Coordinated expression of Hoxa-11 and Hoxa-13 during limb muscle patterning

The limb muscle precursor cells migrate from the somites and congregate into the dorsal and ventral muscle masses in the limb bud. Complex muscle patterns are formed by successive splitting of the muscle masses and subsequent growth and differentiation in a region-specific manner. Hox genes, known as key regulator genes of cartilage pattern formation in the limb bud, were found to be expressed in the limb muscle precursor cells. We found that HOXA-11 protein was expressed in the premyoblasts in the limb bud, but not in the somitic cells or migrating premyogenic cells in the trunk at stage 18. By stage 24, HOXA-11 expression began to decrease from the posterior halves of the muscle masses. HOXA-13 was expressed strongly in the myoblasts of the posterior part in the dorsal/ventral muscle masses and weakly in a few myoblasts of the anterior part of the dorsal muscle mass. Transplantation of the lateral plate of the presumptive wing bud to the flank induced migration of premyoblasts from somites to the graft. Under these conditions, HOXA-11 expression was induced in the migrating premyoblasts in the ectopic limb buds. Application of retinoic acid at the anterior margin of the limb bud causes duplication of the autopodal cartilage and transformation of the radius to the ulna, and at the same time induces duplication of the muscle pattern along the anteroposterior axis. Under these conditions, HOXA-13 was also induced in the anterior region of the ventral muscles in the zeugopod. These results suggest that Hoxa-11 and Hoxa-13 expression in the migrating premyoblasts is under the control of the limb mesenchyme and the polarizing signal(s). In addition, these results indicate that these Hox genes are involved in muscle patterning in the limb buds.     

Involvement of Ras in Bruton's tyrosine kinase-mediated JNK activation

Defects in Bruton's tyrosine kinase (Btk) result in B cell immunodeficiencies in humans and mice. Recent studies showed that Btk is required for maximal activation of JNK, a family of stress-activated protein kinases, induced by several extracellular stimuli including interleukin (IL)-3. On the other hand, IL-3-induced JNK activation is dependent on Ras. In the present study we have investigated whether Ras is involved in Btk-mediated JNK activation in BaF3 mouse pro-B cells. Overexpression of wild-type Btk protein in these cells enhanced JNK activation upon IL-3 stimulation, whereas expression of kinase-dead Btk partially suppressed JNK activation. Induced expression of the dominant negative Ras(N17) in the cells overexpressing wild-type Btk suppressed JNK activation. Importantly, overexpression of Btk enhanced the level of the GTP-bound, active form of Ras in response to IL-3 stimulation. Btk overexpression also increased the Shc-Grb2 association induced by IL-3 stimulation. Expression of either N17Ras or V12Ras did not impose any effects on Btk kinase activity. These data collectively indicate that Ras plays a role of an intermediary signaling protein in Btk-mediated JNK activation induced by the IL-3 signaling pathway.     

Computed tomography analysis of causes of local failure in radiotherapy for cervical carcinoma

BACKGROUND: The authors analyzed the radiation dose to the periphery of the cervix and area of the cervix in relation to local failure of radiotherapy for carcinoma of the cervix using computed tomography (CT) images. METHODS: Between 1981-1990, 127 consecutive patients were treated with definitive radiotherapy. Ninety-nine of these patients had CT images taken at the time of intracavitary therapy. Of these 99 patients, 80 were eligible for this analysis. After CT scanning, isodose curves relative to the point A dose were superimposed on the CT images. The minimum percent dose and minimum dose at the periphery of the cervix were estimated. The area of the cervix also was measured. These factors were examined in relation to the local tumor control rate. RESULTS: Histograms of both the minimum percent dose and the cervical area showed significant differences between the local control and local failure groups (P <0.001). The local control rates were related to both the minimum percent dose and the cervical area, and differed significantly over and below the values of 60% and 18 cm2 (P <0.001 each), respectively. The local control patients, over and below the line: Y = -0.220X + 21.2, in which X (gray [Gy]) and Y (Gy) are the whole pelvis dose and the minimum dose, respectively, could be well differentiated with significance (91.7% vs. 25.0%; P <0.001). CONCLUSIONS: Computed tomography analysis indicated that the local tumor control rate was related strongly to the minimum percent dose, the cervical area, and the pair of whole pelvis and minimum dose values. These factors were found to be more useful than the point A dose in predicting local tumor control.     

