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Mitsuhide Naruse

Publications and source records attributed to Mitsuhide Naruse.

At least 19 recordsLinked to original sources
PubMed2006

Transcatheter arterial embolization for the treatment of liver metastases in a patient with malignant pheochromocytoma.

A 63-year-old male patient was admitted for the treatment of malignant pheochromocytoma with multiple liver metastases. Plasma and urinary levels of catecholamines were elevated. Transcatheter arterial embolization (TAE) with concomitant administration of mitomycin C and gelatin sponge was performed for the treatment of liver metastases. Dose of alpha-1 blocker before TAE was increased to prevent hypertensive crisis during and after TAE. The hepatic metastatic lesion of CT findings was decreased after TAE. Although blood pressure showed a transient hypertension (180/100 mmHg) after every TAE, it returned rapidly to normal. The patient experienced transient abdominal pain, nausea, and loss of appetite after every TAE; however, those symptoms were readily controlled by conventional medications. Slight elevation of liver transaminases was recognized but returned to normal range within 3 weeks. No other major side effects were seen with TAE. While plasma and urinary level of catecholamines were unchanged, plasma chromogranin A (CgA) level was significantly decreased. These results suggest that TAE is a useful treatment for hepatic metastases. Plasma CgA level is a useful marker in the treatment of malignant pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed2005

Clinical and molecular features of a TSH-secreting pituitary microadenoma.

We describe a case of a thyroid stimulating hormone (TSH)-secreting pituitary microadenoma, and report the systematic gene expression profile of the surgically- removed tumor. A 50-year-old woman was referred to our hospital because she had high TSH, free-T4, and free-T3 levels, and a pituitary tumor that was visualized with magnetic resonance imaging. Her basal TSH level was high even after a high T3 loading dose, and increased following administration of thyroid releasing hormone (TRH) even after administration of a high dose of exogenous T3. Her clinical symptoms and peripheral markers for T3 were responsive to exogenous T3. There was no thyroid hormone receptor (TR) beta gene mutation. The patient was diagnosed with a TSH-secreting pituitary adenoma, and trans-sphenoid surgery was performed. The histologic features and immunophenotype were consistent with a TSH-secreting pituitary adenoma. Reverse transcription-polymerase chain reaction analysis of pituitary hormones, pituitary-specific transcription factors, receptors, and transcriptional cofactors of clinical significance was performed on the removed tumor. The tumor expressed TSH, growth hormone, prolactin, alpha-subunit, pituitary transcription factor-1 (pit-1) but not proopiomelanocortin (POMC), prophet of pit-1 (prop-1) and pituitary cell-restricted T box factor (Tpit). TRbeta and TRH-receptor gene expression was normal. Three steroid receptor coactivators (SRC)-1, SRC-2, and SRC-3 were expressed. Nuclear receptor corepressor (N-CoR)2 was absent in the tumor, whereas nuclear receptor corepressor (N-CoR1) was expressed. Somatostatin receptor type 1 expression was significantly decreased, whereas type 4 receptor was expressed, which are unusual characteristics for pituitary tumors. The gene expression pattern in the tumor might have a role in the clinical features of this case.

Adenoma↗
PubMed2005

New genetic causes of pheochromocytoma: current concepts and the clinical relevance.

Pheochromocytoma and paraganglioma are tumors of the autonomous nervous system mainly occurring in the adrenal medulla, but also in the extraadrenal paraganglias of the abdomen, thorax, neck and skull basis. The etiology comprises germline mutations of now 6 genes. About 10 years known are the RET gene susceptible for multiple endocrine neoplasia type 2, the VHL gene for von Hippel-Lindau Disease, and the NF 1 gene for neurofibromatosis Recklinghausen (neuro- fibromatosis type 1). Since 2000 the genes for succinatedehydrogenase subunits SDHB, SDHC, and SDHD have been identified for paraganglioma syndromes type 4, type 3, and type 1 respectively. Investigations of series of pheochromocytoma patients identified germline mutations in one of the genes SDHB, SDHD, VHL and RET in 24% to 50% of the patients. Multifocal tumors, young age and positive family history, known features associated with inheritence, have not been present in all patients. Therefore, analyses of blood DNA for mutations in these genes are recommended. Positive tests provide the patients and their relatives with essential platforms for clinical care. Experiences in this field of medicine have shown that optimal management of patients with pheochromocytoma-associated syndromes is a high challenge. National registries may be instrumental in order to provide with adequate facilities.

