RÉSUMÉ
BACKGROUND: We conducted a historical cohort study of patients with schizophrenia to identify more robust risk factors at discharge that contribute to readmission within a year. METHODS AND FINDINGS: The subjects underwent brief psychoeducation during hospitalization. Multivariate analysis was conducted using factors selected in the univariate analysis. Using logistic regression analysis, the number of hospital admissions (P = .01) and Schedule for Assessment of Insight Japanese version score (P = .04) were identified as risk factors for readmission, with odds ratios of 0.70 and 1.18, respectively. CONCLUSIONS: These results suggest that improvement in insight and early intervention may lead to a more stable community life.
Sujet(s)
Schizophrénie , Études de cohortes , Humains , Sortie du patient , Réadmission du patient , Facteurs de risque , Schizophrénie/épidémiologie , Schizophrénie/thérapieRÉSUMÉ
Osteocytes are considered to act as mechanosensory cells in bone. They form a functional synctia in which their processes become interconnected to constitute a three-dimensional (3D) network. Previous studies reported that in mice, the two-dimensional osteocyte network becomes progressively more regular as they grow, although the key factors governing the arrangement of the osteocyte network during bone growth remain unknown. In this study, we characterized the 3D formation of the osteocyte network during bone growth. Morphological skeletal changes have been reported to occur in response to mechanical loading and unloading. In order to evaluate the effect of mechanical unloading on osteocyte network formation, we subjected newborn mice to sciatic neurectomy in order to immobilize their left hind limb as an unloading model. The osteocyte network was visualized by staining osteocyte cell bodies and processes with fluorescently labeled phalloidin. First, we compared the osteocyte network in the femora of embryonic and 6-week-old mice in order to understand the morphological changes that occur with normal growth and mechanical loading. In embryonic mice, the osteocyte network in the femur cortical bone displayed a random cell body distribution, non-directional orientation of cell processes, and irregularly shaped cells. In 6-week-old mice, the 3D network contained spindle-shaped osteocytes, which were arranged parallel to the longitudinal axis of the femur. In addition, more and longer cell processes radiated from each osteocyte. Second, we compared the cortical osteocyte networks of 6-week-old mice that had or had not undergone sciatic neurectomy in order to evaluate the effect of unloading on osteocyte network formation. The osteocyte network formation in both cortical bone and cancellous bone was affected by mechanical loading. However, there were differences in the extent of network formation between cortical bone and cancellous bone in response to mechanical loading with regard to the orientation, nuclear shape and branch formation.
Sujet(s)
Ostéocytes/cytologie , Animaux , Phénomènes biomécaniques , Femelle , Souris , Souris de lignée C57BL , GrossesseRÉSUMÉ
The rat trigeminal sensory nuclear complex (TSNC) was examined for Fos protein-like immunoreactive (Fos-LI) neurons induced by electrical stimulation (ES) of the lingual nerve (LN) at 2 weeks after injury to the LN or the inferior alveolar nerve (IAN). Intensity-dependent increase in the number of Fos-LI neurons was observed in the subnucleus oralis (Vo) and caudalis (Vc) of the spinal trigeminal tract nucleus irrespective of nerve injury. The number of Fos-LI neurons induced by ES of the chronically injured LN at A-fiber intensity (0.1 mA) was significantly increased in the Vo but not the Vc. On the other hand, in rats with chronically injured IAN, the number of Fos-LI neurons induced by ES of the LN at C-fiber intensity (10 mA) was significantly increased in the Vc but not the Vo. These results indicated that injury of a nerve innervating intraoral structures increased the c-Fos response of Vo neurons to A-fiber intensity ES of the injured nerve. A similar nerve injury enhanced the c-Fos response of Vc neurons to C-fiber intensity ES of a spared uninjured nerve innervating an intraoral territory neighboring that of the injured nerve. The present result show that nerve injury causes differential effects on c-Fos expression in the Vo and Vc, which may explain complexity of neuropathic pain symptoms in clinical cases.
Sujet(s)
Lésions du nerf lingual/métabolisme , Neurones/métabolisme , Protéines proto-oncogènes c-fos/biosynthèse , Noyaux du nerf trijumeau/métabolisme , Animaux , Maladie chronique , Stimulation électrique/méthodes , Lésions du nerf lingual/anatomopathologie , Mâle , Neurogenèse/physiologie , Neurones/cytologie , Rats , Rat Sprague-DawleyRÉSUMÉ
Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mediation of cellular responses to a variety of signaling molecules. The current study demonstrates phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in each subdivision of the trigeminal sensory nuclear complex (TSNC) following lingual nerve injury. Immunohistochemical labeling for phosphorylated ERK (p-ERK) or phosphorylated p38 (p-p38) MAPK was performed in histological sections of the brainstem. A transient increase in the immunoreactivity for p-ERK was found in each subdivision of the TSNC followed by a prolonged increase in the immunoreactivity for p-p38 MAPK after nerve injury. Double immunofluorescence labeling with cell-specific markers revealed that ERK and p38 MAPK were phosphorylated predominantly by OX-42-positive microglia or GFAP-positive astrocytes. Increased immunofluorescence labeling for OX-42 and GFAP indicated that microglia and astrocytes were activated by nerve injury in the TSNC. Activation of MAPKs and glial cells in the rostral subdivisions of the TSNC was comparable with that in the subnucleus caudalis of the trigeminal spinal tract nucleus (Vc). We conclude that differential activation of MAPKs and glial cells in the rostral subdivisions of the TSNC as well as the Vc may have a substantial role in the pathogenesis of neuropathic pain following trigeminal nerve injury.
