Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

BACKGROUND: Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS). We developed the Hybrid Training System (HTS) to maintain an astronaut's musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system's orbital operation capability and utility, as well as its preventative effect on an astronaut's musculoskeletal atrophy. METHODS: HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR). 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks) were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance), MRI (muscle volume), and DXA (BMD, lean [muscle] mass, fat mass). Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force) and a measuring tape (upper arm circumference). RESULTS: The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm) changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule) of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts) of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle) mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR. CONCLUSIONS: These results showed the orbital operation capability and utility, and the preventive effect of HTS for an astronaut's musculoskeletal atrophy. The initial flight data together with the ground data obtained so far will be utilized in the future planning of human space exploration.

Development of a training method for weightless environment using both electrical stimulation and voluntary muscle contraction.

Extreme skeletal muscle atrophy is rampant in astronauts exposed to extended periods of microgravity (muG), and it is one of the main problems in human space exploration. A "Hybrid training" (HYB) method utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a possible solution. A wearable HYB device and a virtual reality (VR) system were developed for use in space, and were verified at muG generated by parabolic flight (PF). A 36-year-old male subject performed HYB of reciprocal flexion and extension as a knee joint exercise training in a seated position at 1G, 2G and muG. The wearable HYB device and VR system developed for the study functioned well during the flight. However knee extension was insufficient at 1G and 2G, and the maximum knee extension angles at 1G and 2G were smaller than at muG. The extension velocity in the latter half of each motion was slower than in the first half at 1G and 2G, but no difference in velocity was observed at muG. The subject could extend the knee joint sufficiently and keep a constant extension velocity, because his legs were weightless at muG. The congruity between the subject's actual joint motions and instructed joint motions during muG was improved, when VR was employed with or without body fixation; accordingly, the subject was able to perform the desired joint motion. The VR system improved HYB exercise performance at muG during PF. HYB is considered a useful training method for future human space exploration.

Locomotion assistance for the person with mobility impairment: fuzzy control of cycling movement by means of surface electrical-stimulation.

Since a wheelchair was originally designed as a transportation vehicle for people who can not walk well due to the degenerative muscles of legs in the case elderly and disabled persons, it was not considered to use lower limbs to drive a wheelchair. Wheelchairs driven by arms cause a shoulder disorder, atrophy of leg muscles and a contracture of leg joints. On the other hand, while wheelchairs driven by legs can prevent or alleviate those symptoms in daily life, it is difficult to drive a wheelchair if the muscles are not strong enough. To solve this problem the functional electrical stimulation is carried out on leg muscles to pedal the wheelchair, and to stabilize the speed a motor is equipped. The leg cycling movement in this paper is controlled by fuzzy logic. Experiments of cycling using three healthy young men are performed on a level surface, and prove the effectiveness of smooth cycling movement. The electrical stimulation is also added to the external oblique of subjects sitting on a chair to examine the possibility to become effective exercise instead of treadmill training by keeping balance.

Adult T-cell lymphoma/leukemia with angioimmunoblastic T-cell lymphomalike features: Report of 11 cases.

In adult T-cell lymphoma/leukemia (ATLL), the neoplastic lymphoid cells are usually medium-sized to large, often with pronounced nuclear pleomorphism compatible with the diagnosis of diffuse pleomorphic peripheral T-cell lymphoma. We describe here 11 patients with the rare morphologic variant of ATLL, angioimmunoblastic T-cell lymphoma (AILT)-like type. The examined lymph nodes showed proliferation of high endothelial venules and presence of various infiltrating inflammatory cells including plasma cells and eosinophils. The lymphoma cells were medium-to-large size with clear cytoplasm. These findings were suggestive of AILT. However, immunohistochemical features of AILT, namely, CD10 and CXCL13 expression in lymphoma cells and proliferation of CD21-positive follicular dendritic cells, were not detected. Two cases were CXCR3-positive, whereas 9 expressed CCR4, which are usually positive in ATLL. All patients were positive for antiadult T-cell leukemia/lymphoma-associated antigen, which is a specific antibody for human T-cell lymphotropic virus type-I. Southern blot analysis revealed proviral DNA integration in lymphoma cells in 9 patients. The latter was not evident in the first biopsy of 2 patients but in the second biopsy obtained within several months after the first biopsy revealed definite proviral integration. Almost all patients showed aggressive clinical course and poor survival (median survival: 5 mo). This is the first report of ATLL with AILT-like morphologic features.

Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells.

Although the cellular and molecular mechanisms governing angiogenesis are only beginning to be understood, signaling through endothelial-restricted receptors, particularly receptor tyrosine kinases, has been shown to play a pivotal role in these events. Recent reports show that EphB receptor tyrosine kinases and their transmembrane-type ephrin-B2 ligands play essential roles in the embryonic vasculature. These studies suggest that cell-to-cell repellent effects due to bidirectional EphB/ephrin-B2 signaling may be crucial for vascular development, similar to the mechanism described for neuronal development. To test this hypothesis, we disrupted the precise expression pattern of EphB/ephrin-B2 in vivo by generating transgenic (CAGp-ephrin-B2 Tg) mice that express ephrin-B2 under the control of a ubiquitous and constitutive promoter, CMV enhancer-beta-actin promoter-beta-globin splicing acceptor (CAG). These mice displayed an abnormal segmental arrangement of intersomitic vessels, while such anomalies were not observed in Tie-2p-ephrin-B2 Tg mice in which ephrin-B2 was overexpressed in only vascular endothelial cells (ECs). This finding suggests that non-ECs expressing ephrin-B2 alter the migration of ECs expressing EphB receptors into the intersomitic region where ephrin-B2 expression is normally absent. CAGp-ephrin-B2 Tg mice show sudden death at neonatal stages from aortic dissecting aneurysms due to defective recruitment of vascular smooth muscle cells to the ascending aorta. EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells plays an essential role in vasculogenesis, angiogenesis, and vessel maturation.

A role of EphB4 receptor and its ligand, ephrin-B2, in erythropoiesis.

Erythropoiesis is regulated not only by erythropoietin but also by microenvironments which are composed of transmembrane molecules. We have previously shown that a receptor tyrosine kinase EphB4 is predominantly expressed on human erythroid progenitors in bone marrow. EphB4 is expressed in approximately 45% of hematopoietic progenitor cells, which are CD34-positive and c-Kit-positive in human umbilical cord blood (hUCB). The transmembrane ligand for EphB4 or ephrin-B2 is expressed on bone marrow stromal cells and arterial endothelial cells. When such EphB4-positive hematopoietic progenitor cells were co-cultured with stromal cells which express ephrin-B2, they were immediately detached from stromal cells and differentiated to mature erythroid cells. At that time, expression of EphB4 immediately down-regulated. In contrast, on ephrin-B2 non-expressing stromal cells, they remained EphB4-positive cells and the generated number of mature erythroid cells was less than that on ephrin-B2 expressing stromal cells. Additionally, ephrin-B2 expression on endothelial cells up-regulated under hypoxic condition. Taken together, we propose that one of the molecular cues that regulate erythropoiesis is ephrin-B2 on stromal cells.