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Yukio Hirata

Publications and source records attributed to Yukio Hirata.

At least 19 recordsLinked to original sources
PubMed2006

A Case of acromegaly associated with subclinical Cushing's disease.

A 54-year-old man with type 2 diabetes was referred to our hospital for endocrine evaluation of acromegaly. Physical examination showed typical acromegalic features without Cushingoid features. Magnetic resonance imaging of the brain revealed the presence of a pituitary macroadenoma. Basal plasma levels of GH and insulin-like growth factor-I under fasting hyperglycemia (202 mg/dl) were markedly elevated. Plasma GH levels paradoxically increased after stimulation with TRH and LH-RH, and decreased after bromocriptine and octreotide administration. Endocrine examination of the hypothalamo-pituitary-adrenal (HPA) axis showed a lack of circadian rhythm of ACTH and cortisol, non-suppressibility to low-dose (1 mg), but suppressibility to high-dose (8 mg) dexamethasone, and normal response to CRH stimulation. The tumor resected by transsphenoidal surgery was histopathologically consistent with the diagnosis of eosinophilic adenoma: positive immunoreactivities of GH, PRL and ACTH were demonstrated, but negative immunoreactivities of prohormone convertase (PC) 1/3 by immunohistochemical method. After surgery, plasma GH and IGF-I levels decreased along with normalization of HPA axis. Metabolic co-morbidities such as diabetes and hypertension disappeared after removal of the pituitary tumor. This is a very rare case of GH-producing pituitary adenoma causing typical acromegaly with concomitant production of ACTH causing subclinical Cushing's disease.

Acromegaly↗
PubMed2006

Presence of immunoreactive salusin-alpha in human serum and urine.

Salusins, identified from a full-length enriched human cDNA library by bioinformatics analyses, show mitogenic, neuromodulatory and hemodynamic activities in rats. They are expressed in a wide variety of human tissues, but their precise structures and levels in human body fluids remain unknown. We developed a radioimmunoassay suitable for the detection of immunoreactive human salusin-alpha and characterized the molecular forms and concentrations of salusin-alpha in human serum and urine. The assay allowed for measurement of immunoreactive salusin-alpha concentrations as low as 1 fmol/tube after extraction of serum with an octyl-silica column, and the concentration required for 50% inhibition of binding was 40 fmol/tube. Cross-reactivities with salusin-beta and other bioactive peptides were negligible. Salusin-alpha-like immunoreactivity in normal human serum and urine ranged from 11.0 to 40.4 pmol/l (mean+/-S.D., 23.3+/-8.1 pmol/l, n=31) and from 18.6 to 367.3 pmol/l (mean+/-S.D., 156.8+/-95.8 pmol/l), respectively. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay detection revealed a major immunoreactive component that coeluted with authentic salusin-alpha. These data indicate the presence of salusin-alpha in human serum and urine, thereby verifying the initially predicted processing sites for salusin-alpha in humans.

Adult↗
PubMed2006

A case of factitious adrenal insufficiency after vascular graft surgery caused by spurious immunometric assays.

A 70-year-old man with abdominal aortic aneurysm underwent surgical repair with Hemashield vascular graft. Postoperatively, he was found to have very low plasma cortisol levels, which failed to increase after stimulation with ACTH. A tentative diagnosis of adrenal insufficiency was made despite the lack of its clinical manifestations and a replacement therapy with hydrocortisone was started. He had also elevated plasma levels of TSH, thyroid hormones and estrogen without any clinical manifestations. Such abnormal hormone levels were spontaneously normalized three months after operation, which was later proven to be factitious by different immunometric assays (IMA). Since the vascular graft coated with bovine type I collagen has been reported to induce a transient immune response in some patients after surgery, we speculated that certain antibodies generated against heterologous collagen and/or yet-unknown components derived from the graft may have caused such factitious data; exogenous addition of bovine type I collagen and albumin to patient's serum, however, failed to affect the assay results. Whatever the cause, caution must be paid that some patients with surgical repair using heterologous materials may have such factitious hormone data by IMAs.

