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 thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals.
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PMID:Effects of neonatal thymic exposure to high doses of X-irradiation. 31 96

It was recently demonstrated that MRL-lpr lymphoid cells transferred into lethally irradiated MRL- +mice unexpectedly failed to induce the early onset of lupus syndrome and massive lymphadenopathy of the donor, instead they caused a severe wasting syndrome resembling graft-vs-host (GvH) disease. The present studies were carried out to characterize the cellular events involved in the severe GvH-like reaction developed in C57BL/6 (B6) recipients of B6-lpr spleen cells, designated as [B6-lpr----B6] chimeras. [B6-lpr----B6] chimeras showed at 2 weeks post transplantation marked splenomegaly consisting predominantly of Lyt2+ T cells (approximately 70%), and subsequently developed acute and severe depletion in spleen cells causing spleen atrophy and fibrosis. Spleen cells from chimeras at 2 weeks posttransfer were not cytotoxic to both recipient and donor ConA blast target cells. In contrast, those cells (irradiated to 3000 rad) considerably suppressed ConA-induced proliferative responses of B6 spleen cells. These nonspecific suppressor cells expressed Thy1 and Lyt2 antigens, but lacked L3T4 and B220 antigens. Furthermore, elimination of Thy1+ or B220+ but neither L3T4+ nor Lyt2+ cells from B6-lpr spleen cells before transfer retarded the generation of nonspecific suppressor cells but did not abrogate the GvH-like disease. These results suggest that the GvH-like disease and lymphoid atrophy in [B6-lpr----B6] chimeras were mediated by Lyt2+ suppressor T cells, and that B220+ T cells played a crucial role in the induction of these suppressor cells. The cell transfer model reported here may be very useful in understanding the immunological function of B220+ T cells in vivo.
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PMID:[Analysis of the mechanism of graft-vs-host like disease in [lpr/lpr----+/+] chimera]. 296 73

Transfer of parental strain T lymphocytes into F1 hybrid rats differing with respect to gene products of the major histocompatibility complex (MHC) causes a graft-versus-host (GvH) reaction. This reaction results from recognition of host allogeneic MHC gene products by specific clones of donor T cells. When given systemically in sufficient numbers, these donor T cells cause a progressive, generally fatal wasting syndrome, an early feature of which includes extensive splenomegaly. A more local, non-fatal GvH reaction, marked by extensive enlargement of the draining lymph nodes, ensues when donor T cells are administered via the footpad. Here, we demonstrate that cells derived from the enlarged draining lymph nodes of A/B F1 animals undergoing local GvH disease caused by donor A T cells contain a subpopulation of host-derived killer T-cell precursors which can be activated to lyse specific blast cells, derived from mixed lymphocyte culture (MLC), reactive to host MHCb alloantigens. These 'anti-idiotypic' cytolytic T cells lyse A anti-MHCb MLC blasts, and also, they lyse anti-MHCb MLC blasts from MHC different, third party rat strains.
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PMID:Anti-idiotypic cytotoxic T cells in rats with graft-versus-host disease. 660 95

Using a new adenoviral vector (Ad) construct, we expressed human thrombopoietin (TPO) cDNA (AdTPO) in mice with various inherited immune deficiency syndromes such as nude, SCID and NOD-SCID mice. Immune normal Balb/c mice and a vector construct without TPOcDNA (AdNull), respectively, were used for controls. All animals (3 per group) were treated with a single application of 10(9) PFU (plaque forming unit) of Ad (AdTPO or AdNull) intraperitoneally on day 0. Four to 5 weeks following AdTPO administration, SCID and NOD-SCID mice demonstrated peak concentration of PLT of 12- to 14-fold normal value simultaneously with maximum concentration of PMNs (10- to 12-fold normal value). Later on these animals had a chronic thrombocytosis. In contrast, Balb/c mice and nude mice experienced PLT peak concentration of 4- to 6-fold normal value without granulocytosis 1 to 2 weeks following AdTPO treatment. Only nude mice had chronically elevated PLTs. In contrast, Balb/c mice developed thrombocytopenia due to cross-reacting anti-TPO antibodies. Animals with chronic thrombocytosis revealed increased content of CFU-G/GM, CFU-GEMM and CFU-Meg in bone marrow compared with controls. In contrast, Balb/c mice showed decreased content of CFUs if anti-TPO-antibodies were present. Histologically, only SCID mice developed severe osteomyelofibrosis and osteomyelosclerosis, hepato-splenomegaly, extramedullary hematopoiesis in liver and lung and ultimately suffered of progressive pancytopenia, anisocytosis, fragmentocytosis and a lethal wasting syndrome. In contrast, NOD-SCID mice which demonstrated similar extent of TPO overexpression and in addition to the B- and T-cellular immune deficiency harbour defective monocytes and macrophages, did not develop fibrotic changes of the bone marrow. From these results, we conclude (1) chronic TPO overexpression in vivo may lead to thrombocytosis and granulocytosis with expansion of CFU-GM, -GEMM and -Meg; (2) in vivo expression of adenovirally mediated TPOcDNA depends on immune competency of the host; (3) functionally normal monocytes and macrophages are indispensable for development of secondary osteomyelofibrosis and (4) adenovirally mediated expression of xenogeneic transgenes may brake immune tolerance for the respective self protein leading to autoimmune phenomena. Our in vivo model might provide further insights into the pathophysiology of secondary osteomyelofibrosis and may prove useful in designing new strategies for immune therapies of cancer.
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PMID:[Adenovirus long-term expression of thrombopoietin in vivo: a new model for myeloproliferative syndrome and osteomyelofibrosis]. 982 87