Adrenal Gland Neoplasms↗
PubMed2004

Hsp90 inhibitors attenuate effect of dexamethasone on activated NF-kappaB and AP-1.

Heat shock protein 90 (Hsp90) regulates the functions of glucocorticoid receptor (GR). Hsp90 inhibitors geldanamycin (GA) and radicicol (Rad) have been studied as anti-inflammatory agents; however, their effects on glucocorticoid-mediated anti-inflammatory mechanism are not known. In the present study, we examined the effects of dexamethasone (Dex) and Hsp90 inhibitors, alone and in combination, on the activation of GR and proinflammatory transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In cell-based reporter assay, Hsp90 inhibitors inhibited Dex-induced nuclear import and transcriptional activity of GR. Both tumor necrosis factor-alpha-activated NF-kappaB and phorbol ester-activated AP-1 were inhibited by Dex and Hsp90 inhibitors alone. When the cells were treated with a combination of these drugs, the inhibitory effect of Dex was significantly attenuated by Hsp90 inhibitors. We further examined the effects of Dex and Rad on lipopolysaccharide-induced gene expressions of the proinflammatory cytokine interleukin (IL)-1beta in macrophages. Dex, but not Rad, inhibited IL-1beta expression. Rad concentration-dependently attenuated the inhibitory effect of Dex. These results suggest that Hsp90 inhibitor itself inhibits the activation of NF-kappaB and AP-1, however, impedes Dex-induced inhibition of IL-1beta induction by attenuating Dex-mediated activation of GR and inhibition of the proinflammatory transcription factors.

Animals↗
PubMed2004

Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90.

Heat shock protein 90 (Hsp90) has been demonstrated in both cytoplasm and nucleus, and regulates cytoplasmic retention of glucocorticoid receptor (GR). However, the role of nuclear Hsp90 in GR trafficking is less characterized. The present study examined the role of Hsp90 in nuclear retention of GR after ligand withdrawal. Hsp90 inhibitors; geldanamycin (GA) and radicicol (Rad), significantly accelerated nuclear export of GR after withdrawal of ligands including dexamethasone, corticosterone and RU486. GA accelerated relocalization of GR in the cytoplasm even when reimport of GR into the nucleus was inhibited by okadaic acid or when novel GR synthesis was inhibited by cycloheximide. Overexpression of wild type or nuclear-targeted Hsp90 attenuated Hsp90 inhibitor-induced acceleration of GR nuclear export, although nuclear Hsp90 showed higher activity than the wild type. Only nuclear-targeted Hsp90 prolonged basal nuclear retention of GR after withdrawal of dexamethasone and corticosterone. These results suggest that nuclear Hsp90 regulates the nuclear retention of GR.

Active Transport, Cell Nucleus↗
PubMed2004

Severe hyperreninemic hypertension associated with spontaneous renal cholesterol crystal embolization.

A 70-year-old man was admitted because of severe hypertension and renal insufficiency. Marked elevation in plasma renin activity (PRA; 34.2 ng/ml per h) was noted. Five days later, the patient developed hemorrhagic duodenal ulcers and panperitonitis, went into shock, and died. An autopsy revealed severe atherosclerosis with marked ulceration in the abdominal aorta. Renal histology showed multiple cholesterol crystal embolization (CCE) associated with infarction. Cholesterol crystals were also detected in the vessels of the gastrointestinal system, including the liver, stomach, colon, and pancreas. Although not common, spontaneous CCE should be considered in elderly patients who present with abrupt onset of severe hypertension associated with renal insufficiency. The most important finding in this patient was severe hyperreninemia. Although potentiation of the renin-angiotensin-aldosterone system is the suggested mechanism for the hypertension in renal CCE, we could not find any reported case of renal CCE with hyperreninemia. It is reasonable to consider that severe hyperreninemia might be overlooked in renal CCE. PRA should be measured in patients with renal CCE, because it may give important information for selecting antihypertensive agents and improving the prognosis. To clarify this possibility, an accumulation of similar cases is necessary.

Acute Kidney Injury↗
PubMed2004

Aldosterone antagonist facilitates the cardioprotective effects of angiotensin receptor blockers in hypertensive rats.

