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Biomedical subjects

R Takeda

Publications and source records attributed to R Takeda.

At least 397 records · Page 22Linked to original sources

ApoVLDL of the Watanabe Heritable Hyperlipidemic rabbit and the cholesterol-fed rabbit.

The Watanabe Heritable Hyperlipidemic rabbit (WHHL rabbit) and the cholesterol-fed rabbit have been reported to show elevations of very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL), and a broad-beta band on agarose-gel electrophoresis. We have studied the lipid and lipoprotein composition of WHHL rabbits and cholesterol-fed rabbits using ultracentrifugal analysis and isoelectric focusing. The total cholesterol (TC)/triglyceride (TG) ratios of VLDL, IDL, and LDL in WHHL rabbits were slightly elevated, but almost normal compared with those of cholesterol-fed rabbits, whose TC/TG ratios were markedly elevated compared with normolipidemic rabbits. ApoVLDL of WHHL rabbits showed no compositional changes in apoE and apoC isoforms, and no marked changes in the apoE/apoC ratios. But apoVLDL of cholesterol-fed rabbits showed a significant decrease of apoC-III, a significant increase of apoC-V, and marked elevation of the apoE/apoC ratio. We conclude that serum lipoprotein compositions in the WHHL rabbit were normal, while the lipoprotein lipid and apolipoprotein composition in the WHHL rabbit are different from those in cholesterol-fed rabbits.

Animals↗

[Effects of 6-oxo-PGE1 on the renin-angiotensin-aldosterone system, blood pressure and platelet aggregability in man].

6-oxo-prostaglandin E1 (6-oxo-PGE1), has recently been postulated as being a possible metabolite of PGI2 and/or 6-oxo-PGF1 alpha. This compound possesses a vasodilatory, renin secretion activity and platelet aggregation inhibiting activity in the dog and rat and is more stable than PGI2. But the systemic effects of 6-oxo-PGE1 on man is not known. The present study was designed, therefore, to determine the effects of 6-oxo-PGE1 on blood pressure (BP), the renin-angiotensin-aldosterone system and platelet aggregability in man. 6 healthy male volunteers (mean age: 24.3 +/- 1.2 years) and one patient with Shy-Drager syndrome (a 57 year old female) were studied. 6-oxo-PGE1, dissolved in physiological saline, was infused intravenously at three different doses of 7.5, 15 and 30 ng/kg/min, for 15 min each. Blood samples were collected every 15 minutes for measurements of plasma renin activity (PRA), plasma aldosterone (PA), plasma cortisol (PC) and platelet aggregation inhibiting activity (Agg-inhibition). BP and pulse rate (PR) were recorded every 2 minutes. PRA, PA and PC did not change during or after the infusion. However, the platelet aggregation was significantly (p less than 0.05) inhibited in a dose-dependent manner, and this was still observed at 30 minutes after the termination of the infusion. Neither systolic or diastolic BP changed during the infusion but rose after the termination of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of corticosteroids in human adrenal tissue by high pressure liquid chromatography.

High pressure liquid chromatography (HPLC) was demonstrated to be a good tool for the separation, identification and quantitation of corticosteroids (CS) extracted from homogenized tissue of adrenal glands and adrenal tumors in patients with hypercorticism. A chromatographic system consisting of Sorbax-SIL and Sorbax-CN columns, organic solvent extraction and a UV detector was used to analyze both more polar and less polar corticosteroids in the adrenal tissue.

Adrenal Cortex Hormones↗

[Antihypertensive mechanism of oral angiotensin I converting enzyme inhibitor (captopril) in renin-independent essential hypertension].

In order to investigate the possible role of bradykinin in the hypotensive mechanism of angiotensin I converting enzyme inhibitor (Captopril) in renin-independent essential hypertension (EHT), we studied the effects of the single administration of 100 mg captopril on plasma bradykinin levels by sensitive radioimmunoassay in 21 EHT, who showed agonistic responses to 1Sar, 8Ile-angiotensin II (A IIA). Fourteen of the patients were low renin and 7 were normal renin EHT. There was no correlation between the baseline plasma renin activity (PRA) and the fall in mean blood pressure (MBP) following captopril administration. When the patients were analyzed according to MBP response, the responders (R) showed a significantly greater bradykinin increment (delta BK, +64%) (p less than 0.05), whereas the nonresponders (NR) did not show such an increase. There was a positive correlation between delta BK and the MBP reduction after captopril in the R group (r = 0.623, p less than 0.05). Plasma aldosterone (PA) decreased profoundly in the R group (-36% from baseline, p less than 0.05). Pretreatment ACE activity was significantly higher in the R group than in the NR group (p less than 0.05). Pressor response to A IIA showed a significantly (p less than 0.05) greater response after captopril administration in the R group. There were no significant differences in blood concentration of captopril between the R and NR groups. The present results suggest that bradykinin may be involved in the hypotensive action of captopril in the EHT subgroup, where the renin-angiotensin system appears to play an inert role for the elevation of blood pressure.

Adult↗

Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia. Additive effects of compactin and cholestyramine.

We studied the effects of the bile acid sequestrant cholestyramine, alone and in combination with the experimental agent compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum levels of lipoproteins in 10 heterozygous patients with familial hypercholesterolemia. After cholestyramine treatment alone for 2 to 16 months, serum total and low-density lipoprotein cholesterol decreased by 20 and 28 per cent, respectively. With the addition of compactin for 12 weeks there was a 39 per cent total decrease in serum cholesterol from the control value--from 356 +/- 14 to 217 +/- 10 mg per deciliter (9.27 +/- 0.36 to 5.64 +/- 0.26 mmol per liter [mean +/- S.E.M.]; P less than 0.001)--and a 53 per cent decrease in low-density lipoprotein cholesterol--from 263 +/- 13 to 125 +/- 10 mg per deciliter (6.84 +/- 0.34 to 3.25 +/- 0.26 mmol per liter; P less than 0.001). High-density lipoprotein cholesterol, which had increased during cholestyramine treatment, remained at its higher level. No adverse effects were observed. If long-term safety can be demonstrated, the compactin-cholestyramine regimen may prove useful in heterozygous familial hypercholesterolemia. prove useful in heterozygous familial hypercholesterolemia.

Adult↗

[The role of prostacyclin(PGI2) in the regulation of blood pressure and aldosterone response to angiotensin II].

The pressor response to angiotensin II (A II) has been shown to be enhanced, and aldosterone production to be attenuated following administration of indomethacin (Ind), a cyclooxygenase inhibitor, pretreatment. Since PGI2 has been proposed to be a potent vasodepressor prostaglandins, with steroidogenic action, the present study was undertaken to evaluate the regulatory role of PGI2 in the blood pressure and aldosterone responses to A II. Ind was administered to suppress the production of endogenous prostaglandins (30 mg/kg. im. Ind-group) and PGI2 was given after Ind pretreatment (2 ng/kg/min. iv. Ind + PGI2 group) to conscious male rabbits (2.5 approximately 3.5 kg). Baseline blood pressure readings were similar in three groups (control, Ind-, and Ind + PGI2-group). The increment of blood pressure by A II infusion were significantly enhanced in the Ind-group (12.6 +/- 1.3 mmHg) compared with the control-group (8.6 +/- 1.5 mmHg). This enhancement was diminished by PGI2 infusion (7.0 +/- 2.3 mmHg). PGI2 infusion alone does not influence blood pressure in the dose of 0.5 approximately 4.0 ng/kg/min. Aldosterone response to A II was significantly attenuated in the Ind-group (1.5 +/- 1.2 ng/dl) compared with the control-group (7.5 +/- 3.1 ng/dl), but was restored in the Ind + PGI2-group (4.5 +/- 1.3 ng/dl). It is suggested that circulating PGI2 may play a role in the regulation of blood pressure by modulating the pressor response and the aldosterone response to A II.

Aldosterone↗

A case of heterozygous familial hypercholesterolemia associated with hyperthyroidism: effects of triiodothyronine on low-density lipoprotein receptor and cholesterol synthesis.

A 58-year-old patient with heterozygous familial hypercholesterolemia (FH) showed normal levels of serum cholesterol (193 mg/dL) in coexistence with hyperthyroidism. After hyperthyroidism therapy with radioiodine and methimazole, the patient's lipid profile showed high concentrations of cholesterol (whole serum 318 mg/dL, VLDL 35 mg/dL, LDL 217 mg/dL, HDL 44 mg/dL). There was a significant inverse correlation between serum cholesterol levels and serum thyroxine levels (r = -0.815, p less than 0.01). Effects of triiodothyronine on LDL degradation and cholesterol synthesis from 14C-labeled acetate were studied in cultured skin fibroblasts. Triiodothyronine (T3) stimulated both LDL degradation and cholesterol synthesis in the cells from normal subjects and patients with heterozygous FH. The T3 increased cellular cholesterol synthesis markedly in the cells from patients with homozygous FH but did not increase LDL receptor activity. These results suggest that normal serum cholesterol levels in our case result in part from an enhancement of LDL receptors by thyroid hormone.

Cells, Cultured↗

Effect of sodium intake on prostacyclin generation in rabbit mesenteric artery.

Effect of sodium intake on prostacyclin (PGI2) generation in response to angiotensin II (A II) or noradrenaline (NA) stimulation was studied using the rabbit mesenteric artery (RMA) perfusion system. 6-oxo-PGF1 alpha, a stable metabolite of PGI2, was continuously released into the effluent at a rate of 10.7 +/- 2.2 ng/min for the initial 60 min. Perfusion pressure and 6-oxo-PGF1 alpha promptly increased in response to A II and NA. Chronic sodium loading caused a significantly (p less than 0.05) smaller PGI2 production following the A II stimulation. Vasoconstrictive responses induced by these stimuli were greater in the high sodium group. Acute changes in potassium concentration at a range between 1.2 and 5.4 mEq/L failed to affect basal PGI2 production, but an augmented response of PGI2 release by A II and NA was observed at the lowest potassium concentration. These results may suggest that vascular prostaglandins may participate in the mechanism of an altered vascular responsiveness during an altered sodium or potassium homeostasis.

6-Ketoprostaglandin F1 alpha↗

Changes of serum total cholesterol and triglyceride levels in normal subjects in Japan in the past twenty years. Research committee on familial hyperlipidemia in Japan.

Serum lipid levels of 10,977 normal Japanese subjects in 1980 were determined by a joint study of 14 institutions, specializing in lipid research, located in 9 districts of Japan. The data obtained were compared with those in 1960 and 1970. Total cholesterol (TC) levels in 1980 increased with age except for the 1st decade and reached maximum (205 mg/dl) at the 7th decade. The mean value in any age was higher than that of 20 years ago by 10-15 mg/dl. Triglyceride (TG) levels also increased with age and reached maximum (130 mg/dl) at the 7th decade. The mean values of subjects over the 5th decade were higher than those of 10 years ago by 10-20 mg/dl. In contrast with TC and TG, HDL-cholesterol levels were highest at the 1st decade and declined gradually with age. TC and TG levels of younger age (1st to 3rd decade) were equal to or even higher than those of Americans in 1972-76. It was concluded that serum lipid levels of Japanese have increased in the past 20 years and approached to the levels of Europeans and Americans.

Adolescent↗

An inhibitory effect of ethanol on adrenergic neuromuscular transmission in the guinea-pig vas deferens.

Effects of ethanol on adrenergic neuromuscular transmission were investigated in the isolated vas deferens of the guinea-pig. The contractile responses to adrenergic nerve stimulation were depressed by ethanol in a concentration-dependent, reversible manner at a concentration range between 25 and 500 mM. Ethanol also depressed the contractions induced by exogenous noradrenaline. The resting membrane potentials recorded intracellularly from the smooth muscle cells were not affected by the alcohol. The excitatory junction potentials (EJPs) evoked by nerve stimulation decreased in amplitude, but the facilitation phenomena observed with repetitive stimulation remained unaltered. Ethanol slightly increased the frequency of the spontaneous EJPs, but decreased their amplitude. The extracellularly recorded action potentials from the small sympathetic nerve bundles innervating the vas deferens were suppressed by high concentrations of ethanol (more than 200 mM). These results indicate that ethanol inhibits adrenergic neuromuscular transmission in the vas deferens probably through depressing the sensitivity of the postsynaptic membrane to the transmitter and a block of axonal conduction in the presynaptic nerve terminals.

Acetylcholine↗

Spontaneous remission of cranial diabetes insipidus due to concomitant development of ADH-producing lung cancer--an autopsied case.

