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)

We explored the immunoincompetence of mice undergoing a chronic graft-vs-host reaction (GVHR) across minor histocompatibility barriers. BALB/c and B10.D2 mice are H-2d and mls b, and differ only with regard to minor histocompatibility antigens (MiHA). A large number of BALB/c mice were unirradiated or were irradiated with 300, 600, or 900 R. They then were injected with 5 X 10(7) spleen cells from either allogeneic B10.D2 or syngeneic BALB/c mice. The spleen cells from these recipient mice were assayed at various times post-irradiation/injection for their proliferative response to Con A and LPS, their ability to suppress the mitogen responses of normal spleen cells, and for the genetic specificity of this suppression. Spleen cells from BALB/c mice that had received 600 or 900 R (but not 0 or 300 R), and allogeneic B10.D2 lymphocytes, became very hyporesponsive to mitogens and became suppressive in vitro by days 7 to 10 post-irradiation/injection. These phenomena persisted for the entire 49 days of the experiment. After an initial period of splenomegaly, the spleens of these mice gradually became depleted of viable lymphocytes. Initial characterization of suppressor cells found in the spleens of GVH mice showed that they were not removed by treatment with anti-Thy-1.2 plus complement. GVH suppressors also were not adherent to plates coated with antiserum directed towards murine Ig. In addition, these cells did not adhere to plastic plates. Thus, we believe that the suppressor cells found in mice undergoing GVHD across MiHA are not mature T cells, B cells, or macrophages, but belong to a class of suppressor cells termed natural suppressor (NS). Genetic analysis of NS cell activity showed that as early as 10 days post-irradiation/injection, NS cells inhibited mitogen responses of all mouse strains tested, the exception being the relative difficulty in suppressing the LPS response of B10.D2 (syngeneic with donor cells). By day 42, this had developed into an almost complete inability to suppress a B10.D2 LPS response, although at this time NS cells were still capable of inhibiting all the other mitogen responses of all strains tested, including the Con A response of B10.D2 spleen cells. Moderate amounts of mitogen unresponsiveness and suppressor activity were seen in the syngeneic groups (BALB/c----BALB/c) but only if recipients received 600 or 900 R. This was a transient phenomenon that was maximal at day 14, and which we believe to be a similar but less severe degree of immunoincompetence when compared with that seen with allogeneic stimulation in the B10.D2----BALB/c GVH model.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity. 316 Jul 74

In this study the ability of prostaglandin E1 (PGE1), Misoprostol (a stable analog of PGE1), and 16,16-dimethyl PGE2 (a stable analog of PGE2) to suppress immune responses in vitro and in vivo was determined. All of the compounds caused a titratable (10(-6) to 10(-9) M) suppression of Con A blastogenesis and the mixed lymphocyte response whereas there was only slight inhibition of the LPS response. When either 16,16-dimethyl PGE2 (30 ug/mouse) or Misoprostol (60 ug/mouse) was administered daily in vivo, there was a significant suppression of splenomegaly in F1 mice (C57Bl/6 x CBA) which had been injected with parental (C57Bl/6) spleen cells. We conclude that prostaglandins of the E series can function as immunosuppressive reagents both in vitro and in vivo. In the future they may serve to augment existing forms of immunosuppressive therapy.
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PMID:The effects of E series prostaglandins on blastogenic responses in vitro and graft vs. host responses in vivo. 324 42

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

When BALB/c mice were first infected with Rauscher murine leukemia virus (MuLV-R) and then superinfected with Herpes simplex virus type 2 (HSV-2) the inhibition of the evolution of splenomegaly was observed. The effect did not depend on the route of HSV-2 administration. Experiments in which potent anti-interferon serum was administered to double infected mice suggested that the antagonism between MuLV-R and HSV-2 was not mediated by endogenous interferon, HSV-2 was found to replicate in the LPS stimulated spleen cells which are also target cells for MuLV-R; this suggested that the intrinsic interference between both viruses could take place. Mice with Rauscher virus induced disease were found to be more susceptible to infection with Herpesviruses than normal mice.
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PMID:Double infection of BALB/c mice with Rauscher murine leukemia and Herpes simplex virus type 2. 625 90

Splenic responses of CBA/J mice infected with 250 embryonated ova of the nematode, Toxocara canis were characterized during the first month post-inoculation (P.I.). By the 6th day of infection, spleen to body weight ratios were over 3.5 times greater in infected mice than uninfected controls. This ratio peaked at 5.0 on day 14 and declined slightly by day 36 P.I. Lymphocyte transformation studies were carried out using the T cell mitogens, Con A and PHA and the B mitogen, LPS. The responses of infected mice to all of the mitogens were greater than or equal to the responses of uninfected mice at all times studied. Unstimulated lymphocytes from infected mice spontaneously incorporated approximately 10-fold more 3H-TdR than did uninfected control mice during the first 2 weeks of infection. Antigen-specific lymphocyte transformation was also performed using a crude extract of homogenized embryonated ova (TEE) as the antigen. Positive responses were obtained at all times examined but were greatest during the first 2 weeks of infection. The T cell basis of this response was demonstrated by Anti-Thy 1.2 plus complement treatment prior to the initiation of the lymphocyte transformation assay. Collectively, these results suggest that in mice, T. canis elicits a striking splenomegaly as early as 1 week after oral inoculation. The lymphocyte transformation studies suggest that the splenomegaly may be due in large part to proliferation of the white pulp based on the amount of spontaneous labelling observed. Increased mitogenic responses indicate that T. canis does not elicit nonspecific immunosuppression and the positive response to the TEE antigen suggests that at least some of the lymphoproliferation is antigen specific.
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PMID:Spleen cell responses in experimental murine toxocariasis. 633 50

Interleukin 10 (IL-10) is a cytokine with both antiinflammatory and immunosuppressive properties. In the present study, we have examined the effects of recombinant human IL-10 (rHuIL-10) on the development of acute graft-vs.-host disease (GVHD) in unirradiated (C57B1/6JxA/J) F1 recipients of parental A/J lymphocytes. rHuIL-10 (2.5 to 100 micrograms/mouse administered subcutaneously) caused a significant reduction in splenomegaly in GVH mice. GVH splenocytes exhibited an augmented capacity to produce IFN-gamma when stimulated in culture with Con A or LPS. The IFN gamma produced in response to LPS stimulation was found to be derived from CD4+ and CD8+ T cells with little or no contribution from the NK1.1+ subpopulation of the GVH spleen. Treatment with IL-10 in vivo was found to diminish the capacity of splenocytes to produce IFN gamma when stimulated with LPS but not with Con A. IL-10 did not protect GVH mice from a lethal dose of LPS but caused a marked reduction in the serum TNF alpha response triggered by the LPS challenge. We conclude that IL-10 may be useful in controlling those clinical manifestations of acute GVHD that arise as a result of the activities of proinflammatory cytokines such as IFN gamma and TNF alpha.
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PMID:Inhibitory effects of recombinant human interleukin 10 on disease manifestations in a P-->F1 model of acute graft versus host disease. 770 86

This report describes the effects of the porphyrin photosensitizers, Photofrin and benzoporphyrin derivative (BPD) on the immunohematopoietic system of normal and immunosuppressed DBA/2 mice in the absence of activating light. Photofrin (10 and 25 mg/kg) significantly increased in vitro colony formation by cells of the granulocyte-macrophage lineage in the spleen and bone marrow. Splenic hypercellularity, splenomegaly and elevated levels of blood leukocytes were observed in these mice 7 days following Photofrin injection. Evidence that Photofrin influenced the lymphohematopoietic compartment was suggested by a significant increase in blood lymphocytes and a population of spleen cells identified by a monoclonal antibody (LR-1) reactive with mouse splenic B lymphocytes. Proliferative responses of spleen cells from Photofrin-treated mice to sub-optimal concentrations of Con A were greater than that observed for controls. However, spleen cell responses to LPS were unaltered by Photofrin administration. In contrast, BPD (10 mg/kg) did not alter any of the immunohematopoietic parameters studied. When Photofrin was administered to mice treated with the myeloablative agent 5-FU there was a significant acceleration in the recovery of total blood leukocyte and spleen cell numbers, relative to the controls. These studies demonstrate that, in addition to its previously documented activities as a photosensitizer, Photofrin can exert stimulatory effects upon murine hematopoiesis.
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PMID:Photofrin, but not benzoporphyrin derivative, stimulates hematopoiesis in the mouse. 828 41

Mice with a targeted disruption of the Rel/nuclear factor-kappaB family member RelB develop a complex inflammatory phenotype, myeloid hyperplasia, and splenomegaly due to extramedullary hemopoiesis. In this work, we report that RelB-deficient mice, in addition to the pathologic changes, were highly susceptible to infection by the facultative intracellular bacterium Listeria monocytogenes. RelB binds transcriptionally active kappaB motifs in the TNF-alpha promoter in normal cells, and in vitro studies with macrophages isolated from RelB-deficient animals revealed impaired production of TNF-alpha in response to LPS and IFN-gamma. RelB-deficient mice also were unable to mount a protective immune response against lymphocytic choriomeningitis virus. These results indicate a defective T cell-macrophage interaction and cytotoxic T cell response, respectively, in mice lacking RelB. Analysis of resting and specific Ab production demonstrated that while RelB is not required for the secretion of Ig isotypes that result from heavy chain class switching, it is necessary for normal production of Ag-specific IgG in response to T cell-dependent and -independent stimuli. Thus, RelB is not only essential for a normal hemopoietic system in the unchallenged animal, but also involved in various specific and nonspecific immune responses.
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PMID:Multifocal defects in immune responses in RelB-deficient mice. 916 38

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

Outer membrane proteins (OMPs) and rough lipopolysaccharide (R-LPS), the main surface antigens of Brucella ovis, display surface-exposed epitopes. Mixtures of monoclonal antibodies (mAbs) to both antigens were previously shown to protect mice against a B. ovis challenge. To further identify the antigens involved, seven mAbs against Brucella OMPs (Omp10, Omp16, Omp19, Omp25, Omp31, Omp2b and Omp1) and three to R-LPS were tested for protection either individually or in combinations. Significant reduction in spleen infection in challenged mice, relative to controls, was used as the protection criteri. Controls included nonimmunized mice and mice given an irrelevant, anti-O-polysaccharide (OPS), mAb. For comparison, a group received a mouse serum containing antibodies to both OMPs and R-LPS; this serum was prepared by immunization with a B. ovis hot-saline extract which, as described previously, induces protective immunity in mice and rams. Significant protection was observed with both mAbs to OMPs and R-LPS. mAbs to Omp16, Omp19 and Omp31 afforded the highest protection and prevented the development of splenomegaly. The protective effect of mAb to Omp31 was not interfered with by nonprotective mAbs in different mixtures. The data presented confirm the protective role of antibodies to OMPs and R-LPS against B. ovis, and identify several OMPs, especially Omp31, which are promising candidates for a subunit vaccine against ram epididymitis.
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PMID:Identification of protective outer membrane antigens of Brucella ovis by passive immunization of mice with monoclonal antibodies. 1086 93


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