The functional human immune system, including T, B, and natural killer lymphocytes, is reconstituted in NOD/Shi-scid/IL-2Rgamma(null) (NOG) mice that receive hematopoietic stem cell transplants. Here, we show that these humanized mice can recapitulate key aspects of Epstein-Barr virus (EBV) infection in humans. Inoculation with approximately 1 x 10(3) TD(50) (50% transforming dose) of EBV caused B cell lymphoproliferative disorder, with histopathological findings and latent EBV gene expression remarkably similar to that in immunocompromised patients. Inoculation with a low dose of virus (

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To predict the prognosis of neuroblastoma patients and choose a better therapeutic protocol, we developed a cDNA microarray carrying 5340 genes obtained from primary neuroblastomas and examined 136 tumor samples. We made a probabilistic output statistical classifier that provided a high accuracy in prognosis prediction (89% at 5 years) and a highly reliable method to validate it. Kaplan-Meier analysis indicated that the patients in an intermediate group defined by existing markers are divided by microarray into two further groups with 5 year survivals for 36% and 89% of patients (p < 10(-4)), i.e., with unfavorably and favorably predicted neuroblastomas, respectively. According to these results, we developed a gene subset chip for a clinical tool, for which our classifier exhibited 88% prediction accuracy.

Receptor tyrosine kinases (RTKs) play an important role in regulating diverse cellular processes, such as proliferation, differentiation, survival, motility, and malignant transformation. The activation of RTKs typically requires ligand-induced receptor oligomerization, which results in tyrosine autophosphorylation of the receptors at tyrosine residues.

Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment.

A 12-year-old Japanese boy who underwent kidney transplantation with a kidney from his mother developed severe proteinuria immediately after the operation. Because his original disease was nephrotic syndrome (focal segmental glomerulosclerosis, or FSGS) and electron microscopic examination of the renal biopsy showed foot process fusion, we diagnosed this as a recurrence of nephrotic syndrome to the transplanted kidney. Four months after the transplantation, posttransplant lymphoproliferative disorder (PTLD) developed, which was pathologically diagnosed as diffuse large B cell lymphoma. Treatment consisting of a reduction in immunosuppression resulted in improvement in PTLD a month after the start of treatment. However, relapse occurred 2 months after the first onset of PTLD, which we treated with rituximab (CD-20 monoclonal antibody 375 mg/m2) once weekly for a total of four doses. The PTLD resolved immediately after the rituximab treatment was started, and, interestingly, urinary protein levels also improved at the same time. Three years later, the boy shows no signs of PTLD, and no proteinuria has been detected. These findings suggest that rituximab may be an effective treatment for recurrence of nephrotic syndrome after transplantation and that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation.

Humanized NOD/Shi-scid/interleukin-2Rgamma(null) (NOG) mice with full T cell development had significantly longer life span after Epstein-Barr virus (EBV) infection, compared with those with minimal T cell development. Removing CD3(+) or CD8(+) T cells from EBV-infected humanized mice by administration of anti-CD3 or anti-CD8 antibodies reduced their life span. CD8(+) T cells obtained from EBV-infected mice suppressed the outgrowth of autologous B cells isolated from uninfected mice and inoculated with EBV in vitro. These results indicate that humanized NOG mice are capable of T cell-mediated control of EBV infection and imply their usefulness as a tool to evaluate immunotherapeutic and prophylactic strategies for EBV infection.

The role of the left and right hemisphere was examined during semantic priming by antonyms, remote associates, and unrelated words. Targets presented directly to the left hemisphere showed an early facilitation and a late developing inhibition, while targets presented directly to the right hemisphere showed a late developing facilitation of strong and weak associations and little evidence of inhibition. When a visual cue was given prior to each target word, reaction times were facilitated equally in both visual fields and for all prime target relationships. When the priming task was combined with shadowing, reaction times generally increased and all evidence of inhibition in left hemisphere processing disappeared. This supported the idea that the inhibition found in the left hemisphere was due to its interaction with the anterior attention network.