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Kazue Takano

Publications and source records attributed to Kazue Takano.

At least 19 recordsLinked to original sources
PubMed2005

Pediatric nonalcoholic steatohepatitis associated with hypopituitarism.

We experienced two cases of pediatric nonalcoholic steatohepatitis (NASH) associated with hypopituitarism. The first patient was diagnosed with a craniopharyngioma at 5 years of age. After an operation to treat the condition, the patient gradually became obese, and an elevation of transaminases was observed. At 16 years of age, the patient was diagnosed as having NASH with liver cirrhosis. He was started on hormone replacement therapy; however, his insulin resistance and liver fibrosis, as evaluated by hyaluronic acid and platelet count, progressed. In addition, his hyperleptinemia continued. The second patient was diagnosed, at 10 years of age, as having pituitary dysfunction due to fetal asphyxia, and he was started on hormone replacement therapy. This patient was noted to have been obese throughout his life. He was diagnosed as having NASH with advanced fibrosis at 18 years of age. It is important for both hepatologists and endocrinologists to be aware of the association between pituitary dysfunction and NASH.

Adiponectin↗
PubMed2005

Diagnosis of thyroid follicular carcinoma by the vascular pattern and velocimetric parameters using high resolution pulsed and power Doppler ultrasonography.

The aim of this study was to define the preoperative diagnosis of thyroid follicular carcinoma by the vascular pattern and velocimetric parameters using high resolution pulsed and power Doppler ultrasonography (US). We compared the vascular pattern and the velocimetric parameters, such as peak systolic velocity (Vmax), end-diastolic velocity (Vmin), pulsatility index (PI), or resistance index (RI) between follicular adenoma (FA, n = 25) and follicular carcinoma (FC, n = 10) and analysed them by means of receiver characteristics curves (ROC). Of 10 patients with FC, 8 (80%) patients presented a moderate increase of intranodular vascularization using power Doppler US. In contrast, the majority (84%, 21 out of 25 cases) of FA cases showed only a peripheral rim of color flow even by power Doppler US. These color flow imagings by power Doppler US were suggested to be a reliable tool for the differential diagnosis of thyroid follicular tumor with a sensitivity of 87.5% and a specificity of 92%. In velocimetric analyses, the Vmax/Vmin ratios, PI, and RI were significantly higher in the patients with FC than those with FA (p<0.001, p<0.005, and p<0.001, respectively). By means of ROC, FC could be diagnosed with a cutoff value of ratio of PI (>1.35), RI (>0.78), and Vmax/Vmin (>3.79). The diagnostic efficiency evaluated by ROC curves were 0.898 for PI, 0.876 for RI, and 0.888 for Vmax/Vmin, respectively. In conclusion, the evaluation of the vascular pattern and the velocimetric parameters using pulsed and power Doppler ultrasound may provide important information that is useful in making correct differential diagnosis of malignant or benign thyroid follicular tumor preoperatively.

Adenocarcinoma, Follicular↗
PubMed2005

Rapid differential diagnosis of Graves' disease and painless thyroiditis using total T3/T4 ratio, TSH, and total alkaline phosphatase activity.

When thyrotoxic patients are first seen in an outpatient clinic, it is important to make a differential diagnosis of Graves' disease (GD) and painless thyroiditis (PT). Using the three parameters of total T3/T4 ratio, TSH and T-ALP activity, all of which can be obtained within one hour in our hospital, 173 untreated patients with thyrotoxicosis were evaluated for the ratio of each parameter. For GD vs. PT, total T3/T4 (ng/microg) ratio (>20), TSH (<0.005 microU/ml) and elevated T-ALP had a likelihood ratio of 2.14, 2.12 and 4.07, respectively. When a patient had all three positive parameters, the likelihood ratio increased to 5.81, which showed effective synergy. These data suggest that, in addition to total T3/T4 ratio and TSH value, T-ALP activity is a useful parameter for the rapid differentiation of GD. The lower T-ALP activity seen in PT is probably due to the fact that patients develop less severe thyrotoxicosis or visit hospital earlier than patients with GD. Therefore, the diagnostic accuracy for Graves' disease might be increased by using the three parameters in combination.

Adult↗
PubMed2005

Ampulla cardiomyopathy after hypoglycemia in three young female patients with anorexia nervosa.

Ampulla cardiomyopathy is named after the echocardiographic abnormalities occurring in this condition, characterized by extensive akinesis (ballooning ) of the apical region with hypercontraction of the basal segment of the ventricle. We describe 3 young female anorexia nervosa patients showing evidence of this cardiac complication after hypoglycemia. One case was complicated by echocardiographically confirmed ampulla cardiomyopathy while the other 2 patients showed increases in myocardial enzymes and transient electrocardiographic abnormalities consistent with this complication. The precipitating event for all three patients was hypoglycemic coma, and this is the first case report in which this factor lead to the complication of ampulla cardiomyopathy in anorexia nervosa patients.

Adolescent↗
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

A young female patient with anorexia nervosa complicated by Mycobacterium szulgai pulmonary infection.

OBJECTIVE: Pulmonary infection with a rare atypical mycobacterium, Mycobacterium szulgai, was discovered during the treatment of anorexia nervosa in a 21-year-old Japanese woman without preexisting pulmonary disease. She had a long history of low body weight below 35 kg. METHODS: On admission, she was examined. She weighed 23 kg and presented with hypoproteinemia, decreased levels of rapid turnover proteins, liver dysfunction, and decreased serum level of insulin-like growth factor-I. RESULTS: Although she had had neither clinical symptom specific for mycobacterium pulmonary infection nor inflammatory data, a chest roentgenogram showed an infiltrative shadow with cavity formation in the right upper lung field. Isolated bacteria from sputum was acid-fast bacilli and identified as M. szulgai using the DNA-DNA hybridization method. DISCUSSION: In anorexia nervosa patients with a long history of severe malnutrition, special attention must be paid to the possibility of opportunistic infections, even in the absence of symptoms or inflammatory data.

Adult↗
PubMed2004

Serum adiponectin levels in adult growth hormone deficiency and acromegaly.

Atherosclerosis and insulin resistance are common complications of adult growth hormone deficiency (GHD) and acromegaly. Circulating adiponectin, an adipocyte-derived protein, has both anti-atherogenic and insulin-sensitising effects. In this study, we measured serum adiponectin levels in patients with either adult GHD or acromegaly to clarify the impact of GH secretory states on the regulation of serum adiponectin levels. Serum adiponectin level was measured by radioimmunoassay in 32 patients with adult GHD, 49 patients with acromegaly and 25 normal subjects. The relationships between adiponectin and insulin sensitivity index assessed as quantitative insulin sensitivity check index (QUICKI), BMI, and serum GH and IGF-I levels were then investigated. The values of QUICKI were significantly lower in patients with acromegaly or adult GHD compared to normal subjects (0.33 +/- 0.03, P < 0.01, 0.35 +/- 0.04, P < 0.05 and 0.36 +/- 0.01, respectively). While patients with adult GHD had significantly lower serum adiponectin levels than patients with acromegaly (6.5 +/- 3.9, 9.2 +/- 5.0, P < 0.01) these levels were not significantly different from those found in normal subjects (7.8 +/- 4.3 mug/ml). There was an inverse correlation between serum adiponectin levels and BMI in both patient groups (GHD r = -0.39, P < 0.05; Acromegaly r = -0.35, P < 0.05). However, serum adiponectin levels correlated positively with QUICKI (R(s) = 0.37, P < 0.05) only in patients with adult GHD. In patients with acromegaly, the levels of circulating adiponectin showed an inverse correlation with serum IGF-I levels (R(s) = -0.34, P < 0.05), but not with basal GH levels. These results demonstrate that adiponectin levels are significantly lower in patients with adult GHD than in patients with acromegaly. Adiponectin levels are similar in patients with GHD and healthy controls, whereas in patients with acromegaly, insulin resistance appears to be not closely related to adiponectin levels compared with BMI. The different relationship between adiponectin and QUICKI observed in the adult GHD and acromegaly groups presumably reflects differences in the mechanisms of insulin resistance under states of GH deficiency or excess.

Acromegaly↗
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

Cushing's syndrome due to a large adrenocortical adenoma with histological features simulating ACTH-independent macronodular adrenocortical hyperplasia.

A 53-year-old woman presented with Cushing's syndrome resulting from an adrenocortical adenoma, 6.5 cm in diameter and 75 g in weight, which is larger than usual. Endocrinological data of this patient showed adrenocorticotropin (ACTH)-independent hypercortisolemia. A computed tomography scan of the adrenal glands revealed a single large and well-encapsulated tumor with an irregularly shaped area of calcification and loss of parenchyma on the left adrenal. The right adrenal gland was atrophic. Laparoscopic removal of the left adrenal tumor was performed. The tumor was lobulated and clearly encapsulated, and the non-neoplastic area of the left adrenal was atrophic without any nodularity. The histological analysis confirmed the diagnosis of adrenal adenoma. In addition, this adenoma displayed histopathological features in common with ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), including clear cell predominance, a pattern of small compact cell nests in clear cell areas, and very long cord-like arrangement of small compact cells. In AIMAH, adrenals are extremely enlarged and are more massive than in any other subtype of Cushing's syndrome. The fact that the present adrenocortical adenoma was larger than those typical adenomas of Cushing's syndrome may reflect an AIMAH-type cellular composition of clear cell predominance and small compact cell nests.

Adrenal Cortex Neoplasms↗
PubMed2004

Metabolic effects of 20-kilodalton human growth hormone (20K-hGH) for adults with growth hormone deficiency: results of an exploratory uncontrolled multicenter clinical trial of 20K-hGH.

The biological effects of 20-kDa human GH (20K-hGH), which is produced in the pituitary by alternative splicing of GH mRNA and comprises approximately 6% of all GH in serum, have not been reported. We have investigated the metabolic effects of recombinant 20K-hGH in adult patients with GH deficiency in an exploratory study. Three doses of 20K-hGH (0.006, 0.012, and 0.024 mg/kg.d), were administered for 16 wk to three groups (consisting of 18 or 19 subjects), respectively. The 20K-hGH dose-dependently increased serum IGF-I and IGFBP-3 levels, and the lowest dose (0.006 mg/kg) was enough to normalize both hormones by wk 4. Serum osteocalcin levels and urinary deoxypyridinoline excretion were also dose-dependently increased. There was a significant decrease in body fat mass with an increase of lean body mass at the lowest dose of 0.006 mg/kg.d. Blood glucose and serum insulin were increased significantly at 4 wk only in the high-dose group (0.024 mg/kg). Glucose tolerance was slightly impaired in 26-39% of patients in all treatment groups as judged by oral glucose tolerance tests, but there was no development of overt diabetes. The major adverse event in the 20K-hGH treatment was peripheral edema, similar to the incidence reported for 22K-hGH. The data demonstrated that 20K-hGH had metabolic effects comparable to those of 22K-hGH in humans. The results suggest that 20K-hGH could be used to treat GH-deficient patients, although further studies may be required to investigate the optimum dose and superiority of 20K-hGH over 22K-hGH in a comparative study.

Abdomen↗
PubMed2004

Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa.

