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R Takeda

Publications and source records attributed to R Takeda.

At least 73 records · Page 4Linked to original sources
PubMed1995

Significance of 19-noraldosterone, a new mineralocorticoid, in clinical and experimental hypertension.

19-Noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, possesses potent mineralocorticoid and hypertensinogenic activities. 18,19-Dihydroxycorticosterone (18,19-(OH)2-B) and 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B), a possible precursor of 19-noraldosterone, have been identified in human urine. These mineralocorticoid hormones are regulated by the renin-angiotensin system and synthesized in adrenal glomerulosa cells. Urinary 19-noraldosterone correlated with urinary 18,19-(OH)2-B, 18-OH-19-nor-B, 18-hydroxycorticosterone (18-OH-B), and aldosterone. Urinary excretion of 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B were increased in patients with aldosterone-producing adenoma (APA) and in those with idiopathic hyperaldosteronism (IHA), but the two did not differ significantly. Urinary 18-OH-B and 18-hydroxycortisol (18-OH-F) were significantly higher in APA compared with IHA. Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, urinary 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B could not be used to distinguish the two subsets of primary aldosteronism. Urinary 19-noraldosterone did not differ in hypertensive and normotensive patients. However, urinary 19-noraldosterone was increased in some hypertensive patients. In spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), urinary 19-noraldosterone was increased at the prehypertensive stage compared with Wistar-Kyoto (WKY) rats. Urinary 19-noraldosterone was decreased in 9-week-old SHR and SHRSP compared with WKY rats. However urinary 19-noraldosterone was higher in SHRSP than in SHR. These elevated levels of 19-noraldosterone may contribute to hypertension in some individuals and in experimental hypertensive rats.

Aldosterone↗
PubMed1995

Effects of short-term aminophylline administration on cardiac functional reserve in patients with syndrome X.

OBJECTIVES: This study sought to evaluate the effect of adenosine receptor blockade by aminophylline on cardiac functional reserve in patients with syndrome X. BACKGROUND: Aminophylline may have a potentially antiischemic effect through the inhibition of adenosine and, thus, the coronary steal phenomenon in patients with syndrome X. METHODS: A single-blind, placebo-controlled study of an intravenous infusion of aminophylline (6 mg/kg body weight over 15 min) or placebo (20 ml of saline solution over 15 min) was performed during continuous radionuclide monitoring of left ventricular ejection fraction in 12 patients performing supine bicycle ergometric exercise. RESULTS: Aminophylline increased exercise time (aminophylline 400 s vs. placebo 355 s, p < 0.01), decreased degree of ST segment depression (aminophylline 1.6 mm vs. placebo 2.4 mm, p < 0.01) and either abolished (seven patients) or diminished (five patients) chest pain during exercise. Aminophylline also increased left ventricular ejection fraction at rest (aminophylline 66.5% vs. placebo 62.3%, p < 0.05) but did not improve its deterioration at peak exercise (aminophylline 60.1% vs. placebo 56.6%, p = NS) or shorten the abnormally prolonged interval between the end of exercise and the overshoot (aminophylline 115 s vs. placebo 130 s, p = NS). CONCLUSIONS: Aminophylline infusion increases ischemic threshold and prolongs exercise duration in patients with syndrome X. It is hypothesized that aminophylline acts by inhibiting the coronary steal phenomenon through adenosine receptor blockade. It does not improve the deterioration in left ventricular function at peak exercise or the delayed response in ejection fraction in the recovery period, presumably because the beneficial effects of aminophylline that result from the redistribution of coronary blood flow are limited.

Aminophylline↗
PubMed1995

Effect of aging on urinary excretion of 19-noraldosterone and 18,19-dihydroxycorticosterone.

19-Noraldosterone, recently shown to be produced in the human adrenal gland, possesses potent mineralocorticoid and hypertensinogenic activity. A possible precursor, 18,19-dihydroxycorticosterone, has been identified in human urine, with both steroids acutely regulated by the renin-angiotensin system. The secretion of aldosterone declines with advancing age. To elucidate the effect of aging on the urinary excretion of 19-noraldosterone and 18,19-dihydroxycorticosterone, we measured their urinary concentrations in 51 normotensive subjects aged 20-70 years. We observed significant negative correlations between age and the urinary excretion of 19-noraldosterone and 18,19-dihydroxycorticosterone (r = -0.69, r = -0.65, P < 0.05, respectively). Urinary and plasma aldosterone and PRA similarly decreased with aging. These results suggest that 19-noraldosterone may be chronically regulated in part by the renin-angiotensin system.

