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A sheep survived for 48 days with the biventricular bypass type total artificial heart.

A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation.</p

Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration

Osteopontin level in synovial fluid is associated with the severity of joint pain and cartilage degradation after anterior cruciate ligament rupture.

To explore the molecular function of Osteopontin (OPN) in the pathogenesis of human OA, we compared the expression levels of OPN in synovial fluid with clinical parameters such as arthroscopic observation of cartilage damage and joint pain after joint injury.Synovial fluid was obtained from patients who underwent anterior cruciate ligament (ACL) reconstruction surgery from 2009 through 2011 in our university hospital. The amounts of intact OPN (OPN Full) and it's N-terminal fragment (OPN N-half) in synovial fluid from each patient were quantified by ELISA and compared with clinical parameters such as severity of articular cartilage damage (TMDU cartilage score) and severity of joint pain (Visual Analogue Scale and Lysholm score).Within a month after ACL rupture, both OPN Full and N-half levels in patient synovial fluid were positively correlated with the severity of joint pain. In contrast, patients with ACL injuries greater than one month ago felt less pain if they had higher amounts of OPN N-half in synovial fluid. OPN Full levels were positively correlated with articular cartilage damage in lateral tibial plateau.Our data suggest that OPN Full and N-half have distinct functions in articular cartilage homeostasis and in human joint pain

OPN N-half levels in synovial fluid are negatively correlated with the severity of joint pain in patients who ruptured ACL greater than 1 month ago.

<p>VAS was collected from patients who ruptured ACL more than 1 month ago using a questionnaire described in Table S2 in an examination room at our university hospital. Number of samples, correlation coefficient, and p value are indicated in each figure.</p

Kinetics of OPN Full and N-half in synovial fluid after joint injury.

<p>(Left panels) Time course changes of OPN Full (upper panel) and OPN N-half (lower panel) protein levels in synovial fluid after ACL rupture. Open bar: within 1 month after rupture n = 14, Closed bar: greater than 1 month after rupture n = 68. (Right panels) OPN Full (upper panel) and OPN N-half (lower panel) protein levels in synovial fluid collected from pre (n = 23) and post (n = 93) ACL reconstruction surgery. Data are indicated mean+/− SEM. **; p<0.01.</p