IL-1β Suppresses the Formation of Osteoclasts by Increasing OPG Production via an Autocrine Mechanism Involving Celecoxib-Related Prostaglandins in Chondrocytes

Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1β stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE2 production. However, the effect of IL-1β on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1β and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1β on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1β; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1β. Conditioned medium from IL-1β-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1β suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs

Validation of normalized pulse volume in the outer ear as a simple measure of sympathetic activity using warm and cold pressor tests: Towards applications in ambulatory monitoring

Normalized pulse volume (NPV) derived from the ear has the potential to be a practical index for monitoring daily life stress. However, ear NPV has not yet been validated. Therefore, we compared NPV derived from an index finger using transmission photoplethysmography as a reference, with NPV derived from a middle finger and four sites of the ear using reflection photoplethysmography during baseline and while performing cold and warm water immersion in ten young and six middle-aged subjects. The results showed that logarithmically-transformed NPV (lnNPV) during cold water immersion as compared with baseline values was significantly lower, only at the index finger, the middle finger and the bottom of the ear-canal. Furthermore, lnNPV reactivities (ΔlnNPV; the difference between baseline and test values) from an index finger were significantly related to ΔlnNPV from the middle finger and the bottom of the ear-canal (young: r = 0.90 and 0.62, middle-aged: r = 0.80 and 0.58, respectively). In conclusion, these findings show that reflection and transmission photoplethysmography are comparable methods to derive NPV in accordance with our theoretical prediction. NPV derived from the bottom of the ear-canal is a valid approach, which could be useful for evaluating daily life stress. © 2013 Institute of Physics and Engineering in Medicine

Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy

BackgroundAnti-phospholipase A2 receptor autoantibody (PLA2R Ab)-associated membranous nephropathy (MN) is the most common form of primary MN (pMN). On the other hand, bucillamine (BCL), an antirheumatic drug developed in Japan, was reported to cause a rare form of secondary MN (sMN). Between these MN forms, comparative proteomic analysis of glomerular proteins has not been performed.MethodsWe used renal biopsy specimens from 6 patients with PLA2R Ab (+) pMN, 6 patients with PLA2R Ab (‒) pMN, 6 patients with BCL-induced sMN, and 5 control cases (time 0 transplant biopsies). Proteins were extracted from laser-microdissected glomeruli and analyzed using mass spectrometry. The quantification values of protein abundance in each MN group were compared with those in the control group.ResultsMore than 800 proteins with high confidence were identified. Principal component analysis revealed a different distribution between the pMN and sMN groups. For further analysis, 441 proteins matched with ≥ 3 peptides were selected. Among the pMN and sMN groups, we compared the profiles of several protein groups based on the structural and functional characteristics, such as immunoglobulins, complements, complement-regulating proteins, podocyte-associated proteins, glomerular basement membrane proteins, and several proteins that are known to be associated with kidney diseases, including MN. In all MN groups, increased levels of immunoglobulins (IgG, IgA, and IgM), complements (C3, C4, and C9), complement factor H-related protein 5, type XVIII collagen, calmodulin, polyubiquitin, and ubiquitin ligase were observed. For some proteins, such as type VII collagen and nestin, the fold-change values were significantly different between the pMN and sMN groups.ConclusionsBetween the pMN and BCL-induced sMN groups, we observed common and different alterations in protein levels such as known disease-associated proteins and potential disease marker proteins

Development of a novel tympanic temperature monitoring system for GT car racing athletes

Motor racing athletes, especially Grand Touring (GT) car racing drivers in the closed-cockpit category, can face lifethreatening situations caused by heat stroke. In this paper, a novel continuous tympanic temperature monitoring system, that could help to reduce this risk, is presented. The system consists of an earpiece containing an infrared-radiation-type tympanic thermometer and a micro-speaker. We validated the reliability of the system for tympanic temperature monitoring in 10 healthy volunteers (21.8 ± 1.0 S.D. years) using a temperature-controlled water bath. In addition, we evaluated the usefulness of the system with 2 professional drivers under real racing conditions in the 2010 SUPER GT International Series. The results showed strong correlation between the infrared-radiation tympanic temperature obtained by the present system and both the direct tympanic temperature (r = 0.994, n = 1119, P < 0.001) and the sublingual temperature (r = 0.972, n = 1119, P < 0.001) as a reference temperature. The mean difference between these temperatures was +0.09°C, and -0.08°C, and 95 % confidence interval (equal to 1.96 S.D.) was 0.21°C, and 0.44°C, respectively. In the field test, involving real competitive racing under severe conditions on a racing circuit, the system functioned well. These results suggest that our novel system has an acceptable performance in a race setting as a reliable tympanic temperature monitor and could help to improve safety of motor sports. © 2013 Springer-Verlag

Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia

Simple Summary Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). Recently, TKIs were discontinued in patients with CML with deep molecular remission, and some patients have been reported to be able to maintain long-term treatment-free remission (TFR). However, there is no certainty regarding which patients can maintain TFR. We focused on immunity in the TFR phase and investigated the immunological mechanism of continuous TFR or recurrence. Our results suggest that the group that maintains the TFR is immunologically activated. In addition, regulatory T cells can be used as a biomarker. These results may have important implications for future strategies for maintaining TFR in CML treatment. Treatment-free remission (TFR) has become a therapeutic goal in chronic myeloid leukemia (CML), and approximately half of the patients with chronic phase-CML (CML-CP) with deep molecular remission (DMR) by tyrosine-kinase inhibitors (TKIs) have achieved TFR. However, the mechanism of continuous TFR is still unclear, as there are fluctuate patients who have BCR-ABL-positive leukemia cells but do not observe obvious relapse. We focused on the immune response and conducted an immune analysis using clinical samples from the imatinib discontinuation study, JALSG-STIM213. The results showed that, in the group that maintained TFR for 3 years, changes in regulatory T (Treg) cells were observed early after stopping imatinib treatment. The effector Treg (eTreg) cells increased transiently at 1 month after stopping imatinib and then returned to baseline at 3 months after stopping imatinib treatment. There was no difference in the Treg phenotype, and CD8(+) T cells in the TFR group were relatively activated. High concentrations of imatinib before stopping were negatively correlated with eTreg cells after stopping imatinib. These data suggest immunological involvement in the maintenance of the TFR, and that Treg cells after stopping imatinib might be a biomarker for TFR. Furthermore, high imatinib exposure may have a negative immunological impact on the continuous TFR

Arthroscopic excision of unstable os acromiale associated with impingement syndrome : a case report

Os acromiale is a rare anatomical variant that is caused by failure of fusion of the acromial apophysis and is usually asymptomatic. We report a case of impingement syndrome of the left shoulder secondary to unstable os acromiale, which was initially overlooked and confirmed only during arthroscopic examination. Arthroscopic excision of the unstable fragment was successful without residual dysfunction of the deltoid muscle

Development of a ubiquitous healthcare monitoring system combined with non-conscious and ambulatory physiological measurements and its application to medical care

The demand for ubiquitous healthcare monitoring has been increasingly raised for prevention of lifestyle-related diseases, acute life support or chronic therapies for inpatients and/or outpatients having chronic disorder and home medical care. From these view points, we developed a non-conscious healthcare monitoring system without any attachment of biological sensors and operations of devices, and an ambulatory postural changes and activities monitoring system. Furthermore in this study, in order to investigate those applicability to the ubiquitous healthcare monitoring, we have developed a new healthcare monitoring system combined with the non-conscious and the ambulatory measurements developed by us. In patients with chronic cardiovascular disease or stroke, the daily health conditions such as pulse, respiration, activities and so on, could be continuously measured in the hospital, the rehabilitation room and subject\u27s own home, using the present system. The results demonstrated that the system appears useful for the ubiquitous healthcare monitoring not only at medical facility, but also during daily living at home. © 2011 IEEE

Development of a ubiquitous healthcare monitoring system combined with non-conscious and ambulatory physiological measurements and its application to medical care.

The demand for ubiquitous healthcare monitoring has been increasingly raised for prevention of lifestyle-related diseases, acute life support or chronic therapies for inpatients and/or outpatients having chronic disorder and home medical care. From these view points, we developed a non-conscious healthcare monitoring system without any attachment of biological sensors and operations of devices, and an ambulatory postural changes and activities monitoring system. Furthermore in this study, in order to investigate those applicability to the ubiquitous healthcare monitoring, we have developed a new healthcare monitoring system combined with the non-conscious and the ambulatory measurements developed by us. In patients with chronic cardiovascular disease or stroke, the daily health conditions such as pulse, respiration, activities and so on, could be continuously measured in the hospital, the rehabilitation room and subject\u27s own home, using the present system. The results demonstrated that the system appears useful for the ubiquitous healthcare monitoring not only at medical facility, but also during daily living at home