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)

DBA/2 mice engrafted with FDC-P1 cells producing high levels of the leukemia-inhibitory factor (LIF) developed high circulating levels of LIF and a fatal syndrome including the accumulation of excess osteoblasts in the marrow and new bone formation. The mice developed a neutrophil leucocytosis, an enlarged spleen, and excess numbers of hemopoietic cells in the spleen and liver. Marrow cellularity was reduced with selective survival of granulocytic cells, but the frequency of hemopoietic progenitor cells in both the marrow and spleen was higher than in control mice. Megakaryocyte numbers were reduced in marrows with pronounced sclerosis. The disease state may represent a useful model of myelosclerosis, but it remains to be established whether the hemopoietic abnormalities in these mice are direct effects of LIF or secondary changes following occlusion of the marrow by osteosclerotic tissue.
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PMID:A myelosclerotic syndrome in mice engrafted with cells producing high levels of leukemia inhibitory factor (LIF). 251 82

Injection of B10.D2 cells into irradiated H-2d compatible (DBA/2xB10.D2)F1 recipients provokes a lethal GVH that can be abrogated by donor preimmunization against host-specific DBA/2 non-H-2 antigens. To study the possible relationship between the observed protection and restoration of immune responsiveness, we compared spleen cellularity, selected T and B cell functions, and NK activity in GVH and protected mice during the 1st month after grafting. Normal and isografted mice served as controls. GVH was found to be characterized by an early stimulation phase associated with splenomegaly and increased percentages (but not numbers) of Lyt-2+ and L3T4+ cells, followed by profound aplasia and abrogation of IL-2 production. Response to a B cell mitogen (LPS) is depressed, and cells from GVH mice exert a strong suppressive effect on the LPS and PHA responsiveness of normal cells. Suppression appears to be mediated by a radioresistant, nylon nonadherent, asialo GM1 negative cell expressing a low level of Thy-1 antigen. In contrast, protection correlates with progressive restoration of spleen cellularity and LPS responsiveness, with decreased but clearly detectable IL-2 production, and transient nonspecific suppressor activity. The immune status of protected mice resembles that of isografted controls. No correlation was found between mortality (or protection) and either PHA responsiveness, which remained depressed in all grafted mice throughout the observation period, or NK activity, which was strongly depressed in both GVH and protected mice. In conclusion, protection correlates with the disappearance of nonspecific suppressor cells and the restoration of cellularity and certain nonspecific immune functions. Donor immunization against host-specific non-H-2 antigens, which protects against mortality, also protects against GVH-associated immune deficiency.
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PMID:Lethal graft-versus-host reaction against non-H-2 antigens. I. Prevention of GVH-associated immunodeficiency by preimmunizing the donor against host-specific non-H-2 antigens. 252 8

In order to obtain evidence for the essential role of the single base insertion occurring at the 3' end of the env-related gene of Friend spleen focus-forming virus (SFFV) encoding the leukemogenic glycoprotein (gp55) a mutant SFFV genome was constructed in which the segment of the gp55 gene of the polycythemia-inducing strain of SFFV containing the single base insertion and the 6-base-pair duplication was replaced by the corresponding sequence of the Friend murine leukemia virus env gene. The mutant SFFV-Friend murine leukemia virus complex did not induce symptoms of the erythroproliferative disease in adult DBA/2 mice. During passage through newborn DBA/2 mice, the mutant virus complex invariably gave rise to weakly pathogenic variant SFFVs. All of the variant SFFVs induced in adult DBA/2 mice a transient mild splenomegaly associated with normal or slightly low hematocrit value, and they produced gp55 with a molecular weight similar to that of gp55 of the wild-type SFFV. For the two isolates of variant SFFV, the 3' portion of the viral DNA intermediate containing the 3' portion of the gp55 gene was molecularly cloned. Nucleotide sequences of these biologically active cloned DNAs were determined and showed that the variant SFFV genomes arose from the mutant SFFV genome by regaining the single base insertion, indicating that the single base insertion is essential for the biological activity of gp55. Evidence is presented indicating that the single base insertion which causes a loss of the cytoplasmic domain of the env-related protein is not related to the localization of the further-glycosylated form of gp55 in the plasma membrane but is involved with the release of gp55 from cells.
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PMID:Requirement of the single base insertion at the 3' end of the env-related gene of Friend spleen focus-forming virus for pathogenic activity and its effect on localization of the glycoprotein product (gp55). 255 55

