Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 55 , Issue 2
Showing 1-26 articles out of 26 articles from the selected issue
REVIEWS
  • Hideaki KANETO, Takeshi MIYATSUKA, Dan KAWAMORI, Kaoru YAMAMOTO, Ken K ...
    2008 Volume 55 Issue 2 Pages 235-252
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: October 15, 2007
    JOURNALS FREE ACCESS
    Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, β-cell differentiation, and maintenance of mature β-cell function. PDX-1 expression is maintained in pancreatic precursor cells during pancreas development but becomes restricted to β-cells in mature pancreas. In mature β-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. MafA is a recently isolated β-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. Furthermore, these transcription factors play an important role in induction of insulin-producing cells in various non-β-cells and thus could be therapeutic targets for diabetes. On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in β-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. It is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for β-cell glucose toxicity found in diabetes.
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  • Dipanjan CHANDA, Jeong-Hoh PARK, Hueng-Sik CHOI
    2008 Volume 55 Issue 2 Pages 253-268
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: November 02, 2007
    JOURNALS FREE ACCESS
    Nuclear receptors (NRs) are a unique superfamily of transcription factors (TFs) which are involved in and play a crucial role in almost all aspects of mammalian physiology. Small Heterodimer Partner (SHP; NR0B2), an exceptional member of this superfamily of NRs, have been identified as a key regulatory factor of the transcription of a variety of genes involved in diverse metabolic pathways, and are thereby an important factor in a variety of physiological functions. Since its discovery a decade ago, considerable progress has been made in the elucidation of the underlying mechanism by which SHP regulates various metabolic processes, and the results of previous studies support its importance in the maintenance of metabolic homeostasis. In this review, we have evaluated the current state of understanding of the molecular mechanisms and the resultant physiological interpretations governed by SHP.
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ORIGINALS
  • Sheng-Fong KUO, Tzu-Chieh CHAO, Chuen HSUEH, Wen-Yu CHUANG, Chung-Han ...
    2008 Volume 55 Issue 2 Pages 269-275
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 25, 2008
    JOURNALS FREE ACCESS
    Controversies remain regarding to the therapeutic methods of papillary thyroid cancer (PTC) in young patients. TNM staging and other risk evaluation system are not perfectly applicable for all young PTC patients in view of disease outcome. The aims of this study are to identify the clinical presentations, prognostic factors and risk analysis methods. From January, 1977, to June, 2006, seventy-seven patients with primary PTC younger than 20 years old at Chang Gung Medical Center in Taiwan were enrolled in this retrospective study. The patients were classified as disease-free or non-disease-free according to presence or absence of distant metastases or local recurrence at the end of follow-up. Clinical data of these patients were analyzed and compared. The average follow-up period was 10.3 years. Two patients died of PTC during the follow-up period; one died of brain metastasis, and one died of airway obstruction. Patients undergoing total thyroidectomy, especially those with disease beyond the thyroid, had better outcomes than patients not undergoing total thyroidectomy (p = 0.003). Moreover, the DeGroot clinical classification system was a better predictor of prognosis than TNM (p<0.001 vs p = 0.007). Our results suggest that prognosis for PTC is not worse in younger patients. However, patients who had undergone total thyroidectomy might have a better prognosis. Clinical classification is a good alternative classification system for predicting disease outcome in young PTC patients. Patients with confined intrathyroid lesion (≤T2, N0, M0) may be regarded "low risk" PTC patients.
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  • Mari SATOH, Sayaka OGIKUBO, Atsuko YOSHIZAWA-OGASAWARA
    2008 Volume 55 Issue 2 Pages 277-284
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 07, 2008
    JOURNALS FREE ACCESS
    About 90% of patients with congenital nephrogenic diabetes insipidus (NDI) have vasopressin type 2 receptor (V2R) gene mutations that are inherited in an X-linked recessive manner. Although most female carriers are asymptomatic, some female carriers show polydipsia and polyuria. The reason why female carriers show NDI symptoms is explained by skewed X-inactivation. We studied X-inactivation patterns of six female carriers with heterozygote V2R gene mutations. The X-inactivation pattern in peripheral blood leukocytes was examined using methylation analysis of the polymorphic CAG repeat in the androgen receptor gene. Two asymptomatic female carriers showed random X-inactivation (61.9% and 60.7%). Skewed X-inactivation patterns (71.6%, 79.4%, and 91.2%) occurring preferentially to normal X alleles were recognized in three female carriers who showed clinical NDI symptoms. However, in one female carrier who showed clinical NDI symptoms, random X-inactivation (55.4%) was recognized. In conclusion, the clinical NDI phenotypes may correlate with the X-inactivation patterns in female carriers with heterozygote V2R gene mutations. However, in some female carriers, we cannot predict the clinical phenotypes by the evaluation of the X-inactivation patterns in peripheral blood leukocytes, because X-inactivation ratios within an individual are sometimes different between tissues.
