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)

Pregnant mice characteristically show elevated numbers of immunoglobulin-secreting cells in their enlarged spleen and para-aortic lymph nodes. A comparative study of pseudopregnancy and syngeneic pregnancy in CBA/Ca mice was made to evaluate the role of maternal hormones in the induction of these changes. To induce pseudopregnancy, CBA/Ca female mice were mated with vasectomized males, the duration of pseudopregnancy induced in this way is 8-10 days. Serum progesterone levels were monitored periodically throughout pseudopregnancy using RIA technique. Changes were recorded in weight of the thymus, spleen and para-aortic lymph nodes, levels of serum IgG and IgM (ELISA-technique), and content of splenic IgG- and IgM-secreting cells (protein A plaque assay). Thymus involution was observed in pregnant and pseudopregnant mice. Patterns of change in the weight of the spleen and the para-aortic lymph nodes (PALN) were similar in pregnant and pseudopregnant mice until day 8. Ig-secretion in the spleen increased slightly day 5-8 in both pregnant and pseudopregnant mice, but to a lesser extent in the latter. No differences were observed in serum Ig levels between the two groups until day 8. A marked decrease in serum IgG levels and, to some extent, IgM levels between days 8 and 12 was observed in pregnant animals.
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PMID:Effects of pseudopregnancy on immunoglobulin-secreting cells in mice. 317 57

Mice were injected with sphingomyelin/cholesterol or phosphatidylcholine/cholesterol (PC/C) liposomes, from twice up to 10 times, on alternate days. Administration of sphingomyelin/cholesterol (SM/C) liposomes gave rise to hepato and splenomegaly, microgranulomatous infections and changes in macrophage numbers and activity in spleen and liver. Enzyme and immuno-cytochemical methods were used, to demonstrate the effect of liposomes on the lymphoid and non-lymphoid cell populations, on cryostat sections of the spleen. Routine histological staining, of sphingomyelin/cholesterol treated animals, showed no drastic changes in morphology or compartmentalization of the spleen, apart from a small enlargement (with some microgranulomas) of the red pulp. No significant differences were found in the presence or localization of T-helper, T-cytotoxic/suppressor, T-total-lymphocytes, B-total-lymphocytes, red pulp macrophages, marginal metallophils, or non-lymphoid dendritic cells. However, a transient suppression of cells expressing marginal zone macrophage surface marker ERTR-9, was observed between the second and eighth (intravenous) administration of sphingomyelin/cholesterol liposomes. Immunization of these animals with trinitrophenyl (TNP)-ficoll, a thymus-independent type-2 antigen which is specifically processed by marginal zone macrophages (MZM), showed that these cells were not suppressed with regard to their immunological function. We conclude that chronic administration of sphingomyelin liposomes influences macrophages, probably through a general phagocytic-system overload, but not permanent or damaging changes in splenic cell populations or immunological functions occur.
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PMID:Effects of chronic injection of sphingomyelin-containing liposomes on lymphoid and non-lymphoid cells in the spleen. Transient suppression of marginal zone macrophages. 321 88

The lpr gene induces marked lymphoproliferation characterized by the massive accumulation of T cells of an unusual phenotype and concomitant autoimmune disease. To clarify the mechanism of the lpr effect, bone marrow cells from B6-lpr/lpr (Ly-1.2) and B6-+/+ (Ly-1.1) mice were transferred into lethally irradiated B6-lpr/lpr mice. As has been previously reported, recipients of the B6-lpr/lpr bone marrow showed the typical lpr phenotype with marked lymphadenopathy, splenomegaly and increased levels of autoantibodies; while the recipients of B6-+/+ bone marrow had normal sized lymph nodes and spleen and no autoantibodies. A third group of mice received an equal mixture of bone marrow cells from the B6-lpr/lpr and B6-+/+ donors. These mice showed both lymphadenopathy and autoantibody production comparable to that of recipients of the B6-lpr/lpr marrow alone. Immunofluorocytometric analysis of the lymphoid populations in these mixed bone marrow recipients established that the T cells from the lpr/lpr and +/+ donors were equivalently represented in the peripheral blood and thymus. In striking contrast, the T cells that accumulated in abnormally large numbers in the lymph nodes were almost entirely from the lpr donor. Their surface phenotype was Thy-1+(dull), Ly-1.2+(dull), Lyt-2-, L3T4-, 9F3+, and 3A1+, which is consistent with that found in intact lpr mice. These results indicate that the lpr gene causes an intrinsic defect directly within the T cells that accumulate in large numbers in lpr mice. In addition, the presence of the +/+ T cells cannot prevent the expression of the lpr abnormalities.
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PMID:The lpr gene causes an intrinsic T cell abnormality that is required for hyperproliferation. 325 51

