著者

Masahiro Ito Tatiana Bogdanova Vladimir Saenko Tatiana Rogounovitch Norisato Mitsutake Hisayoshi Kondo Shigeto Maeda Masahiro Nakashima Shunichi Yamashita

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0239, (Released:2014-09-20)

被引用文献数

5

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Geographic differences have been reported to affect the morphological and molecular features of papillary thyroid carcinomas (PTCs). The area around Chernobyl is well-known to be iodine-deficient in contrast to Japan, an iodine-rich country. We reviewed histological differences in adult PTC between Ukraine and Japan. In total, 112 PTCs from age- and sex-matched adults (Ukraine 56, Japan 56) were evaluated histologically for several factors including tumor size, capsulation, tumor components (papillary, follicular, solid, trabecular), lymph node metastasis, extrathyroid invasion, lymphocytic infiltration, oxyphilic metaplasia, and MIB-1 index. We demonstrated that tumors were smaller (1.56 vs. 2.13 cm, p<0.05) and more solid and that lymph node metastasis was less frequent (14.3% vs. 48.2%, p<0.001) in Ukrainian cases. PTC subtype distribution was significantly different between the two groups. Solid variant (8.9% vs. 1.8%) and mixed subtypes with solid components were more frequent in Ukrainian patients. In contrast, classical papillary carcinomas were more frequent in Japanese cases (10.7% vs. 50.0%, p<0.001). Marked oxyphilic metaplasia was more common in Ukrainian cases (33.9 % vs. 8.9 %, p<0.001). MIB-1 index was significantly higher in Ukrainian cases (2.9% vs. 1.8%, p<0.001). However, the frequencies of tumor capsule formation and background lymphoid follicle formation around the tumor were similar between groups. Morphological differences in adult PTCs were similar to those in pediatric PTCs as reported previously, suggesting that morphogenesis of PTC is influenced by environmental factors, especially dietary iodine, as well as genetic factors.

著者

Chisato Tomoda Yuna Ogimi Fumi Saito Chie Masaki Junko Akaishi Kenichi Matsuzu Akifumi Suzuki Takashi Uruno Keiko Ohkuwa Hiroshi Shibuya Wataru Kitagawa Mitsuji Nagahama Kiminori Sugino Koichi Ito

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ15-0631, (Released:2015-12-10)

被引用文献数

1 6

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Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE.

著者

Tatsuhiko Urakami Remi Kuwabara Masako Aoki Misako Okuno Junichi Suzuki

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ15-0245, (Released:2015-12-03)

被引用文献数

2 12

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We evaluated the efficacy and safety of switching to insulin degludec (IDeg) from insulin glargine (IGlar) as basal-bolus therapy in young people with type 1 diabetes. The subjects were 36 patients, 21.3±1.0 years of age, with type 1 diabetes. IGlar had previously been injected once daily in 25 patients and twice daily in 11. They were then switched from IGlar to once-daily injection of IDeg. Both fasting plasma glucose (FPG) and HbA1c levels decreased significantly from 134±3.9 mg/dL and 7.9±0.2% at baseline to 116±2.2 mg/dL and 7.4±0.2% at 12 months after starting IDeg (P<0.0001 and P=<0.001, respectively). Overall and nocturnal hypoglycemia (PG<70 mg/dL) frequencies also decreased significantly from 4.9±0.7 and 2.0±0.3 times/month to 2.4±0.3 and 0.4±0.1 times/month at 12 months after starting IDeg (P=<0.005 and P<0.0005, respectively). The daily basal insulin dose was significantly reduced from 0.48±004 units/kg/day at baseline to 0.38±0.0.3 units/kg/day at the end of the study period (P<0.0001), which corresponded to 79.2% of the baseline value. Trends were similar in patients receiving the once-daily injection and those given twice-daily injections, but basal-insulin value reductions from baseline were more marked in patients receiving twice-daily injections of basal insulin (76.0% vs. 82.6% of the baseline value). These results suggest that switching from IGlar to an appropriate dose of IDeg may effectively control hyperglycemia while reducing the frequency of hypoglycemia episodes in young Japanese people with type 1 diabetes.