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  • Yasumasa IWASAKI, Takafumi TAGUCHI, Mitsuru NISHIYAMA, Masato ASAI, Ma ...
    2008 Volume 55 Issue 2 Pages 285-290
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 07, 2008
    JOURNALS FREE ACCESS
    While lipopolysaccharides (LPS) are known to activate the hypothalamo-pituitary-adrenal axis, their direct effects on proopiomelanocortin (POMC) and adrenocorticotropin (ACTH) expression at the pituitary level through Toll-like receptors (TLRs) remain unclear. In this study, we examined the effects of LPS on ACTH secretion and the transcription of the POMC gene in the AtT20 mouse pituitary corticotroph cell line. RT-PCR analysis showed that TLR1-4 and 6 subtype mRNAs were expressed in AtT20 cells. When the cells were treated with LPS, a significant increase in the 5'-promoter activity of POMC gene was observed at 24 h, without any stimulatory effect on ACTH secretion. LPS also stimulated the expression of c-Fos gene and protein, and AP1-, but not NF-κB-, mediated transcription. Overall, our data show the expression of TLRs in the pituitary corticotroph cells, and suggest the direct stimulatory effect of LPS on POMC gene expression via TLR (probably TLR4), although the intracellular signaling pathways in the corticotroph may be different from those in immune cells.
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  • Takeshi NIGAWARA, Kazunori KAGEYAMA, Satoru SAKIHARA, Shinobu TAKAYASU ...
    2008 Volume 55 Issue 2 Pages 291-297
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 07, 2008
    JOURNALS FREE ACCESS
    Nonclassical form of 21-hydroxylase deficiency (NC 21OHD) as a frequent variant on the milder end of the disease spectrum has been widely acknowledged, but its potential contribution to adrenocortical tumorigenesis has not been fully elucidated. We report a 66-year old male case of bilateral adrenocortical incidentaloma, associated with partial 21OHD without any episodes of hypoadrenocorticism in his past history. He was demonstrated to be a compound heterozygous mutant of CYP21A2 gene (IVS2-13A/C>G/I172N). The two tumors in the left adrenal, which were interpreted as myelolipoma by imaging studies, were followed by sequential observation, whereas the contralateral large solid tumor associated with inhomogeneous radiological appearance was subsequently removed. The resected tumor was diagnosed an adrenocortical adenoma, which was devoid of P450c21 immunoreactivity. 21OHD is often associated with benign adrenocortical tumors, but bilateral adrenal tumors with heterogeneous components in both adrenals have not been reported to the best of our knowledge.
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  • Kazuhiro TAKEKOSHI, Kazumasa ISOBE, Hiroaki SUZUKI, Sumiko NISSATO, Ya ...
    2008 Volume 55 Issue 2 Pages 299-303
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 25, 2008
    JOURNALS FREE ACCESS
    Recently, nuclear genes encoding two mitochondrial complex II subunit proteins, SDHD and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that a mutation of SDHB is highly associated with abdominal (or thoracic) paraganglioma and the following distant metastasis (malignant paraganglioma). Previously, we identified a novel heterozygous G to A point mutation at the first base of intron 3 of the SDHB gene (IVS3+1G>A) in a malignant abdominal paraganglioma from a Japanese patient. In the present study, we report another case of SDHB mutation (R46Q) in a Japanese patient with both abdominal and thoracic paraganglioma following malignant metastasis. In addition, we identified an asymptomatic carrier of SDHB mutation in this family. Our report highlights the pathogenic role of the SDHB mutation (R46Q) in malignant paraganglioma. We also discuss the desired protocol that should be adopted to follow up an asymptomatic carrier of this mutation.
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  • Noriko AOI, Tomohiro NAKAYAMA, Naoyuki SATO, Kotoko KOSUGE, Akira HAKE ...
