| Project/Area Number |
13671122
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | OSAKA CITY UNIVERSITY |
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Principal Investigator |
INABA Masaaki OSAKA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICINE METABOLISM, ENDOCRINOLOGY, AND MOLECULAR MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (00176405)
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| Co-Investigator(Kenkyū-buntansha) |
IMANISHI Yasuo OSAKA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICINE METABOLISM, ENDOCRINOLOGY, AND MOLECULAR MEDICINE, INSTRUCTOR, 大学院・医学研究科, 助手 (50326253)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | parathyroid hormone / cyclin D1 / calcimimetic / primary hyperparathyroidism / 大動脈石灰化 / 食餌性リン負荷 / cyclin D1癌遺伝子 / 高回転骨 / 副甲状腺機能亢進症 / SPF化 / リン負荷 |
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| Research Abstract |
Transgenic mice with parathyroid-targeted overexpression of the cyctin D1 oncogene, provided direct experimental evidence that the cyclin D1 could drive excessive parathyroid cell proliferation with secretory abnormality of parathyroid hormone (PTH), and then developed hyperparathyroidism. Actually, parathyroid glands were enlarged and accelerated BrdU uptake in 30 weeks old transgenic mice. The mice also showed hypercalcemia at the age of 36 weeks. To determine whether these abnormalities could suppress by stimulating calcium sensing receptor (CaR), calcimimetic KRN1493, the calcium sensing receptor antagonist, was administered to the mice. The single administration of 30 mg/kg BW of KRN1493 suppressed both serum calcium and PTH levels 2 hrs after the administration on wild type mice. The same dose of single administration was also performed on 60-80 weeks old transgenic mice. Serum calcium and PTH levels were lowered on low calcemic group (serum calcium < 12 mg/dl), but were not on high calcemic group (serum calcium > 12 mg/dl). Immunohistochemical analyses showed suppressed CaR expression on low calcemic group compared to high calcemic group, revealing that the expression of CaR seems to regulate the biochemical effect of calcimimetic on parathyroid cell.
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