Sujet(s)
Activation enzymatique/physiologie , Mitogen-Activated Protein Kinases/métabolisme , Névralgie/métabolisme , Névroglie/métabolisme , Noyaux du nerf trijumeau/métabolisme , Animaux , Technique d'immunofluorescence , Immunohistochimie , Lésions du nerf lingual , Mâle , Névralgie/physiopathologie , Phosphorylation , Rats , Rat Sprague-Dawley , Noyaux du nerf trijumeau/physiopathologieRÉSUMÉ
Mouse Nif3l1 gene is highly conserved from bacteria to human. Even though this gene is expressed throughout embryonic development, its biological function is still obscure. Here, we show that Nif3l1 participates in retinoic acid-primed neural differentiation of P19 embryonic carcinoma cells through cooperation with Trip15/CSN2, a transcriptional corepressor/component of COP9 signalosome. We isolated Nif3l1 cDNA from P19 cell cDNA library by a yeast two-hybrid screening using Trip15/CSN2 as a bait. This interaction was confirmed by a pull-down assay and an epitope-tagged coimmunoprecipitation. Although Nif3l1 was mainly detected in the cytoplasm, the translocation of Nif3l1 into the nuclei was observed in retinoic acid-primed neural differentiation of P19 cells and enhanced by the enforced expression of Trip15/CSN2. Furthermore, enforced expression of sense Nif3l1 RNA, but not antisense RNA, enhanced the neural differentiation of P19 cells accompanying the intense down-regulation of Oct-3/4 mRNA expression and the rapid induction of Mash-1 mRNA expression. Luciferase reporter assay showed that Nif3l1 could act as a transcriptional repressor and synergized the transcriptional repression by Trip15/CSN2. These results indicate that Nif3l1 implicates in neural differentiation through the cooperation with Trip15/CSN2.
Sujet(s)
Différenciation cellulaire/physiologie , Neurones/physiologie , Protéines nucléaires , Protéines/physiologie , Récepteurs des hormones thyroïdiennes/physiologie , Facteurs de transcription/physiologie , Séquence d'acides aminés , Animaux , Complexe du signalosome COP9 , Lignage cellulaire , Protéines corépressives , Protéines de liaison à l'ADN/génétique , Régulation de l'expression des gènes au cours du développement , Protéine gliofibrillaire acide/analyse , Souris , Données de séquences moléculaires , Facteur de transcription Oct-3 , Protéines/composition chimique , Protéines/génétique , ARN messager/analyse , Récepteurs des hormones thyroïdiennes/composition chimique , Facteurs de transcription/composition chimique , Facteurs de transcription/génétique , Cellules cancéreuses en cultureRÉSUMÉ
Trip15/CSN2 is a transcriptional corepressor/a component of COP9 signalosome (CSN) and participates in various signaling pathways. However, participation of Trip15/CSN2 in neural differentiation is still obscure. Here, we show that Trip15/CSN2 plays a critical role in neuronal differentiation. The expression of Trip15/CSN2 mRNA was induced at an early stage of neuronal differentiation in the retinoic acid (RA)-treated P19 cells, but not in the triiodothyronine (T3)-primed cardiac muscular cell differentiation. The expression of Trip15/CSN2 mRNA in the rat brain was detected at E14 and the protein was localized in the nuclei of neonatal rat CNS neurons. Enforced expression of sense rat Trip15/CSN2 mRNA caused the downregulation of Oct-3/4 mRNA expression and was sufficient to convert P19 cells into neurons, but not glial cells, only after the aggregation without RA. In the presence of RA, exogenous expression of the sense mRNA caused the intense and rapid induction of neurogenic Brn-2 and Mash-1 mRNA expressions accompanying the strong downregulation of Oct-3/4 mRNA expression, and stimulated both neuronal and glial cell differentiations of P19 cells. In contrast, enforced expression of the antisense mRNA suppressed the commitment of RA-treated aggregation form of P19 cells to neuronal lineage. These data strongly suggest that Trip15/CSN2 could implicate in the commitment of multipotent embryonal carcinoma (EC) cells to neuronal fate through the downregulation of Oct-3/4 which suppresses neurogenic genes. Moreover, in addition to Trip15/CSN2, RA-regulated other factor(s) may be required for glial cell differentiation.