18-Hydroxycorticosterone↗
PubMed1995

Characterization of three cDNAs encoding two isozymes of an isoaspartyl protein carboxyl methyltransferase from human erythroid leukemia cells.

Two different sizes (approximately 1.0 and 1.6 kb) of transcripts of an isoaspartyl protein carboxyl methyltransferase (PIMT) were detected in eight cell lines derived from human hemopoietic cells on Northern blot analysis. We found three different sizes of cDNAs (907, 1,553, and 1,600 bp) in human erythroid leukemia cells (HEL) and a unique cDNA sequence corresponding to the 1.0 kb transcript was identified. These three cDNA sequences encoded two isozymes consisting of 226 (isozyme I) and 227 (isozyme II) amino acids. The 1.6 kb transcript was translated into two isozymes (isozyme I and II), while the 1.0 kb transcript was only translated into isozyme I. These results suggest that the two isozymes deduced from the cDNAs of the human erythroid leukemia cells may exist in normal human erythrocytes.

Amino Acid Sequence↗
PubMed1995

Rapid detection and prevalence of the variants of the angiotensinogen gene in patients with essential hypertension.

OBJECTIVES: The angiotensinogen (AGT) gene has been implicated as a candidate gene of high blood pressure. However, because the variants of the AGT gene are point mutations, it is difficult to detect them in large scale population studies. The aims of this study were to develop a rapid screening method for the point mutations and, using this method, to determine the possible role of the AGT gene variant in high blood pressure in the Japanese population. DESIGN AND SUBJECTS: A rapid screening method for the point mutations by means of primer-specified restriction map modification is described here. Using this method, the distribution of two variants of the AGT gene, M235T and T174M, was determined in 80 patients with essential hypertension (EHT) and 100 normotensive controls (control). RESULT: The hypertensive group showed a significantly (P < 0.05) higher frequency for the T174M variant but the same frequency for the M235T variant. CONCLUSION: These data provide evidence in favour of an association between hypertension and a genetic variant of AGT in human EHT, and a marked ethnic difference in the AGT gene.

Adult↗
PubMed1995

Effects of sevoflurane on respiratory activities in the phrenic nerve of decerebrate cats.

Although the depressive effect of sevoflurane on ventilation has been reported, its potency and mode of action on the neural respiratory activity is still unclear. Therefore, the effects of sevoflurane on the phrenic nerve discharge and the respiratory timing were compared with those of halothane. The efferent activity of the phrenic nerve was recorded from decerebrate, un-anesthetized and artificially ventilated cats, and its power spectrum was calculated. The inspiratory and expiratory periods were measured. Sevoflurane and halothane of the doses of 0.5-1.5 MAC were inhaled for 15 min. With 0.5 MAC, sevoflurane decreased the total power and two dominant spectral components of the high-frequency oscillation and medium-frequency oscillation in the power spectrum. With the same MAC dose, halothane had a greater depressive effect in a normocapnic condition with the vagus nerves being intact. In a state of hypercapnia or after vagotomy, the effect of halothane was considerably attenuated whereas that of sevoflurane remained unaltered. Halothane increased the neural respiratory rate much more than sevoflurane in both normocapnic and hypercapnic states. Vagotomy significantly weakened the effect of halothane to increase the respiratory rate but did not modify the effect of sevoflurane. With 1.0-1.5 MAC, both anesthetics severely decreased the phrenic power spectra and the potency difference became indistinct. The present findings demonstrate that sevoflurane has a weaker depressive effect on the respiratory nerve discharge and a smaller effect on the neural respiratory rate than halothane when the effects of 0.5 MAC were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Urinary excretion of 19-noraldosterone in the spontaneously hypertensive rat and stroke-prone spontaneously hypertensive rat.

