Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 53 , Issue 6
Showing 1-23 articles out of 23 articles from the selected issue
REVIEWS
  • Hideto KOJIMA, Mineko FUJIMIYA, Tomoya TERASHIMA, Hiroshi KIMURA, Lawr ...
    2006 Volume 53 Issue 6 Pages 715-722
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 07, 2006
    JOURNALS FREE ACCESS
    Insulin is a key regulator of life. Until 25 years ago, the pancreatic β-cell was thought to be the only organ that produces insulin in the body. Insulin deficiency, whether absolute (in type 1) or relative (in type 2 diabetes), underlies the metabolic derangements in diabetes mellitus, and investigations on insulin have concentrated on pancreatic insulin production, its regulation and the metabolic consequences of insulin deficiency. The thymus was the next organ that was found to also produce insulin, a process that may tolerize the body to the molecule, protecting the host from developing autoimmune β-cell destruction and (type 1) diabetes. However, now and then there were descriptions of promiscuous insulin production outside the pancreas. During our investigations on diabetes gene therapy in rodents, we serendipitously came across the presence of mysterious cells marked by proinsulin production in unexpected organs, some of which cells may underlie certain chronic diabetic complications. Starting with a historical perspective on insulin expression in brain and thymus, this review focuses mainly on unraveling the mystery of extrapancreatic extrathymic proinsulin/insulin expression in diabetes mellitus.
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  • Kiminori SUGINO, Koichi ITO, Hiroshi TAKAMI
    2006 Volume 53 Issue 6 Pages 723-728
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 07, 2006
    JOURNALS FREE ACCESS
    Recombinant human TSH (rhTSH) brought revolutionary change in the management of patients with differentiated thyroid cancer since it was first approved for clinical use in the United States and Europe. Follow-up management of differentiated thyroid cancer is based on the detection of recurrent or residual cancer, traditionally achieved by measurement of serum thyroglobulin level and various imaging techniques including 131I whole body scan. Previously, TSH stimulation was achieved only by induction of hypothyroidism following withdrawal of thyroid hormone. However, hypothyroidism is uncomfortable and is association with a reduction in quality of life. RhTSH can provide elevated TSH without making patients hypothyroid. In the United States and Europe, rhTSH is approved for use only in monitoring of differentiated thyroid cancer. In this article, we reviewed the role of rhTSH in the diagnosis and management of differentiated thyroid cancer.
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ORIGINALS
  • Alper SONMEZ, Teoman DOGRU, Mahmut Ilker YILMAZ, Ilker TASCI, Ramazan ...
    2006 Volume 53 Issue 6 Pages 729-734
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 07, 2006
    JOURNALS FREE ACCESS
    Smoking is closely associated with insulin resistance, though the mechanism is not clear. Adiponectin, a novel anti-atherosclerotic and anti-inflammatory adipose tissue product, which is closely associated with insulin resistance, was reported to be low in smokers with cofactors for atherosclerosis. However, the effects of smoking on circulating adiponectin levels in otherwise healthy people are unknown. In this study, a case control design was implemented to search for the effect of smoking on plasma adiponectin and insulin sensitivities in healthy people. Sixty-four healthy male smokers, with no family history of hypertension and diabetes mellitus were compared with appropriate 36 age and body mass index matched controls. Both the patients and controls were the soldiers of a troop with regular daily physical activity. Plasma adiponectin, high sensitive C-reactive protein (hsCRP), insulin and lipid levels, and insulin sensitivity as assessed by homeostasis model assessment index (HOMA) of the smokers were measured and compared with those of the controls. The plasma adiponectin, hsCRP, insulin levels and HOMA indexes of the two groups were similar. These parameters were not affected by the amount of cigarettes per day. HDL-cholesterol levels were lower (p = 0.01) and systolic blood pressures were higher (p = 0.02) in the smokers. These results indicate that smoking may not affect plasma adiponectin and insulin levels in young and healthy men with high exercise capacity.
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  • Eijun NISHIHARA, Shuji FUKATA, Akira HISHINUMA, Takumi KUDO, Hidemi OH ...
