentration, low plasma renin activity, and a typical finding of aldosterone-producing adenoma by adrenal scintigraphy. In the present case, similar values for urinary volume, renal function, plasma aldosterone concentration, plasma renin activity, plasma volume, total exchangeable sodium, urinary kallikrein excretion and a similar weight of the resected adenoma, but a shorter duration between the onset of symptom and hospital admission were observed as compared with those in 13 previously experienced cases of primary aldosteronism with hypertension. Thus, a shorter duration of primary aldosteronism appears to be an important factor in explaining the mechanism of normotension. However, we were unable to reach a definite conclusion and this is only a hypothesis. Further investigation will be required to clarify the mechanism of normotension in primary aldosteronism.

Adenoma↗

A simple and sensitive method for determination of human urinary kallikrein activity (kininogenase activity), using human low molecular weight kininogen.

Human low molecular weight kininogen was partially purified and applied to the measurement of human glandular kallikrein as a substrate. The prepared human low molecular weight kininogen did not contain any significant amounts of kinin generating or destroying enzymes. When ethanol was added to the assay tube to stop the enzyme reaction, the substrate was almost completely removed from the incubation solution. Moreover, less than 1.25% ethanol had no effect on the kinin radioimmunoassay. These data suggest that the measurement of generated kinin can be done directly after the addition of ethanol. In this assay system, control tubes were unnecessary since the small volume of the urine samples (0.5 to 2.0 nl) contained negligible amounts of endogenous kinin. In a comparison of the availability as a substrate for human urinary kallikrein among human, dog and bovine low molecular weight kininogens, the enzyme activity was 5 or 100 times as high in the human substrate as in the dog and bovine substrates, suggesting that a human substrate is best for the human enzyme. A significant correlation was found between our previous method using bovine substrate and this method for human urinary kallikrein activity. In both methods, urinary kallikrein excretions were significantly lower in patients with essential hypertension and higher in those with primary aldosteronism, respectively. This simple, specific and sensitive kininogenase assay system seems to be very useful for investigating the physiological or pathophysiological role of the renal kallikrein-kinin system in hypertensive and renal diseases.

Animals↗

Electrocardiographic abnormalities in cerebrovascular accidents.

In order to assess the relationship of electrocardiographic (ECG) changes in acute cerebrovascular accidents (CVA) to the locations of the cerebral lesions, ECG records and brain computerized tomographic (CT) scans which were taken within 48 hours of CVA onset were examined in 39 patients without heart disease and/or treatment with cardiovascular drugs. The ECG was normal in 25% (3/12) of basal ganglial CVA, 22% (2/9) of frontal CVA and 36% (4/11) of temporo-parietal CVA. Nonspecific ST-T changes occurred in basal ganglial CVA (25%), frontal CVA (22%), temporo-parietal CVA (18%) and in the other categories of CVA locations. Corrected QT interval (QTc) elongation was observed not only in frontal (22%), but also in basal ganglial CVA (25%), temporo-parietal CVA (36%) and cerebellar CVA (50%). There were no ECG changes specific to a particular CVA location. These findings suggest that widely distributed neurons and pathways within the central nervous system may influence ECG.

Adult↗

An ectopic, ACTH producing, oncocytic carcinoid tumor of the thymus: report of a case.

A 39-year-old man with an ACTH producing oncocytic carcinoid of the thymus is reported here. His symptoms were pigmentation, facial and pretibial edema, and high blood pressure. Endocrinological examination revealed the ectopic ACTH syndrome and, especially, high content in the intrathoracic venous blood. On histological examination, the tumor was found to be composed of uniform eosinophilic cells, with no argentaffin granules being demonstrated. Ultrastructural findings revealed a large number of mitochondria and numerous distinct electron-dense neurosecretory granules in the cytoplasm. Abnormally high levels of ACTH, beta-endorphin and gamma-MSH were also found in this tumor tissue. By total extirpation of the tumor, clinical symptoms and laboratory data were entirely normalized.

ACTH Syndrome, Ectopic↗

Study on the renal kallikrein-kinin system in normal and low renin subgroups of essential hypertension.

In order to investigate the role of the renal kallikrein-kinin (K-K) system in normal (NRH) and low renin (LRH) subgroups of essential hypertension (EHT), daily excretions of urinary kallikrein (KAL) quantity and activity, kinin (KIN), total and pre-KAL, and kininase I and II were measured in 21 normotensives (NT), 29 patients with NRH and 16 patients with LRH. The daily excretions of both KAL quantity and activity, total and pre-KAL, and KIN were significantly lower in NRH and LRH than in NT. That of kininase I was significantly higher in NRH and LRH than in NT, but that of kininase II was not. In comparing NRH and LRH, the urinary excretions of KAL activity and KIN were lower in LRH than in NRH, and that of kininase I was higher in LRH than in NRH. The KAL/total KAL ratio did not show any significant difference among NT, NRH and LRH. These findings suggest that the suppression of the renal K-K system in EHT seems to be due to both the decrease of KAL through the pre-KAL synthesis in the kidney and an increase of kininase I activity, but not to the inhibition of conversion from pre-KAL to active KAL and the more obvious suppression of this system in LRH than in NRH may be partly explained by KAL inhibitors and/or increased kininase I activity.

Adult↗

The role of the renal kallikrein-kinin system in sodium metabolism in normal and low renin essential hypertension.

In order to investigate the pathophysiological role of the renal kallikrein-kinin system in renin subgroups of essential hypertension, the quantity and activity of urinary kallikrein, urinary kinin excretion, and correlations of kallikrein and kinin excretions with renal sodium handling in the renal tubules were studied in 17 normal subjects, 23 patients with normal renin and 12 patients with low renin essential hypertension. Urine samples were collected by the 2-hour clearance method in the early morning. The quantity and activity of urinary kallikrein, and the urinary excretion of kinin were significantly lower in both low and normal renin patients than in normal subjects. Comparing the normal renin and the low renin group, no significant difference was found in the quantity of urinary kallikrein, while the activity of urinary kallikrein and urinary kinin excretion were significantly lower in low renin patients than in normal renin ones. Fractional excretions of sodium (FENa) and inorganic phosphorus (FEP), which reflect renal tubular and proximal tubular sodium reabsorption, respectively, were significantly lower in the low renin patients than in the normal renin ones. A significantly positive correlation was observed between the urinary kallikrein activity or urinary kinin excretion and FENa or FEP in both normal subjects and normal renin patients, but not in low renin patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