Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo

Side population (SP) cells, which can be identified by their ability to exclude Hoechst 33342 dye, are one of the candidates for somatic stem cells. Although bone marrow SP cells are known to be long-term repopulating hematopoietic stem cells, there is little information about the characteristics of cardiac SP cells (CSPs). When cultured CSPs from neonatal rat hearts were treated with oxytocin or trichostatin A, some CSPs expressed cardiac-specific genes and proteins and showed spontaneous beating. When green fluorescent protein–positive CSPs were intravenously infused into adult rats, many more (∼12-fold) CSPs were migrated and homed in injured heart than in normal heart. CSPs in injured heart differentiated into cardiomyocytes, endothelial cells, or smooth muscle cells (4.4%, 6.7%, and 29% of total CSP-derived cells, respectively). These results suggest that CSPs are intrinsic cardiac stem cells and involved in the regeneration of diseased hearts

Increased prostaglandin e2 has a positive correlation with plasma calcium during goldfish reproduction

We recently demonstrated that prostaglandin E2 PG¿ increases osteoclastic activity and induces bone resorption in both in vitro and in vivo experiments using goldfish. In the fish reproductive period, the plasma calcium (Ca) level in female teleosts increases remarkably to make vitellogenin, which is a major component of egg protein and a Ca-binding protein. In this period, however, there is no reported relationship between PGE2 and Ca metabolism in fish. To clarify the Ca metabolism in fish reproduction, we examined plasma PGE2 and Ca levels and measured tartrate-resistant acid phosphatase (TRAP) activities as an indicator of osteoclastic activity in goldfish. Plasma PGE2 levels in the reproductive stage significantly increased as compared with those in non-reproductive stages. Also, both plasma Ca and TRAP increased in the reproductive stage. Significant positive correlations were recognized between plasma Ca and the gonad somatic index (r=0.81, p<0.001), plasma Ca and plasma PGE2 levels (r=0.635, p<0.05), and plasma Ca and plasma TRAP activities (r=0.584, p<0.05) from the analysis using samples of both reproductive and nonreproductive stages. Taking these data into consideration, we suggested that PGE, acts on osteoclasts and increases plasma Ca as a result of osteoclastic bone resorption, and we concluded that PGE, is an important hormone in Ca metabolism during fish reproduction

Monohydroxylated polycyclic aromatic hydrocarbons inhibit both osteoclastic and osteoblastic activities in teleost scales

金沢大学環日本海域環境研究センター生物多様性研究部門Aims: We previously demonstrated that monohydroxylated polycyclic aromatic hydrocarbons (OHPAHs) bound to a human estrogen receptor (ER) by a yeast two-hybrid assay, but polycyclic aromatic hydrocarbons did not have a binding activity. Therefore, the direct effect of 3-hydroxybenz[a]anthracene (3-OHBaA) and 4-hydroxybenz[a]anthracene (4-OHBaA) on osteoclasts and osteoblasts in teleosts was examined. As a negative control, 1-hydroxypyrene (1-OHPy), which has no binding activity to human ER, was used. Main methods: The effect of OHPAHs on osteoclasts and osteoblasts was examined by an assay system using teleost scale as each marker: tartrate-resistant acid phosphatase for osteoclasts and alkaline phosphatase for osteoblasts. Changes in cathepsin K (an osteoclastic marker) and insulin-like growth factor-I (IGF-I) (an osteoblastic marker) mRNA expressions in 4-OHBaA-treated goldfish scales were examined by using a reverse transcription-polymerase chain reaction. Key findings: In both goldfish (a freshwater teleost) and wrasse (a marine teleost), the osteoclastic activity in the scales was significantly suppressed by 3-OHBaA and 4-OHBaA, although 1-OHPy did not affect the osteoclastic activity. In reference to osteoblasts, the osteoblastic activity decreased with both 3-OHBaA and 4-OHBaA and did not change with the 1-OHPy treatment. However, 17β-estradiol (E2) significantly increased both the osteoclastic and osteoblastic activities in the scales of both goldfish and wrasse. The mRNA expressions of both cathepsin K and IGF-I decreased in the 4-OHBaA-treated scales but increased in the E2-treated scales. Significance: The current data are the first to demonstrate that 3-OHBaA and 4-OHBaA inhibited both osteoclasts and osteoblasts and disrupted the bone metabolism in teleosts. © 2009 Elsevier Inc. All rights reserved

Calcitonin-typical suppression of osteoclastic activity by amphioxus calcitonin superfamily peptides and insights into the evolutionary conservation and diversity of their structures

Calcitonin (CT) is a hormone that decreases serum calcium level by suppressing osteoclastic activity in the vertebrate bone. In vertebrates, the structure-function relationship of CTs has been studied extensively. We recently identified three CT superfamily peptides, Bf-CTFP1 to 3, and clarified the molecular and functional characteristics of their receptor and receptor activity-modifying protein in amphioxus, Branchiostoma floridae. However, the CT activity of Bf-CTFPs has yet to be investigated. In the present study, a functional analysis of Bf-CTFPs was performed using goldfish scales having both osteoclasts and osteoblasts. All Bf-CTFPs suppressed osteoclastic activity via a goldfish CT receptor. Although the primary amino acid sequences of the Bf-CTFPs showed low sequence similarity to vertebrate CTs, Bf-CTFP1 to 3 share three amino acids, Thr25, Thr27, and Pro32-NH2, that are required for receptor binding, with salmon CT. Moreover, homology model analysis revealed that the Bf-CTFPs form alpha-helical structures. The alpha-helical position and length of Bf-CTFP1 and 2 were conserved with those of a highly potent ligand, teleost CT. Interestingly, the composition of the alpha-helix of Bf-CTFP3 differed from those of teleost CT, despite that the action of Bf-CTFP3 on goldfish scales was the same as that of Bf-CTFP1 and 2. Collectively, the present study provides new insights into the structure-function relationship of CT and its functional evolution in chordates. © 2017 Elsevier Inc.Embargo Period 12 month

