Membrane-associated prostaglandin E synthase-1 is upregulated by proinflammatory cytokines in chondrocytes from patients with osteoarthritis

Prostaglandin E synthase (PGES) including isoenzymes of membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES (cPGES) is the recently identified terminal enzyme of the arachidonic acid cascade. PGES converts prostaglandin (PG)H(2 )to PGE(2 )downstream of cyclooxygenase (COX). We investigated the expression of PGES isoenzyme in articular chondrocytes from patients with osteoarthritis (OA). Chondrocytes were treated with various cytokines and the expression of PGES isoenzyme mRNA was analyzed by the reverse transcription–polymerase chain reaction and Northern blotting, whereas Western blotting was performed for protein expression. The subcellular localization of mPGES-1 was determined by immunofluorescent microscopy. Conversion of arachidonic acid or PGH(2 )to PGE(2 )was measured by enzyme-linked immunosorbent assay. Finally, the expression of mPGES-1 protein in OA articular cartilage was assessed by immunohistochemistry. Expression of mPGES-1 mRNA in chondrocytes was significantly induced by interleukin (IL)-1β or tumor necrosis factor (TNF)-α, whereas other cytokines, such as IL-4, IL-6, IL-8, IL-10, and interferon-γ, had no effect. COX-2 was also induced under the same conditions, although its pattern of expression was different. Expression of cPGES, mPGES-2, and COX-1 mRNA was not affected by IL-1β or TNF-α. The subcellular localization of mPGES-1 and COX-2 almost overlapped in the perinuclear region. In comparison with 6-keto-PGF(1α )and thromboxane B(2), the production of PGE(2 )was greater after chondrocytes were stimulated by IL-1β or TNF-α. Conversion of PGH(2 )to PGE(2 )(PGES activity) was significantly increased in the lysate from IL-1β-stimulated chondrocytes and it was inhibited by MK-886, which has an inhibitory effect on mPGES-1 activity. Chondrocytes in articular cartilage from patients with OA showed positive immunostaining for mPGES-1. These results suggest that mPGES-1 might be important in the pathogenesis of OA. It might also be a potential new target for therapeutic strategies that specifically modulate PGE(2 )synthesis in patients with OA

Millimeter-wave Wireless LAN and its Extension toward 5G Heterogeneous Networks

Millimeter-wave (mmw) frequency bands, especially 60 GHz unlicensed band, are considered as a promising solution for gigabit short range wireless communication systems. IEEE standard 802.11ad, also known as WiGig, is standardized for the usage of the 60 GHz unlicensed band for wireless local area networks (WLANs). By using this mmw WLAN, multi-Gbps rate can be achieved to support bandwidth-intensive multimedia applications. Exhaustive search along with beamforming (BF) is usually used to overcome 60 GHz channel propagation loss and accomplish data transmissions in such mmw WLANs. Because of its short range transmission with a high susceptibility to path blocking, multiple number of mmw access points (APs) should be used to fully cover a typical target environment for future high capacity multi-Gbps WLANs. Therefore, coordination among mmw APs is highly needed to overcome packet collisions resulting from un-coordinated exhaustive search BF and to increase the total capacity of mmw WLANs. In this paper, we firstly give the current status of mmw WLANs with our developed WiGig AP prototype. Then, we highlight the great need for coordinated transmissions among mmw APs as a key enabler for future high capacity mmw WLANs. Two different types of coordinated mmw WLAN architecture are introduced. One is the distributed antenna type architecture to realize centralized coordination, while the other is an autonomous coordination with the assistance of legacy Wi-Fi signaling. Moreover, two heterogeneous network (HetNet) architectures are also introduced to efficiently extend the coordinated mmw WLANs to be used for future 5th Generation (5G) cellular networks.Comment: 18 pages, 24 figures, accepted, invited paper

Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin): a preclinical study.

[Background] Treatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT) with porfimer sodium (Photofrin®) has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin) is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin. [Methodology/Principal Findings] Diode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm2, 50 J/cm2, and 100 J/cm2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm2, 498 mm2, and 831 mm2 after irradiation at 25 J/cm2, 50 J/cm2, and 100 J/cm2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue. [Conclusions/Significance]To minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level