著者

Masahiro Yamamoto

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ15-0129, (Released:2015-03-21)

被引用文献数

3 29

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Meta-analyses have revealed that the relative risk of hip fractures in patients with type 1 and type 2 diabetes mellitus is higher than that in non-diabetic subjects. The risk of fracture in patients with diabetes mellitus increases along with a decrease in bone mineral density (BMD) similarly to those in non-diabetic patients. However, the observed risk of fracture is higher than expected one by BMD in both type 1 and type 2 diabetic patients, indicating that precise estimation of bone fragility by BMD values in patients with diabetes is difficult. Bone strength consists of BMD and bone quality, for this reason, poor bone quality is a most suitable and explicable cause for elevated fracture risk in this population. This bone fragility observed in patients with diabetes mellitus is caused by unique pathogenesis in diabetes, suggesting that osteoporosis in diabetic patients may be one of the diabetic complications and that specific diagnostic criteria for this osteoporosis is required. Bone quality indicators closely related to bone fragility are required to be identified to establish a diagnostic method for osteoporosis in patients with diabetes mellitus.

著者

Yasuhiro Ito Akira Miyauchi Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.3, pp.205-213, 2014 (Released:2014-03-30)

参考文献数

67

被引用文献数

17 30

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In this review, we focused on the patient age as an indicator of tumor growth and prognostic significance in both clinical papillary thyroid carcinoma (PTC) and subclinical papillary microcarcinoma (PMC: PTC ≤ 1 cm). In clinical PTC, young age (< 30 years) and old age (≥ 60 years) significantly affected the disease-free survival of patients, and old age was a strong predictor of carcinoma death. In contrast, in subclinical PMC, growth activity significantly decreased with patient age, and young age (< 40 years) was an independent predictor of carcinoma growth, indicating that old patients with subclinical PMC are the best candidates for observation without immediate surgery. Taken together, our findings indicate that the role of patients’ age as an indicator of tumor growth differs significantly between clinical PTC and subclinical PMC.

著者

Tatiana A. Leonova Valentina M. Drozd Vladimir A. Saenko Mariko Mine Johannes Biko Tatiana I. Rogounovitch Noboru Takamura Christoph Reiners Shunichi Yamashita

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0408, (Released:2014-11-05)

被引用文献数

3

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Long-term management of patients with differentiated thyroid cancer (DTC) commonly includes TSH-suppressive therapy with L-T4 and, in case of postsurgical hypoparathyroidism, Calcium-D3 supplementation, both of which may affect skeletal health. Experience with female patients treated for DTC at a young age and who were then receiving long-term therapy with L-T4 and Calcium-D3 medication is very limited to date. This cross-sectional study set out to investigate effects of Calcium-D3 supplementation and TSH-suppressive therapy on bone mineral density (BMD) in 124 young female patients treated for DTC at a mean age of 14 years and followed-up for an average of 10 years. BMD was found to be significantly higher in patients receiving Calcium-D3 medication than in patients not taking supplements. The level of ionized calcium was the strongest factor determining lumbar spine BMD in patients not receiving Calcium-D3 supplementation. Pregnancy ending in childbirth and HDL-cholesterol were associated with a weak adverse effect on spine and femoral BMD. No evidence of adverse effects of L-T4 and of radioiodine therapies on BMD was found. We conclude that Calcium-D3 medication has a beneficial effect on BMD, and that TSH-suppressive therapy does not affect BMD in women treated for DTC at young age, at least after 10 years of follow-up.