Adrenal Insufficiency↗
PubMed2006

Angiotensin II induces monocyte chemoattractant protein-1 expression via a nuclear factor-kappaB-dependent pathway in rat preadipocytes.

Both monocyte chemoattractant protein-1 (MCP-1), a member of chemokine family, and angiotensinogen, a precursor of angiotensin (ANG) II, are produced by adipose tissue and increased in obese state. MCP-1 has been shown to decrease insulin-stimulated glucose uptake and several adipogenic genes expression in adipocytes in vitro, suggesting its pathophysiological significance in obesity. However, the pathophysiological interaction between MCP-1 and ANG II in adipose tissue remains unknown. The present study was undertaken to investigate the potential mechanisms by which ANG II affects MCP-1 gene expression in rat primary cultured preadipocytes and adipose tissue in vivo. ANG II significantly increased steady-state MCP-1 mRNA levels in a time- and dose-dependent manner. The ANG II-induced MCP-1 mRNA and protein expression was completely abolished by ANG II type 1 (AT1)-receptor antagonist (valsartan). An antioxidant/NF-kappaB inhibitor (pyrrolidine dithiocarbamate) and an inhibitor of 1kappaB-alpha phosphorylation (Bay 11-7085) also blocked ANG II-induced MCP-1 mRNA expression. ANG II induced translocation of NF-kappaB p65 subunit from cytoplasm to nucleus by immunocytochemical study. Luciferase assay using reporter constructs containing MCP-1 promoter region revealed that two NF-kappaB binding sites in its enhancer region were essential for the ANG II-induced promoter activities. Furthermore, basal mRNA and protein of MCP-1 during preadipocyte differentiation were significantly greater in preadipocytes than in differentiated adipocytes, whose effect was more pronounced in the presence of ANG II. Exogenous administration of ANG II to rats led to increased MCP-1 expression in epididymal, subcutaneous, and mesenteric adipose tissue. In conclusion, our present study demonstrates that ANG II increases MCP-1 gene expression via ANG II type 1 receptor-mediated and NF-kappaB-dependent pathway in rat preadipocytes as well as adipose MCP-1 expression in vivo. Thus the augmented MCP-1 expression by ANG II in preadipocytes may provide a new link between obesity and cardiovascular disease.

Adipocytes↗
PubMed2006

Glucose-responsive and octreotide-sensitive insulinoma.

Insulinoma is the most common cause of fasting hypoglycemia resulting from autonomous insulin hypersecretion. We describe herein a unique case with paradoxical hypoglycemic episodes induced by hyperglycemia. A 55-year-old female had repeated hypoglycemic episodes after meal or during increased physical activity. Although fasting (10 hr) failed to provoke hypoglycemia, oral glucose tolerance test (GTT) caused an exaggerated insulin response (885 microU/ml) at 30 min, followed by hypoglycemia (36 mg/dl) after 90 min. Moreover, intravenous GTT also induced an exaggerated insulin response (>2900 microU/ml) at 10 min, followed by hypoglycemia (34 mg/dl) after 40 min. Although MRI and CT scan of the abdomen failed to detect any mass lesions in the pancreas, Octreoscan revealed increased radioactive uptake around the pancreatic head region. Treatment with a daily injection of octreotide (100 microg) alleviated her hypoglycemic episodes. At surgery, two islet cell adenomas were identified in the pancreas and resected. Postoperatively, she was free from hypoglycemic episodes after meal. Postoperative oral and intravenous GTT did not induce hypoglycemia. Thus, this is a very rare case of glucose-responsive and octreotide-sensitive insulinoma in whom GTT and octreotide proved to be a useful provocation and treatment for hypoglycemic episodes.

Antineoplastic Agents, Hormonal↗
PubMed2006

Comprehensive two-dimensional capillary supercritical fluid chromatography in stop-flow mode with synchronized pressure programming.

