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 retroviruses human T-cell lymphotrophic virus-I (HTLV-I) and HTLV-III/LAV (lymphadenopathy-associated virus) are clearly linked to human diseases. Patients with HTLV-I-positive neoplasms may respond transiently to traditional chemotherapy, but are not cured. For patients with acquired immune deficiency syndrome (AIDS) there is no curative therapy. In retroviruses of different species, viral propagation crucially depends on reverse transcriptase, an enzyme not present in normal mammalian cells and different from mammalian DNA polymerases, making it a target for specific inhibition. Reverse transcriptase has been well conserved through evolution: an LAV isolate contained a 250-amino-acid-long domain, presumably the reverse transcriptase core sequence, which has 21% homology to Moloney murine leukaemia virus (MoMLV). Because HTLV-III infects only humans and chimpanzees, we substituted murine retroviruses for in vivo evaluation of candidate anti-AIDS drugs after ascertaining similar inhibition in vitro of HTLV-III and MLVs, which were chosen for their short incubation time. The triphosphate of 3'-azido-3'-deoxythymidine (AZT) is incorporated into complementary DNA by retroviral reverse transcriptase, causing premature chain termination. Here we show that chronic AZT treatment of mice infected with Rauscher murine leukaemia virus complex (RLV) prevents infection of splenocytes and development of splenomegaly, and suppresses viraemia if started soon after inoculation. Starting AZT late in the course of disease still leads to significant prolongation of life; anaemia, however is a significant side-effect. By analogy, AZT may have a role in preventing retroviral disease in humans if started early after infection, and it may lead to significant survival gains even if started later in the course of disease.
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PMID:Suppression of mouse viraemia and retroviral disease by 3'-azido-3'-deoxythymidine. 346 67

A case of well-documented and -illustrated megakaryoblastic transformation is described in a patient with thrombocythemia passing through a stage of myelofibrosis without features of chronic granulocytic leukemia. Immunocytologic studies with the use of conventional and monoclonal antibodies against platelet membrane glycoproteins and electron microscopic investigations, demonstrating bull's-eye granules and platelet peroxidase positivity, proved the megakaryocytic differentiation of the blast cells. From the onset of the disease as well as during the megakaryoblastic transformation, the Philadelphia (Ph1) karyotype, 46XX t(9:22) (q34:q11), was found in peripheral blood and bone marrow cells as the only clonal abnormality. Southern blot analysis of DNA extracted from the blast cells revealed a rearrangement within the bcr on chromosome 22 similar to findings in chronic granulocytic leukemia. The presentation with excessive small and abnormal megakaryocytes in the initial and subsequent bone marrow and the rapid progressive myelofibrosis and splenomegaly differentiate the Ph1 chromosome-positive thrombocythemia from the chronic myeloproliferation of thrombocythemia in its primary form or associated with polycythemia vera.
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PMID:Philadelphia chromosome-positive thrombocythemia and megakaryoblast leukemia. 347 3

The clinical, morphological, immunological and molecular features of seven patients with a stable picture of chronic granular lymphocytosis, observed over a period of up to 4 years, were studied. Mild splenomegaly was detected in one patient, while lymphoadenopathy and hepatomegaly were absent. Surface marker analysis showed in five patients the common membrane phenotype of granular T-cell lymphocytosis (T3+, T4-, T8+, Leu-7+); of the remaining two, one presented an unusual phenotype (T3+, T4+, T8+) and the other showed a marked positivity with the Leu-11 and M1 monoclonal antibodies, but lacked the T3, T4, T8 antigens. Three cases had a low (less than 30%) expression of the T1 antigen. Functional studies showed that the proliferative response to PHA and the NK function were reduced in four of the seven cases. Molecular analysis, performed in six cases, revealed a monoclonal rearrangement of the T-cell receptor beta-chain gene in three, a polyclonal T-cell configuration in two and a germ-line arrangement in the last. All three monoclonal cases showed a depressed NK activity and two a reduced PHA response. The results of this study document the heterogeneity of granular lymphocyte expansions and suggest that the clonal or reactive nature of these often indolent proliferations, suspected on the basis of immunologic functional studies, may be recognized at the DNA level.
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PMID:Heterogeneity of large granular lymphocyte proliferations: morphological, immunological and molecular analysis in seven patients. 349 16

