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

Intravenous transfer of BALB/c spleen cells (1-10 X 10(6] immunized against semi-allogeneic hybrid cells bearing H-2k antigens into BALB/c mice resulted in splenomegaly (2- to 6-fold). As few as 2 X 10(4) spleen cells could transfer splenomegaly. A significant spleen enlargement was seen from 2 weeks after cell transfer and reached the peak level at 3 weeks. Those mice with splenomegaly displayed markedly reduced levels of proliferative responses to concanavalin A and lipopolysaccharide. However, the levels of the major Ig classes (i.e., IgG, IgM, and IgA) in the immunodeficient mice were significantly elevated. Such induction of immunodeficiency in mice may help further to understand the acquired immunodeficiency syndrome of humans.
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PMID:Induction of immunodeficiency in mice by injection with syngeneic splenocytes immune to semi-allogeneic hybrid cells. 647 14

A murine model of a spontaneous, transplantable BALB/c B-cell leukemia (BCL1) is described. Extreme leukemia and splenomegaly develop in H-2d-compatible recipients of tumor cells. Tumor cells are medium to large lymphocytes that can be transformed into plasmacytoid cells following in vitro stimulation with lipopolysaccharide. Karyotypic analysis of transformed tumor cells reveals 36 chromosomes with several monosomies and 7 markers chromosomes. The ultrastructure of the tumor cells was studied using transmission and scanning electron microscopy. Although the appearance of tumor cells seems normal by morphological criteria, an impaired capping ability was documented using the fluorescein-conjugated concanavalin A-binding test. Impaired capping ability was documented before leukemia was overt as early as 1 to 3 days following inoculation of tumor cells. The B-cell leukemia (BCL1) provides a useful murine model for the study of various aspects of human bone marrow-derived malignant disorders.
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PMID:Ultrastructural, cell membrane, and cytogenetic characteristics of B-cell leukemia, a murine model of chronic lymphocytic leukemia. 697 94

AKR mice were protected from lethal irradiation and established as long-lived chimeras by transplanting allogeneic C57BL/6 (B6) bone marrow that had been treated in vitro with anti-Thy-1 antiserum without complement. In these chimeras, which were designated [B6 {arrow} AKR], virtually all the thymus and spleen cells were shown to be derived from the B6 donor; several immune functions studied in these chimeras were as follows: (a) The chimeric mice were tolerant of histocompatibility antigens of both donor and recipient strain and nearly fully reactive to antigens of third party, as revealed by Simonsen's splenomegaly assay. The tolerance of these chimeras could not be attributed to suppressor cells but was compatible with clonal depletion. (b) Proliferative responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide as well as natural killer and antibody-dependent cell- mediated cytotoxicity activity of the chimeric mice was normal. (c) Plaque- forming cell (PFC) assays of antibody responses to sheep erythrocytes (SRBC) showed gross deficiency in the primary response of the [B6 {arrow} AKR] and [AKR {arrow} B6] chimeras. By contrast, [B6-H-2(k)(E(k)) {arrow} AKR] H-2-compatible chimeras and [AKR {arrow} AKR] syngeneic marrow transplanted mice had normal primary PFC responses. PFC responses after secondary stimulation with SRBC, however, revealed vigorous direct plaque formation and substantial but somewhat smaller indirect plaque formation in the [B6 {arrow} AKR] chimeras. This observation favors operationally the concept of adaptive differentiation proposed by Katz et al. (44). (d) Analysis of ability of the chimeras to develop and express delayed-type hypersensitivity responses to contact sensitizer (2,4-dinitro-l-fluorobenzene [DNFB]) showed no apparent immunodeficiency of either chimeras to this form of immunization. Development of immunologic tolerance to DNFB, however, was grossly deficient in [B6 {arrow} AKR] chimeras but normal in [AKR {arrow} AKR], [B6 {arrow} B6], and [E(k) {arrow} AKR] chimeras. These findings indicate that full chimeras across major histocompatibility complex have considerable immunologic vigor even though primary immune responses that require histocompatibility between interacting cell types are initially defective.
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PMID:Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice. 698 46

