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Biomedical subjects

R Takeda

Publications and source records attributed to R Takeda.

At least 253 records · Page 14Linked to original sources

Impairment of modulating role of testosterone in growth hormone response to clonidine in essential hypertension.

To investigate the effects of endogenous testosterone (T) on the responsiveness of plasma growth hormone (GH) to central alpha 2 adrenergic stimulation, we administered clonidine (0.15 mg, p.o.) to 16 male patients with essential hypertension (EHT) and 13 age-matched male normotensive controls (NT). Although the basal T level was correlated with the peak GH increment (r = 0.709, p less than 0.01) and with the area under curve of GH (r = 0.714, p less than 0.01) in the NT group, no such correlations were seen in the EHT group. The present study confirmed the potentiating role of endogenous T in GH responsiveness to clonidine in male NT. The lack of correlation between T and GH response in EHT suggests a neuroendocrine disturbance in modulation by T of the GH response to central alpha 2 adrenergic stimulation.

Adult↗

[Two-dimensional echocardiographic and left ventriculographic evaluations of left ventricular diverticula].

Twenty cases of left ventricular diverticula were gleaned from 4,300 consecutive angiocardiographic records (13 males and seven females whose age ranged from 17 to 78 years with a mean of 52 +/- 16 years). Their findings were compared with those of 16 patients with left ventricular aneurysms due to myocardial infarction. In only one patient was a diverticulum first detected by two-dimensional echocardiography before left ventriculography was performed. None of the patient had an associated midline thoracoabdominal defect. Five patients had premature ventricular beats, two of whom had ventricular tachycardia. Three patients complicated mitral valve prolapse and three atrial septal defect. Of the 20 patients, four each had two diverticula, as opposed to 16 others who each had a single diverticulum. The diameter of the diverticula ranged from eight to 70 mm. The sites of 14 diverticula were along the inferior wall; five in the anterior wall; four in the apex. Morphologically 15 diverticula were bulky outpouchings, six were tongue-like, and three hammocking. All diverticula exceeding 15 mm in diameter and originated near the mitral ring could always be detected in the short-axis view of two-dimensional echocardiography. However, those originating in the apex or of a tongue-like configuration could rarely by detected. Comparative two-dimensional echocardiographic analyses of 16 diverticula, 16 left ventricular aneurysms, and 16 normal left ventricular walls disclosed that the left ventricular aneurysmal wall had a higher echo intensity, but the diverticula had the same wall echo intensity as the normal left ventricular wall. Left ventricular end-diastolic wall thickness in an aneurysm (7.6 +/- 1.5 mm) was lower (p less than 0.01) than the normal left ventricular wall (11.1 +/- 1.3 mm), but it did not differ from the normal left ventricular wall in any case of diverticulum (10.2 +/- 1.5 mm). The percent wall thickening ratio in aneurysms (-3.6 +/- 10.7%) was lower (p less than 0.01) than the normal left ventricular wall (39.8 +/- 10.9%), but it did not differ from the normal left ventricular wall in diverticula (45.8 +/- 16.6%). Regional fractional shortening in the diverticula (41.3 +/- 9.2%) did not differ from that in the normal left ventricular wall (34.5 +/- 5.2%). In conclusion, a small diverticulum without a midline thoracoabdominal defect is not rare, and two-dimensional echocardiography is the diagnostic method of choice in many cases based on the echo features described above.

Adolescent↗

[Serial change in serum concentration of type III procollagen N-terminal peptide after TAE in hepatocellular carcinoma, and analysis of gel filtration pattern of the peptide].

In the present study, we have measured the serum concentration of PIIIP in patients with various liver diseases, and studied serial changes in serum PIIIP after TAE and its gel filtration pattern in 10 cases of hepatocellular carcinoma undergone TAE. The following results were obtained. 1) Serum concentration of PIIIP was 12.3 +/- 6.1 ng/ml in normal controls and elevated significantly in liver cirrhosis, liver cirrhosis with hepatocellular carcinoma, chronic active hepatitis, and acute hepatitis. 2) There was no significant difference in the serum concentrations of PIIIP between liver cirrhosis and liver cirrhosis with hepatocellular carcinoma. The result suggested that serum PIIIP cannot be a specific marker of hepatocellular carcinoma. However, the serum PIIIP concentration was decreased 2 or 4 weeks after TAE in effective cases, whereas increased in ineffective cases. Thus, the measurement of serial change in the serum PIIIP after TAE was considered to be useful for evaluating the effectiveness of TAE. 3) In analysing the elution patterns of serum PIIIP by gel chromatography, the peak of 125I-PIIIP antigen decreased 4 weeks after TAE in effective cases, whereas, no change was observed in the elution profile by gel chromatography 4 weeks after TAE in ineffective cases. These results seem to be caused by necrosis of hepatocellular carcinoma by TAE, and suggest the possibility that PIIIP is produced in hepatocellular carcinoma tissue.

