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Kageyama, Kazunori ; Ishigame, Noriko ; Sugiyama, Aya ; Igawa, Akiko ; Nishi, Takashi ; Morohashi, Satoko ; Kijima, Hiroshi ; Daimon, Makoto
概要:
We report a case of a 66-year-old woman who developed hyperparathyroidism due to a large intrathyroid parathyroid adenoma with episodes of acute pancreatitis. She had previously been treated for acute pancreatitis twice. Serum calcium was
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12.4 mg/dL, and intact parathyroid hormone was 253 pg/dL. Ultrasonography and computed tomography of the neck with contrast enhancement revealed a soft tissue mass (28 mm transverse diameter) within the left lobe of the thyroid. Tc-99m-MIBI scintigraphy demonstrated focal accumulation due to increased radiotracer uptake in the left thyroid lobe. Left hemithyroidectomy was performed. Histopathology showed no signs of invasion, and this is consistent with parathyroid adenoma. Immunostaining was positive for expression of chromogranin A and parathyroid hormone. The patient had no episode of pancreatitis after the operation. In a patient with recurrent episodes of pancreatitis, the possibility of complication with hyperparathyroidism should be considered.
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| 2.
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Asari, Yuko ; Kageyama, Kazunori ; Nakada, Yuki ; Tasso, Mizuki ; Takayasu, Shinobu ; Niioka, Kanako ; Ishigame, Noriko ; Daimon, Makoto
概要:
Purpose: The primary cause of Cushing's disease is adrenocorticotropic hormone ( ACTH)producing pituitary adenomas. EGFR signaling induces POMC mRNA-transcript levels and ACTH secretion from corticotroph tumors. The Jak-STAT pathway is
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located downstream of EGFR signaling; therefore, a Jak2 inhibitor could be an effective therapy for EGFR-related tumors. In this study, we determined the effect of a potent and selective Jak2 inhibitor, SD1029, on ACTH production and proliferation in mouse AtT20 corticotroph tumor cells. Materials and methods: AtT20 pituitary corticotroph tumor cells were cultured after transfection with PTTG1- or GADD45 beta-specific siRNA. Expression levels of mouse POMC, PTTG1, and GADD45 beta mRNAs were evaluated using quantitative real-time polymerase chain reaction. ACTH levels were measured using ACTH ELISA. Western blot analysis was performed to examine protein expression of phosphorylated STAT3/STAT3. Viable cells and DNA fragmentation were measured using a cell-proliferation assay and cell-death detection ELISA, respectively. Cellular DNA content was analyzed using fluorescence-activated cell sorting. Results: SD1029 decreased POMC and PTTG1 mRNA and ACTH levels, while increasing GADD45 beta levels. The drug also decreased AtT20-cell proliferation and induced apoptosis, but did not alter cell-cycle progression. SD1029 also inhibited STAT3 phosphorylation. PTTG1 knockdown inhibited POMC mRNA levels and cell proliferation. However, combined treatment with PTTG1 knockdown and SD1029 had no additive effect on POMC mRNA levels or cell proliferation. GADD45 beta knockdown inhibited the SD1029-induced decrease in POMC mRNA levels and also partially inhibited the decrease in cell proliferation. Conclusion: Both PTTG1 and GADD45 beta may be responsible, at least in part, for the Jak2-induced suppression of ACTH synthesis and cell proliferation. Accordingly, therapies that target EGFR-dependent Jak2/STAT3 may have clinical applications for treating Cushing's disease.
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| 3.
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Daimon, Makoto ; Kamba, Aya ; Murakami, Hiroshi ; Mizushiri, Satoru ; Osonoi, Sho ; Yamaichi, Masato ; Matsuki, Kota ; Sato, Eri ; Tanabe, Jutaro ; Takayasu, Shinobu ; Matsuhashi, Yuki ; Yanagimachi, Miyuki ; Terui, Ken ; Kageyama, Kazunori ; Tokuda, Itoyo ; Takahashi, Ippei ; Nakaji, Shigeyuki
概要:
Prolactin (PRL) has roles in various physiological functions. Although experimental studies showed that PRL has both beneficial and adverse effects on type 2 diabetes mellitus, clinical findings in subjects with hyperprolactinemia
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indicate adverse effects on glucose metabolism. However, effects of PRL within the physiological range in human are controversial. A population-based study of 370 Japanese men enrolled in the 2014 Iwaki study (aged 52.0 +/- 14.8 years). In this cross-sectional study, associations between serum PRL levels and homeostatic model assessment (HOMA) indices representing glucose metabolism in a physiological setting were examined using multivariable regression analysis. Although univariate linear regression analyses showed significant associations between serum PRL levels and HOMA indices, adjustment with multiple factors made the association with HOMA-beta (insulin secretion) insignificant, while those with HOMA-R (insulin resistance) remained significant (beta = 0.084, p = 0.035). Non-linear regression analyses showed a regression curve with a peak at serum PRL level, 12.4 ng/mL and a positive association of serum PRL level with HOMA-R below the peak (beta = 0.119, p = 0.004). Higher serum PRL levels within the physiological range seem to be associated with insulin resistance in men.
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| 4.
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Daimon, Makoto ; Kamba, Aya ; Murakami, Hiroshi ; Mizushiri, Satoru ; Osonoi, Sho ; Matsuki, Kota ; Sato, Eri ; Tanabe, Jutaro ; Takayasu, Shinobu ; Matsuhashi, Yuki ; Yanagimachi, Miyuki ; Terui, Ken ; Kageyama, Kazunori ; Tokuda, Itoyo ; Kurauchi, Shizuka ; Nakaji, Shigeyuki
概要:
How the association between the hypothalamus-pituitary-adrenal (HPA) axis and the reninangiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based
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2015 Iwaki study were enrolled (n: 1,016; age: 54.4 +/- 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-beta). Univariate linear regression analyses showed a correlation between PC2 and HOMA-beta (beta = -0.248, p < 0.0001), but not between PC1 and HOMA-beta (beta = -0.004, p = 0.9048). The correration between PC2 and HOMA-beta persisted after adjustment for multiple factors (beta = -0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-beta (<= 68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35-2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population.
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