In patients with common variable immunodeficiency (CVI), we have previously defined a subgroup of patients (CVIHyper) characterized by decreased numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune activation in vivo, particularly of monocytes/macrophages. To further characterize this hyperactivity, parameters of activation of the tumor necrosis factor (TNF) system (TNF alpha and soluble TNF receptors [sTNFRs]) were measured in 24 patients with CVI and 20 healthy controls. Patients with CVI had significantly higher serum levels of TNF alpha and both types of sTNFRs, with the highest levels in the CVIHyper subgroup. In vitro, peripheral blood mononuclear cells (PBMC) and purified monocytes from CVIHyper patients spontaneously released significantly higher levels, and, after lipopolysaccharide (LPS) stimulation, significantly lower levels of TNF alpha and soluble p75-TNFR than cells from both other CVI patients and healthy controls. CVIHyper patients also had significantly higher TNF alpha:sTNFRs ratios in both serum and in unstimulated PMBC supernatants. The present study demonstrates persistent in vivo activation of the TNF system in CVI, particularly in the CVIHyper subgroup. This activation may contribute to the pathogenesis of both clinical and immunologic manifestations in CVI.
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PMID:Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency--possible immunologic and clinical consequences. 855 90

Infection of genetically susceptible C57BL/6 mice with the LP-BM5 isolate of murine retroviruses cause profound splenomegaly, hypergammaglobulinemia, lymphadenopathy, and an immunodeficiency syndrome which includes the development of terminal B-cell lymphomas. Because many of these and the other manifestations of LP-BM5 virus-induced disease are similar to those seen in AIDS, this syndrome has been named murine AIDS, or MAIDS. Previous reports have shown that the onset of MAIDS depends on the presence of both CD4+ T cells and B cells and have suggested that CD4+ T-cell-B-cell interactions are important to disease pathogenesis. Here, we assessed the possibility that interactions between CD40 and its ligand on activated CD4+ T cells, CD40 ligand/gp39, are involved in the development of MAIDS. To test this hypothesis, LP-BM5-infected B6 mice were treated in vivo with anti-gp39 monoclonal antibody. As a result, MAIDS-associated splenomegaly, hypergammaglobulinemia, germinal center formation, and the loss of in vitro responsiveness to the T- and B-cell mitogens concanavalin A and lipopolysaccharide were inhibited. Anti-gp39 monoclonal antibody-treated LP-BM5-infected mice were also able to mount essentially normal alloantigen-specific cytolytic T-lymphocyte responses. These results support the possibility that molecular interactions between CD40 and gp39 are critical to the development of MAIDS.
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PMID:Antibody to the ligand for CD40 (gp39) inhibits murine AIDS-associated splenomegaly, hypergammaglobulinemia, and immunodeficiency in disease-susceptible C57BL/6 mice. 864 87

Intraperitoneal (i.p.) exposure to propanil (3,4-dichloropropionanilide) has previously been shown to affect macrophage cytotoxicity. In this study, we compared the immunotoxic effects of propanil, after different routes of in vivo administration, on cytokine production by thioglycollate-elicited peritoneal macrophages. C57B1/6 mice were treated with either vehicle or 200 mg/kg propanil i.p., or with vehicle, 40, or 400 mg/kg propanil orally. Three or 7 days later, ex vivo production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by macrophages after lipopolysaccharide (LPS) stimulation was determined. Both oral and i.p. propanil exposure resulted in up to a 60-70% reduction in IL-6 and TNF-alpha production by the LPS-stimulated macrophages, depending on the route, postexposure time, and dose of propanil administered. Oral exposure to propanil also caused splenomegaly and thymic atrophy in animals in much the same manner as animals exposed via the i.p. route. In vitro exposure to propanil also significantly reduced macrophage cytokine production. Thioglycollate-elicited macrophages from normal mice were cultured in the continuous presence of 0, 10, or 20 microM propanil plus LPS. This exposure caused a significant reduction in IL-6 and TNF protein production by these macrophages in a concentration-dependent manner. Northern blot analysis demonstrated that the message levels of these cytokines were reduced by approximately the same percentage as the protein levels in propanil-treated macrophages, indicating a possible transcriptional or pretranscriptional target(s) for propanil.
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PMID:The immunomodulatory effects of the herbicide propanil on murine macrophage interleukin-6 and tumor necrosis factor-alpha production. 922 36

TRK-530 is a novel bisphosphonate derivative. We examined the anti-inflammatory effects of TRK-530 on adjuvant arthritis (AA) rats. When TRK-530 at a dose of 2.5 mg/kg was administered for 2 weeks to AA rats, it inhibited destructive changes in arthritic joints such as paw edema, bone loss and joint degeneration. TRK-530 also inhibited splenomegaly and suppressed the increase in serum sialic acid which is measured as a systemic parameter of inflammation. To clarify the inhibitory mechanism of TRK-530, interleukin-1 (IL-1)-like activities of resident peritoneal macrophages in AA rats given TRK-530 were compared with those of control rats. We found that TRK-530 inhibited IL-1-like activity induced by bacterial lipopolysaccharide 6 weeks after administration when the IL-1-like activities of control rats were still at high levels. These findings suggest that TRK-530 exerts anti-inflammatory activities in AA rats.
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PMID:Inhibitory effects of TRK-530 on rat adjuvant arthritis. 959 91