Aged↗

Falsely elevated plasma aldosterone concentration by direct radioimmunoassay in chronic renal failure.

Plasma aldosterone concentration (PAC) in patients with chronic renal failure was measured by radioimmunoassay with and without dichloromethane extraction before the assay. Blood samples were obtained from patients with chronic renal failure who were undergoing maintenance hemodialysis, from patients with chronic renal failure who were not undergoing hemodialysis, and from age-matched normal subjects. With the three radioimmunoassay kits tested, the direct assays without extraction in normal subjects gave PAC values comparable to those obtained after the dichloromethane extraction; in contrast, in patients with chronic renal failure, the direct plasma radioimmunoassays yielded consistently higher values than those obtained after the extraction (p less than 0.001). When various plasma steroid metabolite fractions were separated by high-pressure liquid chromatography (HPLC) with a reverse-phase column, and each fraction was assayed for PAC with the three radioimmunoassay kits, high immunoreactivities were found in the polar fractions in the plasma from patients with chronic renal failure but not in normal plasma. The ratios of the immunoreactivities of these polar fractions to that of the aldosterone fraction, determined after HPLC separation, showed a significant positive correlation (r = 0.746, p less than 0.001) with serum creatinine concentrations in plasma from patients with chronic renal failure who were not undergoing hemodialysis. These results indicate that the values for PAC are falsely elevated in chronic renal failure when PAC is measured by radioimmunoassay kits without prior extraction. Furthermore, plasma from patients with chronic renal failure contains a polar substance(s) that cross-reacts with antialdosterone antibodies. This so far-unidentified substance increases with advancing renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

[Aldosterone metabolites in spontaneously hypertensive rats].

Several aldosterone metabolites are now known to possess some mineralocorticoid activities. In order to test the hypothesis that these metabolites could contribute to the pathogenesis of hypertension, we studied the aldosterone metabolism in SHR in vitro and in vivo. In vitro experiment, male SHR and WKY rats of 4 and 15 weeks of age were used. The microsome, cytosol and heavy mitochondria fractions from liver and kidney were isolated by ultracentrifuge. 10mg protein/ml of each subcellular fraction was incubated with 3H-aldosterone in Tris-HCl buffer at pH 7.4 containing NADPH, glucose-6-phosphate (G-6-P) and G-6-P dehydrogenase as described by Morris, D.J. et al. (Hypertension, 5 (suppl. I]: I-35-I-40, 1983.). Aldosterone and its metabolites synthesized were extracted with Sep-pak C18 cartridges and separated by HPLC on a reverse phase column. In vivo experiments, the urine of male SHR and WKY rats of 15 weeks old injected 10 microCi 3H-aldosterone intraperitoneally was collected for 48 hours, extracted and analyzed by HPLC. Peaks of steroids from SHR were compared with those from WKY. Incubation of aldosterone with liver microsomes yielded at least 10 polar and 3 less polar metabolites (A-ring reduced metabolites). SHR liver microsomes synthesized larger amounts of 3 polar metabolites than WKY liver microsomes. Liver cytosol, liver heavy mitochondria and kidney subcellular fractions mainly synthesized less polar metabolites, but failed to synthesize as much polar metabolites as liver microsomes. Kidney microsomes and cytosol from 4 weeks old SHR synthesized larger amounts of less polar metabolites compared to those from WKY. In vivo experiment, SHR of 15 weeks of age excreted larger amounts of 2 polar metabolites than WKY. The present study suggests that the difference of metabolism of aldosterone between SHR and WKY observed from an early stage in the liver and the target organ, kidney, may be associated with hypertension or its causative factors, and confirms that aldosterone will be metabolized to several polar and less polar forms by rat liver and kidney subcellular fractions.

Aldosterone↗

Quantitation of myocardial fibrosis and its relation to function in essential hypertension and hypertrophic cardiomyopathy.

Myocardial interstitial fibrosis is an important microscopic feature of hypertrophic cardiomyopathy. To determine whether interstitial fibrosis of the myocardium in hypertrophic cardiomyopathy and essential hypertension differ in quality or quantity, and to determine whether fibrosis affects cardiac function directly, we measured the percentage of fibrosis in patients of both categories and compared the severity of fibrosis with several cardiac functions. Left and right ventricular endomyocardial biopsies were performed in 25 patients with essential hypertension and in 19 patients with hypertrophic cardiomyopathy. Interstitial fibrosis was classified into four different microscopic types, and the percentage of total and of each type was calculated using the point-counting method. Although the percentage of total fibrosis was similar between the two groups, the type of fibrosis was different. There was no correlation between the percentage of total fibrosis and the mean size of myocytes in either group. Although there was a significant correlation between the percentage of total fibrosis and the thickness of the interventricular septum in hypertrophic cardiomyopathy, such correlation was lacking in hypertension. There was no correlation between the percentage of total fibrosis and the ejection fraction, cardiac index, or left ventricular end-diastolic pressure in either group. We concluded that the amount of myocardial interstitial fibrosis in hypertrophic cardiomyopathy is no greater than that in essential hypertension, but the type of fibrosis is different. Furthermore, in subjects in whom the ejection fraction is normal or only slightly decreased, fibrosis does not influence global cardiac functions.

Adult↗

Effects of CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipid and apolipoprotein levels in heterozygous familial hypercholesterolemic patients treated by low density lipoprotein (LDL)-apheresis.

Nine heterozygous patients with familial hypercholesterolemia (FH) were treated by low density lipoprotein (LDL)-apheresis using dextran sulfate cellulose columns. After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started. Pre- and post-apheresis serum cholesterol levels were decreased significantly by CS-514, from 289 +/- 24 mg/dl (mean +/- SEM) to 247 +/- 25 mg/dl and from 118 +/- 7 mg/dl to 106 +/- 9 mg/dl, respectively. Pre- and post-apheresis apolipoprotein B levels decreased significantly on CS-514 from 160 +/- 9 mg/dl to 138 +/- 8 mg/dl and from 58 +/- 6 mg/dl to 45 +/- 6 mg/dl, respectively. No adverse effects were observed during the combination therapy. Thus, the addition of an inhibitor of HMG-CoA reductase to LDL-apheresis is a useful method for further reducing serum cholesterol and apolipoprotein B levels in FH heterozygotes.

Adult↗

Removal of apolipoprotein E-enriched high density lipoprotein by LDL-apheresis in familial hypercholesterolaemia: a possible activation of the reverse cholesterol transport system.

The presence of apo E-containing HDL in familial hypercholesterolaemia was investigated and its removal by LDL-apheresis using a dextran sulphate cellulose column was demonstrated by measurement of the apo E/apo A-I molar ratio of serum and by nondenaturing polyacrylamide gel electrophoresis followed by immunoblotting. The molar ratios of apo E/apo A-I in the density greater than 1.063 kg/l fraction of serum obtained from two homozygous patients with familial hypercholesterolaemia were higher (0.021 and 0.030) than that from normal subjects (mean +/- SE 0.011 +/- 0.002) (P less than 0.05). Polyacrylamide gel electrophoresis and immunoblotting showed an increase in apo E-containing HDL similar to HDL2, in the plasma obtained from the homozygous patient with familial hypercholesterolaemia. The increased amounts of apo E-enriched HDL were removed from plasma by adsorption with a dextran-sulphate cellulose column. These results suggested that LDL-apheresis using the dextran-sulphate cellulose column, may cause an increase in the turnover rate of the apo E-containing HDL and thus facilitate cholesterol removal from the peripheral tissues.

Adolescent↗

Agonist-induced substance P receptor down-regulation in rat central nervous system.

Rat brain slices were incubated with substance P (SP), and the SP receptors on the membranes from those slices were characterized by a 3H-SP binding technique. The number of substance P receptors measured in the extensively washed membrane preparations pretreated with 3 x 10(-5) M SP was reduced by 30% compared with that in nontreated membranes. This reduction was dependent on the incubation time and temperature. The metabolic inhibitors sodium azide and 2,4-dinitrophenol protected SP receptors from the reduction. The characteristics of 3H-SP incorporation into rat brain slices were similar to those of SP receptor down-regulation, that is, the 3H-SP incorporation was time, temperature, and energy dependent. Thus these results indicate that the processes of ligand incorporation and receptor down-regulation are closely associated phenomena. These observations may be important in elucidating the phenomenon of SP-induced desensitization.

Animals↗

Effect of metoclopramide on orthostatic hypotension in diabetes mellitus: failure to demonstrate the role of vasoconstrictive hormones.

