Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
35 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
Full Papers
  • Satoshi YAMAGIWA, Yoshinobu SATO, Takafumi ICHIDA, Toru SETSU, Kentaro ...
    2014 年 35 巻 3 号 p. 177-184
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    Progressive liver fibrosis remains a major problem for patients with recurrent chronic hepatitis C(CHC) after liver transplantation (LT). However, the involvement of natural killer (NK) and naturalkiller T (NKT) cells, which predominate in the liver, in recurrent CHC after LT remains unclear.In the present study, we investigated the status of NK and NKT cells in the liver andperipheral blood obtained from 10 patients with recurrent CHC after LT (LT-C), 15 patients withCHC, and 7 normal donors for living donor LT. CD56+ NK cells were separated into two subsets:CD56+bright subset, which is identified as major NK cytokine producer, and CD56+dim subset, whichhas greater spontaneous cytotoxicity. We found a significant decrease in the CD56+bright subset inthe liver of patients with LT-C compared to patients with CHC (P < 0.01) and normal donors(P = 0.03). The expression of inhibitory NK cell receptor NKG2A was significantly increased onintrahepatic CD56+bright subset in LT-C patients, and activated CD69+CD56+dim NK cell subset wassignificantly increased in the liver of LT-C patients. Our results suggest that a significant imbalancebetween CD56+bright and CD56+dim NK cell subsets in the liver may contribute to the progressionof recurrent CHC after LT.
  • Norihiro YOSHIDA, Eri JOJIMA, Hiroyuki SAITO, Tatsuya HAGA
    2014 年 35 巻 3 号 p. 185-192
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    Muscarinic M2, M4, and M2-M4 chimera receptors were transiently expressed in HEK-293tsA201 cells, and agonist-dependent internalization of these receptors and recycling of internalizedreceptors were examined by measuring the amount of cell-surface receptors as [3H]N-methylscopolamine(NMS) binding activity. Coexpression of a dominant negative form of dynamin (DNdynamin,dynamin K44A) greatly reduced the agonist-dependent internalization of M4 receptorsbut not of M2 receptors, as was reported by Vögler et al. (J Biol Chem 273, 12155–12160, 1998).The agonist-dependent internalization of M2/M4-i3/M2 chimera receptors (M2 receptors with thei3 loop replaced by that of M4 receptors) was greatly reduced by co-expression of DN-dynaminas was the case for M4 receptors, whereas the agonist-dependent internalization of M4/M2-i3/M4chimera receptors was hardly affected by co-expression of DN-dynamin as was the case for M2 receptors.Internalized M2/M4-i3/M2 receptors as well as internalized M4 receptors were shown tobe recycled back to the cell surface after removal of agonists, whereas no recycling was observedfor M4/M2-i3/M4 receptors as well as M2 receptors. These results indicate that the i3 loops ofM2 and M4 receptors take a major role in their agonist-dependent internalization and recycling.
  • Tadashi YASUDA
    2014 年 35 巻 3 号 p. 193-199
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    While nuclear factor (NF)-κB is a critical pathway for matrix metalloproteinase (MMP)-13 inductionin chondrocytes, intracellular upstream events for NF-κB activation by the type II collagenpeptide (CB12-II) with catabolic activities remain unclear. Hyaluronan (HA) of high molecularweight is clinically used for treatment of osteoarthritis (OA) by intra-articular injection. AlthoughHA can suppress NF-κB activation by CB12-II, it is still obscure how HA affects intracellular upstreampathways leading to NF-κB up-regulation in response to CB12-II. Thus, this study wasaimed to investigate the involvement of phosphoinositide-3-OH kinase (PI3K)/Akt in the inhibitionof CB12-II-activated NF-κB pathway by HA in OA chondrocytes. In monolayer cultures, pretreatmentwith HA of 2700 kDa significantly inhibited MMP-13 production by CB12-II-stimulatedchondrocytes. CB12-II activated Akt and NF-κB whereas HA down-regulated CB12-II-stimulatedphosphorylation of Akt and NF-κB. Inhibition studies using LY294002 revealed the requirementof PI3K/Akt pathway for CB12-II-stimulated NF-κB activation in association with MMP-13 production.Pretreatment with anti-CD44 antibody reversed the inhibitory effects of HA on CB12-IIinducedproduction of MMP-13 and activation of Akt and NF-κB. Herein, we provided the firstevidence that HA suppresses CB12-II-activated PI3K/Akt pathway leading to down-regulation ofNF-κB with diminished MMP-13 production through interaction with CD44.
  • Kazumasa MATSUMOTO, Masaomi IKEDA, Yuichi SATO, Hidetoshi KURUMA, Yuko ...
