Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia vi-

Objective-Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium. Methods and Results-The human VEGF 165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, ␣-smooth muscle actin-positive cells were most increased in the VEGF group. Key Words: angiogenesis Ⅲ gene therapy Ⅲ myocardial infarction Ⅲ stem cell Ⅲ transplantation C ell transplantation has become a promising novel therapy for ischemic heart disease and heart failure. Recent studies have revealed that various types of cells are effective in cell transplantation after myocardial infarction (MI), such as skeletal myoblasts, 1,2 smooth muscle cells, 3 and bone marrow mononuclear cells. 4 Bone marrow mononuclear cells are especially useful because they contain, among various lineage cells, hematopoietic cells and endothelial progenitor cells; therefore they have the ability to induce angiogenesis in ischemic tissue. A reported clinical trial of cell transplantation with skeletal myoblasts and mononuclear bone marrow cells showed that such therapies can have cardioprotective and angiogenic effects after MI. 5,6 However, selection of the most appropriate cell types for transplantation is controversial. Conclusions-ThisMesenchymal stem cells (MSCs) are isolated from bone marrow mononuclear cells and can be expanded ex vivo. Under appropriate culture conditions, MSCs have the potential to terminally differentiate into osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes, hematopoietic supporting stroma, and endothelial cells. 7 MSCs have also been used in a model of cell transplantation, 8,9 showing that these cells could differentiate into myogenic cells. Therefore, MSCs have many characteristics that make them useful for cellular therapy.Vascular endothelial growth factor (VEGF) is a strong therapeutic reagent for treating ischemia by inducing angiogenesis. 10 It has been reported that direct intramyocardial gene transfer results in localized enhancement of VEGF levels and successful angiogenesis in animal models of MI. 11 Furthermore, recent h...

BackgroundRecently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.MethodsWe retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.ResultsA multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.ConclusionOur data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.

Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WBpositive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions,