Identification and immunoregulatory function of neuromedin U (Nmu) in the Japanese pufferfish Takifugu rubripes.

In this study, immunoregulatory function of neuromedin U (Nmu) in the teleost fish Fugu (Takifugu rubripes) was characterized. Three splicing variants of nmu mRNA encoding preproNMUs consisting of 164 (Nmu1), 139 (Nmu2), and 129 (Nmu3) amino acid residues were found in Fugu.The biologically active C-terminal region of Fugu Nmu showed high homology among fish and other vertebrate NMUs. The genomic organization of Fugu nmu differed from those of zebrafish and mammals. However, in phylogenetic analysis, Fugu Nmu formed a cluster with NMUs of other vertebrates, in addition to neuromedin S. The splicing variants of mRNA were identified in various tissues. Nmu-21 and Nmu-9 were purified as endogenous peptides from Fugu intestine. The synthetic Nmu-21 peptide activated phagocytic cells, and elevated the expression of cytokine mRNA in peripheral blood leukocytes.

Hypothermia Reduces but Hyperthermia Augments T Cell-Derived Release of Interleukin-17 and Granzyme B that Mediate Neuronal Cell Death.

BACKGROUND: T cells infiltrate into the infarcted brain within days after cerebral ischemia and play essential roles in exacerbating the delayed phase of the brain injury by producing pro-inflammatory factors. However, the involvement of these factors in brain damage is also demonstrated systemically. Such periphery-brain abnormalities are interesting because they may constitute a pathway to the central nervous system (CNS), which may be a target of therapeutic hypothermia. Although this therapy protects neurons after severe brain damage, the underlying mechanisms are partly understood. We examined the effects of hypothermic and hyperthermic cultures on peripheral T cell-derived release of interleukin (IL)-17 and granzyme B (GrB) and evaluated whether and how these factors induced neurotoxicity and activated brain endothelial cells. METHODS: We determined levels of IL-17 and GrB produced by several activated, IL-1ß/IL-23-treated activated T cells (naïve CD4(+), CD4(+), CD8(+), and γδ T cells obtained from healthy humans) under hypothermia, normothermia, and hyperthermia. The viability of neuronal SH-SY5Y cells treated with IL-17 or GrB and mRNA expression of adhesion molecules/chemokines by brain endothelial bEND.3 cells treated with IL-17 were also measured. RESULTS: Compared with normothermia, IL-17 and GrB release in these T cells was reduced by hypothermia but augmented by hyperthermia. IL-17 and GrB caused the death of neuronal SH-SY5Y cells, and IL-17 upregulated mRNA expression of several adhesion molecules/chemokines in bEND.3 cells; both effects were concentration-dependent. CONCLUSION: Hypothermia reduced but hyperthermia augmented T cell-derived release of IL-17 and GrB that mediate neuronal cell death, suggesting that the attenuation of T cell-derived release of these factors by therapeutic hypothermia leads to the inhibition of neuronal cell death in the delayed phase of brain injury. Moreover, hypothermia may suppress but hyperthermia may promote the recruitment of inflammatory cells to CNS by regulating brain endothelial activation of IL-17.

Radiographic joint space width in patients with Crowe Type-I dysplastic hips.

UNLABELLED: Radiographic evaluation of preoperative joint space width is believed important to predict the long-term results of osteotomy. We asked whether joint space width differs in the supine and standing positions in patients with Crowe Type-1 osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH). Joint space width was measured in the supine and standing positions in 146 women and 16 men (231 hips) with OA. Subjects had a mean age of 46.7 years (range, 22-59 years). Differences were seen on radiographs in joint space width between supine (2.35 +/- 1.65 mm; range, 0.1-6.2 mm) and standing (2.04 +/- 1.78 mm; range, 0.0-5.9 mm). In 27 of 172 hips with greater than 1 mm joint space in the supine position, joint space width was decreased by greater than 1 mm in the standing position. To evaluate preoperative joint space width in patients scheduled for osteotomy, radiographs should be obtained with the patient in the standing position. LEVEL OF EVIDENCE: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.