Primary Gastric T Cell Lymphoma with Epstein-Barr Virus Infection.

Primary gastric T cell malignant lymphomas are very rare. Here we report a case of primary gastric T cell lymphoma infected with Epstein-Barr virus (EBV). Histologic and immunohistologic features, positive for CD45RO/UCHL1 and negative for CD20/L26, showed this tumor to be a diffuse, large cell type, malignant lymphoma with a T cell phenotype. Genotypic analysis by the South-ern blot method, demonstrating T cell receptor gene rearrangement and a germ-line configuration of the immunoglobulin gene, also supported the T cell origin of this tumor. EBV DNA was detected by polymerase chain reaction and in situ hybridization against EBER1 demonstrated that EBV was located in the lymphoma cells. This is the first Japanese case report of primary gastric malig-nant lymphoma of T cell origin infected with EBV

Role of Adhesion Molecules in Eosinophil Activation: A Comparative Study on the Effect of Adhesion Molecules on Eosinophil Survival

Background: Adhesion molecules participate in an important part of inflammatory process in relation to the accumulation of inflammatory cells, such as eosinophils. The expression of adhesion molecules differs depending upon the cells and tissue. In the present study, to elucidate these differences, a comparative study was performed on the prolongation of eosinophil survival via adhesion molecules. Methods: Blood eosinophils were purified using Percoll and anti-CD16 antibody coated magnetic beads. Eosinophils were incubated with or without the various concentrations of adhesion molecules for 18 or 36 h. Eosinophil survival was analyzed by a flow cytometer with staining by annexin V (AV) and propidium iodide (PI). Results: Intercellular adhesion molecule (ICAM)-1, fibronectin (FN) and cellular fibronectin (cFN), but not vascular cell adhesion molecule (VCAM)-1, significantly prolonged eosinophil survival compared with control. The present comparative study for eosinophil survival showed the following tendency: cFN=FN>ICAM-1>VCAM-1. Moreover, enhancement of prolonged eosinophil survival by connecting segment- 1 was greater than that by FN and cFN. Conclusions: The regulation of adhesion molecules, by not only preventing eosinophil adhesion but also eosinophil activation, may be a potential target in the treatment of allergic inflammatory disorders

RANTES Production from Mononuclear Cells in Response to the Specific Allergen in Asthma Patients

Background: Eosinophils are considered to be the major inflammatory cells in asthma. Since regulated on activation, normal T expressed and secreted (RANTES) is a potent chemoattractant for various important inflammatory cells such as eosinophils as well as memory T cells potentially recruiting these cells to an inflamed focus, RANTES has been considered to play a key role in various allergic disorders such as asthma. Methods: To extend our understanding of the participation of eosinophils and T cells in relation to the production of RANTES in response to the specific allergen in asthma, we examined the production of RANTES from peripheral blood mononuclear cells cultured with specific allergen in atopic asthma patients by a sandwich enzyme-linked immunosorbent assay. Results: It was revealed that mononuclear cells produced RANTES but not eotaxin in response to the specific allergen in asthma. RANTES production from mononuclear cells of asthma patients with eosinophilia was greater than that of asthma patients without eosinophilia. Moreover, in this study, no differences in RANTES production between CD4 negative cells and CD8 negative cells were observed. Conclusions: Taken together, these findings may suggest that mononuclear cells play a crucial role in the pathogenesis, particular in eosinophil and T lymphocyte recruitment into the inflamed focus of asthma through RANTES production in response to the specific allergen

Normal tissue effect and growth delay of transplanted cancer in mice by synchrotron generated microplaner beam

13th International Congress of Radiation Researc

Prostaglandin D2 and Interleukin-5 Reduce Crth2 Surface Expression on Human Eosinophils

Background: Recently, a second prostaglandin D2 (PGD2) receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), was identified. Because PGD2 was reported to have chemotactic activity on eosinophils, CRTH2 expressed on eosinophils attracted interest as a receptor associated with eosinophil migration to, and accumulation at, inflammatory sites. To elucidate the mechanism regulating the expression of CRTH2 on eosinophils, the effects of PGD2, interleukin (IL)-4, IL-5 and interferon (IFN)-γ on CRTH2 expression were investigated. Methods: Blood eosinophils were purified using Percoll and anti-CD16 antibody coated magnetic beads. Eosinophils were incubated with PGD2 and/or IL-4, IL-5 and IFN-γ. The expression of CRTH2 on eosinophils was measured using a FACScan cytometer (Becton Dickinson Immunocytometry Systems, San Jose, CA, USA). Results: Prostaglandin D2 and IL-5, but not IL-4 and IFN-γ, downregulated the expression of CRTH2 on eosinophils. Furthermore, PGD2- and IL-5-induced downregulation of CRTH2 on human eosinophils was inhibited by phenylarsine oxide, a receptor internalization inhibitor. Conclusions: These results suggest that PGD2 and IL-5 regulate CRTH2 expression on eosinophils through CRTH2 internalization. The decreased expression of CRTH2 on tissue eosinophils may make these cells remain at the site of allergic inflammation

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

Abstract Background Klippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS. Results Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1. Conclusions The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway