Talonavicular joint abnormalities and walking ability of patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is often associated with deformities of the feet, and foot pain often arises in the talonavicular joint of patients with RA. The object of this study was to assess the relationship between magnetic resonance imaging (MRI) findings of the talonavicular joint and walking ability. The subjects were 35 RA patients (10 feet in 5 males and 56 feet in 30 females) aged 34-87 years (mean: 70 years +/- 12.1), with a disease duration from 1-54 years (mean: 14 years +/- 12.1). MRI findings were classified as follows: Grade 1, almost normal; Grade 2, early articular destruction; Grade 3, moderate articular destruction; Grade 4, severe articular destruction; and Grade 5, bony ankylosis dislocation. Walking ability was classified into one of 9 categories ranging from normal gait to bedridden status according to the system of Fujibayashi. As the grade of MRI images became higher the walking ability decreased, and these parameters showed a correlation by Spearman's rank correlation coefficient analysis (P = 0.003). Thus, in the present cohort group of patients with RA, the deterioration of walking ability increased with the severity of destruction of the talonavicular joint.</p

A Pilot Study: The Beneficial Effects of Combined Statin-exercise Therapy on Cognitive Function in Patients with Coronary Artery Disease and Mild Cognitive Decline.

Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p&lt;0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age &gt;65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p&lt;0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline

Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation

A novel in vitro survival assay of small intestinal stem cells after exposure to ionizing radiation

The microcolony assay developed by Withers and Elkind has been a gold standard to assess the surviving fraction of small intestinal stem cells after exposure to high (?8 Gy) doses of ionizing radiation (IR), but is not applicable in cases of exposure to lower doses. Here, we developed a novel in vitro assay that enables assessment of the surviving fraction of small intestinal stem cells after exposure to lower IR doses. The assay includes in vitro culture of small intestinal stem cells, which allows the stem cells to develop into epithelial organoids containing all four differentiated cell types of the small intestine. We used Lgr5-EGFP-IRES-CreERT2/ROSA26-tdTomato mice to identify Lgr5+ stem cells and their progeny. Enzymatically dissociated single crypt cells from the duodenum and jejunum of mice were irradiated with 7.25, 29, 101, 304, 1000, 2000 and 4000 mGy of X-rays immediately after plating, and the number of organoids was counted on Day 12. Organoid-forming efficiency of irradiated cells relative to that of unirradiated controls was defined as the surviving fraction of stem cells. We observed a significant decrease in the surviving fraction of stem cells at ?1000 mGy. Moreover, fluorescence-activated cell sorting analyses and passage of the organoids revealed that proliferation of stem cells surviving IR is significantly potentiated. Together, the present study demonstrates that the in vitro assay is useful for quantitatively assessing the surviving fraction of small intestinal stem cells after exposure to lower doses of IR as compared with previous examinations using the microcolony assay

Identification of a β-glucosidase hydrolyzing tuberonic acid glucoside in rice (Oryza sativa L.)

Tuberonic acid (TA) and its glucoside (TAG) have been isolated from potato (Solanum tuberosum L) leaflets and shown to exhibit tuber-inducing properties. These compounds were reported to be biosynthesized from jasmonic acid (JA) by hydroxylation and subsequent glycosylation, and to be contained in various plant species. Here we describe the in vivo hydrolytic activity of TAG in rice. In this study, the TA resulting from TAG was not converted into JA. Tuberonic acid glucoside (TAG)-hydrolyzing β-glucosidase, designated OsTAGG1, was purified from rice by six purification steps with an similar to 4300-fold purification. The purified enzyme migrated as a single band on native PAGE, but as two bands with 4300-fold purification. The purified enzyme migrated as a single band on native PAGE, but as two bands with molecular masses of 42 and 26 kDa on SDS-PAGE. The results from N-terminal sequencing and peptide mass fingerprinting of both polypeptides suggested that the two bands were derived from a single polypeptide, which is a member of glycosyl hydrolase family 1. In the native enzyme, the Km and Vmax values of TAG were 31.7 μM and and 14.7 μmol/min/mg, respectively. OsTAGG1 preferentially hydrolyzed TAG and methyl TAG. Here we report that OsTAGG1 is a specific β-glucosidase hydrolyzing TAG, which releases physiologically active TA

Microstructure of Joint between Stranded Wire and Substrate Welded by Ultrasonic Welding

In order to improvement electronic and mechanical properties, welding between stranded wires and terminals is important. However, welding methods to obtain high-quality joints using stranded wires are still limited. In this report, we applied ultrasonic welding to join a Cu stranded wire to a Cu substrate. Cross-sections of the weldments were taken and observed by several microscopy techniques to elucidate the weldability and soundness of the joints. After ultrasonic welding, each wire in the stranded wire was joined together at the region where the stranded wire was joined to the substrate without any defect. Each wire was welded through the Ag coating layer, and the stranded wire and the substrate was also welded through the outermost coating layers. It was found that ultrasonic welding is an efficient technique for producing high quality joints without any defect at the interface

The 1st YRBAJ Seminar: Techniques and Knowledge to Probe Biological Cellular Responses Occurring in a Hypoxic Microenvironment.

http://www.jstage.jst.go.jp/article/jrr/52/1/52_110/_articl

Enhancement of Osteogenesis by Concanavalin A in Human Bone Marrow Mesenchymal Stem Cell Cultures

This study investigates concanavalin A (ConA) as a novel factor that may enhance osteogenesis of mesenchymal stem cells (MSCs) in vitro. Various factors have been studied as promoting factors for MSC osteogenesis in vivo and in vitro. However, their safety, effectiveness, and cost may not be ideal. So, human MSCs were cultured in osteogenic medium in the presence or absence of ConA. We used calcium assays to compare the effects of ConA and BMP-2 on MSC calcification. Also enzyme-linked immunosorbent assay (ELISA) and quantitative PCR were used to evaluate the expression levels of bone specific markers. ConA was observed to enhance the calcification and this effect was comparable to that of BMP-2. Combination of ConA and BMP-2 further enhanced the calcification slightly but significantly. ConA also increased osteocalcin and BMP-2 protein levels in the medium of MSC cultures. Furthermore, ConA increased osteocalcin, RUNX2, BMP-2, and BMP-4 mRNA expression levels. However, gene expression pattern of MSCs stimulated by ConA was different from that observed with BMP-2. These results, taken together, suggest that ConA and BMP-2 enhance MSC osteogenesis via different pathways. The ConA-induced bone formation in MSC cultures may be useful in regenerative medicine or tissue engineering in clinical studies and in basic research on bone formation