    2008 Volume 55 Issue 2 Pages 305-310
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 25, 2008
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    Background: Gitelman's syndrome is an inherited tubular disorder characterized by sodium wasting, low blood pressure, secondary hyperaldosteronism, metabolic alkalosis, hypokalemia, hypomagnesemia of renal origin, and hypocalciuria. The majority of patients with this syndrome carry inactivating mutations in the SLC12A3 gene encoding the thiazide-sensitive Na (+)-Cl (-) cotransporter (NCC) located in the distal convoluted tubule, which is involved in renal sodium reabsorption. This suggests that the SLC12A3 gene is involved in mediation of blood pressure levels. The aim of the present study was to investigate relationships between single nucleotide polymorphisms (SNPs) in the human SLC12A3 gene and essential hypertension (EH) in Japanese. Method: We selected 3 SNPs in the human SLC12A3 gene (T180K, A569V, L849H), and performed a case-control study of 315 EH patients and 305 normotensive (NT) individuals. Results: There was no significant difference in overall distribution of genotypes or alleles of any of the SNPs between the EH and NT groups. Conclusion: We conclude that the causal gene of Gitelman's syndrome is not involved in determining blood pressure levels.
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  • Tomoyuki IWASAKI, Yu TOGASHI, Yasuo TERAUCHI
    2008 Volume 55 Issue 2 Pages 311-316
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 07, 2008
    JOURNALS FREE ACCESS
    Objective: The aim of this study was to determine the association between serum albumin and the severity of microvascular complications and presence of coronary artery disease in type 2 diabetic patients. Patients and Methods: The presence of diabetic complications was assessed in a total of 130 Japanese patients with type 2 diabetes mellitus. Retinopathy was classified as absent, simple or proliferative diabetic retinopathy. Neuropathy was considered to be present when the patient showed absence of Achilles tendon reflex, and also evaluated by measuring the median motor nerve conduction velocity (MNCV) in the nerve conduction study. Results: In relation to retinopathy, there were 83 patients with no retinopathy (absent), 26 with simple retinopathy and 21 with proliferative retinopathy. There was a significant difference in the serum albumin level between the "absent" group and the other two groups. In relation to nephropathy, there were 68 patients with no evidence of nephropathy, 49 with microalbuminuria and 13 with proteinuria. The results of logistic regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to proliferative retinopathy and proteinuria. In relation to neuropathy, serum albumin was found to be significantly related to the absence of Achilles tendon reflex, MNCV, and MFWL. The results of multiple regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to MNCV and MFWL. Conclusions: Serum albumin was significantly associated with the severity of retinopathy and neuropathy.
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  • Nanako SATO, Yoshihisa SUGIMURA, Yoshitaka HAYASHI, Takashi MURASE, Ya ...
    2008 Volume 55 Issue 2 Pages 317-323
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 07, 2008
    JOURNALS FREE ACCESS
    Epidemiological studies have shown that the risks of fetal malformation such as neural tube defects increase in diabetic pregnancy. To explore the mechanism of fetal malformation induced by diabetes, cDNA subtraction using mouse embryos (E9.5) of diabetic dams and those of controls was performed to identify differentially expressed genes. The expression level of genes identified by cDNA subtraction was further verified by quantitative RT-PCR using E8.5 embryos, and differential expression of 4 genes, Brcc3, Commd3, Ddx1, and SET was confirmed. We also analyzed the expression level of neural tube defect-related genes, and found that Folbp1, EphrinA5 and Sox10 were differentially expressed. Altered expression of these genes mostly persisted throughout the later stages of the development (E10.5-14.5). Hierarchical clustering analysis showed correlation between expression levels of these genes, suggesting that these genes cooperatively play a role in embryonic development. Our results suggest that an altered gene expression profile in embryos underlies the development of congenital malformation in diabetic pregnancies.
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  • Ayhan ZENGI, Muammer KARADENIZ, Mehmet ERDOGAN, Ahmet Gökhan OZGE ...
    2008 Volume 55 Issue 2 Pages 325-330
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 25, 2008
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    Besides the genetic and environmental factors, radiation is an important aetiological cause in the occurrence of thyroid cancer (TC), particularly papillary carcinoma. Chernobyl disaster led to a dramatic increase in the frequency of TC in Eastern Europe. We aimed to determine the data of TC in our unit from 1982 to 2006 and whether Chernobyl disaster has a possible effect on TC distribution. The data of 351 patients with TC are reviewed retrospectively. The dates at diagnosis were classified in five time periods. The ratios of TCs in our unit were concordant with the literature. Comparing the five 5-year periods, there was a significant decrease in the ratio of follicular carcinoma (p<0.01) although the ratio of other thyroid cancers did not change (p>0.05). The ratio of papillary microcarcinoma increased (p<0.01) while the ratio of classical form decreased (p<0.01). The differences between the time periods and the mean ages at diagnosis for each TCs were not significant (p>0.05). If Chernobyl disaster had any effect, the mean age at diagnosis would be younger. The decrease in the ratio of follicular carcinoma in our study may be due to iodine supplementation. The higher ratio of papillary microcarcinoma can be related to increased diagnostic scrutiny. Epidemiological studies are necessary to determine TC incidence in Turkey.
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  • Yoshifumi SAISHO, Hiroshi HIROSE, Yukihiro YAMAMOTO, Hiroshi NAKATANI, ...
    2008 Volume 55 Issue 2 Pages 331-338
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 25, 2008
    JOURNALS FREE ACCESS
    Objective: Serum C-reactive protein (CRP) and adiponectin levels predict atherosclerosis and coronary heart disease. However, the efficacy of the combination of both markers remains unknown. In the present study, we investigated whether the combination of CRP and adiponectin is associated with further metabolic abnormalities compared to each of them alone. Research design and methods: Eighty-three Japanese type 2 diabetic outpatients participated in this study. We measured serum high-sensitive CRP and high molecular weight (HMW)-adiponectin, and investigated their relationship with various metabolic parameters. Results: In univariate analysis, CRP was significantly correlated with diastolic blood pressure and HDL-cholesterol. On the other hand, HMW-adiponectin was significantly correlated with systolic (SBP) and diastolic blood pressure, plasma glucose, HDL-cholesterol, triglycerides and HOMA-IR, but not with CRP. We then classified the subjects into three groups: low CRP and high HMW-adiponectin levels (low risk group, 19%), high CRP and low HMW-adiponectin levels (high risk group, 22%), and others. In Spearman rank correlation coefficient analysis, this classification was significantly associated with a larger number of metabolic risk factors: SBP, glucose, HbA1c, LDL-cholesterol, HDL-cholesterol, triglycerides and HOMA-IR, compared with classification by CRP or HMW-adiponectin alone. Conclusion: These results suggest that combination of CRP and HMW-adiponectin reflects further metabolic abnormalities compared with each of them in type 2 diabetic subjects. The combined measurement of both markers may be useful to detect cardiovascular high risk patients.
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  • Keiko YAMAGAMI, Katsunobu YOSHIOKA, Yoshihiro ISAKA, Takeshi INOUE, Ma ...
    2008 Volume 55 Issue 2 Pages 339-344
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
    JOURNALS FREE ACCESS
    An 18-year-old man with 4-year history of central diabetes insipidus and partial pituitary dysfunction was admitted to our hospital because of headache and nasal discharge. Magnetic resonance imaging (MRI) revealed abnormal mass in the sella turnica invading into the cavernous sinus and sinus maxillaries along with thickened tentorium cerebelli. Histopathology of the mass in the sinus maxillaries revealed spindle-shaped cells arranged in a fascicular pattern with varied myxoid and collagenized regions with various inflammatory cells. Immunostaining revealed the spindle-shaped cells were positive for smooth muscle actin. These features were identical to those of inflammatory myofibroblastic tumor (IMT). He was diagnosed with IMT in the sella turnica and other regions. Corticosteroid therapy improved clinical symptoms and follow-up MRI revealed amelioration of the thickened tentorium cerebelli. However, the other lesions were unchanged and pituitary dysfunction did not improve. Although rare, IMT should be considered in the differential diagnosis of a sellar mass. Early treatment with corticosteroid therapy may reduce the risk of disease progression.
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  • Giovanni CORONA, Carlo BIAGINI, Mario ROTONDI, Andrea BONAMANO, Nadia ...