The p53 gene is rearranged in a high proportion of erythroleukemic cell lines derived from the spleens of mice infected with Friend leukemia virus. These rearrangements result in either the synthesis of a truncated protein or the inactivation of the p53 gene. Here we have molecularly characterized the rearrangements in two murine erythroleukemic cell lines induced by Friend leukemia virus, DP20-1 and CB3, that contain a rearranged p53 gene and fail to express p53 protein. The rearrangement in the DP20-1 cell line is due to the insertion of Friend spleen focus-forming provirus (SFFV) in the 3' end of the p53 gene in intron sequences between exons 9 and 10. Transfection of molecular clones of this SFFV provirus into NIH3T3 cells results in the generation of infectious virus as determined by its ability, in the presence of helper virus, to induce rapid splenomegaly and polycythemia when injected into adult DBA/2J mice. Insertion of SFFV in DP20-1 cells resulted in the expression of an aberrant 2.9 kb RNA species. Analysis of a molecular clone of the rearranged p53 gene in a second cell line, CB3, revealed that the p53 gene in this clone has sustained a large deletion within the p53 gene resulting in the loss of coding sequences between exons 4 and 8. The 5' end of the deletion originates within exon 4 and extends 3' to within the eighth intron. The significance of these findings with regard to the multi-stage nature of Friend virus induced erythroleukemia is discussed.
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PMID:Inactivation of the p53 oncogene by internal deletion or retroviral integration in erythroleukemic cell lines induced by Friend leukemia virus. 284 14

The host response to experimental murine tularemia was examined in different inbred mouse strains. The kinetics of growth of Francisella tularensis live vaccine strain (LVS) in the livers and spleens of A and C57BL/6 mice were monitored, and it was observed that mice of the A strain were more susceptible to the proliferation of LVS than were C57BL/6 mice. The difference was most marked 5 days following infection, when the number of bacteria isolated from the spleens of A mice was found to exceed that of C57BL/6 mice by 100-fold. In addition, the C57BL/6 strain exhibited a more pronounced splenomegaly 8 days after infection than did the A strain. When the response of other inbred strains was evaluated by determining the splenic count of LVS on day 5 postinfection, several levels of antiularemic resistance were observed. Mice of the AKR, BALB/cBy, C57BL/10, and SJL strains were found to be most resistant, while SM mice were most susceptible to the proliferation of LVS. The DBA/2, CBA, 129, C3H/HeJ, and A strains expressed a resistance phenotype which was intermediate between the two extremes, with A and C3H/HeJ mice being somewhat more susceptible than DBA/2, CBA, or 129 mice. The trait of resistance or susceptibility was analyzed genetically in (C57BL/6 x A)F1 hybrid mice and in F2 generation and recombinant inbred (RI) mouse strains derived from C57BL/6 (resistant) and A (susceptible) strain progenitors. The F1 progeny exhibited a level of resistance to infection which was similar to that of the resistant parent. In both the F2 generation mice and the RI strains, a continuous spectrum of resistance levels was observed. The results of these experiments indicate that the genetic background of the host influences host resistance to experimental murine tularemia and that multiple genetic loci are involved in this response.
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PMID:Influence of genetic background on host resistance to experimental murine tularemia. 339 85

The effects of a combined dietary restriction of tyrosine and phenylalanine on metastasis were investigated with the use of 3 rodent tumor cell lines: B16-bladder 6 (BL6) melanoma inoculated into (C57BL/6 X DBA/2)F1 mice, Lewis lung (3LL) carcinoma inoculated into C57BL/6 mice, and RT7-4bs hepatocarcinoma inoculated into BD-IV rats. When examined for effects on spontaneous metastasis, dietary restriction of tyrosine and phenylalanine had no effect on metastasis to draining lymph nodes in either BL6 or 3LL tumors. However, the restriction did reduce metastasis of RT7-4bs cells to draining lymph nodes by 60%. In all tumor systems, the dietary restriction effectively inhibited the subsequent growth of lymph node tumors. The most marked effect of the dietary restriction was on spontaneous hematogenous metastasis, which was almost totally blocked for BL6 cells and was reduced by 85% for RT7-4bs cells. Tumor-associated splenomegaly also was completely inhibited in 3LL tumor-bearing mice. The selective dietary amino acid restriction failed to reduce initial lung colonization in the experimental metastasis assay but clearly inhibited subsequent tumor outgrowth in the lungs. These findings demonstrate that modification of host nutritional status by restriction of the dietary intake of tyrosine and phenylalanine exerts a dramatic antimetastatic effect directed particularly on spontaneous hematogenous metastasis. Although the preliminary data suggest a primary modulating effect on tumor cell populations growing in diet-restricted animals to reduce inherent metastatic ability, the actual mechanisms remain to be defined.
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PMID:Dietary restriction of tyrosine and phenylalanine: inhibition of metastasis of three rodent tumors. 347 May 51

