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Biomedical subjects

Keigo Yasuda

Publications and source records attributed to Keigo Yasuda.

At least 19 recordsLinked to original sources
PubMed2006

Changes in serum sex hormone profiles after short-term low-dose administration of dehydroepiandrosterone (DHEA) to young and elderly persons.

In man, serum concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease with age after the twenties. For this reason, the decline in DHEA and DHEAS concentrations may be related to the development of some chronic diseases that are prevalent in the older age population. In this study, we evaluate the benefit and safety level of DHEA administration to men as a hormone replacement therapy. Twenty-two healthy Japanese males (age 26-63; mean +/- SD, 41.0 +/- 10.0 yrs.) received 25 mg DHEA once a day orally in the morning for two weeks. Serum concentrations of steroid hormones and cytokines were measured before and after the DHEA administration. Glucose tolerance and insulin resistance were also assessed before and after the DHEA administration using a 75 g oral glucose tolerance test and homeostasis model assessment (HOMA-R), respectively. Serum DHEA and DHEAS levels were significantly elevated after the DHEA administration for all ages of test subjects. In subjects who were older than 41 yrs. (older group) serum androstenedione and estradiol levels were elevated after the DHEA administration. Significant negative correlations were observed between the serum DHEA concentration and the serum concentration of fasting insulin, HOMA-R, leptin, and high-sensitivity C-reactive protein for all subjects. Daily administration of 25 mg DHEA increased the serum DHEA, DHEAS, androstenedione, and estradiol levels of the subjects of the older group to the same level as that of younger subjects.

Adult↗
PubMed2006

Longitudinal study of patients with idiopathic isolated TSH deficiency: possible progression of pituitary dysfunction in lymphocytic adenohypophysitis.

The relationship between isolated TSH deficiency and hypophysitis was studied. Six patients (five women and one man) with idiopathic isolated TSH deficiency were longitudinally investigated with an interval of 31 to 60 months. Clinical symptoms, laboratory results and endocrine function were investigated as well as pituitary magnetic resonance imaging (MRI) at the start and the end of the study. Clinically, initial symptoms due to hypothyroidism were ameliorated by the thyroid hormone replacement in all patients. Oligomenorrhea newly appeared during the study in three patients, although no other symptoms appeared. Serum fT3 and fT4 levels were within the reference ranges, and serum TSH level and its response to TRH stimulation remained low in all patients. Peak plasma GH level during GRH stimulation was significantly (p<0.03) decreased, at the end of the study as compared with the start. Peak plasma FSH level to LHRH stimulation was significantly (p<0.03) decreased as well as basal FSH level. In contrast, peak of prolactin during TRH stimulation was significantly (p<0.03) increased at the end of the study as compared with the start as well as basal prolactin level. Endocrine features at the end of the study were compatible with those of lymphocytic adenohypophysitis (LAH). MRI of the pituitary gland showed empty sella in one patient and slight swelling in two patients. These findings remained unchanged during the study period. One patient underwent pituitary biopsy, with histological examination showing atypical form of LAH. LAH can cause idiopathic isolated TSH deficiency and can functionally progress to combine dysfunction of the pituitary gland.

Adult↗
PubMed2005

Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas.

CONTEXT: CYP11B2, the gene encoding aldosterone synthase, has several frequent polymorphisms. In particular, the Lys173Arg (K173R) polymorphism is in complete genetic linkage disequilibrium with the -344T/C polymorphism in the promoter of CYP11B2 that involves a binding site for the steroidogenic factor-1 transcription factor. These polymorphisms have been associated with cardiovascular parameters, including hypertension, but not directly with gene expression. OBJECTIVE: The objective of this study was to correlate CYP11B2 genotype with gene expression in adrenal tissue. DESIGN: We measured mRNA levels of CYP11B2 [presented as a ratio against glyceraldehyde-3-phosphate dehydrogenase (B2/G)] and CYP11B1 in relation to the K173R polymorphism. SUBJECTS: We studied 28 subjects with aldosterone-producing adenomas (APA) and 18 subjects with normal adrenals. MAIN OUTCOME MEASURE: The main outcome measure was CYP11B2 expression levels. RESULTS: Preoperative treatment with spironolactone or beta-blocker in five APA patients was associated with higher B2/G. The B2/G and B2/B1 ratios were much higher even in the remaining 23 APA patients than in subjects with normal adrenals. The B2/G and B2/B1 ratios in normal adrenals and APA were higher in the KK genotype than in the RR genotype. In patients with APA, urinary aldosterone excretion was higher in those with the KK genotype than in those with the KR genotype. Measurement of cDNA band intensities from normal and APA samples of the KR genotype revealed that the R173 allele was transcribed at levels 46.6 +/- 12.2% (mean +/- sd; n = 7) and 49.1 +/- 20.8% (n = 6), respectively, those of the K173 allele. CONCLUSIONS: A CYP11B2 haplotype including -344T and K173 is associated with higher gene expression than the -344C/R173 haplotype, supporting reported associations of -344T with higher aldosterone production and blood pressure.

Adenoma↗
PubMed2005

Paraneoplastic neurologic syndrome and autoimmune Addison disease in a patient with thymoma.

A 48-year-old man with autoimmune Addison disease developed the following paraneoplastic neurologic syndromes (PNNS): limbic encephalitis, opsoclonus/myoclonus, and sensorimotor and autonomic neuropathies. An anterior mediastinal mass detected on a chest computed tomographic scan was found on resection to be a noninvasive lymphocytic thymoma. The PNNS went into remission 1 year after the thymectomy. This is the first case of thymoma associated with autoimmune Addison disease and PNNS to be described in the literature.

Addison Disease↗
PubMed2004

Circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 are associated with early carotid atherosclerosis.

OBJECTIVE: Growth hormone (GH)-insulin-like growth factor (IGF)-1 axis regulates growth and survival of vascular cells and cardiomyocytes. The role of GH-IGF-1 axis in cardiovascular disease is controversial. METHODS AND RESULTS: We assessed the association of circulating levels of IGF-1 and IGF binding protein-3 (IGFBP-3) with early carotid atherosclerosis and atherosclerotic risk factors in 330 Japanese men (age 51.6+/-8.6 years, range 29 to 77, body mass index [BMI] 23.6+/-2.9 kg/m2). Intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. Abdominal visceral adipose and subcutaneous adipose tissue area by computer-assisted tomographic scan were determined. Correlation coefficients were calculated by partial correlation analysis. BMI and plasma insulin showed positive associations with circulating IGF-1 and IGFBP-3. Subcutaneous adipose tissue was correlated with IGF-1. High-density lipoprotein cholesterol was inversely associated with IGF-1. Blood pressure, total cholesterol, triglyceride, and visceral adipose tissue were positively associated with IGFBP-3. IGF-1 and IGFBP-3 were associated with carotid IMT independent of age, BMI, blood pressure, and insulin. Insulin was associated with carotid IMT in univariate analysis. However, it was not correlated with carotid IMT in the multivariate analyses which included IGF-1 or IGFBP-3 as a covariate. CONCLUSIONS: Increased circulating IGF-1 and IGFBP-3 may be stimulators of atherosclerosis.

Adipose Tissue↗
PubMed2004

TNFalpha reduces the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) via the production of ceramide and activation of atypical PKC.

Although tumor necrosis factor alpha (TNFalpha) decreases the expression of peroxisome proliferator-activated receptor gamma (PPARgamma), its mechanism is not understood. We evaluated the effect of ceramide, the second messenger of TNFalpha, on the expression of PPARgamma in primary cultured adipocytes. PPARgamma mRNA and aP2 mRNA levels were measured with real-time PCR. The PPARgamma protein level was measured with immunoblot. C6- and C2-ceramide, but not dihydroC6-ceramide, reduced the expression of PPARgamma in a time and concentration dependent manner. The application of 1 microM C6-ceramide for 36 h reduced PPARgamma mRNA level, aP2 mRNA level, and PPARgamma protein level to 56.3%, 80.4% and 62.1%, respectively. Since ceramide is known to activate atypical PKC, we also studied the role of atypical PKC on the PPARgamma reducing effect. Overexpression of wild type PKCzeta magnified and accelerated the effect of TNFalpha and C6-ceramide on PPARgamma mRNA levels, whereas overexpression of dominant negative PKCzeta abolished the effect. We also found that the overexpression of constitutive active PKCzeta reduced PPARgamma mRNA level, aP2 mRNA level, and PPARgamma protein level to 61.4%, 70.3% and 81.6%, respectively. Furthermore, TNFalpha activated nuclear factor-kappaB (NF-kappaB), known as a downstream effector of PKCzeta to 256.6%, which was enhanced with overexpression of wild-type PKCzeta. On the other hand, treatment with phorbol 12-myristate 13-acetate, another activator of NF-kappaB, also reduced the expression of PPARgamma to 57.8%. These results indicate that the reducing effect of TNFalpha is mediated through ceramide, atypical PKC and NF-kappaB pathway.

Adipocytes↗
PubMed2004

Plasma cortisol and cortisone concentrations in normal subjects and patients with adrenocortical disorders.

Two isozymes of the 11beta-hydroxysteroid dehydrogenase (11-HSD) are responsible for the interconversion of cortisol (F) and cortisone (E). The type 1 isozyme, 11-HSD1, acts mainly as a reductase in vivo, activating E to F, whereas the type 2, 11-HSD2, acts as a dehydrogenase, inactivating F to E. 11-HSD1 is the most abundant in the liver and 11-HSD2 in the kidney. In this study, we attempted to determine which isozyme and organs primarily contribute to equilibrium of plasma F and E concentrations in the peripheral circulation and to clarify differences in 11-HSD activities among adrenocortical disorders. Upon selective catheterizations for adrenocortical and renovascular disorders, plasma F and E concentrations in the femoral vein were closer to those in the renal vein than those in the hepatic vein. Values for mean plasma F/E ratios in the peripheral vein were in-between those of the adrenal and renal veins. A double reciprocal plot between peripheral plasma F and E concentrations in patients with various adrenocortical tumors was almost identical to that in normal subjects. Mean plasma F/E ratio in peripheral blood was higher in patients with Cushing's syndrome and was lower in patients with primary aldosteronism and nonfunctioning adrenocortical adenoma than that in normal subjects. These results suggest that renal 11-HSD2 is a main factor controlling the equilibrium of plasma F and E concentrations in the periphery and that cortisol and aldosterone excess do not change the equilibrium of plasma F and E concentrations in the peripheral circulation, but may alter expression of 11-HSD2. Alternation of 11-HSD2 activities as well as corticosteroid levels may be important in the pathophysiology of adrenocortical disorders.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

Protein kinase C (PKC) beta modulates serine phosphorylation of insulin receptor substrate-1 (IRS-1)--effect of overexpression of PKCbeta on insulin signal transduction.

In vitro phosphorylation of 180-kDa protein, obtained by immunoprecipitation of adipocyte homogenate with anti-IRS-1 antibody was increased with the addition of conventional PKC in the presence of Ca2+, phosphatidylserine (PS) and diolein (DL). Human purified IRS-1 was phosphorylated by purified conventional PKC (cPKC) in the presence of Ca2+/PS/DL. These results suggest that PKC may have a role in the serine phosphorylation of IRS-1. In order to clarify the inhibitory effect of cPKC on glucose transport mechanism, we examined the overexpression of PKCbeta in cultured adipocytes. Overexpression of PKCbeta in adipocytes markedly induced mobility shift and serine phosphorylation of IRS-1, whereas overexpression of dominant negative PKCbeta (DNPKCbeta) blocked this mobility shift and serine phosphorylation of IRS-1. Insulin (10 nM) increased [3H]2-deoxyglucose (2-DOG) uptake to 200% from basal level (100%) in cultured adipocytes transfected with a vector alone. Overexpression of PKCbeta in adipocytes decreased insulin-induced 2-DOG uptake to 110%, whereas overexpression of DNPKCbeta increased it to 230%. These results suggest that PKCbeta negatively regulates glucose uptake via serine phosphorylation of IRS-1 in rat adipocytes.

Adipocytes↗
PubMed2004

Hypopituitarism and diabetes insipidus with localized hypertrophic pachymeningitis (Tolosa-Hunt syndrome) associated with Hashimoto thyroiditis.

We report a 69-year-old woman with intracranial pachymeningitis showing hypopituitarism, diabetes insipidus, and Tolosa-Hunt syndrome associated with Hashimoto thyroiditis confirmed by autopsy. A large tumorous lesion of the hypothalamo-pituitary gland was revealed on magnetic resonance imaging, after the patient complained of gait and visual field disturbance. These symptoms subsided after thyroid hormone supplementation. Hypopituitarism and diabetes insipidus were diagnosed after cessation of the treatment by the patient herself. Multiple cranial nerve palsies and orbito-frontalgia appeared. Methylprednisolone pulse therapy improved the symptoms, but they recurred when the dose of glucocorticoid was decreased. The patient died of brain thrombosis. Autopsy revealed typical findings of Hashimoto thyroiditis and intracranial pachymeningitis involving the cranial base and pituitary gland. The high titer of rheumatoid factor and Hashimoto thyroiditis in this patient suggest an immunological role in the pathogenesis of pachymeningitis.

Aged↗
PubMed2004

Depressive state and paresthesia dramatically improved by intravenous MgSO4 in Gitelman's syndrome.

A 69-year-old woman was referred to our department for evaluation of hypokalemia, which had been treated by oral potassium for more than ten years. She complained of headache, knee joint pain, sleeplessness and paresthesia in extremities and, most prominently, depression. Laboratory data suggested Gitelman's syndrome, which is caused by mutations in the gene encoding the thiazide-sensitive Na-Cl cotransporter. Direct sequencing of the gene in this patient revealed homozygous mutation R964Q in exon 25. Intravenous supplement of MgSO4 dramatically improved both the depression and the paresthesia, suggesting that hypomagnesemia played a role in the clinical manifestations.

Aged↗
PubMed2003

Association of blood pressure with intake of soy products and other food groups in Japanese men and women.

BACKGROUND: Soy diet has been suggested to have antihypertensive effect in animal studies. The present study examined the cross-sectional relationship between blood pressure and intake of soy products and other food groups in Japanese men and women. METHODS: Blood pressure was measured in Japanese 294 men and 330 women (246 premenopausal and 84 peri- and postmenopausal women) who participated in a health check-up program provided by a general hospital. Intake of various food groups and nutrients was estimated from a validated semiquantitative food frequency questionnaire. RESULTS: In men, soy product intake was inversely significantly correlated with diastolic blood pressure (r = -0.12, P = 0.04) after controlling for age, total energy, smoking status, body mass index, and intake of alcohol, salt and seaweeds. The correlation of soy product intake with systolic blood pressure was of borderline significance (r = -0.10, P = 0.09). Systolic blood pressure was inversely correlated with intake of vegetables (r = -0.12, P = 0.04) and dairy products (r = -0.12, P = 0.05). There were no significant correlations between soy product intake and diastolic blood pressure in women. CONCLUSIONS: These results indicate a mild effect of soy intake on blood pressure reduction in men.

Adult↗
PubMed2003

Inhibitory effect of ceramide on insulin-induced protein kinase Czeta translocation in rat adipocytes.

Ceramide has been confirmed to be a signal mediator of apoptosis that is induced by tumor necrosis factor-alpha (TNF-alpha). It has also been reported that ceramide may induce insulin resistance as well as TNF-alpha. We investigated the effect of ceramide on insulin signaling pathways, such as insulin receptor (IR) beta-subunit, insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase Czeta (PKCzeta) in rat adipocytes. We examined insulin-stimulated [(3)H]2-deoxyglucose (2-DOG) uptake in rat adipocytes pretreated with N-hexanoylsphingosine (C(6)-ceramide, 10 to 30 micromol/L). Insulin-induced 2-DOG uptake was significantly reduced by C(6)-ceramide pretreatment. We also examined the effect of various concentrations of C(6)-ceramide pretreatment on insulin-induced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of IRS-1, enzyme activity of PI3K, and membrane-associated PKCzeta immunoreactivity. Pretreatment with C(6)-ceramide significantly reduced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of IRS-1, and enzyme activity of PI3K. Moreover, membrane-associated PKCzeta immunoreactivity and immunoprecipitable PKCzeta enzyme activity, downstream of PI3K, were significantly suppressed by C(6)-ceramide pretreatment. These results suggest that ceramide may induce insulin resistance via the suppression of IRS-1-PI3K signaling, and subsequent activation of PKCzeta.

Adipocytes↗
PubMed2003

Dominant negative protein kinase Cbeta improves 1alpha, 25-dihydroxy vitamin D3-induced insulin resistance.

