Suppression of cell adhesion and spreading activities of fibronectin by arginine-specific ADP-ribosyltransferase from chicken polymorphonuclear leukocytes

AbstractArginine-specific ADP-ribosyltransferase present in secretory granules of chicken polymorphonuclear leukocytes (so-called heterophils) was shown to be released into the extracellular space by secretagogues (Terashima et al., J. Biochem. 120 (1996) 1209–1215). In the present work, we examined fibronectin as an extracellular target protein of the released transferase. Fibronectin was ADP-ribosylated by purified transferase and stoichiometry of ADP-ribose incorporation into fibronectin was 1.0 mol/mol of fibronectin. Cell adhesion and spreading assays revealed that ADP-ribosylation of fibronectin markedly inhibited the adhesion activity of fibronectin. A proteolytic peptide map of ADP-ribosylated fibronectin demonstrated that the modification occurs in the cell binding domain of fibronectin. ADP-ribosylation of the RGD peptide suggests that the RGD sequence is the modification site in the domain. ADP-ribosylation of fibronectin in plasma means that fibronectin can probably serve as the substrate for extracellularly released ADP-ribosyltransferase in vivo. Thus, in the extracellular space, ADP-ribosyltransferase released from polymorphonuclear leukocytes may perhaps be involved in regulation of cell adhesion process by interfering with the activity of fibronectin

Optical Fiber-Based Sleep Apnea Syndrome Sensor

A noninvasive sleep apnea syndrome (SAS) sensor using optical fibers, the “F-SAS sensor,” has been evaluated in a clinical application ranging in age from 13 to 78 years and with BMIs of 19.2–39.3. The respiratory disturbance index (RDI) from the F-SAS sensor corresponded well with the apnea hypopnea index (AHI) from polysomnography (PSG). Concurrent measurement of the RDI and the AHI had a correlation coefficient of 0.71. This means that the F-SAS is well-suited for preliminary SAS screening. They would also be useful for screening potential SAS sufferers during normal sleep at home. Then, we have succeeded in downsizing F-SAS sensor and have recognized that it is highly correlated with PSG and pulse oximetry. Next, we applied the compact F-SAS sensor to examining SAS diagnosis in a child patient (2–12 years) and report on improved pediatric analysis. The analysis results revealed the correlation value to be R = 0.87 was a significant improvement over the correlation value of R = 0.697 between the AHI obtained by a sleep apnea syndrome examination apparatus (SAS 2100) and RDI obtained by the conventional F-SAS sensor

Association between KCNJ6 (GIRK2) Gene Polymorphisms and Postoperative Analgesic Requirements after Major Abdominal Surgery

Opioids are commonly used as effective analgesics for the treatment of acute and chronic pain. However, considerable individual differences have been widely observed in sensitivity to opioid analgesics. We focused on a G-protein-activated inwardly rectifying potassium (GIRK) channel subunit, GIRK2, that is an important molecule in opioid transmission. In our initial polymorphism search, a total of nine single-nucleotide polymorphisms (SNPs) were identified in the whole exon, 5′-flanking, and exon-intron boundary regions of the KCNJ6 gene encoding GIRK2. Among them, G-1250A and A1032G were selected as representative SNPs for further association studies. In an association study of 129 subjects who underwent major open abdominal surgery, the A/A genotype in the A1032G SNP and -1250G/1032A haplotype were significantly associated with increased postoperative analgesic requirements compared with other genotypes and haplotypes. The total dose (mean±SEM) of rescue analgesics converted to equivalent oral morphine doses was 20.45±9.27 mg, 10.84±2.24 mg, and 13.07±2.39 mg for the A/A, A/G, and G/G genotypes in the A1032G SNP, respectively. Additionally, KCNJ6 gene expression levels in the 1032A/A subjects were significantly decreased compared with the 1032A/G and 1032G/G subjects in a real-time quantitative PCR analysis using human brain tissues, suggesting that the 1032A/A subjects required more analgesics because of lower KCNJ6 gene expression levels and consequently insufficient analgesic effects. The results indicate that the A1032G SNP and G-1250A/A1032G haplotype could serve as markers that predict increased analgesic requirements. Our findings will provide valuable information for achieving satisfactory pain control and open new avenues for personalized pain treatment