1. We measured the urinary excretion of 19-noraldosterone in the spontaneously hypertensive rat (SHR) and stroke-prone SHR (SHRSP) during the development of hypertension and compared these measurements with Wistar-Kyoto (WKY) rats. 2. 19-Noraldosterone in rat urine was confirmed using HPLC-MS. Urine samples were collected from 4 and 9 week old SHR (n = 12), SHRSP (n = 12) and WKY rats (n = 9). 19-Noraldosterone was measured by specific radio immunoassay after purification of the urine extracts with HPLC. 3. There were no significant differences in plasma corticosterone among SHR, SHRSP and WKY rats at 4 and 9 weeks of age. Aldosterone levels were increased in the prehypertensive SHR and SHRSP. Nine week old SHRSP showed high plasma concentration of aldosterone compared with SHR or WKY rats of the same age. 4. Urinary excretion of 19-noraldosterone was increased in 4 week old SHR (15 +/- 4.2 pmol/day) and SHRSP (17 +/- 5.0 pmol/day) compared with WKY rats (9 +/- 3.9 pmol/day) at the same age. Nine week old SHR showed decreased urinary excretion of 19-noraldosterone compared with WKY rats at the same age. Urinary levels of 19-noraldosterone were higher in SHRSP (11 +/- 4.9 pmol/day) than in SHR (7 +/- 4.0 pmol/day) at 9 weeks of age. 5. Adrenal mineralocorticoids are suggested to be responsible for the abnormal vascular reactivity observed in SHRSP. Relatively elevated levels of 19-noraldosterone in SHRSP may contribute to malignant hypertension in this model.

Aldosterone↗
PubMed1995

Ceroid pigment deposition in circulating blood monocytes and T lymphocytes in Hermansky-Pudlak syndrome: an ultrastructural study.

An electron microscopic study of peripheral leukocytes obtained from a 39 year old woman with Hermansky-Pudlak syndrome was performed. Ceroid pigment granules were found within the lysosomes in 3.5% of monocytes and 5.4% of lymphocytes. Infrequently, pigment granules were also found in the parallel tubular arrays of lymphocytes. The lymphocytes containing ceroid pigment granules were confirmed to be T cells by immunoelectron microscopy. It was speculated that intralysosomal accumulation of ceroid pigment granules in Hermansky-Pudlak syndrome may be due to lysosomal dysfunction.

Adult↗
PubMed1995

Production of aldosterone in isolated rat blood vessels.

Angiotensin I (Ang I), Ang II, angiotensinogen, and renin are formed locally in the vasculature. We undertook this study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an angiotensin-converting enzyme inhibitor, Ang II, or potassium on aldosterone production in vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 hours. The perfusate was collected and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system. The fraction corresponding to synthetic aldosterone was collected and analyzed by mass spectrometry. The aldosterone concentration in the perfusate from the adrenalectomized rats and rats treated with an angiotensin-converting enzyme inhibitor was measured using radioimmunoassay after HPLC separation. The mass spectra of synthetic aldosterone and aldosterone isolated from the perfusate of rat mesenteric arteries were identical. Aldosterone production in the mesenteric arteries of adrenalectomized rats was increased and of rats treated with an angiotensin-converting enzyme inhibitor was reduced compared with that of controls. Ang II (1.9 x 10(10) mol/L) and potassium (6.0 mmol/L) increased aldosterone production in mesenteric arteries. This study shows that the rat mesenteric artery produces aldosterone and that the intravascular renin-angiotensin-aldosterone system may contribute to vascular tone.

Adrenalectomy↗
PubMed1995

Effects of an endothelin receptor antagonist in rats with cyclosporine-induced hypertension.

Cyclosporine, a potent immunosuppressant, is associated with the development of hypertension and nephrotoxicity. We have previously shown that endothelin release from the arteries is increased in rats with cyclosporine-induced hypertension. We conducted the present study to determine whether the specific endothelin type A (ETA) receptor antagonist FR 139317 prevents cyclosporine-induced hypertension and whether cyclosporine increases ETA receptor mRNA in blood vessels. Cyclosporine (25 mg/kg per day) given for 4 weeks increased blood pressure from 98 +/- 12 to 156 +/- 14 mm Hg; this increase was blunted by coadministration of 10 mg/kg per day FR 139317 (ie, blood pressure was 138 +/- 14 mm Hg) in Wistar-Kyoto rats. Cyclosporine induced greater vasoconstrictor responses to norepinephrine and angiotensin II in isolated mesenteric arteries. FR 139317 normalized the vasoconstrictor responses to angiotensin II and norepinephrine. Cyclosporine (25 mg/kg per day) given for 4 weeks increased ETA receptor mRNA expression in the rat aorta and mesenteric artery (170% and 176%, respectively). Little change was observed in ETB receptor mRNA. These results indicate that cyclosporine may increase blood pressure by increasing not only endothelin production but also ETA receptor in the vasculature. The specific ETA receptor antagonist FR 139317 may prevent the hypertension induced by cyclosporine.