    2014 年 35 巻 3 号 p. 201-206
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    The objective of this study was to determine periplakin expression in normal urothelium and bladdercancer tissues and the relationship to clinicopathological findings. Immunohistochemical stainingfor periplakin was carried out in 92 archival radical cystectomy specimens, with immunoreactivitybeing stratified on a 0–6 scale. Immunohistochemical staining for periplakin was shown to be significantlylower in bladder cancer tissues compared to non-cancerous tissues including inflammation,hyperplasia and normal urothelium. Loss of periplakin expression was associated withpathological stage (P = 0.04). In multivariate Cox regression analysis, loss of periplakin expressionand positive lymph node status were independent prognostic factors for cancer-specific survival(P = 0.03 and 0.015; odds ratio = 2.29 and 2.66; 95% confidence interval = 1.085–4.814 and1.214–5.845, respectively). This new molecular marker may aid in identifying and selecting bladdercancer patients undergoing radical cystectomy who may potentially benefit from neoadjuvantor adjuvant therapy.
  • Kosuke ENDO, Naoko KITO, Yasue FUKUSHIMA, Huachun WENG, Naoharu IWAI
    2014 年 35 巻 3 号 p. 207-213
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    There has been increasing interest in the use of circulating DNA as biomarkers for various tissue injuries, cancers, and fetal conditions. DNA methylation is a well-characterized mechanism underlying the epigenetic regulation of gene expression, and many diagnostic tests based on DNA methylation patterns have been developed. We developed a novel TaqMan-based assay for the detection of acute kidney injury using a hypomethylated promoter region of Slc22a12, a urate transporter specifically expressed in proximal tubular cells. Bisulfite sequencing analysis confirmed that the CpG islands in the promoter region of mouse Slc22a12 were preferentially hypomethylated in the kidney cortex. TaqMan minor groove binder (MGB) probes reliably discriminated the DNA fragments corresponding to the unmethylated and methylated promoter regions of Slc22a12. Plasma levels of unmethylated DNA corresponding to the Slc22a12 promoter region were undetectable at baseline and were significantly elevated after acute kidney cortex necrosis. This study showed the usefulness of the TaqMan system in discriminating methylated and unmethylated DNA fragments, and the similar strategy can be applied for establishing biomarkers for various cellular injuries or pathological conditions.
  • Shogo SHIMIZU, Panagiota TSOUNAPI, Masashi HONDA, Fotios DIMITRIADIS, ...
    2014 年 35 巻 3 号 p. 215-221
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    Possible effect of olmesartan, an angiotensin II receptor blocker (ARB), or nifedipine, an L-type calcium channel blocker, on penile dysfunction in the spontaneously hypertensive rat (SHR) was investigated in this study. Twelve-week-old male SHRs were treated with olmesartan (1 or 3 mg/kg, per orally (p.o.)) or nifedipine (30 mg/kg, p.o.) once a day for 6 weeks. Wistar rats and SHRs with vehicle treatment were used as controls. Penile cGMP and malondialdehyde concentrations, and mRNA levels of endothelial and neuronal NO synthase (eNOS and nNOS) were measured. Penile function was evaluated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The SHR showed significantly increased blood pressure, decreased cGMP concentrations, increased malondialdehyde concentrations, decreased eNOS and nNOS mRNA levels, norepinephrine-induced hyper-contractions, and acetylcholine-induced hyporelaxations in the penile tissue compared to the Wistar rat. Both nifedipine and olmesartan significantly decreased blood pressure, increased cGMP and normalized the hyper-contractions and hypo-relaxations observed in the SHR group. However, not nifedipine but olmesartan improved the malondialdehyde concentrations and increased mRNA levels of eNOS and nNOS in the penis. Our results indicate that the hypertension-associated penile dysfunction might be treated with ARBs such as olmesartan better than calcium channel blockers, such as nifedipine.
Communication
  • Yuichi UWAI, Yuta NAKASHIMA, Emi HONJO, Tatsuya KAWASAKI, Tomohiro NAB ...
    2014 年 35 巻 3 号 p. 223-226
    発行日: 2014/06/01
    公開日: 2014/06/19
    ジャーナル フリー
    The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic acid works in the renal proximal tubule to produce the sulfate of xanthurenic acid as well as the liver, and we recently found that xanthurenic acid is a substrate of renal organic anion transporter OAT1. The purpose of this study was to examine relationship between the transport by OAT1 and diuresis related with xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes represented that probenecid inhibited xanthurenic acid uptake by rat OAT1 (rOAT1). Although no diuresis was recognized by the intravenous injection of xanthurenic acid as a bolus in rats, the addition of its infusion exhibited natriuresis. Simultaneous administration of probenecid significantly decreased the urine volume and excreted amounts of sodium into urine. These findings showed the diuresis by the xanthurenic acid administration, and it was probenecid-sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in part, contribute to its diuretic effect.
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