Octanoylated ghrelin (1-28) (intact ghrelin) is rapidly and easily degraded to desoctanoyl forms or smaller fragments (degraded ghrelin). Plasma levels of intact and degraded ghrelin were examined in 30 patients with anorexia nervosa (AN) (body mass index, 8.81-22.4 kg/m(2)) and 16 age-matched healthy women using several assay methods. Plasma levels of ghrelin measured using immunocomplex transfer-enzyme immunoassay, which specifically detects intact ghrelin, were lower in AN than controls. Plasma ghrelin levels in AN measured using the active ghrelin ELISA kit, which is advertised as specifically detecting intact ghrelin, did not differ significantly from controls. Plasma levels of desoctanoyl ghrelin using the desacyl-ghrelin ELISA kit, N-terminus ghrelin using the ghrelin active RIA kit, and C-terminus ghrelin using the ghrelin total RIA kit were significantly higher in AN than controls, and displayed significant negative correlations with body mass index. Plasma levels of ghrelin determined using immunocomplex transfer-enzyme immunoassay or active ghrelin ELISA during iv glucose infusion were suppressed in both AN and controls, whereas plasma levels of degraded ghrelin levels were not significantly decreased in AN. Plasma levels of intact ghrelin are therefore not higher in AN than controls, whereas degraded forms of ghrelin are elevated in AN. Rapid suppression of plasma intact ghrelin, but not degraded ghrelin, occurs in AN in response to glucose infusion. The profiles of intact and degraded forms of ghrelin in plasma of AN patients differ from those of healthy women.

Adolescent↗
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

An assessment of bone mineral density in patients with Addison's disease and isolated ACTH deficiency treated with glucocorticoid.

Glucocorticoid replacement therapy needs to be tailored to individual patient's requirements in order to avoid risk of over or under medication. We measured bone mineral density (BMD) of lumbar spine using dual X-ray absorptiometory in 10 patients with Addison's disease and 5 patients with isolated ACTH deficiency receiving glucocorticoid replacement therapy. We also examined the effect of glucocorticoid replacement on BMD. Decreased %BMD (less than 80% of age-matched controls) was found in 2 female patients who had received hydrocortisone at a dose of 14.8 and 15.4 mg/m(2)/day. In contrast, no patient receiving a hydrocortisone dose of less than 12.4 mg/m (2)/day had decreased %BMD. There was no correlation between %BMD and hydrocortisone dose (mg/m(2)), duration of therapy, or cumulative hydrocortisone dose when treated with appropriate dose of hydrocortisone (<13.6 mg/m(2)). There was also no statistically significant difference in %BMD with age. We concluded that long-term glucocorticoid replacement therapy does not induce bone loss in patients with glucocorticoid deficiency unless an excessive dose of hydrocortisone is given.

Absorptiometry, Photon↗
PubMed2004

Leptin regulation of the thyroids: negative regulation on thyroid hormone levels in euthyroid subjects and inhibitory effects on iodide uptake and Na+/I- symporter mRNA expression in rat FRTL-5 cells.

Leptin receptors are distributed throughout the body and leptin has been shown to have various effects. As we have recently demonstrated a positive correlation between serum leptin levels and TSH in euthyroid subjects, we investigated the effect of leptin on the thyroids. It was observed that serum leptin levels were negatively correlated with free thyroxine/TSH ratios in the serum of euthyroid female subjects. This suggests that leptin may modulate TSH effects. RT-PCR for leptin receptor expression revealed that FRTL-5 cells possess the gene transcript to the long cytoplasmic form of the receptor. Leptin actually appeared to induce an increase in c-fos mRNA expression. However, it inhibited iodide uptake typically induced by both TSH and dibutyryl cAMP, while leptin did not inhibit TSH-induced cAMP production or TSH-stimulated DNA synthesis in 4H medium (in the absence of insulin and TSH). Leptin also was observed to inhibit TSH- and dibutyryl cAMP-induced Na+/I- symporter and thyroglobulin mRNA expression. Lastly, leptin was seen to inhibit TSH-stimulated thymidine incorporation in 5H medium. Taken together, these results suggest that leptin suppresses TSH-induced thyroid function. Therefore, we hypothesized that leptin may be one of the regulators of thyroid function in obese patients.

Animals↗