A case of mucoepidermoid carcinoma arising in mature cystic teratoma

卵巣粘表皮癌は卵巣悪性腫瘍の中で極めてまれな組織型に分類される。今回、我々は成熟嚢胞性奇形種より発生した卵巣粘表皮癌の症例を経験したので報告する。症例は、69歳、女性、両側の成熟嚢胞性奇形腫を認めたが、SCC 高値とCT、MRI にて左側の腫瘍内に造影される充実性部分を認めたこと、小腸に浸潤を疑う所見を認めたこと、から悪性転化を疑い、手術を施行した。開腹時、両側卵巣腫瘍を認め、左卵巣腫瘍はS状結腸と強固に癒着していた。卵巣腫瘍充実性部分の迅速病理にて低分化癌と診断し、単純子宮全摘出術、両側付属器摘出術、S状結腸合併切除、骨盤リンパ節郭清術、大網切除術を施行した。病理組織学的には、左卵巣腫瘍の嚢胞壁肥厚部に皮膚付属器、脂肪織、軟骨組織、リンパ球集簇、卵巣間質を認め、充実成分に低分化な浸潤性扁平上皮癌を認めた。充実成分には、粘表皮癌に特徴的な、豊富な胞体粘液（PASおよびAlcian blue 染色陽性）を有する異型細胞が胞巣状~不完全な腺管状を呈する領域があり、成熟嚢胞性奇形腫より発生した卵巣粘表皮癌IIb期(pT2bN0M0)と診断した。術後補助化学療法としてDC（ドセタキセル、カルボプラチン）療法を施行し、術後1年8ヶ月現在、再発を認めない。雑誌掲載論

Representative Exposure–Annoyance Relationships Due to Transportation Noises in Japan

This paper focuses on clarifying the relationship between noise exposure and the prevalence of highly annoyed people due to transportation noise in Japan. The authors accumulated 34 datasets, which were provided by Socio-Acoustic Survey Data Archive and derived from the other surveys conducted in Japan. All the datasets include the following micro-data: demographic factors, exposure, and annoyance data associated with specific noise sources. We performed secondary analyses using micro-data and established the relationships between noise exposure (Lden) and the percentage of highly annoyed people (%HA) for the following noise source: road traffic, conventional railway, Shinkansen railway, civil aircraft, and military aircraft noises. Among the five transportation noises, %HA for the military aircraft noise is the highest, followed by civil aircraft noise and Shinkansen railway noise. The %HA for conventional railway noise was higher than that for road traffic noise. To validate the representativeness of the exposure–response curves, we have discussed factors affecting the difference in annoyance. In addition, comparing the Japanese relationship with that shown in the “Environmental Noise Guidelines for the European Region,” we revealed that Japanese annoyance is higher than the WHO-reported annoyance

MCI-186 (edaravone), a free radical scavenger, attenuates ischemia-reperfusion injury and activation of phospholipase A 2 in an isolated rat lung model after 18 h of cold preservation

Abstract Objective: Increased microvascular permeability and extravasation of inflammatory cells are key events in ischemia-reperfusion (IR) injury. We hypothesized that edaravone, a free radical scavenger, is able to attenuate IR lung injury by decreasing oxidative stress and phospholipase A 2 (PLA 2 ) activation, which otherwise may lead to lung injury through PAF receptor (PAF-R) activation. Methods: We used an isolated rat lung model. Five groups were defined (n = 7, each): in the sham and vehicle group, lungs were immediately washed after thoracotomy or perfused for 2 h without an ischemic period, respectively. In the ischemic groups, 10 mg/kg of MCI-186 (edavorane group), 1 mg/kg of PAF-R inhibitor (ABT-491 group) or saline (control group) were i.v. administered 20 min before harvest. Lungs were flushed with LPD solution, stored at 4 8C for 18 h, and reperfused for 2 h. Results: Compared to vehicle group, IR significantly decreased the PO 2 level and increased the wet-to-dry ratio, proteins in bronchoalveolar lavage (BAL), and myeloperoxidase (MPO) activity in the control group, while edaravone treatment maintained the PO 2 similar to the vehicle group and significantly reduced edema formation and neutrophil extravasation. Consistently, IR significantly increased lipid peroxidation, cytosolic-PLA 2 activity mainly via alveolar macrophages, soluble-PLA 2 activity, leukotriene B 4 , and PAF-R expression in control lungs, together with a decreased PAF acetylhydrolase (PAF-AH) activity. Edaravone significantly reduced all of these, but increased PAF-AH activity. Furthermore, pharmacological inhibition of the PAF-R attenuated IR injury resembling edaravone action. Conclusion: Edaravone attenuates lung IR injury by suppressing oxidative damage and PLA 2 activation, which otherwise partially mediates edema formation and neutrophil extravasation through PAF-R activation.

＜Poster＞Alteration of peptides in rat brain treated with angiotensin-converting enzyme Inhibitor, captopril

Although animal studies suggest that centrally active angiotensin-converting enzyme （ACE） inhibitors may protect against dementia beyond HTN control, the mechanism（s） underlying these improvements in cognitive function remains unclear. We measured the brain peptide levels in rat treated with captopril（ 50 mg/kg） for 3 weeks by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI TOF-MS）. Two protein chip arrays were used for peptide profi ling： one with a strong anion- exchanger and the other with a weak cation-exchanger. 　 Comparing with control group, 15 mass peaks were considered specifi c to experimental animals, and 6 peaks were signifi cantly up-regulated and 5 down-regulated