Monoclonal antibodies (MoAb) to L3T4 have been used successfully to suppress autoimmunity in murine models for several human autoimmune diseases. To clarify the immunologic and clinical consequences of treatment with anti-L3T4, we examined the effects of chronic administration of anti-L3T4 on the composition of lymphoid organs, the function of lymphocytes, and the histopathology of autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Weekly treatment with anti-L3T4 (2 mg/mouse) from age 5 to 8 months depleted L3T4+ cells from the spleen and lymph nodes, and prevented the development of splenomegaly and lymphadenopathy. The MoAb bound to target cells in the thymus and modulated their expression of the L3T4 antigen but, in contrast to its effect in extrathymic sites, anti-L3T4 did not deplete the target population from the thymus. In fact, after 3 months of therapy, mice that had been treated with anti-L3T4 had much larger thymuses than control mice that had been treated with saline, suggesting that treatment with anti-L3T4 prevented the thymic atrophy that occurs spontaneously in murine lupus. Despite depleting L3T4+ cells from the spleen, treatment with anti-L3T4 did not diminish the response of splenic lymphocytes to T and B cell mitogens, and it augmented splenic natural killer (NK) cell activity. Finally, treatment with anti-L3T4 decreased the diverse histopathologic manifestations of murine lupus. It dramatically reduced glomerular immunoglobulin and complement deposition and diminished lymphocytic infiltration and vasculitis in the kidneys. Treatment also reduced extrarenal immunopathology, including focal hepatitis and salivary gland infiltration. These observations have implications regarding the use of CD4 MoAb in people with autoimmune diseases.
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PMID:Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease. 326 85

In this study anti-asialo GM1 antibodies (anti-ASGM1) were used to further characterize the effector cells responsible for graft-versus-host (GVH)-induced histopathological lesions: Two different types of ASGM1+ cells were identified: an endogenous ASGM1+ population and an induced ASGM1+ population. Both of the ASGM1+ cell populations exhibited natural killer (NK) cell activity, as assessed by their ability to lyse YAC tumor targets in vitro. Donor C57BL/6 (B6) mice were treated in vivo with anti-ASGM1 to eliminate endogenous ASGM1+ cells. ASGM1+ cells were induced in B6 donor mice by treating the animals with 15 x 10(6) B6 x AF1 (B6AF1) lymphoid cells for 44-48 hr. The induced ASGM1+ cells were eliminated by in vivo treatment with anti-ASGM1. GVH reactions were induced by injecting B6 lymphoid cells into B6AF1 mice. Prior to GVH induction the B6 donor cells were tested for NK cell activity against YAC tumor target cells in vitro and for T and B cell functions by mitogen responses in vitro. GVH reactions were determined by splenomegaly, suppression of the plaque-forming cell (PFC) response to sheep red blood cells (SRBC), suppression of the T and B cell mitogen responses, and the development of GVH-associated histopathological alterations in the thymus, liver, and pancreas. Donor lymphoid cells depleted of endogenous ASGM1+ cells were effective at inducing splenomegaly, severe suppression of immune functions, and histopathological lesions. Donor lymphoid cells depleted of both the endogenous and induced ASGM1+ cells displayed normal T cell mitogen responses and were capable of inducing splenomegaly and partial suppression of the PFC response to SRBC when injected into B6AF1 recipients, however, these lymphoid cells failed to induce both GVH-associated histopathological lesions and severe suppression of T and B cell mitogen responses. These results suggest that semiallogeneic stimulation induces an ASGM1+ population in the donor inoculum that displays NK cell-like function (YAC killing) and that plays a crucial role in inducing GVH-mediated histopathological lesions and severe immunosuppression of both T and B cell responses.
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PMID:Prevention of murine graft-versus-host disease by inducing and eliminating ASGM1+ cells of donor origin. 334 37

