巻号一覧
36 巻 (2015)
- 6 号 p. 347-
- 5 号 p. 279-
- 4 号 p. 225-
- 3 号 p. 159-
- 2 号 p. 71-
- 1 号 p. 1-
36 巻, 3 号
選択された号の論文の7件中1～7を表示しています
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Full Papers
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Mohammod Johirul ISLAM, Keisuke HIKOSAKA, Hidenao NORITAKE, Mohammad K ...2015 年 36 巻 3 号 p. 159-167
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーPatients chronically infected with hepatitis C virus (HCV) are at risk of developing end-stage liver disease and hepatocellular carcinoma. Development of drugs to inhibit hepatocyte damage and a vaccine against HCV is hampered by the lack of a small animal model. We generated mice in which the viral genome RNA was always present in the hepatocytes using a special transgene. Here we show that the HCV genome RNA transcribed by Pol I polymerase can replicate and produce infectious viruses in mice. We obtained a transgenic mouse with 200 copies per haploid which we named the A line mouse. It produced ~ 3 × 106 HCV RNA copies/mL serum, which is at the comparable level as patients with chronic HCV infection. This mouse was immunotolerant to HCV and showed hepatic steatosis without any necroinflammation at the age of 6 months or hepatocellular carcinoma at the age of 15 months. Thus, the A line mouse can be used as an animal model for chronic HCV infection. This will enable better study of the abnormalities in metabolism and signal transduction in infected hepatocytes, and development of drugs that cure abnormalities.抄録全体を表示PDF形式でダウンロード (6330K) -
Takashi KATO, Nobuyuki MIZUGUCHI, Akihiko ITO2015 年 36 巻 3 号 p. 169-177
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーHypertensive nephropathy, a consequence of chronic high blood pressure, is increasingly a cause of end-stage renal diseases and its correct management is very important for clinical outcome. Spontaneously hypertensive rat (SHR/Kpo) and stroke-prone SHR (SHRSP/Kpo) strains represent models of human essential hypertension. However, the kidney injuries in SHR/Kpo and SHRSP/Kpo are not well defined. We therefore characterized the renal pathophysiology of SHR/Kpo and SHRSP/Kpo compared with normotensive control (WKY/Kpo) rats. The SHRSP/Kpo exhibited increased systolic blood pressure at 10 weeks of age, and proteinuria and increased blood urea nitrogen (BUN) and serum creatinine levels at 20 weeks. We simultaneously detected mononuclear cell infiltration, tubular injuries, accumulation of extracellular matrix and marked expression of α-SMA in the tubulointerstitium. Additionally, TGF-β1 and CTGF were up-regulated in the kidney of SHRSP/Kpo. We lastly focused on changes in glomerular cells of SHRSP/Kpo. Nestin, a podocyte marker, was detected but decreased slightly in 20-week-old SHRSP/Kpo. PECAM-1 expression was increased in SHRSP/Kpo glomeruli, indicating the thickening of glomerular endothelial cells. Moreover, we found that α-SMA, a myofibroblast marker, was also upregulated in the glomeruli of SHRSP/Kpo at 20 weeks. These findings suggest that SHRSP/Kpo could be a valuable animal model for human hypertensive nephropathy.抄録全体を表示PDF形式でダウンロード (14133K) -
Taku SAITO, Fumiko YANO, Daisuke MORI, Manabu KAWATA, Kazuto HOSHI, Ts ...2015 年 36 巻 3 号 p. 179-186
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーInduced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.抄録全体を表示PDF形式でダウンロード (14460K) -
Mai MICHISHITA, Kazuo YANO, Ken-ichi KASAHARA, Ken-ichi TOMITA, Osamu ...2015 年 36 巻 3 号 p. 187-194
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーSerotonin (5-hydroxytryptamine; 5-HT)-induced bladder contraction is enhanced after partial bladder outlet obstruction (pBOO) in rats. We investigated time-dependent changes in bladder contraction and expression of 5-HT2A and 5-HT2B receptor mRNA in bladder tissue to elucidate the mechanism of this enhancement. On day 3 and 7 after pBOO, contractile responses of isolated rat bladder strips to 5-HT were increased compared with that in sham-operated rats; on day 14, the response had decreased to the same level as that in sham rat bladders. In contrast, carbacholinduced contraction was not enhanced by pBOO at any time point. In sham rats, 5-HT2A receptor mRNA was expressed in the urothelium, and 5-HT2B receptor mRNA was expressed in the detrusor muscle layer. In pBOO rats, both receptor mRNAs were increased in the detrusor muscle and subserosal layers, but not in the urothelium. The increase of 5-HT2A receptor mRNA was maintained from day 3 to day 14 after pBOO, and 5-HT2B receptor mRNA was increased on day 7 after pBOO. These results suggested that pBOO induced up-regulation of the 5-HT2A and 5-HT2B receptors in the detrusor muscle and subserosal layers of the bladder, and such up-regulation may be related to the enhanced bladder contractile response to 5-HT.抄録全体を表示PDF形式でダウンロード (7229K) -
Satoshi KUSUMI, Daisuke KOGA, Tatsuo KANDA, Tatsuo USHIKI2015 年 36 巻 3 号 p. 195-203
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーAlthough a number of papers have given useful information on splenic microcirculation by light and/or scanning electron microscopy, controversies remain as to the vascular arrangement, especially in the human spleen. The present study re-examined the microvasculature of the human spleen using a three-dimensional reconstruction of immunohistochemically stained tissue sections, and showed that the central artery does not directly issue follicular arteries in the human spleen; follicular arteries are derived from penicillar arteries outside the follicle and end in the white pulp. We found that the splenic follicle is surrounded by an elaborate system of anastomosed capillaries in both the marginal zone and the superficial layer of the white pulp. Most of these capillaries are also branches of the penicillar arterioles that are issued from the central artery in the same, or a different, white pulp system. Because the endothelia of these capillaries are widely open in the marginal zone, this vascular network may play a major role in supplying blood to the marginal zone. The accumulation of sialoadhesin-positive macrophages was also observed around the vascular network, suggesting an important role for this structure as the front line of immune response.抄録全体を表示PDF形式でダウンロード (1379K) -
Meri HISAMOTO, Marie GOTO, Mami MUTO, Junko NIO-KOBAYASHI, Toshihiko I ...2015 年 36 巻 3 号 p. 205-217
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーTooth development is regulated by various growth factors and their receptors. However, the overall mechanism of growth factor-mediated odontogenesis remains to be elucidated. The present study examined expression sites and intensities of major growth factors and receptors in the tooth germ of murine fetuses and neonates. Signals of TGF-β and CTGF in fetuses were released from the enamel epithelium, while their neonatal signals arose in odontoblasts. Moreover, BMP/Smad signaling may affect the differentiation of ameloblasts, in contrast to PDGFα whose signals may cause odontoblast differentiation. Growth factors associated with the formation of the periodontium were IGF1, IGF2, IGFBP3, CTGF, and PDGFα. Concerning cusp formation, the enamel knot selectively expressed FGF4, BMP2, and BMP4 with an expression of PDGFα in the enamel-free area. It is concluded that many molecules play critical roles in the epithelium-mesenchyme interaction of tooth germ differentiation, and their expressions are precisely controlled.抄録全体を表示PDF形式でダウンロード (2024K)
Communication
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Saori TAKAHASHI, Taku YOSHIYA, Kumiko YOSHIZAWA-KUMAGAYE, Toshihiro SU ...2015 年 36 巻 3 号 p. 219-224
発行日: 2015/06/01
公開日: 2015/06/24
ジャーナル フリーAngiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase which is highly homologous to angiotensin-converting enzyme (ACE). ACE2 produces vasodilator peptides angiotensin 1-7 from angiotensin II. In the present study, we synthesized various internally quenched fluorogenic (IQF) substrates (fluorophore-Xaa-Pro-quencher) based on the cleavage site of angiotensin II introducing N-terminal fluorophore N-methylanthranilic acid (Nma) and C-terminal quencher Nε-2,4- dinitrophenyl-lysine [Lys(Dnp)]. The synthesized mixed substrates “Nma-Xaa-Pro-Lys(Dnp)” were hydrolyzed by recombinant human (rh) ACE2. The amount of each product was determined by liquid chromatography mass spectrometry (LC-MS) with fluorescence detection and it was found that Nma-His-Pro-Lys(Dnp) is the most suitable substrate for rhACE2. The Km, kcat, and kcat/Km values of Nma-His-Pro-Lys(Dnp) on rhACE2 were determined to be 23.3 μM, 167 s−1, and 7.17 μM−1 s−1, respectively. Using the rhACE2 and the newly developed IQF substrate, we found rhACE2 inhibitory activity in soybean and isolated the active compound soybean ACE2 inhibitor (ACE2iSB). The physicochemical data on the isolated ACE2iSB were identical to those of nicotianamine. ACE2iSB strongly inhibited rhACE2 activity with an IC50 value of 84 nM. This is the first demonstration of an ACE2 inhibitor from foodstuffs.抄録全体を表示PDF形式でダウンロード (1453K)
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