    2006 Volume 53 Issue 6 Pages 735-740
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 07, 2006
    JOURNALS FREE ACCESS
    Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. We here describe a Japanese woman who had presented with severe hyperthyroidism and advanced bone age as a neonate. She underwent neurosurgical intervention for craniosynostosis, and presented with perodactylia and mild mental retardation with hydrocephalus. Hyperthyroidism has been refractory to antithyroid drug therapy in the absence of antithyrotropin receptor antibodies during follow-up of 20 years, resulting in an enlarged goiter. Analysis of the patient's genomic DNA showed a heterozygous thymine-to-adenine point mutation in exon 10 of TSHR at position 1535 which was not present in the parents' DNA. This mutation, changing leucine to glutamine in codon 512 in the third transmembrane region, was previously identified as a somatic mutation in toxic thyroid nodules and was shown to increase basal cAMP production in vitro. To our knowledge, this is the first report of a germline mutation of TSHR causing sporadic congenital nonautoimmune hyperthyroidism in a Japanese patient.
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  • Tsutomu OGATA, Ikuma FUJIWARA, Eishin OGAWA, Naoko SATO, Toru UDAKA, K ...
    2006 Volume 53 Issue 6 Pages 741-743
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 07, 2006
    JOURNALS FREE ACCESS
    We report on a 14 7/12-year-old Japanese female patient with CHARGE syndrome and CHD7 mutation who also exhibited Kallmann syndrome (KS) phenotype. She had poor pubertal development and apparently impaired sense of smell. A GnRH test showed severely compromised responses of LH (<0.5 → <0.5 IU/L) and FSH (<0.5 → 1.2 IU/L), and magnetic resonance imaging delineated hypoplastic olfactory bulbs. Mutation analysis revealed a heterozygous nonsense mutation at exon 33 of CHD7 (7027C>T, Q2343X). The results provide further support for the notion that KS phenotype can be included in the phenotypic spectrum of CHARGE syndrome, and indicate that CHARGE syndrome with KS phenotype is caused by a CHD7 mutation.
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  • Hiroki FUJITA, Tsukasa MORII, Jun KOSHIMURA, Motoko ISHIKAWA, Masako K ...
    2006 Volume 53 Issue 6 Pages 745-752
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 12, 2006
    JOURNALS FREE ACCESS
    Adiponectin is an adipose-derived protein which has anti-inflammatory and anti-atherogenic properties in addition to insulin-sensitizing effects. To date, the role of adiponectin in the pathogenesis of diabetic nephropathy remains unclear. The aim of the present study was to explore the relationship between adiponectin and renal tubular injury in diabetic nephropathy. We determined serum and urinary adiponectin levels in type 2 diabetic patients with normoalbuminuria (n = 19), microalbuminuria (n = 18), and overt diabetic nephropathy (n = 16), and then analyzed the correlations between serum and urinary adiponectin, urinary N-acetylglucosaminidase (NAG) as a clinical marker of renal tubular injury, urinary monocyte chemoattractant protein-1 (MCP-1) as an inflammatory marker in renal tubulointerstitium, and clinical markers of renal disease. Notably, serum and urinary adiponectin levels were significantly increased in patients with overt diabetic nephropathy compared to those with normoalbuminuria and microalbuminuria. In univariate linear regression analysis, serum adiponectin levels were positively correlated with serum creatinine (r = 0.648, P<0.0001), urinary albumin (r = 0.583, P<0.0001), urinary NAG (r = 0.406, P<0.01), urinary MCP-1 (r = 0.514, P<0.0001), and urinary adiponectin (r = 0.691, P<0.0001) levels in all diabetic patients. Urinary adiponectin levels were also positively correlated with serum creatinine (r = 0.729, P<0.0001), urinary albumin (r = 0.799, P<0.0001), urinary NAG (r = 0.701, P<0.0001), and urinary MCP-1 (r = 0.801, P<0.0001) levels in all diabetic patients. Multiple linear regression analysis showed that serum creatinine and urinary adiponectin levels were independently associated with serum adiponectin levels (r2 = 0.522), and that serum creatinine, urinary NAG, urinary MCP-1, and serum adiponectin levels were independent determinants of urinary adiponectin levels (r2 = 0.851). These results collectively indicate that renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in overt diabetic nephropathy. We presume that an increase in circulating adiponectin in overt diabetic nephropathy might be a physiological response to mitigate renal tubular injury and to prevent the further progression of diabetic nephropathy through its anti-inflammatory and anti-atherogenic effects.
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  • Yuji HIROMATSU, Tomoka FUKUTANI, Michiko ICHIMURA, Tokunori MUKAI, Hir ...
    2006 Volume 53 Issue 6 Pages 753-759
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 12, 2006
    JOURNALS FREE ACCESS
    Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction - restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.
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  • Shinichiro MINE, Yosuke OKADA, Chie KAWAHARA, Takahiro TABATA, Yoshiya ...
    2006 Volume 53 Issue 6 Pages 761-766
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 12, 2006
    JOURNALS FREE ACCESS
    Accumulation of hyaluronan (HA) around smooth muscle cells in lesions of atherosclerosis in diabetic patients suggests that this protein plays an important role in diabetic angiopathy. The aim of this study was to determine the correlation between serum HA concentrations and diabetic angiopathy. Diabetic patients treated with or without an oral hypoglycemic agent and/or insulin for at least 1 year were recruited (n = 95). We also included 20 non-diabetic control subjects. We measured serum levels of HA, body mass index (BMI), fasting plasma glucose (FPG), HbA1c, total cholesterol, triglyceride, glycated albumin (GA), high sensitivity CRP (hs-CRP), monocyte chemoattractant protein (MCP)-1 and evaluated diabetes mellitus history, drug use and presence of related complications. Serum HA levels were significantly (P<0.05) higher in diabetic patients (83.6 ± 5.6 ng/ml, mean ± SEM) than in normal subjects (41.7 ± 12 ng/ml). In diabetic patients, serum HA concentration significantly correlated with FPG, HbA1c, GA, triglyceride and also significantly correlated with BMI, hs-CRP and MCP-1 and tended to be higher in diabetic patients with complications than in those without such complications. Our data suggest that serum HA level correlates with poor blood glucose control and diabetic angiopathy and that it could be used as a marker of diabetic angiopathy.
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  • Yoshiaki TAMURA, Atsushi ARAKI, Yuko CHIBA, Toshiyuki HORIUCHI, Seijir ...
    2006 Volume 53 Issue 6 Pages 767-771
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 12, 2006
    JOURNALS FREE ACCESS
    We recently encountered a 96-year-old Japanese woman who suffered from frequent hypoglycemia. Endocrinological and imaging data eliminated the possibility of insulinoma, whereas oral glucose tolerance testing revealed impaired glucose tolerance and subsequent reactive hypoglycemia. The patterns between insulin or C-peptide secretions and glucose excursions demonstrated that the discrepancy occurred in the late postprandial stage. Administration of small doses of alpha-glucosidase inhibitor (α-GI) dramatically inhibited the rapid rise and subsequent precipitous fall of plasma glucose. Reactive hypoglycemia may be one of the important cause of hypoglycemia in the elderly, and α-GI could effectively and safely prevent such hypoglycemic attacks in those patients.
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  • Henry VÖLZKE, Sybille GRUSKA, Dirk VOGELGESANG, Wolfgang KERNER, ...
    2006 Volume 53 Issue 6 Pages 773-781
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 19, 2006
    JOURNALS FREE ACCESS
    Increased intracellular calcium concentrations ([Ca2+]i) and enhanced sodium-lithium countertransport (Na/Li CT) activities may play a role in the development of diabetic complications such as diabetic nephropathy. The present study was designed to test the hypothesis that albuminuria in patients with type 2 diabetes is associated with increased [Ca2+]i in response to stimulation with platelet-activating factor (PAF) or with enhanced Na/Li CT activities. The study population comprised 203 type 2 diabetic patients. Albuminuria was defined as an albumin excretion rate exceeding 30 mg/d (117 cases). PAF-evoked rises in [Ca2+]i and Na/Li CT activities were determined in Epstein-Barr-virus-immortalized lymphoblasts. Albuminuria was related to high stimulated [Ca2+]i but not to high basal [Ca2+]i. The association was independent of age, sex and several non-diabetes related confounders, but depended on diabetes-related factors, such as the duration of diabetes. The risk of albuminuria was highest in subjects with high [Ca2+]i who reported a diabetes duration of ≤10 years. There was no association between Na/Li CT activities and albuminuria. The present results support the hypothesis that albuminuria in type 2 diabetic patients is associated with a primary defect in intracellular calcium homeostasis. The association between stimulated [Ca2+]i and albuminuria is most prominent in early diabetes.
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  • Takashi YAMADA, Ichiro KOMIYA, Yasuhiro MIYAHARA, Mitsuhiro KOMATSU, I ...
    2006 Volume 53 Issue 6 Pages 783-788
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 19, 2006
    JOURNALS FREE ACCESS
    In this study we confirmed our previous findings on the importance of IgE in Graves' disease and further investigated the relationships existing among Graves' disease, IgE, and interleukin-4. Two hundred and thirty-two newly diagnosed Graves' disease patients were treated with methimazole for 2 years, and were classified into 3 groups according to their response to the therapy. Incidence of IgE elevation (IgE≥170 IU/ml) before treatment was lowest, 23.8%, in the group who achieved remission without recurrence, while it was 41.7% in the group who achieved remission but recurrence occurred within 4 years. Incidence of IgE elevation before treatment was highest, 60.7%, in the group who failed to achieve remission, significantly higher than that of the group without recurrence. Incidence of IgE elevation before treatment in all these patients of Graves' disease were 35.3%, significantly higher than those of Hashimoto's thyroiditis (17.5%) and of simple goiter (7.0%). Serum IL-4 levels before treatment were significantly higher in the patients of Graves' disease with IgE elevation than in those without IgE elevation. Serum T4 concentration and TSAb titration before treatment were also significantly higher in elevated IgE group than in normal IgE group. These results support our previous findings and suggest that IL-4 may play important roles in the elevation of IgE, TBII, and TSAb in patients of Graves' disease, and that IL-4 and IgE may be involved in the development, progression, and maintenance of Graves' disease.
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  • Satoko YAMADA, Yoritsuna YAMAMOTO, Masahiro NAGASAWA, Akemi HARA, Tsut ...
    2006 Volume 53 Issue 6 Pages 789-795
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 19, 2006
    JOURNALS FREE ACCESS
    Adenovirus-mediated gene transfer of pancreatic duodenal homeobox transcription factor PDX-1, especially its super-active version (PDX-1/VP16), induces the expression of pancreatic hormones in murine liver and reverses streptozotocin-induced hyperglycemia. Histological analyses suggest that hepatocytes are the major source of insulin-producing cells by PDX-1 gene transfer, although the conversion of cultured hepatocytes into insulin-producing cells remains to be elucidated. The present study was conducted to address this issue. Hepatocytes were isolated from adult rats. Then, PDX-1 or PDX-1/VP16 gene was introduced by using adenovirus vector. Two days later, the expression of insulin was detected at mRNA and protein levels. Transfection of PDX-1/VP16 was more efficient in converting hepatocytes to insulin-producing cells. Immunoreactivity of albumin was downregulated in transdifferentiated cells and some of them almost completely lost albumin expression. During the course of transdifferentiation, upregulation of mRNA for CK19 and α-fetoprotein was observed. When cultured in collagen-1 gel sandwich configuration, hepatocytes maintained their mature phenotype and did not proliferate. In this condition, transfer of PDX-1/VP16 also induced the expression of insulin. These results clearly indicate that hepatocytes possess a potential to transdifferentiate into insulin-producing cells in vitro.
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  • Masaaki SHIOHARA, Riyo SHIOZAWA, Kenji KURATA, Hiroki MATSUURA, Fumi A ...
