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The GIRs were higher than the PIRs in Japanese junior soccer players. A lower overall PIR suggested that players in the U-12 age group practiced under appropriate conditions. However, the higher GIR in this age category needs to be decreased.

Ras gene mutations occur in 30% to 40% of patients with multiple myeloma (MM), and farnesylation is the first and most important step in the posttranslational modification of Ras proteins. R115777 is a newly synthesized potent farnesyl transferase inhibitor (FTI) and has recently demonstrated significant antitumor activities in vitro and in vivo. Therefore, we examined the effect of R115777 on the growth of fresh and cloned myeloma cells in vitro. R115777 inhibited the growth of fresh and cloned myeloma cells dose dependently, and effects were not dependent on the status of N-Ras mutation in fresh myeloma cells. Flow cytometric analysis using annexin V and 7-aminoactinomycin D (7AAD) showed that R115777 induced apoptosis of 2 of 3 myeloma cell lines at a concentration of 1.0 ؋ 10 ؊8 M. R115777 appears to be a potent inducer of apoptosis, and its effects depend on the status of Ras mutation in cloned myeloma cells but not on IntroductionMultiple myeloma (MM) is a malignancy of B cells characterized by the monoclonal proliferation of malignant plasma cells and osteolytic bone destruction. Several chemotherapeutic regimens have been used to improve the survival of patients with MM. Although high-dose melphalan supported by autologous stem cell transplantation (auto-SCT) has improved the survival of patients with MM, many patients were found to relapse during a long follow-up period. 1,2 Allogeneic stem cell transplantation (allo-SCT) is possibly the only genuinely curative therapy for MM, and a graft-versus-myeloma effect by immunocompetent donor lymphocytes has been demonstrated but the treatment-related mortality is high. 3,4 Recently, nonmyeloablative SCT has been reported to provide a stable engraftment of allogeneic stem cells and tolerable toxicity in patients with MM, but a longer follow-up period is necessary to evaluate late mortality. 5,6 Therefore, there is an obvious need for new therapeutic strategies.Ras proteins are prototypical G proteins that have been shown to play a key role in signal transduction, cell proliferation, and malignant transformation. Ligand-stimulated activation of the cell-surface receptor, receptor-associated tyrosine kinase, or agonist mediated through G protein-coupled receptors results in the activation of Ras protein. The Ras gene family consists of 3 functional genes, H-Ras, N-Ras, and K-Ras. Activating point mutations in all 3 Ras genes have been detected in a wide variety of human malignancies and are one of the most common alternations in hematologic malignancies. [7][8][9] In MM, Ras gene activation is observed in 30% to 40% of cases and one of the most frequent point mutations. [10][11][12][13] Although Ras protein undergoes several steps of posttranslational modification, farnesylation is the first and most important step for its membrane localization and cell-transforming activity. Thus, farnesyltransferase (FTase) is a very attractive target for the development of anticancer agents. R115777 (Zarnestra, Johnson & Johnson, Raritan, NJ), a potent and selective farnesy...

Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K-Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling.

Game injury rates were higher than practice injury rates in Japanese mini-basketball players. The high practice injury rate in this study may be due to specific factors related to growth, such as individual differences in height, or to skills, such as inexperience in ball handling.

A 60-year-old man with multiple myeloma (MM) (IgG-kappa, stage IIIA) had been treated with minodronate at 6 mg orally as a phase 1 clinical trial for myeloma bone disease for 13 months (total dose, 4032 mg). Then he received incadronate at 10mg intravenously every 1 to 4 weeks (total dose, 350 mg). In July 2005, he complained of mild right mandibular pain, and bone scintigram showed a hot spot at the right side of the mandible. Panoramic radiograph showed osteonecrosis of the jaw (ONJ) and axial and 3-dimensional computed tomography confirmed ONJ. Oral examination showed massive gingival swelling of the right side of the mandible without exposed necrotic bone. He was given clarithromycin in addition to levofloxacin, followed by hyperbaric oxygen (HBO) therapy, which resulted in the complete disappearance of the pain. This is a first reported case of ONJ induced by incadronate. The present case suggests that early detection of ONJ by regular dental check-ups is important in the management of patients with MM who have received bisphosphonate therapy, and HBO in combination with antibiotic therapy is effective in the early stage of ONJ.