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This study was designed to describe and clarify muscle activities which occur while walking in water. Surface electromyography (EMG) was used to evaluate muscle activities in six healthy subjects (mean age, 23.3 +/- 1.4 years) while they walked on a treadmill in water (with or without a water current) immersed to the level of the xiphoid process, and while they walked on a treadmill on dry land. The trials in water utilized the Flowmill which has a treadmill at the base of a water flume. Integrated EMG analysis was conducted for the quantification of muscle activities. In order to calculate the %MVC, the measurement of maximal voluntary contraction (MVC) of each muscle was made before the gait analysis, thus facilitating a comparison of muscle activities while walking in water with those on dry land. The %MVCs obtained from each of the tested muscles while walking in water, both with and without a water current, were all found to be lower than those obtained while walking on dry land at a level of heart rate response similar to that used when walking on dry land. Furthermore, the %MVCs while walking in water with a water current tended to be greater when compared to those while walking in water without a water current. In conclusion, the present study demonstrated that muscle activities while walking in water were significantly decreased when compared to muscle activities while walking on dry land, that muscle activities while walking in water tended to be greater with a water current than without, and that the magnitude of the muscle activity in water was relatively small in healthy humans. This information is important to design water-based exercise programs that can be safely applied for rehabilitative and recreational purposes.

When Axin, a negative regulator of the Wnt signaling pathway, was expressed in COS cells, it coeluted with glycogen synthase kinase-3b (GSK-3b), b-catenin, and adenomatous polyposis coli protein (APC) in a high molecular weight fraction on gel ®ltration column chromatography. In this fraction, GSK-3b, b-catenin, and APC were co-precipitated with Axin. Although bcatenin was detected in the high molecular weight fraction in L cells on gel ®ltration column chromatography, addition of conditioned medium expressing Wnt3a to the cells increased b-catenin in the low molecular weight fraction. However, Wnt-3a-dependent accumulation of b-catenin was greatly inhibited in L cells stably expressing Axin. Axin also suppressed Wnt-3a-dependent activation of Tcf-4 which binds to b-catenin and acts as a transcription factor. These results suggest that Axin forms a complex with GSK-3b, b-catenin, and APC, resulting in the stimulation of the degradation of bcatenin and that Wnt-3a induces the dissociation of bcatenin from the Axin complex and accumulates bcatenin.

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The human LEKTI gene encodes a putative 15-domain serine proteinase inhibitor and has been linked to the inherited disorder known as Netherton syndrome. In this study, human recombinant LEKTI (rLEKTI) was purified using a baculovirus/insect cell expression system, and the inhibitory profile of the full-length rLEKTI protein was examined. Expression of LEKTI in Sf9 cells showed the presence of disulfide bonds, suggesting the maintenance of the tertiary protein structure. rLEKTI inhibited the serine proteinases plasmin, subtilisin A, cathepsin G, human neutrophil elastase, and trypsin, but not chymotrypsin. Moreover, rLEKTI did not inhibit the cysteine proteinase papain or cathepsin K, L, or S. Further, rLEKTI inhibitory activity was inactivated by treatment with 20 mM DTT, suggesting that disulfide bonds are important to LEKTI function. The inhibition of plasmin, subtilisin A, cathepsin G, elastase, and trypsin by rLEKTI occurred through a noncompetitive-type mechanism, with inhibitory constants (K(i)) of 27 +/- 5, 49 +/- 3, 67 +/- 6, 317 +/-36, and 849 +/- 55 nM, respectively. Thus, LEKTI is likely to be a major physiological inhibitor of multiple serine proteinases.

We previously investigated the utility of μ-oxo N,N′- bis(salicylidene)ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anti-cancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.

CD109 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein whose expression is up-regulated in squamous cell carcinomas (SCCs) of the lung, esophagus, and uterus. The purpose of this study was to evaluate CD109 expression in oral tumors, including premalignant lesions, and to assess the clinical application of CD109 in oral cancer. CD109 expression in oral normal and tumor tissues from 124 patients was examined by immunohistochemical staining with anti-CD109 antibody, and significant relations between clinical features and CD109 expression were statistically assessed. We found that high levels of CD109 expression were frequently detected in SCCs and premalignant lesions of the oral cavity, but not in normal squamous epithelia. The CD109 expression level was higher in well-differentiated SCCs than in poorly differentiated SCCs. Furthermore, premalignant lesions highly expressing CD109 showed higher risk to progress to SCCs. Oral SCC cell lines overexpressing CD109 exhibited accelerated cell growth in vitro compared with control cell lines. In addition, overexpression of CD109 impaired the transforming growth factor (TGF)-b1-mediated suppression of cell growth. These findings suggest that CD109 plays a role in the development of oral cancers, and is a useful prognostic marker to predict malignant transformation of premalignant lesions. (Cancer Sci 2008; 99: 1916-1923 U p-regulation or down-regulation of the expression of some genes, including oncogenes and tumor suppressor genes, trigger the development of human tumors; the products of these genes are potentially good molecular targets for cancer diagnosis and treatment. In oral cancers, despite the ease of clinical examination, most cancer patients are diagnosed with advanced-stage cancer and are difficult to treat because of the anatomic location of the lesions or because the treatment would impact on the patients' quality of life. Therefore, early diagnosis of high-risk premalignant lesions is most important for good prognosis.CD109 is a glycosylphosphatidylinositol (GPI)-anchored cellsurface glycoprotein and is a member of the α2-macroglobulin-C3, C4, and C5 family of thioester-containing proteins.(1-3) The CD109 protein was first identified as a cell-surface antigen detected by a monoclonal antibody raised against the primitive lymphoid/ myeloid cell line KG1a.(1) It has been reported that CD109 is expressed on a subset of fetal and adult CD34 + bone marrow mononuclear cells, mesenchymal stem cell subsets, phytohemagglutinin (PHA)-activated T lymphoblasts, thrombin-activated platelets, leukemic megakaryoblasts, endothelial cells, and some human tumor cell lines, but not on fresh peripheral leukocytes and normal bone marrow leukocytes.(1,2,4,5) It was also shown that CD109 carries the biallelic platelet-specific alloantigen Gov, which is implicated in refractoriness to platelet transfusion, post-transfusion purpura, and neonatal alloimmune thrombocytopenia. We identified CD109 as a gene up-regulated in cells overexpressing oncogenic RET tyrosine kinas...