We performed a prospective study to determine the effects of introducing low-load muscular training with moderate restriction of blood flow during the first 16 weeks after reconstruction of the anterior cruciate ligament. 44 subjects (average age 29 (18-52) years) were randomized into a group that trained restriction of blood flow (group R, n = 22) and a group that trained without restriction (group N, n = 22). Both groups followed the same training schedule. Evaluations of knee extensor and flexor torques before surgery and 16 weeks after it showed a significant increase in muscular strength in group R as compared to group N. The preoperative/16-week postoperative ratio of the crosssectional area of the knee extensor muscles showed a statistically significant enlargement in group R as compared to group N. 16 weeks after surgery, the short diameters of type 1 and type 2 fibers of M. vastus lateralis tended to be larger in group R (n = 8) than in group N (n = 8), although the differences were not significant. These findings show that low-load resistance muscular training during moderate restriction of blood flow is an effective exercise for early muscular training after reconstruction of the anterior cruciate ligament.  Recently, many studies have reported stable postoperative results of ligament reconstruction by autologous tendon grafting of the anterior cruciate ligament (ACL), a procedure which permits early rehabilitation according activities of daily living and sports. However, an important issue is how early the patients can return to athletic activities. Currently, several techniques of ACL reconstruc

Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O 2 . ), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O 2 . generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions.

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN−/− mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN−/− mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN−/− mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN−/− mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN−/− mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.

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Tendon harvest causes significant weakness of hamstring muscle strength at high knee flexion angles, but such weakness can be minimized if the gracilis tendon is preserved.

Purpose: We aimed to develop prognostic biomarkers for gastrointestinal stromal tumors (GIST) using a proteomic approach. Experimental Design: We examined the proteomic profile of GISTs using two-dimensional difference gel electrophoresis. The prognostic performance of biomarker candidates was examined using a large-scale sample set and specific antibodies. Results: We identified 43 protein spots whose intensity was statistically different between GISTs with good and poor prognosis. Mass spectrometric protein identification showed that the 43 spots corresponded to 25 distinct gene products. Eight of the 43 spots derived from pfetin, a potassium channel protein, and four of the eight pfetin spots had a high discriminative power between the two groups.Western blotting and real-time PCR showed that pfetin expression and tumor metastasis were inversely related.The prognostic performance of pfetin was also examined by immunohistochemistry on 210 GISTcases.The 5-year metastasis-free survival rate was 93.9% and 36.2% for patients with pfetin-positive and pfetin-negative tumors, respectively (P < 0.0001).Univariate and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinicopathologic variables examined, including risk classification and c-kit^or platelet-derived growth factor receptor A mutation status. Conclusions: These results establish pfetin as a powerful prognostic marker for GISTs and may provide novel therapeutic strategies to prevent metastasis of GIST.

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ABSTRACT. Mechanical stretch affects the healing and remodeling process of the anterior cruciate ligament (ACL) after surgery in important ways. In this study, the effects of mechanical stress on gene expression of type I and III collagen by cultured human ACL cells and roles of transforming growth factor (TGF)-β1 in the regulation of mechanical strain-induced gene expression were investigated. Uniaxial cyclic stretch was applied on ACL cells at 10 cycles/min with 10% length stretch for 24 h. mRNA expression of the type I and type III collagen was increased by the cyclic stretch. TGF-β1 protein in the cell culture supernatant was also increased by the stretch. In the presence of anti-TGF-β1 antibody, stretch-induced increase in type I and type III mRNA expression was markedly ablated. The results suggest that the stretch-induced mRNA expression of the type I and type III collagen is mediated via an autocrine mechanism of TGF-β1 released from ligament cells.