1alpha,25-Dihydroxy vitamin D3 (1,25D3) activates conventional PKC and may subsequently lead to insulin resistance. Previous studies from our laboratory have shown that pretreatment with 10 nM-10 microM 1,25D3 dose-responsively suppressed insulin-induced glucose. To assess PKC(beta)-mediated inhibition of insulin-induced glucose uptake in rat adipocytes, we preincubated with Go6976 and LY379196, conventional PKC inhibitors, and found they abolished the 1,25D3-mediated inhibitory effect on insulin-induced 2-deoxyglucose (DOG) uptake. Moreover, the inhibitory effect of 1,25D3 on insulin-induced DOG uptake was abrogated in adipocytes overexpressed with dominant negative PKC(beta), but not in those overexpressed with wild type PKC(beta). These results suggest that 1,25D3 reduces insulin-induced glucose uptake via activation of PKC(beta) in rat adipocytes.

Adipocytes↗
PubMed2003

Soy product intake is inversely associated with serum homocysteine level in premenopausal Japanese women.

Soybeans, which are an excellent source of folate, vitamin B-6 and minerals, may reduce serum homocysteine level. However, there is a possibility that dietary soy raises the serum homocysteine level because isoflavones, which are weak estrogens contained in soybeans, may exert antiestrogenic effects in a high estrogen environment, such as in premenopausal women. The present study examined a cross-sectional relationship between soy product intake and serum homocysteine level in 201 premenopausal Japanese women. Intakes of soy products, folate, methionine and vitamins B-6 and B-12 were estimated by a semiquantitative food frequency questionnaire. Folate status was also assessed by measuring serum folate. Soy product intake in terms of soy protein as well as soy isoflavone intake was modestly but significantly inversely associated with serum homocysteine level (r = -0.15, P = 0.04) after controlling for covariates. Soy product intake was also significantly positively correlated with serum folate (r = 0.15, P = 0.04). Although it is unclear the extent to which each component of soy, such as folate and isoflavones, is associated with the serum homocysteine concentration, this biochemical complex appears to have a favorable effect on homocysteine metabolism in premenopausal women.

Adult↗
PubMed2003

Chlamydia pneumoniae resists antibiotics in lymphocytes.

Chlamydia pneumoniae infection of lymphocytes in blood has been well documented, and it is apparent that control of this pathogen in these cells may be critical in the development of chronic inflammatory diseases associated with infection by this bacterium. The activity of antibiotics against C. pneumoniae in lymphocytes was assessed in this study by utilizing an in vitro infection model with lymphoid cells. The results obtained indicated that although all of the antibiotics tested showed remarkable activity against bacterial growth in epithelial cells, C. pneumoniae in lymphocytes was less susceptible to antibiotics than was bacterial growth in epithelial cells, which are widely used for the evaluation of anti-C. pneumoniae antibiotics.

Animals↗
PubMed2003

Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Japanese women.

Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).

Adult↗
PubMed2003

Dehydroepiandrosterone down-regulates the expression of peroxisome proliferator-activated receptor gamma in adipocytes.

Dehydroepiandrosterone (DHEA) is expected to have a weight-reducing effect. In this study, we evaluated the effect of DHEA on genetically obese Otsuka Long Evans Fatty rats (OLETF) compared with Long-Evans Tokushima rats (LETO) as control. Feeding with 0.4% DHEA-containing food for 2 wk reduced the weight of sc, epididymal, and perirenal adipose tissue in association with decreased plasma leptin levels in OLETF. Adipose tissue from OLETF showed increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) protein, which was prevented by DHEA treatment. Further, we examined the effect of DHEA on PPARgamma in primary cultured adipocytes and monolayer adipocytes differentiated from rat preadipocytes. PPARgamma protein level was decreased in a time- and concentration-dependent manner, and DHEA significantly reduced mRNA levels of PPARgamma, adipocyte lipid-binding protein, and sterol regulatory element-binding protein, but not CCAAT/enhancer binding protein alpha. DHEA-sulfate also reduced the PPARgamma protein, but dexamethasone, testosterone, or androstenedione did not alter its expression. In addition, treatment with DHEA for 5 d reduced the triglyceride content in monolayer adipocytes. These results suggest that DHEA down-regulates adiposity through the reduction of PPARgamma in adipocytes.

Adipocytes↗