Quantitative determination of IgG and IgM antibodies to cardiolipin (anti-CL) was performed with a newly developed sensitive and specific ELISA method. We studied a cohort of 361 unselected patients with various autoimmune rheumatic diseases (ARD), 69 patients with thromboembolic phenomena (TEP) unassociated with ARD, and 267 healthy blood donors (HBD). Anti-CL of at least one immunoglobulin class were found in 42 (11.6%) of the ARD patients, in 3 (4.3%) of the TEP patients (2 with myocardial infarction and 1 with pulmonary emboli), and in 6 (2.3%) of the HBD. In ARD patients anti-CL were more prevalent in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Significant correlations included CNS involvement (particularly seizures) and features of immune hyperreactivity (splenomegaly-lymphadenopathy, ANA, and antibodies to Ro(SSA), U1-nRNP, and double-stranded DNA). No statistical correlation could be demonstrated between the presence of anti-CL and thrombotic events, hematologic disorders, or recurrent abortions in the ARD patients.
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PMID:Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients. 349 46

Highly purified populations of C57BL/6 (B6) L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to exert alloreactivity to class I vs. class II H-2 differences in vivo. B6 Lyt-2+ cells responded strongly to the class I different mutant, bm1, as manifested by DNA synthesis in the spleen of irradiated mice followed by entry of blast cells into thoracic duct lymph, induction of splenomegaly in newborn mice, production of lethal GVHD in irradiated mice, and skin allograft rejection. By all of these parameters, B6 Lyt-2+ cells showed almost total unresponsiveness to the class II-different mutant, bm12. Reciprocal results were observed with B6 L3T4+ cells, these cells responding strongly against bm12 but not against bm1. In the case of purified T cell subsets from other strains, CBA/Ca and B10.BR L3T4+ cells both responded well to a full H-2 difference. Responses by Lyt-2+ cells from these strains were weaker, especially for CBA/Ca cells. The implications of these findings are discussed.
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PMID:Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences. 351 63

Although ultraviolet (UV) light is generally harmful to patients with systemic lupus erythematosus, most clinical and immunologic studies of UV exposure have evaluated the effects of UV-B (280-320 nm). The long-wavelength UV-A band (320-400 nm), however, is less toxic than UV-B and has different immunologic actions. Therefore, we studied the effect of UV-A irradiation on survival and immunologic function in the (New Zealand black x New Zealand white)F1 hybrid mouse model of systemic lupus erythematosus. Twenty-one (New Zealand black x New Zealand white)F1 mice were treated with 3.5 joules/cm2/day of UV-A light for 5 days each week, beginning at age 10 weeks. A control group consisted of 20 untreated animals. All UV-A-irradiated mice survived to 32 weeks, compared with 12 of 20 mice in the nonirradiated group (P = 0.0013). Splenomegaly was significantly decreased in the irradiated mice (P less than 0.03). Mice that received UV-A treatment combined with depilation had significantly improved lymphocyte responses to phytohemagglutinin and lipopolysaccharide and significantly decreased levels of anti-DNA antibodies compared with mice that received neither treatment. Reductions in spleen size and anti-DNA antibody titer were significantly correlated with improved parameters of lymphocyte function. These results suggest that a relatively small dose of UV-A exerts significant therapeutic action in murine lupus, perhaps through an effect on immunologic regulation.
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PMID:Ultraviolet-A light prolongs survival and improves immune function in (New Zealand black x New Zealand white)F1 hybrid mice. 359 37

Recently, it has been suggested that there is an immunological mechanism in the etiology of idiopathic portal hypertension (IPH) and that the spleen plays a very important role. In the present study, the extract of human IPH spleen with Freund's complete adjuvant (FCA) was injected into rabbits, which were then examined both immunologically and pathologically. The results of the study are summarized as follows: Portal venous pressure was significantly increased in rabbits sensitized for more than one hundred days. Portal venous pressure of 175 mm H2O or more was observed in approximately 80% of the animals. Splenomegaly of 3.0 g or more was noted in all sensitized rabbits. Maximum spleen weight was 8.0 g. Peripheral blood cell counts decreased as the duration of sensitization increased. In immunological examination, smooth muscle antibodies, anti-DNA antibodies and antimitochondrial antibodies, were noted in some rabbits. In histological examination, the livers of sensitized rabbits in the early stage showed the infiltration of small round cells and fibrosis into Glisson's capsule. These changes were found to increase in later stages. In some rabbits, fibrosis around the interlobular bile duct was observed. The spleens of sensitized rabbits in the early stage showed splenitis with infiltration of small round cells and plasma cells. Sinus hyperplasia and fibrosis in the red and white pulp increased progressively as the period of sensitization lengthened. These results are similar in many respects to the clinical and pathological features of IPH. Thus, it is strongly suggested that the immunological mechanism may affect the pathogenesis of IPH in human.
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PMID:[Experimental studies on idiopathic portal hypertension (IPH)--prolonged sensitization of rabbits with human spleen of IPH]. 378 35