The histopathology of the thymus and spleen and the response of spleen cells to mitogenic stimuli were evaluated in Sprague-Dawley CF-1 mice infected with Ehrlichia risticii. Intraperitoneal injection of 10(4) or 10(6) E. risticii-infected U-937 cells into mice resulted in 100% morbidity and partial mortality. Thymic atrophy became significant between 1 and 2 weeks postinfection and remained for the duration of the study. The atrophy appeared associated with antecedent destruction and rarefaction of lymphocytes, resulting in the loss of corticomedullary demarcation. Splenomegaly was prominent; significantly increased weights were detected 7 days postinfection. Histopathologic examination revealed rarefaction of lymphocytes around central arteries, the presence of necrotic debris in histiocytes, and replacement of erythropoiesis by granulopoiesis in the red pulp. Marked and acute reduction of in vitro proliferative responses of spleen cells to concanavalin A (ConA) and phytohemagglutinin were observed in mice infected with 10(4) or 10(6) E. risticii-infected U-937 cells. Interleukin-2 activity in the supernatant of ConA-stimulated spleen cells was also severely reduced. Both changes were time- and dose-dependent and were not associated with decreased spleen cell viability. Neither morbidity nor mortality occurred in mice infected with 10(2) E. risticii-infected U-937 cells. Although there was temporal reduction in phytohemagglutinin-driven lymphocyte proliferation, reduction in neither ConA-driven lymphocyte proliferation nor interleukin-2 activity was observed with this dosage. All E. risticii-inoculated mice seroconverted between days 18 and 25, as detected by the indirect fluorescent-antibody procedure. The findings indicate for the first time the hypoimmune responsiveness and histopathologic changes in lymphoid organs associated with E. risticii infection.
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PMID:Reduced immune responsiveness and lymphoid depletion in mice infected with Ehrlichia risticii. 349 79

Protein and lipid analyses were conducted on isolated erythrocyte and lymphocyte plasma membranes from 7-wk-old male C57BL copper-deficient and copper-supplemented mice to investigate mechanisms for the altered immunity that accompanies dietary copper deficiency. Beginning at parturition, dams were fed a diet low in copper (0.5 mg/kg) and the offspring were weaned to this diet. Half the dams and their respective offspring received supplemental copper (20 mg/L) in the drinking water (+Cu) and served as controls. Unsupplemented offspring (-Cu) had lower activity of cuproenzymes serum ceruloplasmin, spleen and thymus cytochrome-c oxidase and copper, zinc-superoxide dismutase. The -Cu mice exhibited anemia, splenomegaly and thymic atrophy. Based on the marker enzyme alkaline phosphodiesterase I (APDE-I), lymphocyte plasma membranes were enriched 7- to 10-fold for spleen and thymus, respectively, after discontinuous sucrose density centrifugation. The activity of APDE-I was higher in spleen and thymus samples from -Cu mice than from those of +Cu mice for both crude homogenates and purified plasma membranes. Proteins were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining. A yellow-appearing band, Mr 74,000, present in all splenic membrane samples from +Cu mice was not evident in the samples from -Cu mice. Fatty acid methyl esters (FAME) were quantified by gas chromatography. Compared to splenic membranes from +Cu mice, the samples from -Cu mice demonstrated significant changes in all FAME (lower 16:0, 18:0 and 20:3n-6 and higher 18:1n-9, 18:2n-6 and 20:4n-6), including a higher unsaturation index. FAME composition of erythrocyte ghosts from -Cu mice demonstrated similar changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary copper deficiency alters protein and lipid composition of murine lymphocyte plasma membranes. 359 18