A comparative analysis of responses between resistant and susceptible hosts revealed that DBA/2 mice, after treatment with variant surface coat glycoprotein (VSG) from virulent or avirulent African trypanosomes, developed splenomegaly as the result of a near-doubling of the splenic cell population, had less polyclonal activation of B cells and were protected upon challenge with homologous trypanosomes. The susceptible C3H/Anf and C3H/HeJ mice on the other hand increased their splenic cell population by only 12%, had about twice the production of unelicited antibodies and were not immunized by the VSG treatments. This indicated that (a) proliferation of spleen cells during African trypanosomiasis may reflect an attempt to generate a specific and protective immune response and is not merely the result of polyclonal activation of lymphocytes; (b) production of unelicited antibodies is not merely a "bystander reaction" to the generation of antigen-specific responses; and (c) polyclonal antibody production in response to VSG is not linked to the LPS gene. Nonspecific immunosuppression as measured in mitogen assays was not elicited by VSG in either resistant or susceptible mice, indicating that polyclonal lymphocyte activation and nonspecific immunosuppression are unlinked phenomena. Mice injected with VSG from either virulent or avirulent isolates at levels normally encountered by hosts during severe, acute infection developed the same degree of splenomegaly and production of unelicited (polyclonal) antibodies. Therefore, any differences in polyclonal activation of lymphocytes measured between mice with acute vs. chronic African trypanosomiasis can be attributed to quantitative and not qualitative differences in VSG.
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PMID:Mice varying in resistance to African trypanosomiasis respond differently to treatments with variant surface glycoprotein. 387 99

Two types of quantitative response to the F-B strain of Friend virus in segregating generations of a cross involving a susceptible (DBA/2 or BALB/c; H-2(2)) and a resistant (C57BL/6; H-2(b)) mouse strain show a marked correlation with the H-2 type of the mice. Essential susceptibility, as determined by the splenomegalic response to high virus doses, is controlled by a single pair of alleles which segregates independently with respect to the H-2 locus. However, relative susceptibility, as determined by the incidence of the splenomegalic response at moderate or low levels of virus dosage, is significantly greater among mice homozygous or heterozygous for the H-2(d) allele than among H-2(b) homozygotes in these populations. In addition, the incidence of recovery from splenomegaly induced by a given level of virus dosage is significantly greater in H-2(b) homozygotes than in segregants of other H-2 types among their littermates. Possible mechanisms responsible for these effects are discussed.
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PMID:The effect of histocompatibility-2 type on response to friend leukemia virus in mice. 563 54

The effects of several biochemically derived fractions of Corynebacterium parvum and chemically treated intact organisms on the generation of cytotoxic T-lymphocytes (CTL) were assessed in a tumor allograft model with the use of C57BL/6 and DBA/2 mice. The acid-modified, active and inactive fragmented preparations and pyridine extract and residue were all capable of inhibiting primary spleen cell allocytotoxicity. Only the active fragmented, pyridine residue and unfractionated preparations caused splenomegaly and prevented the secondary in vitro generation of CTL. Periodate treatment, acid modification, and pyridine extraction abrogated the ability of C. parvum to activate suppressor macrophages. Although incapable of activating suppressor macrophages, the phenol and pyridine extracts significantly enhanced suppressor T-cell activity. The effect of whole C. parvum organisms on T-cell-mediated cytotoxicity is thus extremely complex and due to the direct activation or inhibition of various cell types that interact with each other.
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PMID:Effects of different fractions of Corynebacterium parvum on the cytotoxic T-cell response to alloantigens in mice. 621 7

The possible involvement of host macrophages in the passive serum therapy of Friend leukemia virus (FLV)-induced disease has been examined with the use of agents inhibiting normal macrophage functions, including silica and a tumor-produced macrophage chemotaxis inhibitor. Under conditions in which macrophage chemotaxis inhibitor. Under conditions in which macrophage functions are at least transiently abrogated by these agents, no effect was seen on the anti-fLV protection afforded by the passive administration of chimpanzee anti-FLV antiserum to infected DBA/2 mice, as monitored by the development of virus-induced splenomegaly and the level of infectious virus. The macrophage inhibitors also did not influence the appearance of the host antiviral humoral immune response which normally accompanies serum protection. These results suggest that the normal functioning of host macrophages do not play a central role in the passive serum therapy protective mechanism leading to resistance to FLV infection.
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PMID:Absence of macrophage involvement in the passive serum therapy of Friend leukemia virus-induced disease. 625 83


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