全身性エリテマトーデスと抗リン脂質抗体症候群患者の抗プロトロンビン抗体はその結合部位により病態に違いがある

Thesis (Ph. D. in Medical Sciences)--University of Tsukuba, (A), no. 2416, 2000.3.24Joint authors: T. Akama, I. Kono, T. SumidaOffprint. Originally published: Lupus, v. 8, pp. 761-766, 1999Includes supplementary treatisesIncludes bibliographical reference

Stress responsive miR-23a attenuates skeletal muscle atrophy by targeting MAFbx /atrogin-1

Muscle atrophy occurs in many pathological states and results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. We used dexamethasone to induce muscle wasting and investigated the role of a microRNA (miRNA) in the control of muscle-specific E3 ubiquitin ligase MAFbx/atrogin-1. Here we show that miR-23a suppresses MAFbx/atrogin-1 translation by binding to 3'UTR of the mRNA. Furthermore, ectopic expression of miR-23a is sufficient to protect myocytes from atrophy in vitro and in vivo in response to dexamethasone treatment, and heat stress-induced miR-23a protects muscle from dexamethasone-induced muscle atrophy. Our surprising discovery of the physiological role of miR-23a in preventing the atrophy program should lay the basis not only for further understanding of the mechanisms of muscle wasting in diverse diseases, but also for developing novel therapies for these debilitating conditions

MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity

The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia

DHEA Administration Activates Local Bioactive Androgen Metabolism in Cancellous Site of Tibia of Ovariectomized Rats

It is not known whether local androgen metabolism is involved in the mechanisms underlying the dehydroepiandrosterone (DHEA) administration-induced improvement of bone mineral density (BMD) in an estrogen-deficiency state. The aim of the present study was to clarify whether DHEA administration would improve local androgen metabolism and BMD in cancellous site of tibia of ovariectomized (OVX) rats. Twenty-two female rats, 6 weeks old, were randomized into three groups: sham-operated rats, OVX control rats, and OVX rats that received DHEA treatment. DHEA was administered intraperitoneally at 20 mg/kg body weight for 8 weeks. The concentrations of free testosterone and dihydrotestosterone (DHT) in cancellous site of tibia did not change as a result of ovariectomy, while the DHT concentration increased following DHEA administration. We revealed that DHEA administration improved the reduction of 17β- and 3β-hydroxysteroid dehydrogenases and clearly reversed the reduction of 5α-reductase types 1 and 2 and androgen receptor in the cancellous site of tibia of OVX rats. DHEA administration suppressed estrogen deficiency relative to the decrease in the cancellous BMD, which was positively associated with local DHT concentration. These findings indicate that DHEA administration enhances local bioactive androgen metabolism in the cancellous tibia of young OVX rats, suggesting that local DHT may play a part in the DHEA administration-induced improvement of cancellous BMD

PO-112 The exploration of constitutively expressed myokines utilizing tissue-engineered skeletal muscle

Objective Recent evidence has identified skeletal muscle as a secretory organ. Many myokines, which are bioactive substances secreted from skeletal muscle, have been identified in plane muscle culture cells. Compared to the plane muscle culture cells, the tissue-engineered muscle is an excellent model as culture system mimicked native skeletal muscle. However, constitutively expressed genes and secreted compounds from tissue-engineered muscle have not been analyzed sufficiently. The purposes of this study were 1) to clarify kinetics of constitutively secreted compounds, and 2) to explore constitutively expressed genes in the tissue-engineered muscle. Methods C2C12 cells embedded within collagen gel solution were placed between two tendons made up of elastase-treated acelluar porcine blood vessel. The constructs were cultured in growth media for 2 days and cultured in differentiation media for 6 days. To compare with plane culture cells, C2C12 cells were cultured in plane under the same condition as the construct. The culture media were obtained, and analyzed by MALDI-TOF Mass Spectrometry. Furthermore, constitutively up-regulated genes in tissue-engineered skeletal muscle were explored based on microarray analysis and confirmed by RT-PCR. Results MALDI-TOF Mass Spectrometry revealed that the number of detected peaks in tissue-engineered muscle was abundant compared to that of plane muscle culture cells, especially at range of low molecular weight. Furthermore, the detected peaks were substantially different among these culture media and specific peaks were identified in tissue-engineered muscle. Based on microarray analysis, the transcription of cholecystokinin identified, and confirmed the up-regulation in tissue-engineered skeletal muscle by RT-PCR. Conclusions These results suggested that the tissue-engineered muscle constitutively secreted many compounds compared to plane culture cells, especially at range of low molecular weight. Furthermore, the transcription of cholecystokinin was up-regulated in tissue-engineered skeletal muscle. Besides of the plane muscle culture cells, it is possible to expect to obtain novel myokines utilizing tissue-engineered muscle

Prevalence of the Risk of Exercise Addiction Based on a New Classification: A Cross-Sectional Study in 15 Countries

Exercise addiction is widely studied, but an official clinical diagnosis does not exist for this behavioral addiction. Earlier research using various screening instruments examined the absolute scale values while investigating the disorder. The Exercise Addiction Inventory-3 (EAI-3) was recently developed with two subscales, one denoting health-relevant exercise and the other addictive tendencies. The latter has different cutoff values for leisure exercisers and elite athletes. Therefore, the present 15-country study (n = 3,760) used the EAI-3 to classify the risk of exercise addiction (REA), but only if the participant reported having had a negative exercise-related experience. Based on this classification, the prevalence of REA was 9.5% in the sample. No sex differences, and few cross-national differences were found. However, collectivist countries reported greater REA in various exercise contexts than individualist countries. Moreover, the REA among athletes was (i) twice as high as leisure exercisers, (ii) higher in organized than self-planned exercises, irrespective of athletic status, and (iii) higher among those who exercised for skill/mastery reasons than for health and social reasons, again irrespective of athletic status. Eating disorders were more frequent among REA-affected individuals than in the rest of the sample. These results do not align with recent theoretical arguments claiming that exercise addiction is unlikely to be fostered in organized sports. The present study questions the current research framework for understanding exercise addiction and offers a new alternative to segregate self-harming exercise from passionate overindulgence in athletic life

Prevalence of the Risk of Exercise Addiction Based on a New Classification: A Cross-Sectional Study in 15 Countries

Exercise addiction is widely studied, but an official clinical diagnosis does not exist for this behavioral addiction. Earlier research using various screening instruments examined the absolute scale values while investigating the disorder. The Exercise Addiction Inventory-3 (EAI-3) was recently developed with two subscales, one denoting health-relevant exercise and the other addictive tendencies. The latter has different cutoff values for leisure exercisers and elite athletes. Therefore, the present 15-country study (n = 3,760) used the EAI-3 to classify the risk of exercise addiction (REA), but only if the participant reported having had a negative exercise-related experience. Based on this classification, the prevalence of REA was 9.5% in the sample. No sex differences, and few cross-national differences were found. However, collectivist countries reported greater REA in various exercise contexts than individualist countries. Moreover, the REA among athletes was (i) twice as high as leisure exercisers, (ii) higher in organized than self-planned exercises, irrespective of athletic status, and (iii) higher among those who exercised for skill/mastery reasons than for health and social reasons, again irrespective of athletic status. Eating disorders were more frequent among REA-affected individuals than in the rest of the sample. These results do not align with recent theoretical arguments claiming that exercise addiction is unlikely to be fostered in organized sports. The present study questions the current research framework for understanding exercise addiction and offers a new alternative to segregate self-harming exercise from passionate overindulgence in athletic life

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray