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Yoshiyu Takeda

Publications and source records attributed to Yoshiyu Takeda.

16 recordsLinked to original sources
PubMed2006

Medical treatment of benign insulinoma using octreotide LAR: a case report.

In some patients with insulinoma, surgery is not possible due to either difficulties in detecting the tumor or advanced age. These patients need medical treatment for hypoglycemia. We report a case of benign insulinoma using the long-acting octreotide formulation, octreotide long-acting repeatable (octreotide LAR), as a medical therapy. A 67-year-old woman was referred to our hospital for examinations of hypoglycemia. A blood sample taken during a hypoglycemic episode revealed low plasma glucose concentration, hyperinsulinemia and a high C-peptide level. An abdominal CT scan demonstrated a hypervascular tumor in the body of pancreas. She was diagnosed with insulinoma. As the patient refused surgical resection of the pancreas tumor, we started to use the somatostatin analogue, octreotide, for treatment of hypoglycemia. After the treatment her plasma glucose levels were elevated and serum immunoreactive insulin (IRI) levels were decreased. For long-term treatment, we changed the treatment from daily subcutaneous injection of octreotide to monthly intramuscular administration of octreotide LAR. This treatment was also effective and hypoglycemic attacks disappeared. Both plasma glucose levels and serum IRI levels were improved. Our case demonstrated that octreotide LAR was useful for long-term medical treatment of insulinoma.

Aged↗
PubMed2006

Pathophysiological roles of the adrenal renin-angiotensin system in patients with primary aldosteronism.

The mechanism of overproduction of aldosterone in primary aldosteronism is unclear. The intraadrenal renin-angiotensin system (RAS) has been suggested to possess the functional role of the synthesizing aldosterone and regulating blood pressure. In order to clarify the pathophysiological roles of adrenal RAS in aldosterone-producing adenoma (APA), we studied the expressions of the messenger RNAs (mRNAs) of renin, angiotensinogen, type 1 (AT1R) and type 2 angiotensin II receptor (AT2R), CYP11B1 (11 beta-hydroxylase gene) and CYP11B2 (aldosterone synthase gene) in 8 patients with angiotensin II-responsive (ATII-R) APA and compared them with the expressions of the same mRNAs in 8 patients with angiotensin II-unresponsive (ATII-U) APA. Quantification of the mRNA of each gene was done using a real-time polymerase chain reaction with specific primers. There were no significant differences between ATII-R APA and ATII-U APA in the mRNA levels of renin, angiotensinogen, AT1 R, CYP11B1 and CYP11B2. The amount of AT2R mRNA was significantly higher in the patients with ATII-R APA than in those with ATII-U APA (p<0.05). These results may suggest that AT2R partially contributes to the overproduction of aldosterone in ATII-R APA.

Adrenal Glands↗
PubMed2005

The expression of messenger RNA for ADP-ribosyl cyclase in aldosterone-producing adenomas.

OBJECTIVE: Cyclic ADP-ribose (cADPR) has been reported to be as potent and powerful at releasing intracellular Ca(2+) as inositol triphosphate (IP(3)). To determine whether the cADPR system plays a signalling role in angiotensin II (Ang II)-induced aldosterone synthesis in the human adrenal gland, we investigated the effects of Ang II on ADP-ribosyl cyclase activity in human adrenal cortical tissue. In addition, the expression of ADP-ribosyl cyclase messenger RNA was evaluated in aldosterone-producing adenomas (APAs) and compared with normal adrenal tissue and nonfunctioning adenomas. DESIGN: ADP-ribosyl cyclase activity was measured in crude membrane fractions of human adrenocortical tissues with Ang II or with Ang II plus the Ang II receptor (AT(1)R) antagonist losartan or plus the AT(2)R antagonist PD123319. The effect of 8-bromo-cADPR on Ang II-induced aldosterone production from adrenal tissue was estimated. The expression of ADP-ribosyl cyclase, CYP11B2 and AT(1)R mRNA was measured in APAs, nonfunctioning adenomas, adjacent adrenal tissue and normal adrenal tissue. MEASUREMENTS: ADP-ribosyl cyclase activity was measured by using high-performance liquid chromatography (HPLC) and [(3)H] NAD(+). mRNA expression was measured by competitive reverse-transcription polymerase chain reaction (RT-PCR). Results Ang II (10(-7) and 10(-8) mol/l) significantly increased ADP-ribosyl cyclase activity in a dose-dependent manner. This increase was inhibited by pretreatment with losartan but not with PD123319. Treatment with 8-bromo-cADPR (50 micromol/l) reduced Ang II-induced aldosterone secretion. ACTH did not significantly increase the enzyme activity. The expression of ADP-ribosyl cyclase, CYP11B2 and AT(1)R mRNA was increased in APAs compared with that of nonfunctioning adenomas, adjacent adrenal tissue or normal adrenal tissue. CONCLUSIONS: These results demonstrated the existence of a signalling pathway from the Ang II receptor to ADP-ribosyl cyclase in the human adrenal gland and suggest that the cADP-ribose signalling system might play an important role in the pathogenesis of APAs.

