RGMa inhibition promotes axonal growth and recovery after spinal cord injury

Repulsive guidance molecule (RGM) is a protein implicated in both axonal guidance and neural tube closure. We report RGMa as a potent inhibitor of axon regeneration in the adult central nervous system (CNS). RGMa inhibits mammalian CNS neurite outgrowth by a mechanism dependent on the activation of the RhoA–Rho kinase pathway. RGMa expression is observed in oligodendrocytes, myelinated fibers, and neurons of the adult rat spinal cord and is induced around the injury site after spinal cord injury. We developed an antibody to RGMa that efficiently blocks the effect of RGMa in vitro. Intrathecal administration of the antibody to rats with thoracic spinal cord hemisection results in significant axonal growth of the corticospinal tract and improves functional recovery. Thus, RGMa plays an important role in limiting axonal regeneration after CNS injury and the RGMa antibody offers a possible therapeutic agent in clinical conditions characterized by a failure of CNS regeneration

Investigation of Steam Turbine blade failure

Case StudyBlade failure was observed on a backpressure steam turbine (driving a centrifugal compressor) after it was in service for more than one year. This paper presents details of observations, inspections carried out and root cause analysis of the turbine blade failure

ホウレンソウ雌性間性株における突然変異誘発ならびに低シュウ酸個体の選抜

This study was conducted to evalute mutagenesis in gynomonoecious spinach (Spinacia oleracea L.) plants for inducing low oxalate variants.Gamma-ray and ion beams of 220 MeV12C5+ and 50MeV 4He2+ ware used as mutagen in seed irradiation. Optimum dosages for irradiation were determined to be about 100Gy, 15-20Gy and 150-200Gy in gamma-ray, 12C5+ and 4He2+, respectively. In M2 generation, there was one line segregating albino seedlings, one line segregating xantha seedlings and two lines segregating dioesious spinach. To save on labor and time for analysis, selection of low oxalate variants in M2generation was conducted by a two-step selebtion which consisted of the first snalysis of bulked leaves from 2 plants as one specimen followed by the second analysis of selected individual plants. In the first analysis of 813 specimens, we selected 13 specimens as low and 9 specimens as high in oxalate content. In the second analysus, there was consistency in the distribution of low and high oxalate content corresponding to the first screening, indicating that selebtion of low oxalate variants could be achived by this two-step selebtion with half the labor and time for analysis as compares to non-bulked method. There were no clear differences in distribution of oxalate content between M3progenies of plants selected as low or high oxalate content, suggesting that the low oxalate content in plants isolated in M2generation was not of a genetic origin. From these results, it seems to be necessary to explore a variant with obvious deviation from the bontinuous variation of oxalate content in the M 2 generation.本実験では，ホウレンソウ雌性間性株における突然変異誘発ならびに低シュウ酸個体の選抜を試みた．種子照射の変異原としては，γ線と220MeV 12

Preliminary Trial of Rebamipide for Prevention of Low-Dose Aspirin-Induced Gastric Injury in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study

Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum

Targeting PD-1/PD-L1 inhibits rejection in a heterotopic tracheal allograft model of lung transplantation

Immune checkpoint molecules such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have revolutionized the field of lung cancer treatment. As part of our study, we examined the role of these proteins in acute rejection in a mouse model of heterotopic tracheal transplantation. Recipient mice were untreated (Allo group) or treated with anti-PD-L1 (aPDL1 group) or PD-L1 Fc recombinant protein (PD-L1 Fc group). A further group of C57BL/6 mice received isografts (Iso group). The occlusion rate was significantly higher in the Allo group than in the Iso group (p = 0.0075), and also higher in the aPD-L1 group (p = 0.0066) and lower in the PD-L1 Fc group (p = 0.030) than in the Allo group. PD-L1 Fc recombinant protein treatment significantly decreased interleukin-6 and interferon-γ levels and reduced the CD4+/CD8+ T cell ratio, without increasing PD-1 and T-cell immunoglobulin mucin 3 expression in CD4+ T cells. These data suggest that PD-L1 Fc recombinant protein decreases the levels of inflammatory cytokines and the proportion of CD4+ T cells without exhaustion. The PD-L1-mediated immune checkpoint mechanism was associated with rejection in the murine tracheal transplant model, suggesting a potential novel target for immunotherapy in lung transplantation