著者

Masato Kotani Fumihiko Katagiri Tsuyoshi Hirai Jiro Kagawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0137, (Released:2014-08-22)

被引用文献数

2 13

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The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/ml in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/ml in a male with Kallmann’s syndrome, 40.7 fmol/ml in a male with azoospermia, 323.2 fmol/ml in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/ml (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann’s syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann’s syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

著者

Keisuke Enomoto Yukie Enomoto Shinya Uchino Hiroto Yamashita Shiro Noguchi

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.60, no.5, pp.629-635, 2013 (Released:2013-05-31)

参考文献数

37

被引用文献数

7 41

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Children and adolescents represent 1–1.5% of all patients with thyroid cancer (TC). The vast majority of TC in children and adolescents is papillary TC; follicular TC (FTC) is exceedingly rare. In this study, we evaluate the clinical and pathological features of FTC in children and adolescents. We also report the risk factors for post-operative tumor recurrence and the associated outcomes. Twenty children and adolescents (under 21 years old) with FTC have been treated and followed at Noguchi Thyroid Clinic and Hospital Foundation since 1946. All patients underwent surgery (lobectomy, 11; subtotal thyroidectomy, 8; and total thyroidectomy, 1), and 8 patients received postoperative external beam radiation therapy. The incidence of FTC in children and adolescents was 1.9% among all FTC patients treated in our hospital. Histopathology revealed vascular and capsular invasion in 9 and 20 patients, respectively. The tumor recurrence rate in FTC with vascular invasion is significantly higher than in those without it (p = 0.038). No other factors were significant. Patients with recurrences were treated with completion thyroidectomy and 131I radioactive iodine therapy. There were no significant differences in the rates of disease-free survival or cause-specific survival when pediatric/adolescent FTC patients were compared to adults with FTC. FTC is very rare among children and adolescents, but the outcomes are similar to those observed among adults. Vascular invasion is poor prognostic indicator in pediatric/adolescent FTC patients.

著者

Hiroyuki Ariyasu Hiroshi Iwakura Naoichiro Yukawa Toshinori Murayama Masayuki Yokode Harue Tada Kenichi Yoshimura Satoshi Teramukai Tatsuya Ito Akira Shimizu Atsushi Yonezawa Kenji Kangawa Tsuneyo Mimori Takashi Akamizu

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0088, (Released:2014-04-17)

被引用文献数

6 20

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The majority of patients with systemic sclerosis (SSc) have gastrointestinal (GI) tract involvement, but therapies using prokinetic agents are usually unsatisfactory. Ghrelin stimulates gastric motility in healthy human volunteers. In this study, we investigated whether ghrelin could improve gastric emptying in patients with gastrointestinal symptoms due to SSc. The study was performed in a randomized, double-blind, placebo-controlled crossover fashion on two occasions. Ten SSc patients with GI tract involvement received an infusion of either ghrelin (5.0 μg/kg) or saline, and gastric emptying rate was evaluated by 13C-acetic acid breath test. Gastric emptying was significantly accelerated by ghrelin infusion in patients with SSc (ghrelin vs. saline: 43.3 ± 11.4 min vs. 53.4 ± 5.4 min, P≡0.03). No serious adverse effects were observed. Our results suggest that ghrelin might represent a new therapeutic approach for GI tract involvement in patients with SSc.

著者

Tomoyasu Fukui Tsutomu Hirano

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.7, pp.561-569, 2012 (Released:2012-07-31)

参考文献数

33

被引用文献数

6 13

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The reduced levels of high-density lipoprotein (HDL) 2-cholesterol (C) in diabetes and other metabolic disorders associated with a high risk of cardiovascular disease are well established. Few studies, however, have compared the HDL subspecies in type 1 diabetes (T1D) with those in type 2 diabetes (T2D) with or without insulin. We examined HDL subspecies in 27 T1D with insulin, 33 T2D with insulin or insulin plus oral-anti-diabetic drugs (OADs), 36 T2D with OADs or diet/exercise, and 25 non-diabetic controls. Insulin was injected four times daily in a basal-bolus manner for both T1D and T2D. Plasma levels of C, apolipoprotein (apo) AI, and AII were determined in HDL2 and HDL3 by the single precipitation method. HDL-C levels were significantly higher in T1D and lower in T2D, compared with the controls. Insulin-treated T2D had higher HDL-C than non-insulin-treated T2D. T1D had higher HDL2-C and HDL2-apo AI levels than T2D. Insulin-treated T2D had higher HDL2-C and HDL2-apo AI levels than non-insulin-treated T2D. All of these differences were more pronounced for men than for women. HDL3 levels were comparable among controls,T1D and T2D. HDL2-C levels were inversely associated with BMI, HbA1c, triglyceride, small dense LDL-C, and LDL-C. Multiple regression analysis revealed that HDL2-C was independently associated with triglyceride, LDL-C, and intensive insulin therapy but not with HbA1c. In conclusion, these results suggest that intensive insulin therapy is associated with alterations of HDL subspecies, irrespective of the type of diabetes.

著者

Ritsuko Yamamoto-Honda Yoshihiko Takahashi Yasumichi Mori Shigeo Yamashita Yoko Yoshida Shoji Kawazu Yasuhiko Iwamoto Hiroshi Kajio Hidekatsu Yanai Shuichi Mishima Nobuhiro Handa Kotaro Shimokawa Akiko Yoshida Hiroki Watanabe Kazuhiko Ohe Takuro Shimbo Mitsuhiko Noda

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ16-0521, (Released:2017-03-18)

被引用文献数

6

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Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

著者

Ken-ichi Takayama

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.10, pp.933-946, 2017 (Released:2017-10-28)

参考文献数

99

被引用文献数

12

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Hormonal alterations with aging contribute to the pathogenesis of several diseases. Androgens mediate their effects predominantly through binding to the androgen receptor (AR), a member of the ligand-dependent nuclear receptor superfamily. By androgen treatment, AR is recruited to specific genomic loci dependent on tissue specific pioneer factors to regulate target gene expression. Recent studies have revealed the epigenetic modulation by AR-associated histone modifiers and the roles of non-coding RNAs in AR signaling. Androgens are male sex hormone to induce differentiation of the male reproductive system required for the establishment of adult sexual function. As shown by several reports using AR knockout mouse models, androgens also have anabolic functions in several tissues such as bone, muscle and central nervous systems. Notably, AR has a central role in prostate cancer progression. Prostate cancer is the most frequently diagnosed cancer in men. Androgen-deprivation therapy for cancer patients and decline of serum androgen with aging promote several diseases associated with aging and quality of life of older men such as osteoporosis, sarcopenia and dementia. Thus, androgen replacement therapy for treating late onset hypogonadism (LOH) or new epigenetic regulators have the potential to overcome the symptoms caused by the low androgen, although adverse effects for cardiovascular diseases have been reported. Given the increasing longevity and consequent rise of age-related diseases and prostate cancer patients, a more understanding of the AR actions in male health remains a high research priority.

著者

Yuuki TAKAMURA Keiichi NAKANO Takashi URUNO Yasuhiro ITO Akihiro MIYA Kaoru KOBAYASHI Tamotsu YOKOZAWA Fumio MATSUZUKA Kanji KUMA Akira MIYAUCHI

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.50, no.5, pp.595-601, 2003 (Released:2003-11-12)

参考文献数

39

被引用文献数

15 30

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TSH receptor antibodies (TRAb) are generally regarded as mediators of thyroid stimulation in Graves' disease. In addition, a high serum TRAb value during pregnancy is one of the risk factors for intrauterine death, prematurity, and fetal or neonatal hyperthyroidism. Recently, correlations between a high serum TRAb value and endocrine opthalmopathy were also suggested. Surgical resection of the thyroid is usually followed by a reduction of serum TRAb levels in variable degrees. The relation between the extent of the thyroidectomy and the degree of reduction is still controversial. In addition, the changes in the TRAb value after total thyroidectomy (TT) over a long period of time have never been studied. We studied the changes in serum TRAb values after TT and subtotal thyroidectomy (ST) for more than 7 years. Forty-one patients with Graves' disease underwent TT, and 99 patients underwent ST. The serum TRAb values and the ratio of the patients who achieved normal values among each group (normalization rates of TRAb) at 3 and 6 months, 1, 3, 5 and 7 years after surgery were compared between the TT group and ST group. The mean preoperative TRAb values were not significantly different between the TT and ST groups, and the mean TRAb values measured 3, 6 and 12 months after surgery were not significantly different between the groups. However, the TRAb values measured 3, 5 and 7 years after surgery were significantly (p

著者

Satoshi Narumi Larry A Fox Keisuke Fukudome Zenichi Sakaguchi Chiho Sugisawa Kiyomi Abe Kaori Kameyama Tomonobu Hasegawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0194, (Released:2017-09-01)

被引用文献数

9

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Thyroid peroxidase (TPO) deficiency, caused by biallelic TPO mutations, is a well-established genetic form of congenital hypothyroidism (CH). More than 100 patients have been published, and the patients have been diagnosed mostly in the frame of newborn screening (NBS) programs. Correlation between clinical phenotypes and TPO activity remains unclear. Here, we report clinical and molecular findings of two unrelated TPO mutation-carrying mildly hypothyroid patients. The two patients were born at term after an uneventful pregnancy and delivery, and were NBS negative. They sought medical attention due to goiter at age 8 years. Evaluation of the thyroid showed mild elevation of serum TSH levels, normal or slightly low serum T4 levels, high serum T3 to T4 molar ratio, high serum thyroglobulin levels, and high thyroidal 123I uptake. We performed next-generation sequencing-based genetic screening, and found that one patient was compound heterozygous for two novel TPO mutations (p.Asp224del; c.820-2A>G), and the other was homozygous for a previously known mutation (p.Trp527Cys). In vitro functional analyses using HEK293 cells showed that the two amino acid-altering mutations (p.Asp224del and p.Trp527Cys) caused partial loss of the enzymatic activity. In conclusion, we report that TPO mutations with residual activity are associated with mild TPO deficiency, which is clinically characterized by marked goiter, mild TSH elevation, high serum T3 to T4 molar ratio, and high serum thyroglobulin levels. Our findings illuminate the hitherto under-recognized correlation between clinical phenotypes and residual enzymatic activity among patients with TPO deficiency.

著者

Atsushi Hattori Yuko Katoh-Fukui Akie Nakamura Keiko Matsubara Tsutomu Kamimaki Hiroyuki Tanaka Sumito Dateki Masanori Adachi Koji Muroya Shinobu Yoshida Shinobu Ida Marie Mitani Keisuke Nagasaki Tsutomu Ogata Erina Suzuki Kenichiro Hata Kazuhiko Nakabayashi Yoichi Matsubara Satoshi Narumi Toshiaki Tanaka Maki Fukami

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0150, (Released:2017-08-03)

被引用文献数

38

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Although mutations in ACAN, FGFR3, NPR2, and SHOX typically lead to skeletal dysplasia, and mutations in GHRHR, GH1, GHR, STAT5B, IGF1, IGFALS, and IGF1R usually underlie hormonal defects of the growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis, such mutations have also been identified in patients with idiopathic short stature (ISS). Of these, SHOX abnormalities are known to account for a certain percentage of ISS cases, whereas the frequency of mutations in the other 10 genes in ISS cohorts remains unknown. Here, we performed next-generation sequencing-based mutation screening of the 10 genes in 86 unrelated Japanese ISS patients without SHOX abnormalities. We searched for rare protein-altering variants. The functional significance of the identified variants was assessed by in silico analyses. Consequently, we identified 18 heterozygous rare variants in 19 patients, including four probable damaging variants in ACAN, six pathogenicity-unknown variants in FGFR3, GHRHR, GHR, and IGFALS, and eight possible benign variants. Pathogenic variants in NPR2, GH1, and IGF1 were absent from our cohort. Unlike previously reported patients with ACAN mutations, our four patients with ACAN variants manifested non-specific short stature with age-appropriate or mildly delayed bone ages, and had parents of normal stature. These results indicate that ACAN mutations can underlie ISS without characteristic skeletal features, and that such mutations are possibly associated with de novo occurrence or low penetrance. In addition, our data imply that mutations in FGFR3, NPR2, and GH-IGF1 axis genes play only limited roles in the etiology of ISS.