BACKGROUND: There is increasing evidence to support the importance of blocking aldosterone to prevent target-organ damage in hypertension. We recently demonstrated an aldosterone breakthrough phenomenon during administration of an angiotensin type 1 receptor blocker (ARB). OBJECTIVE: To elucidate the pathophysiological significance of residual aldosterone by investigating the influence of the aldosterone antagonist on the cardioprotective effects of the ARB in hypertensive rats. METHODS: Injection vehicle alone, ARB (1.0 mg/kg per day candesartan by mouth), aldosterone antagonist (10 mg/kg per day spironolactone, subcutaneously), or combined treatment were administered to male stroke-prone spontaneously hypertensive rats for 24 weeks from the age of 4 weeks. Blood pressure, plasma angiotensin II and aldosterone concentrations, left ventricular weight, expression of type I and type III collagen mRNA, and histological findings were determined. RESULTS: In the ARB-treated group, aldosterone concentrations remained unchanged (1.10 +/- 0.20 nmol/l, compared with 1.17 +/- 0.46 nmol/l in the control group), whereas systolic blood pressure (178 +/- 9 mmHg), left ventricular weight (0.372 +/- 0.035 g/100 g body weight), expression of collagen mRNA, and cardiac interstitial and perivascular fibrosis all decreased significantly compared with the control group (systolic blood pressure: 222 +/- 10 mmHg, P < 0.05; left ventricular weight: 0.483 +/- 0.021 g/100 g body weight, P < 0.05). Although blood pressure (217 +/- 9 mmHg) and left ventricular weight (0.467 +/- 0.027 g/100 g body weight) remained unchanged in the group receiving spironolactone, the expression of both types of collagen mRNA and cardiac interstitial and perivascular fibrosis showed a significant decrease compared with the vehicle-treated group. In the rats receiving combined treatment with the ARB and spironolactone, left ventricular weight (0.352 +/- 0.005 g/100 g body weight, P < 0.05), expression of collagen mRNA, and cardiac interstitial and perivascular fibrosis all showed a further improvement compared with both the ARB and spironolactone groups. CONCLUSIONS: These results demonstrate that residual aldosterone has a significant impact on target-organ damage in hypertension, even during chronic administration of an ARB. The addition of an aldosterone antagonist has an advantage in facilitating the cardioprotective effects of ARBs.

Aldosterone↗
PubMed2004

Effects of AT1 receptor antagonist and spironolactone on cardiac expression of ET-1 mRNA in SHR-SP/Izm.

Angiotensin II stimulates and angiotensin-converting enzyme inhibitor decreases endothelin-1 expression. Effects of the angiotensin-type 1 antagonist (angiotensin receptor blocker) on tissue expression of endothelin-1 in hypertension remained unknown. We investigated the effects of angiotensin-type 1 antagonist with and without co-administration of the aldosterone receptor antagonist spironolactone on cardiac expression of endothelin-1 mRNA. Angiotensin receptor blocker (candesartan, 1.0 mg/kg per day) was orally administered to male spontaneously hypertensive stroke-prone rats/Izm from 4 weeks of age for 4 weeks, 12 weeks and 28 weeks (angiotensin receptor blocker group). Lowdose spironolactone (10 mg/kg per day, s.c.), which does not affect blood pressure, was co-administered with angiotensin-type 1 antagonist for 28 weeks (angiotensin-type 1 antagonist + spironolactone group). Cardiac expression of endothelin-1 mRNA was determined. In the angiotensin receptor blocker group, although cardiac expression of endothelin-1 mRNA was significantly decreased after 4 weeks of treatment, it was significantly increased after 12 weeks and 28 weeks of treatment. In the angiotensin receptor blocker + spironolactone group, while systolic blood pressure did not show a further decrease from that in the angiotensin receptor blocker group, cardiac expression of endothelin-1 mRNA was decreased to the level in the untreated group. These results suggest that effects on endothelin-1 expression could modify the cardioprotective effects of angiotensin receptor blocker. Coadministration of angiotensin receptor blocker with low-dose spironolactone is recommended for further cardioprotection via suppression of endothelin-1 expression.

Administration, Oral↗
PubMed2004

The diagnostic standard of preclinical Cushing's syndrome: evaluation of the dexamethasone suppression test using various cortisol kits.

