Faculty Bibliography

Hemangioma is the most common soft-tissue tumor of infancy. Despite the frequency of these vascular tumors, the origin of hemangioma-endothelial cells is unknown. Circulating endothelial progenitor cells (EPCs) have recently been identified as vascular stem cells with the capacity to contribute to postnatal vascular development. We have attempted to determine whether circulating EPCs are increased in hemangioma patients and thereby provide insight into the role of EPCs in hemangioma growth. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from hemangioma patients undergoing surgical resection (N = 5) and from age-matched controls (N = 5) undergoing strabismus correction surgery. PBMCs were stained with fluorescent-labeled antibodies for AC133, CD34, and VEGFR2/KDR. Fluorescent-labeled isotype antibodies served as negative controls. Histologic sections of surgical specimens were stained with the specific hemangioma markers Glut1, CD32, and merosin, to confirm the diagnosis of common hemangioma of infancy. EPCs harvested from healthy adult volunteers were stained with Glut1, CD32, and merosin, to assess whether cultured EPCs express known hemangioma markers. Hemangioma patients had a 15-fold increase in the number of circulating CD34 AC133 dual-staining cells relative to controls (0.78+/-0.14% vs.0.052+/-0.017%, respectively). Similarly, the number of PBMCs that stained positively for both CD34 and KDR was also increased in hemangioma patients (0.49+/-0.074% vs. 0.19+/-0.041% in controls). Cultured EPCs stained positively for the known hemangioma markers Glut1, CD32, merosin. CONCLUSIONS: This is the first study to suggest a role for EPCs in the pathogenesis of hemangioma. Our results imply that increased levels of circulating EPCs may contribute to the formation of this vascular tumor

Calpains modulate processes that govern the function and metabolism of proteins key to the pathogenesis of Alzheimer's disease, including tau and amyloid precursor protein. Because activation of the calpain system might contribute to the impairment of synaptic transmission in Alzheimer's disease, we are currently testing the hypotheses that a treatment with calpain inhibitors might restore normal cognition and synaptic transmission in a transgenic model of Alzheimer's disease, the APP (K670N:M671L)/PS1(M146L) mouse. Findings derived from these studies will provide a novel approach to cognitive enhancement in Alzheimer's disease

The Manko tidal flat in the southern part of Okinawa Island is an important visiting and wintering area for migratory birds and was added to the Ramsar Convention Register of Wetlands in 1999. This area used to be an inlet extending to the inner part of Naha Port, but recent reclamation projects have restricted its connection to the East China Sea. As is typical in rural regions of subtropical islands, the inhabitants in the Manko basin raise livestock, especially pigs, without employing sufficient waste treatment methods. As sewage treatment works are considered to be one of the main sources of environmental estrogens in urban areas, the significance of livestock farming as a source of estrogens in rural area is examined in this study. In the present study, total estrogenic activities in water and sediment samples from the Manko tidal flat and its basin were measured using a recombinant yeast screen method. Estrogenic activities (equivalent to 17beta-estradiol, E2) were around 10 ng l(-1) in water samples and more than 10 microg kg(-1) in some sediment samples. In addition, the concentrations of estrone (E1) and E2 in water samples measured using LC/MS/MS indicated a high contribution of environmental estrogens from livestock wastes.

Purpose of review: Osteoarthritis is the most common form of arthritis, affecting a large population of mostly elderly people. No cure for osteoarthritis currently exists. Ultimate treatment is joint replacement. Understanding the mechanisms causing onset and progression is critical. This review describes recent findings that provide new insights into changes of cellular phenotype in osteoarthritis as a possible reason for tissue failure. Recent findings: Recent findings suggest that articular chondrocytes, when stimulated, can undergo hypertrophic and terminal differentiation events similar to those occurring during endochondral bone formation. Interestingly, collagenase-3 (matrix metalloproteinase-13), a main matrix-degrading enzyme in osteoarthritis, is expressed only in terminally differentiated chondrocytes during normal development. Summary: Although terminal differentiation events are required for endochondral bone formation, they lead to cartilage destruction when occurring in articular chondrocytes. Maintaining the articular chondrocyte phenotype and preventing these cells from undergoing hypertrophic and terminal differentiation might provide novel therapeutic targets to prevent onset or progression of osteoarthritis