    2008 Volume 55 Issue 2 Pages 345-350
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
    JOURNALS FREE ACCESS
    Objective: the aim of present study is to determine possible contributions of INF-γ inducible chemochine CXCL-10 in the thyroid color doppler ultrasound (CDU) parameters typical of autoimmune disorders. Methods: we studied a consecutive series of 25 patients with autoimmune thyroid disease and 10 healthy control subjects. All subjects underwent a thyroid CDU examination by the same investigator, who was unaware of the laboratory values at the time of the examination. Moreover, all subjects underwent a clinical evaluation, CXCL-10 and thyroid hormonal assessment. Results: CXCL-10 levels were significantly higher in patients with autoimmune diseases and as well as in subjects with an increased thyroid vascularization at CDU. Moreover, CXCL-10 levels were significantly (p<0.05) correlated with inferior thyroid arteria peak systolic velocity (ITA-PSV; r = 0.376) and with thyroid volume even after adjustment for confounding factors. No difference was observed between vascular thyroid pattern at CDU and thyroid circulating hormones while, ITA-PSV was significantly associated with TSH (Adj. r = -0.373; p<0.05). Conclusions: our data seem to suggest that CXCL-10 could play an important role in the intra-thyroid angiogenesis modulation, explaining, at least partiality, CDU findings typical of thyroid autoimmune diseases. Moreover we confirmed previous reports considering ITA-PSV as the best CDU parameters in the differential diagnosis of thyroid autoimmune disorders.
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  • Avraam AVRAMIDIS, Stergios A. POLYZOS, Zoe EFSTATHIADOU, Marina KITA
    2008 Volume 55 Issue 2 Pages 351-357
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
    JOURNALS FREE ACCESS
    Background: A 38-year-old woman first presented complaining of foot enlargement, finger numbness, arthralgia, fatigue, galactorrhoea and oligomenorrhea. Her symptoms in conjunction with her coarsened facial features and prognathism led to the suspicion of acromegaly. Basic procedures: Oral glucose tolerance tests (OGTT) were performed at initial presentation and almost yearly thereafter for a period of 14 years. Pituitary computerized tomographies (CT) were performed annually for the first six years and magnetic resonance imaging every two years thereafter. Main findings: The diagnosis of acromegaly was confirmed by OGTT at presentation. A pituitary CT revealed a large invasive pituitary macroadenoma. She remained acromegalic after adenomectomy (evidently partial tumor resection), but was controlled with subsequent long-term somatostatin analogue (SRL) administration. After eight years of SRL administration, she had acceptable stabilization of acromegaly and at that point SRL administration was discontinued. The patient maintained the same control for the following six years up to the present time without further SRL administration. Principal conclusion: This is the first case with stabilization of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) to nearly normal levels and clinical inactivity of acromegaly after withdrawal of long-term treatment with SRLs.
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  • Ozer MAKAY, Tayfun KAYA, Yesim ERTAN, Gokhan ICOZ, Mahir AKYILDIZ, Mus ...
    2008 Volume 55 Issue 2 Pages 359-364
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
    JOURNALS FREE ACCESS
    We report three cases of squamous cell carcinoma of the thyroid, which is an unusual malignant tumor that needs to be distinguished from other thyroid pathologies due to its aggressive behaviour. Three men, with an average of 63 years old, presented with progressive enlargement in the neck, hoarse voice or weight loss. Physical and radiological examinations revealed clues where malignancy was suspected and surgical resections were performed. Histopathological examination of the specimens was diagnosed as squamous cell carcinoma. Proper workup excluded the possibility of any primary site of SCC other than the thyroid. All patients died within 5 months. Adjuvant therapy evaluation is still inconclusive. Complete surgical resection still remains the primary choice for cure. We believe that radical resection with clear surgical margins followed by adjuvant chemo-radiation therapy is a curative strategy for achieving any chance of long-term survival.
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  • Özgür ÖMÜR, Zehra ÖZCAN, Bülent YAZICI, ...
