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)

The toxic oil syndrome is characterized by IgE elevation and eosinophilia, as well as scleroderma-like skin manifestations and other symptoms of autoimmune disease. Fatty acid anilides, found in large amounts in adulterated cooking oil, were suspected to be the etiologic agent in this disease. The capacity of oleic acid anilide to induce features of autoimmunity in vivo was investigated. B10.S mice were continuously treated i.p. with oleic acid anilide for 6 wk by using osmotic pumps. A significant increase in IgE and IgM serum levels was observed after 1 to 3 wk; subsequently five of six mice developed IgG1 levels 3.5- to 10-fold higher than the controls. Anilide-treated mice developed splenomegaly with a 2.1- and a 3.5-fold increase in IgM- and IgG-bearing splenocytes, respectively, and a 5.6- and 29-fold elevation in functional IgM- and IgG-secreting cells, respectively. Increased serum levels of predominantly IgM antibodies to histone, denatured DNA, and DNP as well as rheumatoid factor were detected. In vivo expression in the spleen of 10 cytokine genes was also examined, and mRNA encoding IL-1 beta and IL-6 were significantly elevated in splenocytes of anilide-treated mice. The enhanced Ig production suggests that anilide induced a cytokine-mediated polyclonal activation of B cells. Elicitation of IgM antibodies to denatured forms of autoantigens indicates that anilide treatment partially broke autoimmune tolerance in these mice. Anilide-treated mice may be a useful animal model for further exploring the mechanism and pathogenesis of systemic autoimmunity in the toxic oil syndrome.
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PMID:Isotype-restricted hyperimmunity in a murine model of the toxic oil syndrome. 158 38

PD-1, an Ig superfamily member, contains an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic tail. It is expressed in a minor fraction of CD4-CD8- normal thymocytes and induced in peripheral lymphocytes following activation. To assess the possible roles of PD-1 in the immune responses, PD-1-deficient (PD-1-/-) mice were generated by a gene-targeting strategy. PD-1-4- mice developed and grew normally. Although the thymus was apparently normal, PD-1-/- mice showed moderate but consistent splenomegaly, which reflected the increased cellularity of both lymphoid and myeloid cells. The proliferative response of B cells by anti-IgM antibodies, but not of T cells by an anti-CD3 (145-2C11) mAb in vitro, was augmented in PD-1-/- mice as compared with control littermates. PD-1-/- mice showed increased serum levels of IgG2b, IgA and most strikingly IgG3, while those of IgM and IgG1 were comparable with control mice. Furthermore, PD-1-/- mice exhibited significantly augmented IgG3 anti-DNP antibody response to a type 2 T-independent antigen, DNP-Ficoll, with comparable IgM and IgG1 antibody responses with littermate controls. In the peritoneal cavity, the B-1 cell population in PD-1-/- mice exhibited significantly reduced expression of CD5, a negative regulator of B-1 cell activation, despite a marginal increase in the number of B-1 cells. Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of B cell proliferation and differentiation including class switching.
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PMID:Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. 979 23

Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is a known immunomodulator. At high doses, BaP is immunosuppressive but at low doses it can enhance the immune response. Studies were conducted to determine if BaP would exacerbate the development of autoimmune disease in genetically prone NZB/WF1 mice. Five week old female NZBW/F1 mice were exposed dermally to 5, 20 and 40 mg/kg BaP for 30 days. Vehicle mice were exposed to an acetone:olive oil mixture for 30 days. BaP did not increase total IgG, anti-DNP-HSA or anti-dsDNA antibody levels. However, hematological evaluation revealed a decrease in erythrocyte number, hemoglobin and hematocrit and an increase in mean corpuscular volume and red cell distribution width in the 20 and 40 mg/kg dose groups. Liver and spleen weights were increased in the high dose groups; however, an increase in spleen cell number was not observed. Histopathological evaluation revealed splenic red pulp expansion in a mouse treated with 40 mg/kg BaP. An increase in splenic CFU-e production was observed in mice treated with 20 and 40 mg/kg BaP. A decrease in splenic total B cells, total T cells, CD4(+) and CD8(+) T cells was observed in mice treated with 20 and 40 mg/kg BaP. An increase in splenic null cells (non-T, non-B cells) was also observed in the high dose groups, consistent with extramedullary hematopoiesis. Coombs' tests, flow cytometry and an immune-mediated hemolysis assay indicated that the anemia was not autoimmune-mediated. Although no change was observed in the percentage of reticulocytes in these animals, further bone marrow analysis is needed to determine if the anemia is due to bone marrow suppression, possibly caused by BaP exposure, or chemical-induced hemolysis, perhaps contributed to by erythrocyte fragility inherited from a parent strain, NZB, which spontaneously develops autoimmune hemolytic anemia and subsequent splenomegaly.
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PMID:Benzo(a)pyrene-induced anemia and splenomegaly in NZB/WF1 mice. 1593 65