シュウガクテキ チリョウ ガ ソウコウ シタ シンコウ チョウカンマク アクセイ リンパシュ ノ 1レイ

Mesenteric malignant lymphoma is comparative rare and has a poor prognosis in anadvanced case.Here, we report a patient with intestinal obstruction due to mesenteric malignantlymphoma treated successfully by gastrointestinal bypass operation, chemo-and radiotherapy.A 67-year-old man was admitted to our hospital because of abdominal pain andnausea. An abdominal CT scan revealed a huge tumorous lesion with a soft tissue density,which involved descending colon. Since the symptoms was persisted after conservativetreatment, gastrointestinal bypass procedures were surgically formed. During the laparotomy,an open incisional biopsy was performed. Histological examination showed non-Hodgkinlymphoma with diffuse, large-sized and B-cell type. This case was classified into high-risk groupacccording to International Prognostic Index (IPI). After the operation, 5 courses of combinedchemotherapy (THP-COP) and 30 Gy radiation were performed. These multidisciplinarytreatment is considered to be very effective. Since then complete response and goodpatient’s QOL has been attained for these 3.5 years

Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma

Background Octamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. To date, however, the function of human OCT4 in somatic and/or tumour tissues is largely unknown. Methods RT-PCR was used to identify full-length splice forms of OCT4 transcripts in normal and cancer cells. A FLAG-tagged OCT4 genomic transgene was used to identify OCT4-positive cancer cells. A potential role for OCT4 in somatic cancer cells was examined by cell ablation of OCT4-positive cells using promoter-driven diphtheria toxin A. OCT4 and secreted phosphoprotein 1 (SPP1) transcripts in early-stage lung adenocarcinoma tumours were analysed and compared with pathohistological features. Results The results show that, unlike in murine cells, OCT4A and OCT4B variants are transcribed in both human cancer cells and in adult tissues such as lung, kidney, uterus, breast, and eye. We found that OCT4A and SPP1C are co-expressed in highly aggressive human breast, endometrial, and lung adenocarcinoma cell lines, but not in mesothelial tumour cell lines. Ablation of OCT4-positive cells in lung adenocarcinoma cells significantly decreased cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinoma tumours. Conclusions Co-expression of OCT4 and SPP1 may correlate with cancer aggressiveness, and the OCT4A/SPP1C axis may help identify early-stage high-risk patients with lung adenocarcinoma. Contrary to the case in mice, our data strongly suggest a critical role for OCT4A and SPP1C in the development and progression of human epithelial cancers

Effects of excitation light intensity on parathyroid autofluorescence

The intraoperative identification and preservation of the parathyroid glands are vital techniques, which are largely dependent on a surgeon’s experience. Therefore, a simple and reproducible technique to identify the parathyroid glands during surgery is needed. Parathyroid tissue shows near-infrared (NIR) autofluorescence, which enables the intraoperative identification of the parathyroid gland. We herein present two cases that underwent surgery on the parathyroid glands, which were observed using the NIR fluorescence imaging system LIGHTVISION® (Shimazu, Kyoto, Japan). In a case of papillary thyroid carcinoma, the system was adopted to preserve normal parathyroid glands during left hemithyroidectomy. The left lower parathyroid gland was identified using the imaging system under white light; however, its autofluorescence was visualized more clearly with the excitation light of NIR. In a case of primary hyperparathyroidism due to MEN1, the system was adopted to identify and remove all of the parathyroid glands during total parathyroidectomy. The autofluorescence of diseased glands was weaker than that of normal glands, even with the excitation light of NIR. When the parathyroid glands were irradiated with a red laser pointer, the intensity of autofluorescence significantly increased. However, the largest gland, which was pathologically proven to contain strongly proliferating chief cells, did not show autofluorescence. These results suggest that normal or less diseased parathyroid glands, which are generally small and difficult to identify during surgery, showed relatively strong autofluorescence. A stronger excitation light increases the autofluorescence of parathyroid glands, which enhances sensitivity for detecting parathyroid glands during surgery. In conclusion, LIGHTVISION® is a useful device to identify parathyroid glands and an additional excitation light of a red laser pointer increases the detection sensitivity

The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration

Glomerular hyperfiltration is a common pathway leading to glomerulosclerosis in various kinds of kidney diseases. The 5/6 renal ablation is an established experimental animal model for glomerular hyperfiltration. On the other hand, low-grade inflammation is also a common mechanism for the progression of kidney diseases including diabetic nephropathy and atherosclerosis. Here we analyzed the gene expression profile in the remnant kidney tissues of 5/6 nephrectomized mice using a DNA microarray system and compared it with that of sham-operated control mice. The 5/6 nephrectomized mice showed glomerular hypertrophy and an increase in the extracellular matrix in the glomeruli. DNA microarray analysis indicated the up-regulated expression of various kinds of genes related to the inflammatory process in remnant kidneys. We confirmed the up-regulated expression of platelet factor-4, and monocyte chemoattractant protein-1, 2, and 5 in remnant kidneys by RT-PCR. The current results suggest that the inflammatory process is involved in the progression of glomerulosclerosis and is a common pathway of the pathogenesis of kidney disease