    2006 Volume 53 Issue 6 Pages 797-802
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 19, 2006
    JOURNALS FREE ACCESS
    Hypoparathyroidism caused by gain-of-function mutations of the calcium-sensing receptor (CaR) in the transmembrane domain is usually severe and difficult to manage. A patient with severe hypoparathyroidism, caused by CaR activating mutation F821L, was treated for 3 days (Day 1 to Day 3) with synthetic human parathyroid hormone 1-34 (teriparatide, PTH). An Ellsworth-Howard test of the patient revealed normal responses of urine phosphate and cyclic AMP excretion, indicating that the patient's renal tubules normally responded to extrinsic PTH. On Day 1 to Day 3, 0.9 μg/kg/day of PTH was administered subcutaneously twice daily at 0800 and 2000. On Day 1, the serum calcium level that was 1.8 mmol/l before PTH administration increased to 2.1 mmol/l at 1200, and gradually decreased to 1.8 mmol/l at 2000. On Days 2 and 3, the maximum calcium levels were 2.5 and 2.4 mmol/l, respectively, at 1200. At 2000, they returned to or below basal levels at 0800. On Day 4 without PTH administration, the calcium levels were maintained at the basal levels at Day 0. The urine calcium/creatinine (Ca/Cr) ratio that was high (>0.4) before PTH injection decreased after PTH administration (0.4>). Changes in the ionized calcium levels were almost parallel with the total calcium levels. The serum inorganic phosphate (IP) level decreased to 2.4 mmol/l at 1000, but gradually increased before the second PTH injection to the level at 0800 on Day 1. The minimum IP level on Days 2 and 3 was 2.1 mmol/l and 2.0 mmol/l, respectively. In contrast to the remarkable changes in the serum calcium level by PTH treatment, the serum magnesium levels showed few changes. These results indicate that PTH therapy could be effective in correcting serum and urine calcium and the phosphate levels in hypoparathyroidism caused by activating mutation of CaR.
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  • P. DEL MONTE, L. FOPPIANI, C. CAFFERATA, A. MARUGO, D. BERNASCONI
    2006 Volume 53 Issue 6 Pages 803-809
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 19, 2006
    JOURNALS FREE ACCESS
    Increasing evidence of impaired pituitary function in many subjects with primary empty sella (PES) has been reported. We conducted a retrospective analysis of our patients with PES, in order to ascertain presenting symptoms and endocrine status on diagnosis and during follow-up. Magnetic resonance imaging (MRI) of the pituitary leading to the diagnosis of PES was performed in 8 patients (5 F and 3 M, age: 60.1 ± 3.3 years, M ± SE; group 1) after the diagnosis of global anterior hypopituitarism (H), and in 20 patients (F, age 56.9 ± 2.2 years, group 2) for other clinical reasons. Baseline determinations of pituitary and target gland hormones and of IGF-I were performed. GH response to GHRH plus arginine stimulation was also evaluated. Ten age- and BMI-matched subjects (7 F, 3 M, age: 53.0 ± 4.0 years) with normal pituitary function served as controls (C). In group 1, the presenting symptoms leading to the diagnosis of H were consciousness disturbances, hyponatremia and chronic fatigue. The GH response to stimulation was absent (peak:1.0 ± 0.3 ng/ml) and IGF-I levels (60.1 ± 9.3 ng/ml) were significantly lower (p<0.001) than in C and group 2 PES patients. Among group 2 PES patients, the main presenting symptoms were headache and visual alterations. Baseline hormone levels proved normal in 17 subjects, while slight hyperprolactinemia was observed in 2 and hypogonadotropic hypogonadism in one. The GH response to stimulation (12.9 ± 3.4 ng/ml) and IGF-I levels (141.7 ± 12.0 ng/ml) were lower (p<0.05) than in C (GH: 33.4 ± 8.8 ng/ml, IGF-I: 193.1 ± 20.3 ng/ml). PES is a heterogeneous condition that ranges from hypopituitarism to various degrees of isolated GH deficiency, and which needs careful endocrine assessment, treatment and follow-up.
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  • Atsuko YOSHIZAWA, Sayaka OGIKUBO
    2006 Volume 53 Issue 6 Pages 811-818
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 26, 2006
    JOURNALS FREE ACCESS
    We found that androgen and IGF-I up-regulated IGFBP-5 mRNA in androgen-responsive normal human fibroblast, which was blocked by co-treatment with 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole, but not cycloheximide. IGFBP-5 promoter activity was stimulated by androgen. Nuclear run-on assay revealed that IGFBP-5 transcripts were increased in response to androgen, which was not enhanced by co-addition of IGF-I. These results collectively indicate that IGFBP-5 synthesis is regulated by androgen through transcriptional mechanisms in androgen responsive cells.