ADP-ribosyl Cyclase↗
PubMed2005

Role of cardiovascular aldosterone in hypertension.

Aldosterone plays an important role in the pathogenesis of cardiovascular disease. We have reported that aldosterone is synthesized in cardiovascular tissues and local aldosterone synthesis plays important roles for hypertension and cardiac hypertrophy. High sodium intake develops and accelerates vascular injury and cardiac hypertrophy in SHRSP. Plasma aldosterone concentrations and PRA were decreased by high salt intake in SHRSP. Aldosterone production, the expression of CYP11B2 mRNA and angiotensin II receptor AT1R mRNA in blood vessels were significantly increased by high salt intake. These results suggest that high salt intake increases aldosterone production and expression of the AT1R mRNA in the vascular tissue in SHRSP, which may contribute to the development of malignant hypertension in salt-loaded SHRSP. However, there are several reports of conflicting data. Mineralocorticoid receptor (MR) binding is tightly regulated by the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which selectively metabolizes glucocorticoids to inactive metabolites, thus allowing for MR activation by aldosterone. We have reported that decreased 11beta-HSD2 in blood vessels in Dahl salt-sensitive (DS) rats, a model for salt-sensitive hypertension. Local aldosterone excess may play a significant role in the salt sensitivity and development of hypertension. High sodium intake decreased circulating rennin-angiotensin-aldosterone system and increased blood pressure and cardiac hypertrophy in DS rats, which were prevented by the treatment with a selective MR antagonist, eplerenone. Eplerenone also improved endothelial nitric oxide synthase (eNOS) activity and eNOS mRNA expression in blood vessels in DS rats. These results further suggest that not only circulating aldosterone but also local aldosterone is of critical importance in the pathophysiology of cardiovascular disorders.

Aldosterone↗
PubMed2004

Vascular synthesis of aldosterone: role in hypertension.

The author showed direct evidence that blood vessels are aldosteronogenic. The expression of CYP11B2 mRNA and synthesis of vascular aldosterone were decreased in rats treated with angiotensin converting enzyme inhibitor. Angiotensin II increased production of aldosterone in blood vessels. Vascular aldosterone and CYP11B2 mRNA levels of 2-week-old SHRSPs were significantly increased compared with that in WKY rats of the same age. High sodium intake develops and accelerates vascular injury and cardiac hypertrophy in SHRSP. Plasma aldosterone concentrations and plasma renin concentration were decreased by high salt intake in SHRSP. Aldosterone production, the expression of CYP11B2 mRNA and type I angiotensin II receptor (ATiR) mRNA in blood vessels were significantly increased by high salt intake. These results suggest that high salt intake increases aldosterone production and expression of the ATiR mRNA in the vascular tissue in SHRSP, which may contribute to the development of malignant hypertension in salt-loaded SHRSP.

Aldosterone↗
PubMed2004

Pleiotropic actions of aldosterone and the effects of eplerenone, a selective mineralocorticoid receptor antagonist.

