GINS, a heterotetramer of SLD5, PSF1, PSF2, and PSF3 proteins, is an emerging chromatin factor recognized to be involved in the initiation and elongation step of DNA replication. Although the yeast and Xenopus GINS genes are well documented, their orthologous genes in higher eukaryotes are not fully characterized.In this study, we report the genomic structure and transcriptional regulation of mammalian GINS genes. Serum stimulation increased the GINS Mrna levels in human cells. Reporter gene assay using putative GINS promoter sequences revealed that the expression of mammalian GINS is regulated by 17β-Estradiolstimulated estrogen receptor α, and human PSF3 acts as a gene responsive to transcription factor E2F1. The goal of this study is to present the current data so as to encourage further work in the field of GINS gene regulation and functions in mammalian cells.

Background : The effects of rehabilitation on hemodialysis patients are unknown. We assessed the effects and investigated the association between rehabilitation treatment effects and all-cause mortality. Methods : This prospective cohort study included 120 patients on maintenance hemodialysis. ADL was assessed using the Functional Independence Measure (FIM) score (total points, 126), which comprises 13 motor items (total points, 91) and five cognitive items (total points, 35). A survival curve was constructed using the Kaplan-Meier analysis and stratified into an increase or no-increase of the FIM score. Multivariable logistic regression analysis was used to determine factors associated with the effects of rehabilitation. Discriminative sensitivity of FIM cognitive items for an increase in total FIM was estimated using the area under the receiver operating characteristic (AuROC) curve. Results : The average total FIM score increased from 64.2±3.6 to 75.8±3.0, and the increase in FIM motor and cognitive items was 11.0±1.3 and 0.5±0.6, respectively. The cumulative survival rate within 2.5 years was significantly higher in the FIM increase group than that in the FIM no-increase group. FIM cognitive items and anemia were significantly associated with rehabilitation effects, and AuROC showed that a cutoff of 34 points in cognitive FIM had moderate discriminative sensitivity for a total FIM increase (AuC, 0.719 ; p<0.0008). Conclusions : Rehabilitating hemodialysis patients improved their FIM score (particularly the motor items), and a higher FIM score resulted in a better prognosis. The effectiveness of rehabilitation depends on maintaining a perfect FIM cognitive score.

Methods: Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column. Results: The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively. Conclusions The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. Conclusions This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

BACKGROUND/AIMS: To confirm the feasibility of using newly developed endoscopic ultrasound (EUS) with Zone sonography(TM) technology (ZST; Fujifilm Corp.). METHODS: Seventy-five patients with pancreatic disorders were enrolled: 45 with intraductal papillary mucinous neoplasm; 15 with ductal carcinoma; five with neuroendocrine tumors; three with serous cystic neoplasms; and seven with simple cysts. The endoscopes used were EG-530UR2 and EG-530UT2 (Fujifilm Corp.). Two items were evaluated: visualization depth among four frequencies and image quality after automatic adjustment of sound speed (AASS), assessed using a 5-scale Likert scale by two endosonographers blinded to disease status. Because sound speed could be manually controlled, besides AASS, image quality at sound speeds of 1,440 and 1,600 m/sec were also assessed. RESULTS: In all cases, sufficient images were obtained in the range of 3 cm from the EUS probe. Judgments of image quality before AASS were 3.49+/-0.50, 3.65+/-0.48, respectively. After AASS, A and B scored 4.36+/-0.48 and 4.40+/-0.49 (p<0.0001). There were significant differences in the data before and after AASS and plus 60 m/sec, but no significant difference between the datasets were seen after AASS and at sound speeds manually set for minus 100 m/sec. CONCLUSIONS: EUS with ZST was shown to be feasible in this preliminary experiment. Further evaluation of this novel technology is necessary and awaited.
Endoscopes ; Endosonography ; Humans ; Judgment ; Mucins ; Pancreatic Diseases