Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A transplantable mouse T cell leukemia, DL 812, is characterized by high sensitivity to 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-chloroethyl)-1-nitrosourea hydrochloride (ACNU) and intensive systemic infiltration. When subcutaneously inoculated, DL812 cells invade many organs and cause marked splenomegaly without forming local tumors. Disseminated DL812 leukemias are clinically completely cured by a single intraperitoneal injection of 1 mg ACNU, but more ACNU-resistant leukemias relapse immediately. A novel antitumor antibiotic, spergualin, is effective against various mouse leukemias. The effects of its analog with stronger anti-leukemia activity, 15-deoxyspergualin (DSG), on the relapse of DL812 leukemias after ACNU treatment were investigated. DDD mice were subcutaneously inoculated with 10(6) DL812 cells and intraperitoneally injected with 1 mg ACNU once on day 11 and with 100 micrograms DSG daily from day 12 on. The relapses were clinically completely suppressed for at least 30 days. Winn assays with spleen cells revealed that host immunity did not play a major role in maintenance of the clinical cure. Thus, when DSG treatment was discontinued after 15 or 30 daily injections, leukemias relapsed immediately. When it was extended to 50 daily injections, permanent cure was attained in 1 of 15 mice but relapses occurred under DSG treatment in the others. DSG is available for combined treatment of the leukemia. The current and previous results suggest that DL812 leukemias may serve as a model in study on immunochemotherapy of the disease.
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PMID:Spergualin treatment-dependent delayed relapse of mouse T cell leukemia (DL812) after chemotherapy. 179 66

Seven transplantable leukemia lines were established from spontaneous leukemias and screened for 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(chloroethyl)-1-nitrosourea hydrochloride (ACNU) sensitivity in DDD mice. Three of them were classified as highly sensitive, two as sensitive and two as resistant to ACNU. A highly sensitive line, DL812, was extensively characterized from a therapeutic point of view. DL812 cells were so invasive as to produce enlargement of spleens and lymph nodes but not local tumors when injected s.c., markedly sensitive to in vitro ACNU exposure and moderately immunogenic. The invasion process of DL812 cells differed with the status of host immunity. Advanced DL812 leukemias were macroscopically completely cured with normalization of spleen and lymph node sizes 3-7 days after an i.p. injection of 0.5 mg ACNU, but more ACNU-resistant leukemias with splenomegaly and enlarged lymph nodes recurred thereafter. Recurring DL812 cells were approximately four times more resistant to in vitro ACNU exposure but maintained similar immunogenicity as compared to the original ones. Permanent cures of advanced leukemias were achieved by ACNU treatment plus subsequent adoptive transfer of immune splenocytes in 15% of diseased mice. The results suggest the importance of host antitumor immunity for permanent cures of highly drug-sensitive leukemias, overcoming drug resistance and relapse.
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PMID:Importance of antitumor immunity for complete cure of highly drug-sensitive leukemia in mice. 275 24

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.
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PMID:Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans. 282 12

Based on the previous observation that a single major autosomal gene controls susceptibility to Friend leukemia virus in mice, an attempt was made to place the gene for susceptibility, Fv(s), from susceptible DDD mice into the genetic complement of resistant C57BL/6 mice. The backcross system was adopted for this purpose, the heterozygotes being selected by progeny test at each generation. During successive backcrosses, the effect of gene Fv(s) was not diluted out, and progeny were almost always obtained as expected from the single-gene hypothesis, with respect to both genotype and phenotype. With the eighth backcross generation, brother-sister mating was done between the heterozygotes, and it produced mice homozygous for gene Fv(s). These susceptible homozygotes and their progeny produced by incross could be assumed congenic with C57BL/6 mice except for susceptibility to Friend leukemia virus. The results indicate that the appearance of early splenomegaly in Friend virus-infected mice is under the control of a single major autosomal gene.
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PMID:Inheritance of susceptibility to Friend mouse leukemia virus. V. Introduction of a gene responsible for susceptibility in the genetic complement of resistant mice. 579 44

Two newly established mouse strains which are congenic with standard inbred strains were used for the study of the locus Fv which controls the susceptibility to Friend leukemia virus in mice. A strain in each congenic pair shares the major histocompatibility gene with the corresponding partner strain but differs from the latter in the Fv locus. Mice with Fv(r)/Fv(r) genotype (DDD-Fv(r), C57BL/6) do not develop marked spleen enlargement upon virus challenge, whereas spleens of mice with Fv(s)/Fv(s) genotype (DDD, C57BL/6-Fv(s)) become large even with a virus inoculum 1/10(3) to 1/10(5) times that used for the resistant strains. Mice of each strain were heavily irradiated, inoculated with bone marrow cells taken from either syngenic or corresponding congenic mice, and challenged later with the leukemia virus. When Fv(s)/Fv(s) mice had been restored with bone marrow cells taken from Fv(r)/Fv(r) mice, the spleens remained small after the virus inoculation. In contrast, Fv(r)/Fv(r) mice receiving Fv(s)/Fv(s) cells responded to the virus with marked spleen enlargement. In the enlarged spleens of the C57BL/6 mice which do not otherwise allow the virus multiplication, a considerable amount of infectious virus was found. The altered response seems to be due to repopulation of destroyed tissues by the transplanted bone marrow cells. It is concluded that the locus Fv is expressed on hemopoietic cells, and cells derived from bone marrow play a predominant role in the development of splenomegaly by Friend leukemia virus.
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PMID:Inheritance of Susceptibility to Friend Mouse Leukemia Virus: VI. Reciprocal Alteration of Innate Resistance or Susceptibility by Bone Marrow Transplantation Between Congenic Strains. 1678 15