Lyn and Btk play a critical role in B cell development and intracellular signaling. Lyn-deficient mice exhibit splenomegaly, elevated serum levels of IgM, production of autoantibody and glomerulonephritis with age. On the other hand, xid mice, which carry a point mutation in the btk gene, show a decrease in numbers of peripheral mature B cells, reduced serum levels of IgM and IgG3, disappearance of CD5+ B-1 cells, and low proliferative response to anti-IgM or LPS stimulation in vitro. In order to investigate the interaction between Lyn and Btk during B cell development, we established lyn-deficient xid mice. Lyn-deficient xid mice exhibited greatly reduced numbers of peripheral mature B cells, disappearance of CD5+ B-1 cells, markedly reduced serum levels of IgM and IgG3, low proliferative response to anti-IgM or lipopolysaccharide stimulation and no evidence for autoimmune disease. In addition, splenomegaly in lyn-deficient mice, which was mainly due to the accumulation of Mac-1+, cytoplasmic IgM+ lymphoblast-like cells, was also diminished in lyn-deficient xid mice. Thus, immunological abnormalities found in lyn-deficient mice were strongly affected by the absence of Btk. The present results suggest that the autoimmune symptoms in lyn-deficient mice may be caused by not only the abnormal response of B-2 cells but also that of B-1 cells, and that the interaction between Lyn and Btk is partly in tandem at the signaling pathway in B cells.
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PMID:Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk gene. 962 May 99

We compared lethal toxicity and potential for splenomegaly and disseminated intravascular coagulation (DIC) of the lipid A derivative DT-5461 with those of compound 506 (C506) and bacterial lipopolysaccharide (LPS). These agents were given intravenously, by either bolus intravenous injection (2 ml/min) or drip infusion (3 ml/4 h), into the tail vein of rats under various regimens. In naive rats, the lethal dose after bolus intravenous injection was clearly higher than that after drip infusion for C506 and LPS, but not for DT-5461. In partially hepatectomized or D-galactosamine-treated rats, a marked enhancement of the lethality was observed for all agents relative to that in naive rats. Splenomegaly was commonly seen in all surviving rats after treatment, and histopathological examination revealed lymphoid hyperplasia in the B-cell area of the white pulp zone and lympho-reticular cell proliferation of the red pulp zone. When administered intravenously by drip infusion to rats pretreated with 0.4 M lactic acid, both C506 and LPS provoked DIC. This was manifested by a decrease in platelet counts, prolongation of activated partial thromboplastin time (APTT), and an increase in fibrin-fibrinogen degradation products (FDP), with hepatocellular necrosis and glomercular fibrin thrombus formation. In contrast, DT-5461 showed no such toxic events with the same protocol. In14-day intravenous toxicity studies of DT-5461, rats were more susceptible to hepatocellular necrosis and splenomegaly than squirrel monkeys. These results demonstrate that DT-5461 is a promising compound, with antitumor activity dissociated from its toxic potential.
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PMID:Toxic characteristics of the synthetic lipid A derivative DT-5461 in rats and monkeys. 1041 79

In this report, we examined the involvement of the cytokines tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-4, and IL-10 as well as nitric oxide (NO) in the lipopolysaccharide (LPS)-induced experimental abortion model in BALB/c mice. Although in vivo administration of LPS in pregnant mice showed a 72% decrease of serum IL-10, no significant difference in serum TNF-alpha, IFN-gamma, and IL-4 levels, compared to controls, could be detected. At the same time, a correlation of fetal abortion and maternal splenomegaly with an important increase of NO synthesis in the serum was obtained. Simultaneous administration of LPS and aminoguanidine (AG; an inhibitor to NO synthase) rescued the LPS-induced fetal abortion, reduced maternal spleen weight to physiological levels, and decreased serum NO concentration to control levels. In vitro experiments showed that LPS directly induced NO production in primary placental cells and the TPOPHO-1 trophoblast cell line by stimulating the inducible isoform of NO synthase, which ultimately could be blocked by the NO synthase inhibitors AG and L-NAME. The results indicate that LPS, despite its beneficial involvement in intracellular infections, participates in inflammatory/autoimmune damage during pregnancy, leading to embryotoxicity, which is closely linked to the NO pathway.
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PMID:Inhibition of nitric oxide production rescues LPS-induced fetal abortion in mice. 1044 53


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