Angiotensin II↗
PubMed1995

Effects of angiotensin-converting enzyme inhibitor and aldosterone antagonist on myocardial collagen in cardiomyopathic hamsters.

To examine the effects of angiotensin-converting enzyme (ACE) inhibitor and aldosterone antagonist on myocardial collagen in the cardiomyopathic hamster, the collagen concentration was measured by determining the hydroxyproline concentration, and the ratio of type I to type III collagen (type I/III ratio) was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Five-week-old Bio14.6 cardiomyopathic hamsters were treated with the ACE inhibitor captopril (20 mg/kg per day) or the aldosterone antagonist K-canrenoate (20 mg/kg per day) in drinking water for 20 weeks, and the collagen concentration and type I/III ratio at 25 weeks were compared with those in 25-week-old untreated Bio14.6 and normal F1b hamsters. The collagen concentration markedly increased and the type I/III ratio significantly decreased (ie, type III collagen dominant) in untreated Bio14.6 compared with F1b at 25 weeks. Captopril and K-canrenoate treatment significantly reduced the collagen concentration and reversed the changes in the type I/III ratio in cardiomyopathic hamster. These results suggest that ACE inhibitor and aldosterone antagonist improve myocardial collagen in the cardiomyopathic hamster, not only quantitatively but also qualitatively, and that the mechanism of this improvement may be related to the cardiac renin-angiotensin-aldosterone system.

Aging↗
PubMed1995

Endocrine and auto-paracrine factors in the pathogenesis of primary hypertension.

Referring to the mosaic theory of Page, the authors present an overview of recent topics related to the participation of endocrine and auto-paracrine factors, such as steroids, ouabain-like substance, insulin, renin-angiotensin and endothelin, in the pathogenesis of primary hypertension. These factors promote the development of hypertension in either a direct or indirect manner; in addition, they promote, to some extent, the proliferation of vascular smooth muscle cells. Future research should attempt to elucidate interactions between these factors in cardiovascular tissues and to define how these factors interact with various vasodepressor substances to regulate blood pressure.

Animals↗
PubMed1995

Septic pulmonary emboli secondary to pyogenic liver abscess in a diabetic patient.

A 70-year-old woman with poorly controlled diabetes mellitus was admitted because of persistent remittent fever. Soon a liver abscess was detected as the cause of the fever by ultrasonography, and antibiotic therapy was started. However, suddenly serious dyspnea with chest and back pain developed. The morbid condition was definitely diagnosed as septic pulmonary emboli (SPE) with pulmonary perfusion scan. It should be recognized that liver abscess can be a latent focus of systemic metastatic complications such as SPE, and not only early detection but also prompt appropriate drainage of liver abscesses is essential.

Aged↗
PubMed1995

Increased plasma levels of immunoreactive endothelin and von Willebrand factor in NIDDM patients.

OBJECTIVES: To elucidate the significance of plasma levels of endothelin (ET) and von Willebrand factor (vWF) as possible markers for endothelial dysfunction in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Plasma levels of ET and vWF were determined in 22 NIDDM patients with or without retinopathy and 10 normal control subjects. RESULTS: The plasma levels of immunoreactive endothelin (irET) and vWF in NIDDM patients were 0.78 +/- 0.06 pmol/l and 218.3 +/- 18.4%, respectively, which represented significant (P < 0.05, P < 0.01, respectively) differences from the values in the control group (0.50 +/- 0.06 pmol/l and 139.1 +/- 11.1%, respectively, n = 10). However, when the diabetic patients were divided into two groups according to the presence or absence of diabetic retinopathy, the plasma levels of irET and vWF in the NIDDM patients with retinopathy were significantly higher (1.01 +/- 0.07 pmol/l and 283.0 +/- 21.4%, respectively, n = 12) compared with the control group and NIDDM patients without retinopathy (0.59 +/- 0.06 pmol/l and 164.3 +/- 17.0%, respectively). Plasma levels of irET showed a significant (P < 0.01) positive correlation with the levels of vWF. CONCLUSIONS: These data strongly suggest that increased plasma irET reflects the endothelial cell damage in NIDDM.

Adult↗
PubMed1995

The frequency of 4977 base pair deletion of mitochondrial DNA in various types of liver disease and in normal liver.

Using a polymerase chain reaction (PCR) method, we tested for the hepatic mitochondrial DNA (mtDNA) deletion in 40 hepatic tumors (28 hepatocellular carcinomas [HCCs], 9 other malignant tumors, and 3 benign tumors) and in the livers of 71 patients, including 16 pediatric patients with end-stage liver disease who underwent living related donor liver transplantation and 16 liver donors. A 4977 base pair (bp) deletion of mtDNA was detected in 36 of 55 specimens of non-tumor portions of adult liver (65.5%). However, none of the specimens obtained from cirrhotic livers of the 16 pediatric patients younger than 13 years of age had the 4977 bp deletion. The frequency of mtDNA deletion was significantly decreased compared with normal liver in HCCs (7 of 28) and other malignant liver tumors (2 of 9). The frequency of this deletion was unrelated to the presence of liver cirrhosis, patient's gender, hepatitis B virus surface antigen status, and hepatitis C virus antibody status.

Adolescent↗
PubMed1995

Effect of FK 506 on the expression of endothelin receptor mRNA in the vasculature.

Tacrolimus (FK 506) is a new, more powerful immunosuppressant and is more effective in the prevention and treatment of allograft rejection in humans than cyclosporine (CysA). The present study was conducted to determine whether FK 506 increases ET(A) receptor mRNA in blood vessels in rats. FK 506 5 mg/kg/day for 4 weeks increased blood pressure and expression of ET(A) receptor mRNA in mesenteric arteries of Wistar-Kyoto rats. However, 0.5 mg/kg/day of FK 506 did not increase blood pressure or ET(A) mRNA levels in the vasculature. The dose of 0.1 microM CysA used in clinical practice induced expression of ET(A) receptor mRNA in cultured rat vascular smooth-muscle cells (VSMCs). A clinical dose (0.01 microM) of FK 506 did not increase expression of ET(A) receptor mRNA in VSMCs. However, 0.1 microM FK 506 increased the levels of ET(A) receptor mRNA in VSMCs. These results indicate that the upregulating effect of FK 506 on the ET(A) receptor in the vasculature may contribute to the genesis of FK 506-induced hypertension. The lower incidence of complications seen with FK 506 may be due in part to its use at a lower clinical dose compared to that of CysA.

Animals↗
PubMed1994

A unique receptor-mediated mechanism in vagal chemoreception of somatostatin in the hepatoportal area.

Our previous results have indicated that the hepatic vagus is receptive to intraportal appearance of somatostatin-14 (SS), a gastroenteropancreatic peptide hormone, in rat. To examine the actual involvement of the SS receptor mechanism in the neural reception, the receptor function was modified with monoclonal antibody against rat neural SS receptor. Our monoclonal antibody of IgG1(kappa) isotype bound to the SS binding site of the receptor in competition with the ligand. Intraportal SS injection at a physiological dose (3.05 pmol) significantly facilitated the afferent firing discharge rate of the hepatic vagus in rats anesthetized with urethane and chloralose. The antibody ascites, but not the control ascites, administered intraportally 5 min prior to the SS injection abolished completely the SS-induced increase in discharge rate. However, when the antibody was administered more than 15 min after the SS injection, the SS-induced increase in discharge rate did appear, implying an unique post-receptor mechanism in reception. The present results indicate that the SS receptor mechanism operates in the neurochemoreception of SS, suggesting the existence of a hepatic vagal, receptor-mediated system for monitoring the hormone secreted from the splanchnic organs.

Afferent Pathways↗