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  • Mari IMANAKA, Keiji IIDA, Kentaro TAKAHASHI, Kazuo TSUJI, Hitoshi NISH ...
    2006 Volume 53 Issue 6 Pages 819-827
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 26, 2006
    JOURNALS FREE ACCESS
    Von Hippel-Lindau (VHL) disease (VHLD) is a hereditary autosomal dominant syndrome that causes various benign and malignant tumors. VHLD is caused by mutations in the VHL tumor suppressor gene. Here, we report a mutation in the VHL gene in a Japanese family with VHLD type 2A, characterized by pheochromocytoma (PHE), and hemangioblastomas (HAB) in both the retina and thoracic spinal cord but without renal cell carcinoma (RCC). We identified a heterozygous A to G point mutation at the second base of codon 131 of the VHL protein (pVHL). This mutation was predicted to convert codon 131 from asparagine to serine (N131S). Although most mutations in VHLD type 2A have been detected in the α domain of pVHL, the present mutated amino acid was located at the region encoding the β domain of pVHL. Previous patients with the N131K or N131T mutation in pVHL developed VHLD type 2B with RCC or VHLD type 1 without PHE, respectively. We also identified somatic loss of heterozygosity (LOH) at chromosome 3p25-26 in the adrenal tumor of the patient. The results of our study suggest that not only the location of mutation but also the altered amino acid may be critical for determining the clinical phenotype of VHLD. LOH was associated with the development of PHE in a patient with the N131S mutation in pVHL.
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  • Naoyuki SHIGEMATSU, Hiroshi TAKAMI, Atsushi KUBO
    2006 Volume 53 Issue 6 Pages 829-839
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 26, 2006
    JOURNALS FREE ACCESS
    Although surgery has been the mainstay of treatment for patients with well-differentiated thyroid cancer, the extents of thyroid resection and lymph node dissection adopted in Japan differ from those in other countries. Furthermore, regarding the indications for postoperative radiation therapy and hormonal therapy, and treatment modalities for cancer recurrence, there are marked discrepancies between Japan and other countries. A questionnaire survey was thus conducted among domestic and overseas thyroid surgeons to ascertain the actual treatment policy for well-differentiated thyroid cancer in Japan and various foreign countries. For small papillary carcinomas of 2.0 cm or less (T1), thyroid resection was more extensive in foreign countries than in Japan, although the extent of lymph node dissection was limited in the former. For large papillary carcinomas exceeding 3.0 cm (T2), on the other hand, total thyroidectomy was the treatment of first choice for all overseas respondents, but of only 20% in Japan, despite lymph node dissection being more extensive in Japan than in other countries. Overseas surgeons were much more likely to favor postoperative TSH suppression therapy and high-dose 131I therapy. For recurrence following surgery for papillary thyroid cancer, both domestic and overseas respondents indicated surgical resection to be the most common treatment option, and favored high-dose 131I therapy as well. In Japan, however, high-dose 131I therapy is available only in a few institutions. Such limited indications for high-dose 131I therapy in Japan may reflect a discrepancy in the frequency of total thyroidectomy, a prerequisite for postoperative high-dose 131I therapy, between Japan and other countries. This is the first questionnaire study conducted in both Japan and other countries in relation to treatment modalities for thyroid cancer. The results reveal that there is a clear disparity in treatment policies between Japan and foreign countries.
