Cytotoxic T‐lymphocyte‐associated protein 4 expressed by melanoma cells does not affect melanoma‐specific cytotoxic T lymphocytes in the effector phase

Cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the important molecules that regulate the anti‐melanoma T‐cell response. Currently, there are some reports showing that CTLA‐4 is expressed not only by T cells but also by various kinds of tumor cells, including melanoma cells. However, there is no report that shows the role of CTLA‐4 expressed by melanoma cells in melanoma‐specific cytotoxic T‐lymphocyte (CTL) response. In this report, we confirmed substantial CTLA‐4 expression and the localization of CTLA‐4 in melanoma cell lines and tissues. Also, we examined its impact on melanoma‐specific CTL in vitro, and found that CTLA‐4 expressed by melanoma cells does not affect melanoma‐specific CTL in the effector phase. Our findings suggest the importance of elucidating the role of CTLA‐4 expressed by melanoma cells, particularly in anti‐CTLA‐4 antibody therapy.     

Current status of diagnosis and treatment of invasive fungal infections in Japan: the influence of the new Japanese guidelines

One year after the release of the Japanese “Guidelines for the Diagnosis and Treatment of Deep-Seated Mycosis” we conducted a survey of clinicians to determine the extent to which the new guidelines had penetrated clinical practice, and compared these results with those of a previous survey. The responses to the current survey regarding the diagnosis and treatment had changed from those of the previous survey to reflect the new recommendations, showing that the guidelines have had an effect on clinical practice. However, the current survey highlights a need to provide more practical information in the guidelines for use in the clinical settings. In particular, physicians expect the guidelines to proactively provide more information about the features of both current and new drugs. In addition, an effective drug against the genus Aspergillus is eagerly awaited. However, because it is difficult to differentiate among filamentous fungi, there is a need for a drug with broad-spectrum coverage against filamentous fungi. Investigation of combination therapy consequently becomes necessary. Definitive diagnoses of invasive fungal infection are too scarce at the national level. The cooperation of clinicians for organizing more definitive diagnoses would be appreciated when the guidelines are revised.     

Synergism between interleukin-11 and bone morphogenetic protein-2 in the healing of segmental bone defects in a rabbit model.

Recombinant human interleukin-11 (rHuIL-11) and recombinant human bone morphogenetic protein-2 (rHuBMP-2) have been shown to act synergistically in the induction of osteoblast differentiation. To determine whether these two proteins can be used clinically in fracture healing and reconstructive surgery, we investigated whether rHuIL-11 and rHuBMP-2 act synergistically to heal segmental bone defects in a rabbit model. A 1.5-cm segmental defect was created in the right ulnar diaphysis of 20 Japanese white rabbits. Polylactic-co-glycolic acid (PLGA)-coated gelatin sponges (PGS) permeated with rHuBMP-2 (n = 8), rHuIL-11 plus rHuBMP-2 (n = 8), or rHuIL-11 (n = 4) were implanted into the bone defects. Radiographs were scored by two independent observers for bone formation and union rates after 2, 3, 4, and 8 weeks. Bone formation was higher in rabbits implanted with rHuBMP-2 plus rHuIL-11 than in those implanted with rHuBMP-2 alone, reaching statistical significance after 4 weeks. At early time points, the union rate in rabbits implanted with rHuBMP-2 plus rHuIL-11 was higher than in rabbits implanted with rHuBMP-2. At 2, 4, and 8 weeks, new bone volume was significantly higher in rabbits administered rHuIL-11 plus rHuBMP-2 than in those given rHuBMP-2 alone. In contrast, mechanical testing after 8 weeks showed that bone strength in the two groups of rabbits was equivalent. These findings show that rHuIL-11 and rHuBMP-2 act synergistically to accelerate bone formation without affecting bone strength. Treatment with a combination of rHuIL-11 and rHuBMP-2 may thus be of great benefit in fracture healing and for patients undergoing reconstructive surgery.     

In vitro and in vivo anti-allergic activity of soy sauce

Soy sauce (Shoyu) is a traditional fermented seasoning of Japan and available throughout the world. Polysaccharides were obtained from dialysate of Shoyu, and these Shoyu polysaccharides (SPS) were examined for anti-allergic activity in vitro and in vivo. The SPS originated from partially-degraded polysaccharides of soybeans by mold enzymatic hydrolyses, and Shoyu contained about 1% (w/v) SPS. First, the inhibitory effects of SPS on hyaluronidase, which is known to be related to inflammation and allergic responses, were as potent as those of an anti-allergic medicine, disodium cromoglycate. Second, SPS significantly inhibited the release of histamine from rat basophilic leukemia (RBL-2H3) cells, which had been induced by the antigen. Third, orally administered SPS had a significant suppressive effect on passive cutaneous anaphylaxis induced in the ears of mice. These results suggest that SPS may have anti-allergic activities, and soy sauce is a potentially promising seasoning for the treatment of allergic diseases through food.     

Control of 3D limb dynamics in unconstrained overarm throws of different speeds performed by skilled baseball players

This study investigated how the human CNS organizes complex three-dimensional (3D) ball-throwing movements that require both speed and accuracy. Skilled baseball players threw a baseball to a target at three different speeds. Kinematic analysis revealed that the fingertip speed at ball release was mainly produced by trunk leftward rotation, shoulder internal rotation, elbow extension, and wrist flexion in all speed conditions. The study participants adjusted the angular velocities of these four motions to throw the balls at three different speeds. We also analyzed the dynamics of the 3D multijoint movements using a recently developed method called "nonorthogonal torque decomposition" that can clarify how angular acceleration about a joint coordinate axis (e.g., shoulder internal rotation) is generated by the muscle, gravity, and interaction torques. We found that the study participants utilized the interaction torque to generate larger angular velocities of the shoulder internal rotation, elbow extension, and wrist flexion. To increase the interaction torque acting at these joints, the ball throwers increased muscle torque at the shoulder and trunk but not at the elbow and wrist. These results indicates that skilled ball throwers adopted a hierarchical control in which the proximal muscle torques created a dynamic foundation for the entire limb motion and beneficial interaction torques for distal joint rotations.     

Temperature‐ and pH‐Sensitive Nanocomposite Gels with Semi‐Interpenetrating Organic/Inorganic Networks

An intelligent nanocomposite hydrogel with a semi‐interpenetrating organic/inorganic network was synthesized through in situ free‐radical polymerization of NIPA in the presence of an inorganic clay and linear PAA. The resulting semi‐interpenetrating nanocomposite gels (sI‐NC gels) showed mechanical and swelling/deswelling properties greatly superior to those of other PNIPA/PAA hydrogels. The sI‐NC gels repeatedly changed their swelling behavior in response to both temperature and pH while retaining their remarkable mechanical properties. The structure and homogeneity of these networks were studied and related to the properties of sI‐NC gels and the hydrogen bonding interactions among the constituents.