Aldosterone plays an important role in the pathogenesis of cardiovascular and renal disease that is independent of angiotensin II. Mineralocorticoid receptors are expressed in nonepithelial tissues such as the heart and blood vessels. Although mineralocorticoid receptor antagonism reduces mortality in patients with congestive heart failure, the progestational and antiandrogenic side effects of the nonspecific mineralocorticoid receptor antagonist, spironolactone, have limited its usefulness in the treatment of cardiovascular diseases. This review examines the expanding role of aldosterone, including its broad spectrum of non-classical effects, and the recent clinical and experimental trials with the selective mineralocorticoid receptor antagonist, eplerenone.

Aldosterone↗
PubMed2003

Pathophysiological roles of vascular 11beta-hydroxysteroid dehydrogenase and aldosterone.

Mineralocorticoid receptor (MR) binding is tightly regulated by the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSDII) which selectively metabolizes glucocorticoids to inactive metabolites, thus allowing for MR activation by aldosterone. To examine whether this enzyme is involved in the pathophysiology of salt-sensitive hypertension, 11beta-HSDII activity and messenger RNA (mRNA) levels were determined in blood vessels of Dahl Iwai salt-sensitive (DS) and salt-resistant (DR) rats. Decreased 11beta-HSDII activity and mRNA levels in mesenteric arteries were observed in 8-week-old DS rats on a high-salt diet, indicating that 11beta-HSDII may play a significant role in salt sensitivity and hypertension. It has been suggested that mineralocorticoids act on blood vessels, leading to increased vasoreactivity and peripheral resistance. We present direct evidence that blood vessels are aldosteronogenic. The production of aldosterone in blood vessels was compared between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. Vascular aldosterone and CYP11B2 mRNA levels were significantly increased in 2-week-old SHRSP versus WKY rats. However, the vascular aldosterone levels in 4- and 9-week-old SHRSP and WKY rats were similar. High sodium intake further increased both blood pressure and vascular aldosterone synthesis in the SHRSPs. Both the local renin-angiotensin-aldosterone system (RAAS) and the vascular 11beta-HSDII level are critically important in the pathophysiology of cardiovascular disorders.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Completely skewed X-inactivation in a mentally retarded young female with pseudohypoparathyroidism type IB and juvenile renin-dependent hypertension.

Genetic analysis of the GNAS gene was performed in a patient with idiopathic renin-dependent hypertension, PTH resistance, and Albright's hereditary osteodystrophy-like characteristics such as a round face, short stature, obesity, and mental retardation (IQ, 49). Mutational analysis showed no mutations in exons 1-13 or in any exon-intron boundary. However, methylation-status analysis revealed a bialleic methylation defect in GNAS exon 1A, indicating that a GNAS-imprinting defect is the cause of her PTH resistance, as commonly observed in pseudohypoparathyroidism type IB. The imprinting defect, however, could not explain her renin-dependent hypertension and Albright's hereditary osteodystrophy-like phenotype. There are many types of X-linked mental retardation. Syndromic X-linked mental retardation, such as X-linked alpha-thalassemia mental retardation syndrome and Rett syndrome, is reportedly associated with abnormal imprinting. To further investigate this unexplained phenotype, we tested whether this patient showed skewed X-inactivation (SXI) presumably as a result of postinactivation selection against cells with a mutated gene on the active X-chromosome. Completely SXI was observed in the DNA from her leukocytes, urinary sediment, and renal tissue. A mutation of the X-chromosome might be correlated with this phenotype because of a close association between completely SXI and X-chromosomal mutation.

Adult↗
PubMed2002

Calcineurin inhibition attenuates mineralocorticoid-induced cardiac hypertrophy.

BACKGROUND: It remains unclear how mineralocorticoids induce cardiac hypertrophy and fibrosis. Recently, activation of the calcium-dependent phosphatase, calcineurin, has been shown to induce cardiac hypertrophy. In the present study, we examine the role of calcineurin in mineralocorticoid-induced cardiac hypertrophy and fibrosis. METHODS AND RESULTS: Uninephrectomized Wistar-Kyoto rats were placed on a 1.0% NaCl diet and treated with aldosterone (0.75 microg x h(-1)) for 6 weeks with or without the calcineurin inhibitors, FK506 (0.5 mg x kg(-1) x d(-1)) or cyclosporine A (10 mg x kg(-1) x d(-1)). The effect of the angiotensin II type 1 receptor antagonist, losartan (10 mg x kg(-1) x d(-1))on aldosterone-induced cardiac hypertrophy was also studied. Treatment with aldosterone increased the heart weight/body weight ratio, cardiomyocyte size, and collagen amount. The expression of mRNA of both type-III collagen and atrial natriuretic peptide in the heart were increased by aldosterone administration. Both calcineurin activity and its mRNA expression were also increased in aldosterone-induced hypertrophic heart. Treatment with losartan, FK506, or cyclosporine partially prevented aldosterone-induced cardiac hypertrophy and fibrosis. CONCLUSION: These results suggest that calcineurin is involved in the development of cardiac hypertrophy and fibrosis induced by mineralocorticoid excess. Inhibition of calcineurin may therefore prevent cardiac hypertrophy and fibrosis in mineralocorticoid hypertension.

Aldosterone↗
PubMed2002

Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus.

Study of two families containing individuals with nephrogenic diabetes insipidus (NDI) indicated different types of 21.3 kb and 26.3 kb deletions involving the AVPR2 and ARHGAP4 (RhoGAP C1) genes. In the case of the 21.3 kb deletion, the deletion consensus motif (5'-TGAAGG-3') and polypurine runs, known as the arrest site of polymerase alpha, were detected in the vicinity of the deletion junction. Inverted repeats (7/8 matches), believed to potentiate DNA loop formation, flank the deletion breakpoint. We propose this deletion to be the result of slipped mispairing during DNA replication. In the case of the 26.3 kb deletion, the 12,945 bp inverted region with the 10,003 bp internal deletion was accompanied with the 2,509 bp deletion in the 5'-side and the 13,785 bp deletion in the 3'-side. We defined three deletion junctions in this rearrangement (DJ1, DJ2, and DJ3) from the 5'-side. The surrounding sequence of DJ1 (5'-CCC-3') closely resembled that of DJ3 (5'-AGGG-3') (DJ1; 5'-cCCCgaggg-3', DJ3; 5'-ccccAGGG-3'), and DJ1 was located in the 5'-side of DJ3 without any overlapping in sequence. The immunoglobulin class switch (ICS) motif (5'-TGGGG-3') was found around the complementary sequence of DJ3. There was a 10-base palindrome (5'-aGACAtgtct-3') in the alignment of the DJ2 (5'-GACA-3') region. From these findings, we propose a novel mutation process with the rearrangement probably resulting from stem-loop induced non-homologous recombination in an ICS-like fashion. Both patients, despite lacking ARHGAP4, had no morphological, clinical, or laboratory abnormalities except for those usually found in patients with NDI.

Adult↗
PubMed2002

19-Noraldosterone in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal morbidity and mortality. 19-Noraldosterone, which was shown to be synthesized in the human adrenal gland, exhibits potent mineralocorticoid and hypertensive activity. To examine the role of mineralocorticoids in the pathophysiology of PIH, we studied urinary 19-noraldosterone, tetrahydroaldosterone, free cortisol, and cortisone concentrations and mineralocorticoid receptor levels in peripheral blood mononuclear leukocytes, from 17 women with PIH and 16 normal pregnant women as controls. Sequence analysis of the mineralocorticoid receptor gene in PIH patients was also done. The 24-h urinary excretion of 19-noraldosterone was significantly lower in PIH (120 +/- 38 pmol/day) than in controls (358 +/- 55 pmol/day) (P < 0.05). Urinary tetrahydroaldosterone was also decreased in PIH compared with controls. Ratios of urinary free cortisol to cortisone (a measure of 11beta-hydroxysteroid dehydrogenase 2 activity) did not differ significantly between groups. Mineralocorticoid receptor density was significantly (P < 0.05) decreased in the PIH group (133 +/- 15 binding sites/cell) compared with controls (255 +/- 21 binding sites/cell). No mutations were found in the coding region of the mineralocorticoid receptor gene in PIH. These results suggest that circulating aldosterone, 19-noraldosterone, and renal 11beta-hydroxysteroid dehydrogenase2 do not contribute to the pathogenesis of PIH. Regulatory factors that cause the down-regulation of the mineralocorticoid receptor in PIH should be clarified.

Adolescent↗