著者

Shoichiro Tanaka Kaoru Aida Yoriko Nishida Tetsuro Kobayashi

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0222, (Released:2013-06-18)

被引用文献数

11 31

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Fulminant type 1 diabetes is characterized by a rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetic complications. This review summarizes new findings related to the pathophysiology of accelerated β-cell failure in fulminant type 1 diabetes. Immunohistological examination revealed the presence of enterovirus in pancreatic islet cells and exocrine tissues and hyperexpression of pattern recognition receptors (PRRs) including melanoma differentiation-associated antigen 5 (MDA5), retinoic acid-inducible gene-I (RIG-I), Toll-like receptor (TLR)3 and TLR4, essential sensors of innate immunity, in islet cells and mononuclear cells (MNCs) infiltrating islets. Interferon (IFN)-α and IFN-β, products of PRR cascades, were expressed in both islet cells and infiltrating MNCs. Phenotypes of infiltrating cells around and/or into islets were mainly dendritic cells, macrophages and CD8+ T cells. Islet β-cells simultaneously expressed CXC chemokine ligand 10 (CXCL10), IFN-γ and interleukin-18, indicating that these chemokines/ cytotoxic cytokines mutually amplify their cytoplasmic expression in the islet cells. These positive feedback systems might enhance adaptive immunity, leading to rapid and complete loss of β-cells in fulminant type 1 diabetes. In innate and adaptive/autoimmune immune processes, the mechanisms behind bystander activation/killing might further amplify β-cell destruction. In addition to intrinsic pathway of cell apoptosis, the Fas and Fas ligand pathway are also involved as an extrinsic pathway of cell apoptosis. A high prevalence of anti-amylase autoantibodies was recognized in patients with fulminant type 1 diabetes, which suggests that Th2 T-cell reactive immunity against amylase might contribute to β-cell destruction in fulminant type 1 diabetes.

著者

Masanori Tamaki Kazutoshi Miyashita Aika Hagiwara Shu Wakino Hiroyuki Inoue Kentaro Fujii Chikako Fujii Sho Endo Asuka Uto Masanori Mitsuishi Masaaki Sato Toshio Doi Hiroshi Itoh

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.Suppl., pp.S47-S51, 2017 (Released:2017-06-24)

参考文献数

14

被引用文献数

25

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Chronic kidney disease (CKD) impairs physical performance in humans, which leads to a risk of all-cause mortality. In our previous study, we demonstrated that a reduction in muscle mitochondria rather than muscle mass was a major cause of physical decline in 5/6 nephrectomized CKD model mice. Because ghrelin administration has been reported to enhance oxygen utilization in skeletal muscle, we examined the usefulness of ghrelin for a recovery of physical decline in 5/6 nephrectomized C57Bl/6 mice, focusing on the epigenetic modification of peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. The mice were intraperitoneally administered acylated ghrelin (0.1 nmol/gBW; three times per week) for a month. Muscle strength and exercise endurance were measured by using a dynamometer and treadmill, respectively. Mitochondrial DNA copy number was determined by quantitative PCR. The methylation levels of the cytosine residue at 260 base pairs upstream of the translation initiation point (C-260) of PGC-1α, which has been demonstrated to decrease the expression, was evaluated by methylation-specific PCR and bisulfite genomic sequencing methods after the ghrelin administration. Ghrelin administration improved both muscle strength and exercise endurance in the mice and was associated with an increase in muscle mass and muscle mitochondrial content. Ghrelin administration decreased the methylation ratio of C-260 of PGC-1α in the skeletal muscle and increased the expression. Therefore, ghrelin administration effectively reduced the physical decline in 5/6 nephrectomized mice and was accompanied with an increased mitochondrial content through de-methylation of the promoter region of PGC-1α in the muscle.