Vision-based sensor for real-time measuring of surface traction fields

The desire to reproduce and expand the human senses drives innovations in sensor technology. Conversely, human-interface research aims to allow people to interact with machines as if they were natural objects in a cybernetic, human-oriented way. We wish to unite the two paradigms with a haptic sensor as versatile as the sense of touch and developed for a dual purpose: to improve the robotic capability to interact with the physical world, and to improve the human capability to interact with the virtual world for emerging applications with a heightened sense of presence. We designed a sensor, dubbed GelForce, that acts as a practical tool in both conventional and novel desktop applications using common consumer hardware. By measuring a surface traction field, the GelForce tactile sensor can represent the magnitude and direction of force applied to the skin's surface using computer vision. This article is available with a short video documentary on CD-ROM.     

Effect of a topically applied neutralizing antibody against vascular endothelial growth factor on corneal allograft rejection of rat

BACKGROUND: Studies in corneal transplant rejection remain important because acute immunologic rejection continues to be the leading cause of human corneal transplant failure. As the permeability of vessels and the neovascularization induce cells infiltration into the graft, we considered the possibility that vascular endothelial growth factor (VEGF), a potent permeability-increasing factor and angiogenesis-mediating factor, could participate in the immune response. METHODS: As the established corneal transplant model for rejection, the corneal transplant between Lewis and Fisher rats has been reported. First, we evaluated VEGF production in the graft by immunohistochemical method in the animal model. Next, we tried to neutralize the effect of VEGF by topical administration of anti-VEGF antibody. We administered anti-VEGF antibody as eye drops for 10 days just after the transplantation of the established animal corneal transplant model. RESULTS: VEGF was strongly produced from the infiltrative cells into the graft. Anti-VEGF antibody significantly suppressed the acute rejection compared with saline or rabbit IgG. CONCLUSIONS: The inhibition of VEGF by topically applied neutralizing antibody is a new potential therapeutic strategy for the treatment of corneal transplantation.     

Spinal meningeal melanocytoma presenting with superficial siderosis of the central nervous system. Case report and review of the literature

1. We recently demonstrated that intrathecal administration of prostaglandin E2 (PGE2) and PGF2alpha induced allodynia through a pathway that includes the glutamate receptor and nitric oxide (NO)-generating systems from pharmacological studies. In order to clarify the involvement of NO in prostaglandin-induced allodynia, we measured NO released from rat spinal cord slices by a chemiluminescence method. 2. PGE2 stimulated NO release from both dorsal and ventral regions all along the spinal cord. PGE2 stimulated the release within 10 min and increased it in a time-dependent manner. 3. The PGE2-induced NO release was observed at 100 nM-10 microM. PGF2alpha stimulated the release at concentrations higher than 1 microM, but PGD2 (up to 10 microM) did not enhance it. 4. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and sulprostone (EP1 < EP3) were as potent as PGE2, but PGE1 was less potent, in stimulating NO release. While M&B 28767 (EP3) did not enhance the release, butaprost (EP2) stimulated it at 1 microM. The PGE2-evoked release was blocked by ONO-NT-012, a bifunctional EP1 antagonist/EP3 agonist. 5. The PGE2-evoked release was Ca2+-dependent and blocked by MK-801 (NMDA receptor antagonist) and L-NAME (NO synthase inhibitor). The release was also inhibited by PGD2 and dibutyryl-cyclic AMP. 6. The present study demonstrated that PGE2 stimulates NO release in the rat spinal cord by activation of NMDA receptors through the EP1 receptor, and supports our previous findings that the NO-generating system is involved in the PGE2-induced allodynia.