A comprehensive two-dimensional capillary supercritical fluid chromatography method was developed. The interface consisted of a ten-port valve, a capillary trap and two fused silica restrictors. The primary column was operated in stop-flow mode: the flow in the primary column was stopped during the separation of the second dimension. The pressure of the system was controlled with a single pump. The pressure program was synchronized with the sampling: the pressure was only ramped up during the sampling time, when the primary column effluent was transferred from the first dimension to the trap, and was maintained constant during the second-dimension separation. All of the operations were automated using in-house software. The separation characteristics of the present system can be readily regulated by changing the size of the restrictors and/or the programmed pressure rate. The use of synchronized pressure programming allowed the sampling duration and/or the second-dimension separation time (and therefore, the total analysis time) to be changed without affecting the separation pattern. Widely different selectivities were attained depending on the combination of the three columns with different polarities (such as the nonpolar DB-1, the medium-polarity DB-17 and the polar DB-WAX columns) used. The present system afforded improved separation and identification capabilities for analytes in complex mixtures.

Journal Article↗
PubMed2006

Role of C-terminus of Kir7.1 potassium channel in cell-surface expression.

Inward rectifier K+ channel Kir7.1 is predominantly expressed on the plasma membrane of a variety of ion-transporting epithelia. The electrophysiological property of Kir7.1 has been well characterized but the mechanism underlying the plasma-membrane targeting remains elusive. To address this issue, we examined the effect of deletion and site-directed mutagenesis on the plasma-membrane localization of Kir7.1 in Madin-Darby canine kidney cells by immunofluorescence microscopy and cell-surface biotinylation. Although deletions of up to 37 amino acid residues from the C-terminus had no effect, further deletion resulted in accumulation of the mutant proteins in intracellular membranes. No sequence motif for subcellular targeting was found in the distal C-terminal region. The cell-surface expression of the deletion mutant lacking 38 or 40 C-terminal residues was restored by addition of one or three alanine residues, respectively, to the C-terminus end. These results suggest that the C-terminal length plays an important role in the plasma-membrane localization of Kir7.1.

Amino Acid Sequence↗
PubMed2006

A case of estrogen-secreting adrenocortical carcinoma with subclinical Cushing's syndrome.

A 25-year-old man was found to have a large right adrenal mass detected by abdominal echography and computed tomography, and presented with a mild gynecomastia. Endocrine study showed increased serum concentrations and urinary excretion of estrogens and dehydroepiandorosterone sulfate (DHEA-S). The patient had no Cushingoid features but autonomous cortisol secretion, compatible with the diagnosis of subclinical Cushing's syndrome. Surgical removal of the adrenal tumor led to normalization of serum and urinary excretion of estrogens and DHEA-S. Histopathological examination revealed a high-grade adrenocortical carcinoma (ACC). The disorganized expression of all the steroidogenic enzymes in individual tumor cells was demonstrated by immunohistochemical analysis, and the abundant expression of both aromatase mRNA and insulin-like growth factor (IGF)-II mRNA was shown by RT-PCR. These data suggest the excessive secretion of estrogen as well as the ineffective steroidogenesis by the adrenal tumor. This is a very rare case of estrogen-secreting ACC associated with subclinical Cushing's syndrome.

Adrenal Cortex Neoplasms↗
PubMed2006

Development of supercritical fluid extraction coupled to comprehensive two-dimensional supercritical fluid chromatography (SFE-SFCxSFC).

Supercritical fluid extraction was coupled to comprehensive two-dimensional supercritical fluid chromatography with conventional packed columns. With this system, three modes of operations were feasible, such as SFE-SFC, SFCxSFC, and SFE-SFCxSFC. The operations for valve switching and data acquisition were automated using in-house software. In order to evaluate the present system, SFE-SFC for polymer additives in polypropylene, SFCxSFC for a mixture of benzene derivatives with different polarities, and SFE-SFCxSFC for styrene oligomers in polystyrene were performed. With SFE-SFCxSFC, diastereomers were resolved for linear tetramers and pentamers as well as trimers with the tetraline moiety.

Journal Article↗
PubMed2006

[Salusin].

Explore the source record for details and available documents.

Adenosine Triphosphatases↗
PubMed2005

Aldosterone increases osteopontin gene expression in rat endothelial cells.

Aldosterone is currently recognized as one of the important risk hormones for cardiovascular disease. However, the cellular mechanism by which aldosterone affects the process of cardiovascular injury has not been well understood. In the present study, we investigated whether aldosterone induces pro-inflammatory genes expression in rat aortic endothelial cells. Aldosterone significantly increased steady-state osteopontin mRNA and protein levels, but not those of adhesion molecules or chemokine. The stimulatory effect of aldosterone on osteopontin expression was time-dependent (3-24h) and dose-dependent (10(-10)-10(-6)M), and abolished by a mineralocorticoid receptor (MR) antagonist spironolactone, but not by a glucocorticoid receptor antagonist RU486. The aldosterone-induced osteopontin mRNA expression was completely blocked by a transcription inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide. Thus, the present study demonstrated for the first time that aldosterone directly acts on endothelial cells to induce osteopontin gene expression via MR-mediated genomic action, which may be responsible for the initiation of inflammation and fibrosis in cardiovascular tissue induced by aldosterone.

Aldosterone↗
PubMed2005

Expression profiles of EphA3 at both the RNA and protein level in the developing mammalian forebrain.

The ephrin/Eph system is well known to regulate various aspects of brain development. In this study, we analyzed the expression profiles of EphA3 at both the RNA and protein level in developing mouse forebrains. Although the EphA3 gene is known to encode two isoforms of the receptors, a full-length transmembrane form, and a short, secretory form, only the full-length isoform was detected in the developing forebrain. We found that, in the early developmental stages, while EphA3 mRNA was expressed in the dorsal thalamus and the cortical intermediate zone (IMZ), the EphA3 protein was detected in the IMZ and the internal capsule, but not in the dorsal thalamus. In the later stages the mRNA was expressed in the most superficial region of the cortical plate, while the protein was expressed in the IMZ. This discrepancy between the mRNA and protein expression patterns might be attributed to the possibility of the protein being transported to the axons to regulate the thalamocortical and corticofugal projection. The results of double-immunostaining for L1 and EphA3 or TAG-1 and EphA3 suggested that EphA3 protein was produced mainly in the thalamocortical axons and only partially in the corticofugal axons. In addition, the EphA3 protein was also detected in various other structures, such as the lateral olfactory tract, anterior commissure, and corpus callosum, suggesting the possibility that EphA3 might regulate the formation of various neuronal networks in the developing brain, including the TC projection and the commissural fibers.

Animals↗
PubMed2005

Aldosterone induces angiotensin converting enzyme gene expression via a JAK2-dependent pathway in rat endothelial cells.

Aldosterone is currently recognized as a risk hormone for cardiovascular disease. However, the cellular mechanism by which aldosterone acts on vasculature has not been well understood. In the present study, we investigated whether aldosterone affects angiotensin-converting enzyme (ACE) gene expression in rat endothelial cells. Cultured rat aortic endothelial cells (RAECs) from Sprague-Dawley rats were used in the study. ACE mRNA levels and its enzyme activities in RAECs were examined by real-time RT-PCR and enzyme assay using hippuryl-His-Leu as substrates, respectively. Aldosterone significantly increased steady-state ACE mRNA levels and its enzymatic activities. This effect was dose dependent and time dependent and abolished by mineralocorticoid receptor antagonist spironolactone or transcription inhibitor actinomycin D. Dexamethasone also increased steady-state ACE mRNA levels, whose effect was completely blocked by glucocorticoid receptor antagonist RU486, but not by spironolactone. By contrast, the aldosterone-induced ACE mRNA expression was only partially blocked by RU486. The stimulatory effect of aldosterone on ACE mRNA expression was completely blocked by a protein tyrosine kinase inhibitor (genistein) and JAK2 inhibitor (AG490), partially by Src kinase inhibitor (PP2) and epidermal growth factor receptor kinase inhibitor (AG1478), but not by platelet-derived growth factor receptor kinase inhibitor (AG1296). Transfection of dominant-negative JAK2 construct, but not wild-type construct, significantly blocked the aldosterone-induced ACE mRNA up-regulation. Furthermore, aldosterone induced phosphorylation of JAK2, whose effect was blocked by spironolactone and actinomycin D. In conclusion, the present study demonstrates for the first time that aldosterone induces ACE gene expression and its enzyme activity mainly via a mineralocorticoid receptor-mediated and JAK2-dependent pathway in rat endothelial cells. This may constitute a positive feedback loop for a local renin-angiotensin system, possibly involved in the development of aldosterone-induced endothelial dysfunction and vascular injury.

Aldosterone↗
PubMed2005

Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin II type 1a receptor.

Given that angiotensin II (AII) type 1 and 2 receptors (Agtr1 and Agtr2) are expressed in adipose tissue, AII may act directly on adipose tissue. However, regardless of whether AII directly modulates adipose tissue growth and metabolism in vivo and, if so, whether it is mediated via Agtr1 are still matters of debate. To understand the functional role of Agtr1 in adipose tissue growth and metabolism in vivo, we examined the metabolic phenotypes of mice lacking Agtr1a (Agtr1a-/- mice) during a high-fat diet. The Agtr1a-/- mice exhibited the attenuation of diet-induced body weight gain and adiposity, and insulin resistance relative to wild-type littermates (Agtr1a+/+ mice). They also showed increased energy expenditure accompanied by sympathetic activation, as revealed by increased rectal temperature and oxygen consumption, increased expression of uncoupling protein-1 mRNA in brown adipose tissue, and increased urinary catecholamine excretion. The heterozygous Agtr1a-deficient mice (Agtr1a+/- mice) also exhibited metabolic phenotypes similar to those of Agtr1a-/- mice. Using mouse embryonic fibroblasts derived from Agtr1a+/+ and Agtr1a-/- mice, we found no significant difference between genotypes in the ability to differentiate into lipid-laden mature adipocytes. In primary cultures of mouse mature adipocytes, AII increased the expression of mRNAs for some adipocytokines, which was abolished by pharmacological blockade of Agtr1. This study demonstrates that Agtr1a-/- mice exhibit attenuation of diet-induced weight gain and adiposity through increased energy expenditure. The data also suggest that AII does not affect directly adipocyte differentiation, but can modulate adipocytokine production via Agtr1.

Adipose Tissue↗
PubMed2005

Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma.

Gentisic acid, an aspirin metabolite, has an antioxidant effect, although its detailed mechanism remains elusive. The present study was designed to determine whether it inhibits low-density lipoprotein (LDL) oxidation and the formation of lipid hydroperoxides in human plasma. The susceptibility of LDL oxidative modification was investigated by a method using 2,2'-azobis or Cu2+. To study the effect of gentisic acid on free radical-induced damage to plasma lipids, cholesterol ester hydroperoxides generated by incubating human fresh plasma with Cu2+ and gentisic acid was analyzed. Gentisic acid inhibited LDL oxidation in a concentration-dependent manner. It significantly inhibited the formation of cholesterol ester hydroperoxides in plasma, and was consumed after the depletion of ascorbic acid and reduced form of coenzyme Q-10 (CoQH2-10), whereas concentrations of other antioxidants remained unchanged. Gentisic acid had a potent free radical scavenging activity with a minimal chelating effect. The potent antioxidant property of gentisic acid may partly account for the anti-atherogenic effects of aspirin.

Antioxidants↗