Autologous fat transplantation is a popular and useful technique in plastic and reconstructive surgery. The efficiency and survival of such grafts is predictable in many cases, but there are still issues to be resolved, such as how to improve graft volume retention. To address the issue of volume retention, we studied the effect of revascularization from the recipient on the size and function of adipocytes in fat grafts. Treatment of mice with TNP-470, an angiogenesis inhibitor, reduced blood flow from the recipient into the graft after subcutaneous transplantation of epididymal fat. The weight of transplanted tissues and the size of adipocytes in the grafts were significantly lower in mice treated with TNP-470 (TNP mice) than in control mice. Expression of genes for enzymes related to lipid accumulation was decreased in the grafts of TNP mice compared with control mice. Moreover, the expression of adipocyte-derived angiogenic peptides, VEGF and leptin, was significantly lower in the grafts of TNP mice than in grafts from control animals. The expression of VEGF and leptin by cultured human adipocytes was increased in the presence of conditioned medium from cultured vascular endothelial cells. These results show that the inhibition of the revascularization of fat grafts after transplantation reduces graft volume retention and cellular function. Early and adequate revascularization may be important for both the supply of nutrients and vasoactive interactions between vascular endothelial cells and adipocytes in graft.

A member of tetraspanin CD151 is a scaffold protein of laminin-binding integrins and it plays an important role in stable interaction between cells and basement membrane. Although the upregulation of CD151 in tumor cells is thought to accelerate tumor invasion and metastasis, detailed pathological investigation on CD151 and its association with integrins has not been well documented, yet. In the present study, we showed that the expression levels of CD151 and its associated integrin subunits in epidermal carcinoma cell HSC5 were higher than those in immortalized epidermal cell HaCaT. By the stimulation of epidermal growth factor, CD151 was dissociated from cell surface and dispersed in the cytoplasm, and a3b1 integrin was concomitantly internalized. To understand the significance of CD151 in tumor cell dynamics, CD151 in HSC5 was knocked down (HSC5 CD151À ), and the expression of integrin subunits and matrix metalloproteinases (MMPs) were investigated. In HSC5 CD151À, striking morphological alteration on Matrigel and laminin, and cytoskeletal rearrangements were demonstrated. a3b1 integrin was internalized in part, and a6b4 integrin was re-distributed from basal site to cell periphery. Quantitative RT-PCR, Western blot and zymography revealed that the expression levels of MMP2, MMP7 and MMP9 were markedly downregulated in HSC5 CD151À. Immunoprecipitation assay demonstrated that MMP7 was co-immunoprecipitated with CD151. In double stainings, MMP7 was colocalized with CD151 at the leading edge of lamellipodia under migratory status. These results elucidated the importance of CD151 as one of the key molecules for integrin-dependent carcinoma-stroma interaction. It is indicated that CD151 might contribute not only to cell stabilization by associating with adhesion complexes but also to cell migration by inducing integrins re-localization and MMPs production.

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These results indicate that changes in DNA methylation may play an important role in the manifestation of cleft palate only caused by environmental factors such as maternal exposure to all-trans retinoic acid.

A case of so-called inflammatory pseudotumor (IPT), occurring in the spleen of a 77-year-old woman, is reported. The spleen contained a well-circumscribed mass with central hemorrhage and necrosis. Histologically, spindle cells were dispersed in a background of abundant inflammatory cells, predominantly lymphocytes and plasma cells. The cells possessed enlarged, sometimes twisted or irregularly folded, nuclei that contained vesicular chromatin, and small but distinct, centrally located nucleoli. Immunohistochemically, the spindle cells were diffusely positive for vimentin, and focally positive for follicular dendritic cell (FDC) markers (Ber-MAC-DRC for CD35 and CNA.42). The Epstein-Barr virus (EBV) was exclusively detected in the spindle cells by in situ hybridization analysis. The cells also expressed the latent membrane protein-1 (LMP-1) of EBV, and polymerase chain reaction (PCR) analysis revealed that the LMP-1 gene had a 30-bp deletion and three point mutations, although their significance remains controversial. Inflammatory pseudotumor is a descriptive term that encompasses several different entities, and recent investigations have revealed the existence of neoplastic entities among IPT. One of the neoplastic IPT, recently designated 'IPT-like FDC tumor', is characterized by proliferation of EBV-positive FDC and commonly occurs in the liver and spleen. Because such tumors are capable of recurrence and metastasis, it is important to consider the possibility of an IPT-like FDC tumor when making a diagnosis of a hepatic/splenic IPT-like lesion.