Effect of metoclopramide (MCP), a dopaminergic antagonist, on orthostatic hypotension associated with diabetes mellitus, was investigated to prove its plausible role of renin-angiotensin-aldosterone and catecholamine activation by comparative study in 6 diabetics with orthostatic hypotension (OH) and 9 diabetics without OH. With MCP treatment, drop of systolic blood pressure (SBP) on standing was significantly improved. However, the postural responses of plasma renin activity (PRA), plasma aldosterone and norepinephrine were not enhanced by MCP treatment. Moreover, MCP treatment did not modify the vascular reactivity to the exogenously infused angiotensin II and norepinephrine. Thus, it would be interesting to speculate that MCP can improve SBP through its suppressive effect on some depressor substance(s) such as bradykinin which liberates exaggeratively in diabetic OH.

Administration, Oral↗

Comparative effects of captopril and nifedipine on split renal function in renovascular hypertension.

Comparative effects of angiotensin-converting enzyme inhibitor (ACEI) captopril and calcium entry blocker nifedipine on the split renal function were studied in six patients with renovascular hypertension (RVH) with unilateral stenosis (38 +/- 5 years). Both captopril and nifedipine showed potent antihypertensive effects; the mean arterial pressure was reduced from 131 +/- 16 to 105 +/- 8 mm Hg (P less than 0.001) by captopril, and from 128 +/- 15 to 109 +/- 11 mm Hg (P less than 0.001) by nifedipine. The glomerular filtration rate (GFR) in the stenotic kidney was 24 +/- 6 mL/min, which decreased to 11 +/- 2 mL/min (P less than 0.01) during captopril administration, and only slightly decreased (18.8 +/- 5 mL/min) during nifedipine administration. The effective renal plasma flow (ERPF) increased in the nonstenotic kidneys in response to both drugs. These results show that angiotensin II rather than renal perfusion pressure may be important for maintaining GFR in the stenotic kidney, and further suggest that nifedipine may be used relatively safely in treating patients with RVH, although caution should be exercised in terms of their ability to preserve the renal function in individual kidneys.

Adult↗

Role of intestinal bacteria in the metabolism of aldosterone in man.

Urinary aldosterone metabolites were measured before and after the administration of 1 g/day of kanamycin, a nonabsorbable antibiotic, for 7 days, in 6 normal volunteers and in 11 patients with liver cirrhosis. Urinary excretion of 21-deoxytetrahydroaldosterone (21-deoxy-THAldo) decreased by 40 and 86% from the control values in normal volunteers and in patients, respectively (p less than 0.05), after kanamycin administration. Urinary excretion of 21-deoxyaldosterone (21-deoxy-Aldo) also fell by 48 and 89% in normal subjects and in patients, respectively, but the decrease was significant only in the normal subjects (p less than 0.05). In normal volunteers, urinary free aldosterone and THAldo remained constant, whereas the ratio of 21-deoxy-Aldo to aldosterone and 21-deoxy-THAldo to THAldo decreased from 10.2 to 3.7 and 2.1 to 0.3, respectively (p less than 0.01). These results indicate that intestinal bacteria participate in the metabolism of aldosterone during enterohepatic circulation in man.

Adrenal Cortex Hormones↗

Biological activity of partially purified digitalis-like substance and Na-K-ATPase inhibitor in rats.

In order to study the biological activity of endogenous digitalis-like substance (DLS) and Na-K-ATPase inhibitor (ATPI), human urine was partially purified and administered to rats, and its effects on the urinary volume, urinary Na excretion and blood pressure (BP) were determined. In addition, the effect on myocardial Na-K-ATPase activity was also measured. After the extraction of 40L of urine with a reversed phase cartridge column (S-fraction), 20 ml of chloroform was added and extraction was repeated. The chloroform layer was applied to an open silica gel column, and at a fraction with ethylacetate: methanol (60: 40, T-1 fraction), DLS and ATPI were eluted at the highest concentration. The water layer was treated with charcoal (D-1 fraction). The acute administration of K-1, T-1 fraction to rats in vivo caused significant rises in urinary volume, urinary Na excretion and BP. In chronic administration of K-1 fraction, urinary Na excretion was significantly elevated and myocardial Na-K-ATPase activity was also significantly suppressed. These results suggest that DLS and ATPI cause increase in the urinary volume and urinary Na excretion and also possess a hypertensive action; and moreover, these substance may affect the heart like cardiotonic steroids and regulate BP by increasing cardiac contractility.

Animals↗