著者

Koji Shiraishi Hideyasu Matsuyama

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0001, (Released:2017-01-19)

被引用文献数

65

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Microdissection testicular sperm extraction and intracytoplasmic sperm injection have made it possible for men with non-obstructive azoospermia (NOA) to conceive a child. A majority of men cannot produce sperm because spermatogenesis per se is believed to be “irreversibly” disturbed. For these men, it and has been thought that any hormonal therapy will be ineffective. Further understandings of endocrinological regulation of spermatogenesis are needed and LH or FSH receptor knock out (KO) mice have revealed the roles of gonadotropin separately. Spermatogenesis has been shown to shift during evolution from FSH to LH dominance because LH receptor KO causes infertility while FSH receptor KO does not. High concentrations of intratesticular testosterone secreted from Leydig cells, ranging from 100- to 1,000-fold higher than in the systemic circulation, has pivotal roles during spermatogenesis. This is especially important during spermiogenesis, a post-meiotic step for progression from round to elongating spermatids. Sertoli cells are the target of FSH and have numerous androgen receptors, indicating that Sertoli cells are regulated by FSH and the paracrine functions of testosterone. In combination with Leydig cell-derived growth factors, particularly epidermal growth factor-like growth factors, Sertoli cells support spermatogenesis, especially at proximal levels of spermatogenesis (e.g., spermatogonial proliferation). Taken together, the current knowledge from human studies indicating that testosterone optimization by clomiphene, hCG and/or aromatase inhibitors and high dose hCG/FSH treatment can, at least in part, improve spermatogenesis in NOA. Accordingly hormonal therapy may open a therapeutic window for sperm production in selected patients.

著者

Takahiro Miyakoshi Rie Oka Yasuto Nakasone Yuka Sato Keishi Yamauchi Rie Hashikura Masayuki Takayama Yudai Hirayama Kazuko Hirabayashi Hideo Koike Toru Aizawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.63, no.9, pp.857-865, 2016 (Released:2016-09-30)

参考文献数

25

被引用文献数

11

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To develop diabetes risk score (RS) based on the current definition of diabetes, we retrospectively analyzed consecutive 4,159 health examinees who were non-diabetic at baseline. Diabetes, diagnosed by fasting plasma glucose (FPG) ≥7.0 mmol/L, 2hPG ≥11.1 mmol/L and/or HbA1c ≥6.5% (48 mmol/mol), developed in 279 of them during the mean period of 4.9 years. A full RS (RSFull), a RS without 2hPG (RS-2hPG) and a non-invasive RS (RSNI) were created on the basis of multivariate Cox proportional model by weighted grading based on hazard ratio in half the persons assigned. The RSs were verified in the remaining half of the participants. Positive family history (FH), male sex, smoking and higher age, systolic blood pressure (SBP), FPG, 2hPG and HbA1c were independent predictors for RSFull. For RS-2hPG, 7 independent predictors, exclusive of 2hPG and smoking but inclusive of elevated triglycerides (TG) comparing to RSFull, were selected. FH, male sex, and higher age, SBP and HbA1c were independent predictors in RSNI. In the validation cohort, C-statistic (95%CI) of RSFull, RS-2hPG and RSNI were 0.80 (0.76-0.84), 0.75 (0.70-0.78) and 0.68 (0.63-0.72), respectively, which were significantly different from each other (P <0.01). Absolute percentage difference between predicted probability and observed diabetes were 1.9%, 0.7% and 0.9%, by the three scores, respectively, and not significantly different from each other. In conclusion, diabetes defined by the current criteria was predicted by the new diabetes risk scores with reasonable accuracy. Nonetheless, RSFull with a postchallenge glucose value performed superior to RS-2hPG and RSNI.

著者

Kiyoshi HASHIZUME Satoru SUZUKI Ai KOMATSU Kunihide HIRAMATSU Jun-ichiro MORI Masanori YAMAZAKI Teiji TAKEDA Tomoko KAKIZAWA Takahide MIYAMOTO Yoichi KOIZUMI Kazuo ICHIKAWA

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.54, no.2, pp.319-327, 2007 (Released:2007-05-17)

参考文献数

29

被引用文献数

12 16

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This article was retracted. Please see retracted notification.