著者

Hirofumi Tsuru Hidekazu Ishida Jun Narita Ryo Ishii Hidehiro Suginobe Yoichiro Ishii Renjie Wang Shigetoyo Kogaki Masaki Taira Takayoshi Ueno Yohei Miyashita Hidetaka Kioka Yoshihiro Asano Yoshiki Sawa Keiichi Ozono

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.85, no.5, pp.677-686, 2021-04-23 (Released:2021-04-23)

参考文献数

38

被引用文献数

9

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Background:Restrictive cardiomyopathy (RCM) is characterized by impaired ventricular relaxation. Although several mutations were reported in some patients, no mutations were identified in cardiomyocyte expressing genes of other patients, indicating that pathological mechanisms underlying RCM could not be determined by cardiomyocytes only. Cardiac fibroblasts (CFs) are a major cell population in the heart; however, the pathological roles of CFs in cardiomyopathy are not fully understood.Methods and Results:This study established 4 primary culture lines of CFs from RCM patients and analyzed their cellular physiology, the effects on the contraction and relaxation ability of healthy cardiomyocytes under co-culture with CFs, and RNA sequencing. Three of four patients hadTNNI3mutations. There were no significant alterations in cell proliferation, apoptosis, migration, activation, and attachment. However, when CFs from RCM patients were co-cultured with healthy cardiomyocytes, the relaxation velocity of cardiomyocytes was significantly impaired both under direct and indirect co-culture conditions. RNA sequencing revealed that gene expression profiles of CFs in RCM were clearly distinct from healthy CFs. The differential expression gene analysis identified that several extracellular matrix components and cytokine expressions were dysregulated in CFs from RCM patients.Conclusions:The comprehensive gene expression patterns were altered in RCM-derived CFs, which deteriorated the relaxation ability of cardiomyocytes. The specific changes in extracellular matrix composition and cytokine secretion from CFs might affect pathological behavior of cardiomyocytes in RCM.

著者

Rieko Takatani Takuo Kubota Masanori Minagawa Daisuke Inoue Seiji Fukumoto Keiichi Ozono Yosikazu Nakamura

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

vol.33, no.11, pp.569-573, 2023-11-05 (Released:2023-11-05)

参考文献数

18

被引用文献数

2

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Background: Pseudohypoparathyroidism (PHP) and nonsurgical hypoparathyroidism (NS-HypoPT) are rare diseases with hypocalcemia, hyperphosphatemia, and high and low parathyroid hormone levels, respectively. In Japan, over 20 years have passed since the last survey on these diseases. We carried out a nationwide cross-sectional survey to estimate the prevalence of these diseases in 2018.Methods: We conducted a nationwide mail-based survey targeting hospitals in 2018. From a total of 13,156 departments throughout Japan, including internal medicine, pediatrics, neurology, and psychiatry, 3,501 (27%) departments were selected using a stratified random sampling method. We asked each included department to report the number of patients with PHP and NS-HypoPT in 2017.Results: The overall survey response rate was 52.0% (1,807 departments). The estimated number of patients with PHP and NS-HypoPT was 1,484 (95% confidence interval [CI], 1,143–1,825) and 2,304 (95% CI, 1,189–3,419), respectively; the prevalence per 100,000 population was 1.2 and 1.8, respectively.Conclusion: In this study, we generated estimates of the national prevalence of PHP and NS-HypoPT in Japan during 2017, which were found to be higher than those previously reported.

著者

Toshimi Michigami Yasuhisa Ohata Makoto Fujiwara Hiroshi Mochizuki Masanori Adachi Taichi Kitaoka Takuo Kubota Hideaki Sawai Noriyuki Namba Kosei Hasegawa Ikuma Fujiwara Keiichi Ozono

出版者

The Japanese Society for Pediatric Endocrinology

雑誌

Clinical Pediatric Endocrinology (ISSN:09185739)

巻号頁・発行日

vol.29, no.1, pp.9-24, 2020 (Released:2020-01-09)

参考文献数

48

被引用文献数

28

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Hypophosphatasia (HPP) is a rare bone disease caused by inactivating mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Patients with HPP have varied clinical manifestations and are classified based on the age of onset and severity. Recently, enzyme replacement therapy using bone-targeted recombinant alkaline phosphatase (ALP) has been developed, leading to improvement in the prognosis of patients with life-threatening HPP. Considering these recent advances, clinical practice guidelines have been generated to provide physicians with guides for standard medical care for HPP and to support their clinical decisions. A task force was convened for this purpose, and twenty-one clinical questions (CQs) were formulated, addressing the issues of clinical manifestations and diagnosis (7 CQs) and those of management and treatment (14 CQs). A systematic literature search was conducted using PubMed/MEDLINE, and evidence-based recommendations were developed. The guidelines have been modified according to the evaluations and suggestions from the Clinical Guideline Committee of The Japanese Society for Pediatric Endocrinology (JSPE) and public comments obtained from the members of the JSPE and a Japanese HPP patient group, and then approved by the Board of Councils of the JSPE. We anticipate that the guidelines will be revised regularly and updated.

著者

Ryo Okazaki Keiichi Ozono Seiji Fukumoto Daisuke Inoue Mika Yamauchi Masanori Minagawa Toshimi Michigami Yasuhiro Takeuchi Toshio Matsumoto Toshitsugu Sugimoto

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ16-0548, (Released:2016-12-20)

被引用文献数

37

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Vitamin D is indispensable for the maintenance of bone and mineral health. Inadequate vitamin D action increases the risk for various musculoskeletal/mineral events including fracture, fall, secondary hyperparathyroidism, diminished response to antiresorptives, rickets/osteomalacia, and hypocalcemia. Its most common cause in recent years is vitamin D deficiency/insufficiency, clinically defined by low serum 25-hydroxyvitamin D [25(OH)D] level. Guidelines for vitamin D insufficiency/deficiency defined by serum 25(OH)D concentrations have been published all over the world. In Japan, however, the information on the associations between serum 25(OH)D and bone and mineral disorders has not been widely shared among healthcare providers, partly because its measurement had not been reimbursed with national medical insurance policy until August 2016. We have set out to collect and analyze Japanese data on the relationship between serum 25(OH)D concentration and bone and mineral events. Integrating these domestic data and published guidelines worldwide, here we present the following assessment criteria for vitamin D sufficiency/insufficiency/deficiency using serum 25(OH)D level in Japan. 1) Serum 25(OH)D level equal to or above 30 ng/ml is considered to be vitamin D sufficient. 2) Serum 25(OH)D level less than 30 ng/ml but not less than 20 ng/ml is considered to be vitamin D insufficient. 3) Serum 25(OH)D level less than 20 ng/ml is considered to be vitamin D deficient. We believe that these criteria will be clinically helpful in the assessment of serum 25(OH)D concentrations and further expect that they will form a basis for the future development of guidelines for the management of vitamin D deficiency/insufficiency.

著者

Keiichi Ozono Toshimi Michigami Noriyuki Namba Shigeo Nakajima Takehisa Yamamoto

出版者

The Japanese Society for Pediatric Endocrinology

雑誌

Clinical Pediatric Endocrinology (ISSN:09185739)

巻号頁・発行日

vol.15, no.4, pp.129-135, 2006 (Released:2006-11-03)

参考文献数

45

被引用文献数

3 3

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Serum phosphate levels are regulated in both calcium-dependent and -independent fashions. Active vitamin D increases while PTH decreases serum phosphate levels in association with the elevation of serum calcium. On the other hand, a calcium-independent phosphaturic factor, historically called phosphatonin is believed to exert a physiological function based on findings in hereditary and tumor-induced diseases characterized by hypophosphatemia with normocalcemia. Among them, autosomal dominant hypophosphatemic rickets (ADHR) has contributed greatly to its elucidation because the gene responsible for ADHR encodes fibroblast growth factor 23 (FGF23) that has been found to have a phosphaturic effect. In addition, FGF23 has been proved to be involved in most cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets that are also characterized by hypophosphatemia and normocalcemia. Moreover, familial tumoral calcinosis, which represents the metabolic mirror image of hypophosphatemic conditions, is caused by a loss-of-function mutation in the FGF23 gene in some patients. Very recently, hereditary hypophosphatemic rickets with hypercalciuria has been found to be caused by mutations in the SLC34A1 gene which encodes a type of sodium phosphate cotransporter. These findings may provide new strategies for treating patients with abnormal phosphate metabolism.

著者

Ryo Okazaki Keiichi Ozono Seiji Fukumoto Daisuke Inoue Mika Yamauchi Masanori Minagawa Toshimi Michigami Yasuhiro Takeuchi Toshio Matsumoto Toshitsugu Sugimoto

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.1, pp.1-6, 2017 (Released:2017-01-30)

参考文献数

31

被引用文献数

12 37

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Vitamin D is indispensable for the maintenance of bone and mineral health. Inadequate vitamin D action increases the risk for various musculoskeletal/mineral events including fracture, fall, secondary hyperparathyroidism, diminished response to antiresorptives, rickets/osteomalacia, and hypocalcemia. Its most common cause in recent years is vitamin D deficiency/insufficiency, clinically defined by low serum 25-hydroxyvitamin D [25(OH)D] level. Guidelines for vitamin D insufficiency/deficiency defined by serum 25(OH)D concentrations have been published all over the world. In Japan, however, the information on the associations between serum 25(OH)D and bone and mineral disorders has not been widely shared among healthcare providers, partly because its measurement had not been reimbursed with national medical insurance policy until August 2016. We have set out to collect and analyze Japanese data on the relationship between serum 25(OH)D concentration and bone and mineral events. Integrating these domestic data and published guidelines worldwide, here we present the following assessment criteria for vitamin D sufficiency/insufficiency/deficiency using serum 25(OH)D level in Japan. 1) Serum 25(OH)D level equal to or above 30 ng/mL is considered to be vitamin D sufficient. 2) Serum 25(OH)D level less than 30 ng/mL but not less than 20 ng/mL is considered to be vitamin D insufficient. 3) Serum 25(OH)D level less than 20 ng/mL is considered to be vitamin D deficient. We believe that these criteria will be clinically helpful in the assessment of serum 25(OH)D concentrations and further expect that they will form a basis for the future development of guidelines for the management of vitamin D deficiency/insufficiency.

著者

Takuo Kubota Masanori Adachi Taichi Kitaoka Kosei Hasegawa Yasuhisa Ohata Makoto Fujiwara Toshimi Michigami Hiroshi Mochizuki Keiichi Ozono

出版者

The Japanese Society for Pediatric Endocrinology

雑誌

Clinical Pediatric Endocrinology (ISSN:09185739)

巻号頁・発行日

vol.29, no.1, pp.25-42, 2020 (Released:2020-01-09)

参考文献数

79

被引用文献数

19

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Achondroplasia (ACH) is a skeletal dysplasia that presents with limb shortening, short stature, and characteristic facial configuration. ACH is caused by mutations of the FGFR3 gene, leading to constantly activated FGFR3 and activation of its downstream intracellular signaling pathway. This results in the suppression of chondrocyte differentiation and proliferation, which in turn impairs endochondral ossification and causes short-limb short stature. ACH also causes characteristic clinical symptoms, including foramen magnum narrowing, ventricular enlargement, sleep apnea, upper airway stenosis, otitis media, a narrow thorax, spinal canal stenosis, spinal kyphosis, and deformities of the lower extremities. Although outside Japan, papers on health supervision are available, they are based on reports and questionnaire survey results. Considering the scarcity of high levels of evidence and clinical guidelines for patients with ACH, clinical practical guidelines have been developed to assist both healthcare professionals and patients in making appropriate decisions in specific clinical situations. Eleven clinical questions were established and a systematic literature search was conducted using PubMed/MEDLINE. Evidence-based recommendations were developed, and the guidelines describe the recommendations related to the clinical management of ACH. We anticipate that these clinical practice guidelines for ACH will be useful for healthcare professionals and patients alike.

著者

Hiroyuki Koyama Satoshi Yasuda Shota Kakoi Yasuhisa Ohata Yuki Shimizu Chie Hasegawa Akiko Hayakawa Tomoyuki Akiyama Takashi Yagi Daisuke Aotani Kenro Imaeda Keiichi Ozono Hiromi Kataoka Tomohiro Tanaka

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.3298-19, (Released:2019-11-29)

参考文献数

24

被引用文献数

8

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A 40-year-old Japanese woman presented to our hospital with general fatigue and muscle weakness. She had a history of premature loss of deciduous teeth at 4 years old, her serum alkaline phosphatase (ALP) activity was as low as 91 U/L, and radiologic studies revealed thoracic deformity and sacroiliac calcification. Genetic sequencing revealed a heterozygous c.1559delT mutation in the tissue non-specific alkaline phosphatase gene (ALPL). Based on these findings, she was diagnosed with hypophosphatasia (HPP), and treatment with asfotase alfa, a recombinant human tissue-nonspecific alkaline phosphatase (TNSALP), was initiated. After six months of treatment with asfotase alfa, improvements were observed in the SF-36 score, six-minute walk distance, and grasping power. Although the overdiagnosis needs to be avoided, HPP should be considered in patients with undiagnosed musculoskeletal symptoms and a low serum ALP activity.

著者

Hiroaki Ichimori Shigetoyo Kogaki Kunihiko Takahashi Hidekazu Ishida Jun Narita Nobutoshi Nawa Hiroki Baden Toshiki Uchikawa Yoko Okada Keiichi Ozono

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-12-0997, (Released:2013-05-18)

参考文献数

37

被引用文献数

5 8

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Background: To investigate the possible role of sex hormones in the pathogenesis of pulmonary arterial hypertension (PAH), the effect of β-estradiol (E2) on bone morphogenetic protein (BMP) signaling, a key signaling pathway involved in PAH, was studied in human pulmonary arterial endothelial cells (HPAEC). Methods and Results: BMP signaling molecules, including BMP receptor, Smad1/5/8 and Id1, were studied in HPAEC under 1% O2 (hypoxia) and 21% O2 (normoxia) as well as the effect of hypoxia-inducible factor (HIF)-1α expression in the presence of E2 on BMP signaling. The effects of an estrogen receptor (ER) antagonist (ICI 182,780) and cycloheximide, and the interaction of ER with Smad or HIF-1α were also studied. In the presence of E2, BMP signaling was augmented under normoxia but suppressed under hypoxia. HIF-1α accumulation suppressed BMP signaling, whereas HIF-1α inhibition augmented signaling. These effects were cancelled by ICI 182,780. Moreover, binding between ER, HIF-1α and phosphorylated (p)-Smad1/5/8 proteins occurred only under hypoxia. On inhibition of de novo synthesis with cycloheximide, however, p-Smad1/5/8 expression was suppressed only under normoxia. Conclusions: The effects of E2 on BMP signaling in HPAEC altered depending on O2 concentration and different mechanisms may be involved. BMP and sex hormones may play an important role in PAH development.