The SH2 domain-containing inositol 5Ј-phosphatase (SHIP) is crucial in hematopoietic development. To evaluate the possible tumor suppressor role of the SHIP gene in myeloid leukemogenesis, we examined primary leukemia cells from 30 acute myeloid leukemia (AML) patients, together with eight myeloid leukemia cell lines. A somatic mutation at codon 684, replacing Val with Glu, was detected in one patient, lying within the signature motif 2, which is the phosphatase active site. The results of an in vitro inositol 5Ј-phosphatase assay revealed that the mutation reduced catalytic activity of SHIP. Leukemia cells with the mutation showed enhanced Akt phosphorylation following IL-3 stimulation. K562 cells transfected with the mutated SHIP-V684E cDNA showed a growth advantage even at lower serum concentrations and resistance to apoptosis induced by serum deprivation and exposure to etoposide. These results suggest a possible role of the mutated SHIP gene in the development of acute leukemia and chemotherapy resistance through the deregulation of the phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3)/Akt signaling pathway. This is the first report of a mutation in the SHIP gene in any given human cancer, and indicates the need for more attention to be paid to this gene with respect to cancer pathogenesis.

SUMMARY: Twenty-three rat lung specimens collected in outbreaks of hemorrhagic fever with renal syndrome (HFRS) in three medical institutions were inoculated onto the VERO-E6 cell monolayers. After several blind passages, an agent growing serially in the cell cultures and reacting specifically with known HFRSpositive sera was isolated from two of these specimens. The two isolates were antigenically identical each other. The agent, named strain SR-11, was identified as the causative virus of HFRS by its antigenic identity with E6 cell-adapted HFRS virus, Hantaan 76-118 strain, and the specific reactions with sera from various HFRS cases.

No abstract

An enterotropic avirulent Newcastle disease virus (NDV-Ishii) the bursa-dependent lymphoid system, and probably on IgA antibody which is produced locally by lymphoid cells of the lamina propria.

Antigens of the viruses that cause hemorrhagic fever with renal syndrome (HFRS) and antibodies to these antigens were titrated in an immune adherence hemagglutination (IAHA) test and a CF test. Vero-E6 cells infected with the SR-11 strain of HFRS virus, an isolate from rats associated with a laboratory outbreak in Japan, and the 76-118 strain of Hantaan virus, the etiologic agent of Korean hemorrhagic fever, were used as antigens in the IAHA, CF, and indirect immunofluorescent antibody (IFA) tests. Sera from patients with different types of HFRS were tested against both strains of virus. Titers of antibody detected by the IFA test were similar for the two strains, but the IAHA test discriminated between antibodies to the two types of HFRS virus. Antigenic differences between HFRS viruses were suggested by the results of the IAHA test.