    2008 Volume 55 Issue 2 Pages 365-372
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: February 15, 2008
    JOURNALS FREE ACCESS
    AIM: Patients with differentiated thyroid carcinoma (DTC) have long-life expectancy and are at risk for developing a second primary cancer. Aim of this study was to assess the occurrence of DTC in conjunction with other primary neoplasms. It was also aimed to explore the possibility of synchronous or metachronous other malignancies having an impact on clinical course of thyroid carcinoma. MATERIAL & METHODS: Clinical records of 1680 DTC patients treated and followed in our institution over last twenty years were reviewed. Forty-five second primary tumors were found in 42 patients. These patients were classified into 3 groups as antecedent (group I), synchronous (group II) or subsequent (group III) according to the timing of occurrence of non-thyroidal malignancy. The initial characteristics of thyroid neoplasm were compared between patients with DTC plus another tumor and DTC only. Kaplan-Meier Survival Analysis was used to estimate the survival probability for patients with DTC alone and DTC plus another primary tumor. RESULTS: There were 15 synchronous and 30 metachronous tumors in 42 patients. Three of them had triple tumors. The most common second primary was lympho-haematological and upper aero digestive system tumors in group I and II respectively, whereas a variety of tumors were noted in group III. Despite the more common occurrence of unfavourable prognostic factors in patients with multiple cancers than thyroid cancer alone, complete response to radioiodine therapy and recurrence free survival rate was similar in both groups (p>0.05). CONCLUSION: The results of the current series imply that the occurrence of multiple primary tumors is not uncommon in patients with DTC. Close medical surveillance and the use of advanced screening modalities might lead to the detection of second primary tumors in DTC. However, the presence of second primary seems not to affect the clinical course of DTC.
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  • Kayoko MOTOJIMA, Kosuke AZUMA, Yoshiro KITAHARA, Kyoko MIURA, Tomoya M ...
    2008 Volume 55 Issue 2 Pages 373-379
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
    JOURNALS FREE ACCESS
    To compare the effects of postprandial hypertriglyceridemia and postprandial hyperglycemia on monocyte adhesion to endothelial cells, we investigated the effects of twice-daily standard diet (5% fat) and high-fat diet (30% fat) for 3 weeks on monocyte adhesion to endothelial cells and the expression of adhesion molecules in the aortic artery in non-obese type 2 diabetic Goto-Kakizaki rats. Fasting glucose, insulin, non-esterified fatty acid (NEFA), HbA1c, and body weight were comparable between the two diet groups. Postprandial glucose and insulin were higher in the standard diet group, while postprandial NEFA and triglyceride were higher in the high fat diet group, compared with the other group. The number of monocyte adherent to endothelial cells was higher in the high-fat diet group than the standard diet group. Consumption of high-fat diet resulted in overexpression of heme oxygenase-1, intercellular adhesion molecule-1 (ICAM-1), and connecting segment-1 fibronectin on the arterial wall, compared with standard diet. Thus, our data demonstrated that short-term intermittent high-fat diet prevented postprandial hyperglycemia in a model of type 2 diabetes without a significant increase in body weight. However, the resulting postprandial hypertriglyceridemia induces more monocyte adhesion to endothelial cells than postprandial hyperglycemia. This increased monocyte adhesion is associated with the increased aortic expression of adhesion molecules such as ICAM-1, and connecting segment-1 fibronectin.
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  • Jasem M. K. ABBAS, Jagadish CHAKRABORTY, Abayomi O. AKANJI, Suhail A. ...
    2008 Volume 55 Issue 2 Pages 381-389
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 02, 2008
    JOURNALS FREE ACCESS
    There is evidence of an association between hypothyroidism and coronary heart disease. We decided to look at the relationship between hypothyroidism and LDL subclasses' pattern including small, dense LDL to define a biochemical basis for better management of the CHD risk of these patients. We utilized a case-control design to evaluate differences in lipid parameters between cases and controls. Univariate analysis revealed that many factors were associated with LDL particle size. Binary logistic regression however revealed that only thyroid status and serum triglyceride (TG) levels were independently associated with LDL particle size. Results from this study support an independent association between LDL particle size phenotype and both plasma TG concentrations and thyroid status. After adjusting for TG levels, other insulin resistance syndrome (IRS) traits were not associated with LDL size phenotype, suggesting that the IRS related sdLDL is linked most strongly to alterations in TG levels.
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  • Toshinori YOSHIDA, Yasumasa IWASAKI, Tohru KAGAWA, Atsushi SASAOKA, Ta ...
    2008 Volume 55 Issue 2 Pages 391-395
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 02, 2008
    JOURNALS FREE ACCESS
    A 75-year-old woman was admitted to our hospital because of general fatigue. She had suffered from sarcoidosis during her 40s with remission, but subsequently she experienced progression of hypercalcemia and renal dysfunction for 7 years. On admission, she showed marked hypercalcemia (up to 15.5 mg/dl) and renal failure (serum creatinine 2.5 mg/dl). Plasma intact PTH level was elevated (up to 190 pg/ml), and thyroid ultrasonography and 99m Tc-MIBI scintigraphy detected a parathyroid mass, which was surgically removed and histologically confirmed to be a parathyroid adenoma. However, even after surgery her serum calcium remained elevated, but subsequent administration of glucocorticoid for sarcoidosis completely normalized her hypercalcemia. The simultaneous occurrence of primary hyperparathyroidism and sarcoidosis is rare, and our data suggest that high plasma PTH and 1,25(OH)D exerted an additive effect on the occurrence of severe hypercalcemia.
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  • Ken-ichi KASHIMADA, Makoto ONO, Toshikazu ONISHI, Satimi KOYAMA, Takio ...
    2008 Volume 55 Issue 2 Pages 397-404
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 02, 2008
    JOURNALS FREE ACCESS
    We report four cases of nonclassical 21-hydroxylase deficiency (21-OHD) diagnosed in neonate or early childhood. The four patients comprised a 6-year, 5-month-old male (case 1); a 3-year, 10-month-old female (case 2); a 13-year, 11-month-old female (case 3) and a 17-year, 1-month-old male (case 4). Cases 3 and 4 were siblings. None had any signs of virilization or salt wasting at birth. 21-OHD was diagnosed using ACTH loading test and other adrenal steroid evaluations. Mutations of the CYP21 gene were detected in all patients. Three patients (cases 1, 3 and 4) had positive results in neonatal mass screening. Cases 1 and 2 showed no apparent signs of virilizaton and were observed without conventional treatment. In cases 3 and 4, because of increased growth velocity and accelerated bone maturation, hydrocortisone administration was initiated from their late infantile period. In spite of hydrocortisone treatment, in case 4, the final height of 159.7 cm was less than his predicted final height. Besides he revealed adrenal insufficiency at the age of 9 years and 2 months old caused by viral infection. Hydrocortisone supplementation therapy may cause adrenal insufficiency in nonclassical patients due to suppression of the hypothalamus-pituitary-adrenal axis. The clinical courses in these cases were various, and it was difficult to predict the appearance of any symptoms of virilization. Careful observation is necessary.
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  • Kotaro YOKOYAMA, Mahoko HAYASHI, Chihiro MOGI, Yoshihiro SASAKAWA, Gen ...
    2008 Volume 55 Issue 2 Pages 405-414
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
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    Glucocorticoids are known to stimulate growth hormone (GH) production but to suppress prolactin (PRL) production. However, previous data were obtained with rather high doses of corticosterone. In this study we examined the effects of various doses (10 -12 -10 -7 M) of corticosterone on GH and PRL production in a rat pituitary somatomammotropic cell line, MtT/SM cells, and found that GH mRNA expression was facilitated by high doses (10 -7 and 10 -8 M). In contrast, a biphasic effect of corticosterone on PRL mRNA expression and secretion was observed, i.e., high doses (10 -7 and 10 -8 M) suppressed and low doses (10 -12 -10 -10 M) facilitated them. In an immunofluorescent staining study, the number of PRL immunopositive cells increased with low doses of corticosterone while it decreased with high doses of it, which corresponded to PRL mRNA expression and hormone secretion, respectively. These effects of corticosterone on PRL production were abolished by a glucocorticoid receptor (GR) antagonist, mifepristone. In addition, co-treatment with low doses of corticosterone (10 -12 -10 -10 M) and 17β-estradiol (E2, 10 nM) additively increased the number of PRL immunopositive cells. Moreover, a 24 h BrdU incorporation experiment suggested that the increase in the number of PRL immunopositive cells treated with low dose corticosterone was caused by novel synthesis of PRL while, on the other hand, that of those treated with E2 resulted from PRL cell proliferation. Thus, we concluded that corticosterone biphasically regulates PRL production and the sensitivity of E2 to different degrees.
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  • Zhe Feng YUAN, Hua Qing MAO, Yan Fei LUO, Yi Dong WU, Zheng SHEN, Zhen ...