The very rare occurrence of an ADH-producing small cell carcinoma of the lung in a 52 year old male patient with cranial diabetes insipidus since childhood is described. In this case diabetes insipidus disappeared concomitantly with development of lung cancer and re-appeared with shrinkage of the lung tumour by radiation therapy. Further progressive expansion of the primary and metastatic tumours induced the syndrome of inappropriate ADH secretion once again (SIADH). This deterioration in the clinical course was reflected in the plasma levels of ADH and neurophysins. The existence of vasopressin in the tumour tissue was also demonstrated by means of an immunohistochemical staining technique combined with anti-vasopressin serum.

Carcinoma, Small Cell↗

Serum and lipoprotein lipid levels in diabetic patients with familial hypercholesterolemia.

To examine the influence of glucose intolerance in familial hypercholesterolemia (FH) on coronary heart disease (CHD), we measured serum and lipoprotein lipid levels in heterozygous FH patients with and without glucose intolerance. The patients with FH were classified as having normal (N), borderline (B) and diabetic (D) glucose tolerance by 50 g OGTT according to the criteria of the Japan Diabetic Society. Fasting blood glucose levels (mean) were 78 mg/100 ml (N, n = 8), 97 (B, n = 10) and 199 (D, n = 9) in females and 85 (N, n = 12), 93 (B, n = 21) and 185 (D, n = 15) in males, respectively. Prevalence of CHD was 50% (N), 56 (B) and 89 (D) in females and 58 (N), 67 (B) and 50 (D) in males, respectively. Serum cholesterol (Chol) and triglyceride (TG) levels (mean) were 351 mg/100 ml and 112 mg/100 ml (N), 323 and 102 (B), and 342 and 187 (D) in females and 356 and 93 (N), 338 and 121 (B), and 305 and 161 (D) in males, respectively. Serum Chol in D was significantly lower than in N in males (p less than 0.02). Serum TG in D was significantly higher than in N (p less than 0.05) in both males and females. Chol and TG of VLDL in D (n = 15) were significantly higher than in B (n = 19) (p less than 0.02 and p less than 0.05) and in N (n = 15) (p less than 0.05 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of gliclazide and glibenclamide treatment in non-insulin-dependent diabetes.

Gliclazide has been reported to decrease platelet function and to inhibit the progression of diabetic retinopathy in addition to having a hypoglycemic effect. To confirm these effects we performed a double-blind randomized study using glibenclamide as a reference drug. Thirty-eight hospitals from eight university groups in Japan performed the study on type II diabetic subjects. Evaluation of blood glucose control, platelet adhesiveness, platelet aggregation and blood lipids over 24 weeks were assessed by the central committee. Two hundred and eighty-nine patients were enrolled in the study. Twelve were excluded and 277 were statistically analysed. Homogeneity between the two diabetic groups was demonstrated for background factors. Forty mg of gliclazide was comparable to 2.5 mg of glibenclamide in the potency of hypoglycemic efficacy. Funduscopic aggravations were observed in a statistically smaller number of cases in the gliclazide group than in the glibenclamide group and in evaluation of serum lipids, the gliclazide group was also superior to the glibenclamide group. No significant difference between the two groups was found in platelet adhesiveness and aggregation. Gliclazide is a useful drug in the therapy of diabetes mellitus.

Adult↗

A case of juvenile hepatocellular carcinoma associated with liver cirrhosis in a family clustering of HBs antigen carriers and liver diseases.

We describe a case of hepatocellular carcinoma in a 16-year-old boy whose mother, aunts, uncles, and cousins had liver dysfunction associated with HBs-Ag. Postmortem examination in this case revealed a hepatocellular carcinoma with a trabecular and partially pseudoglandular pattern involving the whole left and most of the right lobe, associated with liver cirrhosis of the postnecrotic type. Postmortem examination of the liver revealed numerous HBs-Ag positive hepatocytes demonstrated by Orcein staining in the nontumorous cirrhotic area, but not in the tumorous hepatocytes. Vertical transmission of HBV from his mother to the patient was suspected, and autopsy findings revealed continuous infection of HBV. Hepatocellular carcinoma in a young patient, especially when associated with HBs-Ag positive liver cirrhosis, as described here is rare in the English and Japanese literature.

Adolescent↗