Polychlorinated biphenyl (118) activates osteoclasts and induces bone resorption in goldfish

To analyze the effect of polychlorinated biphenyl (PCB) 118 on fish bone metabolism, we examined osteoclastic and osteoblastic activities, as well as plasma calcium levels, in the scales of PCB (118)-injected goldfish. In addition, effect of PCB (118) on osteoclasts and osteoblasts was investigated in vitro. Immature goldfish, in which the endogenous effects of sex steroids are negligible, were used. PCB (118) was solubilized in dimethyl sulfoxide at a concentration of 10 ppm. At 1 and 2 days after PCB (118) injection (100 ng/g body weight), both osteoclastic and osteoblastic activities, and plasma calcium levels were measured. In an in vitro study, then, both osteoclastic and osteoblastic activities as well as each marker mRNA expression were examined. At 2 days, scale osteoclastic activity in PCB (118)-injected goldfish increased significantly, while osteoblastic activity did not change significantly. Corresponding to osteoclastic activity, plasma calcium levels increased significantly at 2 days after PCB (118) administration. Osteoclastic activation also occurred in the marker enzyme activities and mRNA expressions in vitro. Thus, we conclude that PCB (118) disrupts bone metabolism in goldfish both in vivo and in vitro experiments. © 2012 The Author(s)

膀胱癌, 口腔底癌, 胃癌, 肺癌による異時性四重複癌の1例

67歳男性.患者は1998年12月に口腔底に発生した高分化型扁平上皮癌に対して, 放射線療法後(40Gy, 17回), 外科的治療を受けた(pT2, pN2b, M0).その際, 全身検索において胃に高分化型腺癌を発見されたため, 胃亜全摘出術を施行した(pT2, pN0, M0, P0, CY0).更に2004年4月にフォローの胸部CT検査において左肺上葉に孤在性の低分化型腺癌が発見され, 肺部分切除術を施行された(pT1, N0, M0, P0, Br-).以後, 経過を観察されていたが, 2000年11月に膀胱から後部尿道にかけての尿路上皮癌の再発を認めたため, 根治的膀胱全摘術ならびに両側尿管皮膚瘻作成術を施行した(pT4a, pN2, M0, pL2, pV0, pR0)A 67-year-old man, who had smoked heavily for many years, was found in 1997 to have bladder tumors, and transurethral resection of the bladder tumor (TUR-Bt) was performed. Histopathological diagnosis was urothelial carcinoma (G2>G3, pTa, N0, M0, ly0, v0). In December, 1998, he noticed an oral cavity tumor. After preoperative radiation therapy (total 40 Gy, 17 times), surgical treatment was undertaken. Histopathological diagnosis was well differentiated squamous cell carcinoma (pT2, pN2b, M0). In February, 2000, gastric tumor was detected by endoscopic examination, and subtotal gastorectomy and Roux en Y operation were performed. Histopathological diagnosis was well differentiated adenocarcinoma (pT2, pN0, M0, P0, CY0). A chest computed tomographic (CT) scan revealed a solitary lung tumor in April, 2000. Partial peumonectomy was performed, and histopathological diagnosis was poorly differentiated adenocarcinoma (pT1, N0, M0, P0). In April, 2000, multiple lesions of bladder cancer in the neck of the urinary bladder and posterior urethra were found and radical cystoprostatourethrectomy combined with lymph node dissection and bilateral cutaneous ureterostomy were performed (urothelial carcinoma, G3, pT4a, pN2, M0, pL2, pV0, pR0). Since then, the patient has been followed carefully

皮膚転移によって発見された腎細胞癌の1例

79歳男性.患者は右胸部の無痛性腫瘤を主訴とした.腫瘤を外科的に切除したところ病理組織学的診断ではclear cell carcinoma(alveolar type, Gl)であり, 乳腺組織との関連性は認められなかったため, 胸部皮膚組織への転移巣と考えられた.さらに全身検索を行ったところ, 腹部超音波検査およびMRI検査において右腎下極に内部不均一な腫瘤が認められた.超音波エコーガイド下に針生検を行い病理組織診断を行ったところ, 同じくclear cell carcinoma(alveolar type, Gl)で, これが原発巣だと考えられた.積極的治療を望んだが, 患者より同意を得られず, 現在はインターフェロン-α療法を施行している.なお, 本症例は胸部皮膚転移を契機として腎細胞癌が発見された比較的稀な1例であり, 我が国では23例目の症例報告となったA case of renal cell carcinoma, found after skin metastasis is presented. A 79-year-old man visited Osaka JR hospital, complaining of a painless nodular mass on his right chest. The mass was resected and histopathological examination revealed a clear cell carcinoma (alveolar type, G1) with no involvement of the mammary gland. Abdominal ultrasound and magnetic resonance imaging revealed a heterogenous lower pole mass in the right kidney. Ultrasound-guided needle biopsy of the right renal mass was performed for histopathological diagnosis, which was clear cell carcinoma (alveolar type, G1). At that time, multiple metastases appeared in bilateral lung fields. The patient is currently receiving interferon-alpha therapy, without surgical treatment