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  • Kazuhiko MURAKI, Shigeru OKUYA, Yukio TANIZAWA
    2006 Volume 53 Issue 6 Pages 841-851
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 26, 2006
    JOURNALS FREE ACCESS
    There are many clinical and experimental reports demonstrating that estrogens and insulin interact when affecting their target organs. Estrogen receptors consist of two isoforms, estrogen receptors-alpha (ER-α) and -beta (ER-β), but their roles in insulin-induced glucose uptake in mature adipose tissue have yet to be clarified. To evaluate the roles of ER-α, expressed predominantly in adipocytes, we have investigated the effects of estradiol (E2), an ER-α selective agonist (PPT), and its selective antagonist (MPP) on glucose uptake and insulin action in 3T3-L1 adipocytes. 3T3-L1 adipocytes were exposed to E2 or PPT and/or MPP at different concentrations. The cells were then subjected to 2-deoxy-D-glucose transport assay, western blot analysis, or RT-PCR analysis. Treatment of these cells with E2 or PPT resulted in biphasic effects on glucose transport, that is high (10-5 M or 3 × 10-6 M each) and low (10-8 M) doses produced inhibition and stimulation, respectively. The favorable effect observed at 10-8 M of E2 was diminished by treatment with MPP. Western bolt analysis revealed that these effects of E2, PPT and MPP paralleled the level of IRS-1 tyrosine phosphorylation. However, IRS-1 serine phosphorylation, suppressor of cytokine signaling (SOCS)-1,-2,-3 and protein tyrosine phosphatase 1B (PTP1B) expression did not change compaired to control subjects. Our data clearly show that ER-α contributes to insulin stimulated glucose uptake through regulation of the tyrosine phosphorylation of IRS-1 protein.
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  • Kazuo CHIHARA, Akira SHIMATSU, Yuzuru KATO, Hitoshi KOHNO, Toshiaki TA ...
    2006 Volume 53 Issue 6 Pages 853-858
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 26, 2006
    JOURNALS FREE ACCESS
    Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (−3.8 ± 3.3%, p<0.001) and week 48 (−3.1 ± 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by −24 ± 28 mg/dl (p<0.001) at week 24 and −17 ± 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.
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NOTES
  • Tetsu HASHIDA, Masanobu YAMADA, Koshi HASHIMOTO, Tetsuro SATOH, Shuich ...
    2006 Volume 53 Issue 6 Pages 859-863
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 12, 2006
    JOURNALS FREE ACCESS
    An 80-year-old man was referred to our department for evaluation of repetitive loss of consciousness and faintness with hypokalemia. He had relatively low blood pressure, hypomagnesemia, hypocalciuria and chondrocalcinosis in the knee, clinically suggesting Gitelman's syndrome. A renal clearance study could not be carried out due to the patient's age and complications of the heart. Sequence analysis of the gene of thiazide-sensitive Na-Cl cotransporter (TSC) showed a heterozygous missense mutation from C to T at 1712 base pairs from the translation start site, with resultant changes in codon 569 from alanine to valine (A569V). Treatment with oral administration of potassium chloride improved all the symptoms. Although Gitelman's syndrome has been considered to be autosomal recessive, cases of only heterozygous mutation detected have recently been reported. Therefore, the mutation found in this patient may be responsible for Gitelman's syndrome.
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  • Yoshihiro KIYA, Shin-ichiro MIURA, Bo ZHANG, Hidenori URATA, Keijiro S ...
    2006 Volume 53 Issue 6 Pages 865-868
    Published: 2006
    Released: December 28, 2006
    [Advance publication] Released: September 26, 2006
    JOURNALS FREE ACCESS
    The patient was a 51-year-old Japanese female who had been diagnosed with hyperlipidemia. At the first medical examination, her serum levels of total cholesterol (TC) and triglyceride (TG) were 482 and 205 mg/dl, respectively. Since hyperlipidemia was not improved by pravastatin, atorvastatin or niceritrol, and since the levels of thyroid-stimulating hormone (TSH) and free T4 were 730 IU/ml and 0.3 ng/dl, respectively, the patient was diagnosed as secondary hyperlipidemia with hypothyroidism. A method for the charge isolation of lipoproteins using capillary isotachophoresis (cITP) is proposed as a clinical application because it allows us to quantitatively measure electronegative low-density lipoprotein cholesterol (LDL-C), a potent marker of coronary heart disease. After 5 months of treatment with levothyroxine, Serum TC and LDL-C levels drastically decreased without statin treatment and high-density lipoprotein cholesterol (HDL-C) increased. In the lipoprotein profiles as assessed by cITP after treatment with levothyroxin, all HDL-C subfractions were increased and fast-migrating LDL/electronegative LDL appeared to be greatly reduced after treatment, while the area under the non-modified LDL peak was increased. The cITP analysis was able to obtain more information about coronary risk factors and may be clinically useful for evaluating the effect of treatment with levothyroxine in patients with hypothyroidism and secondary hyperlipidemia.
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