We investigated the presence of colony-stimulating factor (CSF) in supernatants obtained from TS/A, a new metastatic murine cell line, and from its high-and low-metastatic clonal derivatives (E and F clones, respectively). TS/A cells produced a CSF in vitro that induced proliferation and differentiation of murine monocytic and granulocytic progenitors in agar cultures. In TS/A-bearing mice remarkable splenomegaly, blood granulocytosis and thymus depletion were observed along with a stimulatory activity in serum and a strong proliferative activity both in spleen and in bone marrow populations. Conditioned media from E clones showed an in vitro colony-stimulating activity greater than those of F clones. Mice injected subcutaneously with cells of all clones studied showed granulocytosis, splenomegaly and thymus depletion, although to varying degrees. However, no direct correlation between granulocytosis-splenomegaly and the number of spontaneous lung metastases was observed.
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PMID:Colony-stimulating activity from the new metastatic TS/A cell line and its high- and low-metastatic clonal derivatives. 387 61

We investigated the possible role of protein kinase C (PKC) in the progression of Moloney murine leukemia virus (Mo-MuLV)-induced lymphoma in BALB/c mice. Mice injected with Mo-MuLV on the first day after birth developed lymphoma within 1 1/2-3 months. The development of lymphoma was characterized by a gradual increase in the number of spleen cells. However, no analogous changes could be detected in the thymuses of these mice, although cells of both organs were found to be virus producers as early as 3-4 weeks after inoculation. PKC activity, which was assayed in extracts of spleen and thymus cells, declined gradually during the development of lymphoma. Concomitantly with this decline, a progressive appearance of Ca2+/lipid-independent protein kinase activity was observed. TPA treatment of intact cells from normal mice reduced the level of soluble PKC activity, while inducing Ca2+/lipid-independent phosphorylation. By contrast, TPA had no effect on these enzymatic activities in cells derived from leukemic mice. Spleen enlargement caused by injection of a non-leukemogenic inflammatory agent such as mineral oil was ineffective in this respect, suggesting that the PKC-Ca2+/lipid-independent protein kinase modulation is associated with the virally induced leukemogenesis.
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PMID:Modulation of protein kinase C and Ca2+ lipid-independent protein kinase in lymphoma induced by Moloney murine leukemia virus in BALB/c mice. 395 64

A short-cut procedure is described which allows to construct new mouse strains which are double congenic for the nu gene (nude, athymic) and the lpr gene (lymphoproliferation). Since both nu and lpr genes are recessive and that the lack of thymus impairs the expression of the lpr phenotype in euthymic animals, the homozygosity of nude animals for the lpr gene was based on the results of progeny analyses. A C57BL/6 nu/nu lpr/lpr (B6 nu/nu, lpr/lpr) was made in four generations starting from C57BL/6 nu/nu (B6 nu/nu) and C57BL/6 lpr/lpr (B6 lpr/lpr). This possibility stems from an absence of close linkage of the nu and lpr genes. The emergence of the nude phenotype at the different steps of the pedigree was less frequent than expected if the nu and lpr genes were completely independent. However, this is probably due to environmental factors causing a negative selection of nude littermates. The B6 nu/nu lpr/lpr represents a new important tool for the study of how the thymus modulates the lpr gene controlled acceleration of autoimmunity. Preliminary data indicate that the lpr phenotype (massive lymphadenopathy and splenomegaly accompanied by severe auto-immune disease with features of systemic lupus erythematosus) appears when a thymus is grafted to the B6 nu/nu lpr/lpr.
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PMID:The C57BL/6 nu/nu lpr/lpr mouse. II. Pedigree and preliminary characteristics. 404 79


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