Incidental discovery of an adrenal mass, the so-called adrenal incidentaloma, has been increasing due to the advances in non-invasive diagnostic imaging tools. The criteria of diagnosis for preclinical Cushing's syndrome (preCS) in Japan were made by Nawata et al. supported by the Ministry of Health and Welfare in 1995. The results of suppression of cortisol by dexamethasone (DEX) (plasma cortisol above 3 microg/dl after 1 mg of DEX and above 1 microg/dl after 8 mg of DEX) are essential for the diagnosis of preCS due to an adrenal adenoma. However, plasma cortisol levels after the two doses of DEX suppression tests were found to be discrepant and repeated DEX suppression tests sometimes yielded different results. Therefore, we examined the cortisol values of DEX suppression tests in patients with preCS using four different cortisol assay kits: Amerlex cortisol kit (AMA), SPAC-S cortisol kit (SPA), ADVIA-Centaur cortisol assay (ADV) and ECLusys 2010 cortisol assay (ECL). The diagnosis for preCS was done using the AMA kit. Correlation between the kits was good. However, cortisol levels measured by SPA, ADV and ECL were lower than those measured by AMA. In the 1 mg DEX test, the cortisol levels measured with the SPA, ADV and ECL kits were suppressed in 2 patients with preCS. With 8 mg of DEX, cortisol levels measured with the SPA and ADV kits were suppressed in 2 patients with preCS. The diagnosis of preCS is decided by the cortisol kit used, but the cortisol levels differ among the kits. It is suggested that the lack of the standardization of cortisol measurement is one of the causes of confusion in the diagnosis of preCS.

Aged↗
PubMed2004

Adrenocortical hyperplasia associated with ACTH-dependent Cushing's syndrome: comparison of the size of adrenal glands with clinical and endocrinological data.

Diffuse or nodular hyperplasia of adrenal glands is associated frequently with ACTH-dependent Cushing's syndrome. We carried out a retrospective analysis of 28 patients with ACTH-dependent Cushing's syndrome admitted to our institution between 1984 and 1999 in order to clarify the incidence of adrenal hyperplasia in ACTH-dependent Cushing's syndrome and also to determine the correlation between adrenal gland images and clinical, biochemical and endocrinological data. Of the 28 patients, 16 (57%) showed diffuse adrenal hyperplasia while only 3 had focal adrenal nodules in the hypertrophied adrenals. There was a positive, significant correlation between the width of the adrenal glands measured on CT and circulating plasma ACTH, cortisol levels and urinary free cortisol (UFC) levels. Duration of the disease also correlated positively with adrenal width. No correlation was found between age and adrenal size and there was no difference in the prevalence of diffuse hyperplasia between normotensive and hypertensive patients. These results suggest that chronic ACTH hypersecretion may lead to diffuse adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed2004

[Aldosterone].

Aldosterone is one the representative cardiovascular hormones involved in the blood pressure and body-fluid homeostasis. Elevation of aldosterone leads to systemic hypertension through its action on the mineralocorticoid receptor (MR) in the kidney. More recent studies demonstrated that aldosterone may produce target organ damage through its direct actions on the non-epithelial MR of the heart in addition to its systemic effects. Clinical experience in primary aldosteronism supports the concept that aldosterone is a risk factor of cardiovascular complications, since concentric type of cardiac hypertrophy is most common in primary aldosteronism among various types of endocrine hypertension. Clinical mega-trial in congestive heart failure (RALES study, EPHESUS study) demonstrated blocking angiotensin II action is not sufficient for cardioprotection unless aldosterone action is equally blocked. An important phenomenon related to this issue is the aldosterone breakthrough which implies a reelevation of plasma aldosterone during chronic administration of ACE inhibitors and Angiotensin receptor antagonists. Normal level of aldosterone could still be a risk factor. Combination of ACE inhibitor or ARB with aldosterone antagonist could result in a better cardioprotection in cardiovascular diseases. Although spironolactone has been the only one aldosterone antagonist, a new antagonist eplerenone has been developed. Eplerenone is specific to MR and is practically devoid of the major side effect gynecomastia of spironolactone. Another topic of aldosterone is its very quick cardiovascular effect presumably via a non-genomic action. All these recent findings support that this adrenocortical steroid hormone is as important as angiotensin II. Determining aldosterone levels is therefore much morel important than before in the diagnosis and treatment of cardiovascular diseases.

Aldosterone↗