Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.
 ...
PMID:Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans. 282 12

C3H 10T1/2 mouse fibroblasts were transfected with a plasmid vector composed of EJ, the mutated c-Ha-ras, and a metallothionein promotor that induced amplified ras expression when activated by culture in the presence of zinc. Experiments were conducted to compare the effect of induction on killing by activated natural killer (NK) cells, cytotoxic T lymphocytes, activated macrophages, and antibody plus complement. The only effector that recognized increased ras expression and exhibited high-inducible cytolysis was an activated NK cell. The effectors from spleen were poly I.C. boostable, Lyt-1.1 negative, NK 1.2 positive, and asialo GM1 positive. Spleen cells from T cell-deficient nude mice, but not NK-deficient beige mice, exhibited high levels of killing activity, and experiments with NK cell clones demonstrated that these lines were also highly cytolytic and killed Ha-ras transfectants in parallel to YAC. Transfection of the same fibroblast line with c-myc did not alter the level of activated NK sensitivity. Cold target competition experiments revealed that Ha-ras-transfected and non-transfected 10T1/2 fibroblasts competed equally for lysis of either YAC or Ha-ras transfectants. Rat-1 fibroblasts did not compete, but gained this capacity when transformed with the v-Ki-ras oncogene but not v-fps. These data suggest that Ha-ras acts in target cells at a post-binding step, whereas Ki-ras may affect expression of target-effector binding structures. The findings that activated NK cell lysis may be specifically influenced by ras expression support a role for NK cells in host surveillance against early neoplastic changes.
 ...
PMID:Enhanced lytic susceptibility of Ha-ras transformants after oncogene induction is specific to activated NK cells. 349 78