We investigated the relationship between the increased cell diameter of Lyt-2+ T cells and the development of autoimmune disease in aging NZB and NZB X NZW F1 hybrid (BW) mice. Individual animals were analyzed for Lyt-2+ T cell size (by narrow-angle forward light scatter), anti-erythrocyte autoantibodies, anemia, proteinuria, and splenomegaly. The peak light scatter of the Lyt-2+ T cells correlated with the level of anti-erythrocyte autoantibodies and severity of hemolytic anemia, but not with proteinuria or splenomegaly. The cell size of this T cell subset did not increase in old BW or in NZB mice homozygous for the xid gene (NZB.xid). The in vivo administration of bacterial lipopolysaccharide to young NZB mice did not stimulate the enlargement of Lyt-2+ T cells. Ly-2+ T cells from old NZB mice could be stimulated by concanavalin A (Con A) to express interleukin 2 (IL 2) receptors and to synthesize DNA in vitro. However, in vivo administration of Con A to old NZB mice did not induce the expression of IL 2 receptors on Lyt-2+ T cells. Further, in vivo T suppressor function was impaired in old NZB mice with enlarged Lyt-2+ T cells. Thus, the enlargement of Lyt-2+ T cells in old NZB mice appears related to impaired T cell function in vivo and is associated with the development of anti-erythrocyte autoantibodies and autoimmune hemolytic anemia.
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PMID:Enlargement of Lyt-2-positive T cells is associated with functional impairment and autoimmune hemolytic anemia in New Zealand Black mice. 392 48

Virazole is a synthetic nucleoside active in tissue culture against at least 16 DNA and RNA viruses. Applied topically, it inhibits herpetic keratitis in rabbits and tail lesions induced by herpes, vaccinia, and vesicular stomatitis viruses in mice. Injected intraperitoneally into mice, it inhibits splenomegaly and hepatomegaly induced by Friend leukemia virus and respiratory infections caused by influenza A(O), A(2), and B viruses and parainfluenza 1 virus. infections is also effective.
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PMID:Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. 434 Sep 49

Lead acetate was administered continuously in the drinking water to CD-1 male mice beginning at 4 weeks of age. An LD(10-20) of the lytic viruses or 300 plaque-forming units of RLV was inoculated intrapertioneally at 6 weeks of age. Lead increased the response of the mice to all classes of viruses against which it was tested: an RNA picornavirus-encephalomyocarditis (EMCV), a DNA herpesvirus-pseudoribies, an RNA leukemia-virus-Rauscher leukemia (RLV), an RNA arbovirus B-St. Louis encephalitis, and an RNA arbovirus A-western encephalitis. Most studies were performed between lead and EMCV. Increases in EMCV mortality in lead treated mice over controls ranged from 2x at a lead level of 0.004M to 7x (100% mortality) at a 0.1M lead level. Splenomegaly with spleens 800 to 1100 mg in weight containing high titers of RLV occurred in lead (0.03M)-treated mice 3 and 6 weeks after RLV inoculation; spleens or RLV controls were normal in weight (200 mg) and were free of virus. Lead did not reduce the protective effect of mouse interferon (IF) against the lethal action of EMCV, but it did repress the EMCV antiviral effect of poly I/poly C (PIC) and of Newcastle disease virus (NDV) against EMCV mortality. These data indicate several new facts concerning adverse effects lead may have on an animal: (1) lead aggravates viral disease, most likely in part, through reduced IF synthesis; (2) lead represses the anti-EMCV protective effects of both PIC and of NDV, which, in other reports, were shown to induce IF in radioresistant macrophages (PIC) or in radiosensitive lymphocytes (NDV); (3) lead may then be said to repress IF induction in two kinds of cells; (4) however, lead does not inhibit IF action.
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PMID:Lead aggravates viral disease and represses the antiviral activity of interferon inducers. 436 44


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