    2008 Volume 55 Issue 2 Pages 415-423
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 01, 2008
    JOURNALS FREE ACCESS
    The aim of the present study was to investigate the mutation/variant of thyrotropin receptor (TSHR) and thyroid transcription factor-1 (TTF-1) genes in Chinese children with congenital hypothyroidism (CH). Seventy-nine and forty-nine Chinese children with CH were enrolled for molecular analysis of the TSHR gene and TTF-1 gene, respectively. One hundred normal children were evaluated as control. The coding regions of TSHR and TTF-1 genes were amplified by polymerase chain reaction and sequenced. Sequencing of the TSHR gene revealed a compound heterozygous variants (Pro52Thr/Val689Gly) and a heterozygous variant (Gly245Ser) in 2 of 79 patients. In 30 patients and 33 controls the normal cytosine at position 2181 in exon 10 of TSHR gene was replaced by a guanineCresulting in the replacement of Asp 727 by Glu. In 47 patients and 50 controls, the normal thymidine at position 561 in exon 7 of TSHR gene was replaced by a cytosine. This substitution did not change the amino acid in position 187. Sequencing of the TTF-1 gene revealed no mutation or polymorphism in 49 patients and 100 controls. In conclusion, three heterozygous variants (Pro52Thr, Gly245Ser, Val689Gly) of TSHR gene were firstly detected in Chinese children with CH. There were polymorphisms in exon 10 at nucleotide 2181 (C/G) and in exon 7 at nucleotide 561 (T/C) in TSHR gene. No mutation or polymorphism was detected in the coding region of TTF-1 gene. The mutation/variant of TSHR and TTF-1 genes is relatively rare in Chinese children with CH.
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  • Hiroshi MARUYAMA, Yasumasa IWASAKI, Makoto TSUGITA, Naoko OGAMI, Koich ...
    2008 Volume 55 Issue 2 Pages 425-428
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 02, 2008
    JOURNALS FREE ACCESS
    An 81-year-old man was admitted to our hospital because of general fatigue. Hormonal examination showed that he had panhypopituitarism and central diabetes insipidus. MRI imaging revealed the presence of large cystic mass with suprasellar extension in his hypothalamo-pituitary region. Interestingly, the cystic mass shrank following the start of glucocorticoid replacement, and since then relatively high doses of cortisol administration were needed to prevent the re-enlargement of cystic size. Because of the concern over possible side effects of supraphysiological doses of glucocorticoid replacement, surgical treatment was eventually carried out, confirming the pathological feature of Rathke's cleft cyst. The present case suggests that the inflammatory nature of Rathke's cleft cyst may explain the observed short-term size changes in response to glucocorticoid administration.
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  • Takao TANIGUCHI, Akihiro HAMASAKI, Motozumi OKAMOTO
    2008 Volume 55 Issue 2 Pages 429-432
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: March 25, 2008
    JOURNALS FREE ACCESS
    Pre(sub)clinical Cushing's disease is a recently described entity defined by the autonomous secretion of ACTH and the absence of a cushingoid appearance. We screened 77 hospitalized patients with diabetes mellitus for subclinical hypercortisolism and detected pre(sub)clinical Cushing's disease in 2 (2.6%) of them. In both patients, transsphenoidal surgery was performed and a microadenoma was removed. Their metabolic clearance rate of glucose measured by a glucose clamp study, an index of insulin sensitivity, significantly improved after surgery. Our results indicate that screening for subclinical hypercortisolism in diabetic patients might be useful, as surgery improves glucose tolerance and insulin sensitivity.
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  • Yoshifumi SAISHO, Hiroshi HIROSE, Chihiro HORIMAI, Kiichi MIYASHITA, I ...
    2008 Volume 55 Issue 2 Pages 433-438
    Published: 2008
    Released: May 10, 2008
    [Advance publication] Released: April 02, 2008
    JOURNALS FREE ACCESS
    Aims: Recent studies suggest that nuclear factor-κB (NF-κB) activation has an important role in leading to beta cell dysfunction in both type 1 and type 2 diabetes. In this study we tested this hypothesis by investigating the effects of dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-κB inhibitor, on tumor necrosis factor-α (TNF-α)-induced beta cell dysfunction. Methods: INS-1 cells were incubated with TNF- α and with or without DHMEQ for 24 hours. Glucose-stimulated insulin secretion, cell viability, mRNA expression and NF-κB activation were investigated. Results: DHMEQ suppressed TNF-α-induced NF-κB activation and partially ameliorated glucose-stimulated insulin secretion in a dose-dependent manner. DHMEQ also partially ameliorated decreased cell viability and insulin mRNA level induced by TNF-α. Conclusion: DHMEQ suppressed NF-κB activation and ameliorated beta cell dysfunction induced by TNF- α. Inhibition of activated NF-κB in beta cells may be important to ameliorate beta cell dysfunction in diabetes.
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