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)

An antibiotic, prodigiosin 25-C, preferentially suppresses cytotoxic T lymphocytes (CTL) without affecting antibody production. Here, we investigated the effect of prodigiosin 25-C on delayed-type hypersensitivity (DTH), graft versus host reaction (GvHR) and allogeneic skin graft rejection. DTH reactions were markedly inhibited by ip treatment of the mice with prodigiosin 25-C. Cell transfer experiments indicated that prodigiosin 25-C exerted its suppressive effect on the late efferent phase rather than on the induction phase of DTH. Prodigiosin 25-C suppressed induction of anti-host CTL when GvHR was induced by iv inoculating splenocytes of parental C57BL/6 mice to adult unirradiated BDF1 mice. It had little effect on GvHR-induced splenomegaly observed 2 weeks after the inoculation, but significantly delayed the subsidence of splenomegaly as revealed 8 weeks later, suggesting that suppression of CTL converts immunosuppressive GvHR to immunostimulative one as reported by G. M. Shearer. However, reduction of interleukin-2 (IL-2) production and mitogen responses induced by GvHR were not rescued by prodigiosin 25-C treatment. Prodigiosin 25-C moderately prolonged survival of major histocompatibility (MHC)-mismatched skin grafts. Since the mode of action of prodigiosin 25-C is distinct from those of cyclosporin A and FK506, these results demonstrate potential usefulness of the antibiotic for a supplementary immunosuppressant.
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PMID:Immunomodulating properties of prodigiosin 25-C, an antibiotic which preferentially suppresses induction of cytotoxic T cells. 139 51

Immunotherapy with recombinant human interleukin-2 (IL-2) and allogeneic spleen cells has led to significant antitumor effects in B-cell leukemia- (BCL1) bearing mice following transplantation with T-lymphocyte-depleted allogeneic bone marrow cells. Graft versus leukemia (GVL) effects were studied in a model mimicking minimal residual disease following bone marrow transplantation (BMT). Lethally irradiated (BALB/c x C57BL/6)F1 recipients were reconstituted with 20 x 10(6) T-lymphocyte-depleted C57BL/6 bone marrow cells mixed with 10(4) to 10(6) BCL1 cells followed by administration of sequential increments of allogeneic C57BL/6 spleen cells; 10(6) cells on Day +1, 10(7) cells on Day +5, and 5 x 10(7) cells on Day +9, with or without concomitant IL-2 treatment (intraperitoneal injections of 20,000 U twice daily for 3 days) together with each spleen cell administration. All mice receiving 10(4)-10(6) BCL1 cells developed marked splenomegaly by Day +21 and all adoptive recipients of 10(5) spleen cells obtained from these mice developed leukemia within 21-36 days. Treatment of mice which received 10(4) BCL1 cells by either three courses of low dose IL-2 or three increments of allogeneic spleen cells alone and certainly by a combination of both resulted in normalization of splenomegaly on Day +21, but only adoptive recipients of 10(5) spleen cells obtained from mice treated by both allogeneic spleen cells and IL-2 (10/10) or allogeneic spleen cells alone (8/10) were disease free (greater than 100 days). Mice inoculated with 10(5) BCL1 cells developed mild splenomegaly on Day +21 after IL2 treatment alone, but showed no clinical evidence of disease following administration of allogeneic spleen cells or both allogeneic spleen cells and IL-2. Following adoptive transfer of 10(5) spleen cells obtained from each treated group no leukemia (greater than 100 days) was evident in recipients of spleen cells obtained from mice treated with both allogeneic spleen cells and IL-2 (10/10) whereas a partial effect was observed in mice treated by allogeneic spleen cells only (4/10). Mice inoculated with a high dose of BCL1 cells (10(6] showed some delay in onset of splenomegaly, but no curative antileukemic effects could be observed even following a synergistic combination of IL-2 and allogeneic spleen cells. Our data suggest that immunocompetent allogeneic lymphocytes may play an important role against leukemic relapse and thus cell therapy may be used therapeutically to treat minimal residual disease after BMT even following initial reconstitution with T-cell-depleted bone marrow cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of recombinant human interleukin-2 in conjunction with bone marrow transplantation as a model for control of minimal residual disease in malignant hematological disorders: I. Treatment of murine leukemia in conjunction with allogeneic bone marrow transplantation and IL-2-activated cell-mediated immunotherapy. 173 11

Allogeneic immunocompetent T cells injected into chicken embryos induce a graft-versus-host reaction (GVHR) whose most prominent manifestation is splenic hyperplasia. The highly inbred CC and CB strains of chickens used here are, respectively, homozygous for the B4 or B12 MHC haplotypes. By means of a panel of immunological reagents, including alloantisera and monoclonal antibodies against public domains of the T-cell receptor, CD4, CD8, and the inducible interleukin-2-receptor light chain (CD25), it is shown that the bulk of cells in the enlarged spleen are of host origin and do not express markers typical of mature T or B lymphocytes. Among recipient splenocytes, the quantitatively most important population consists of TCR alpha beta-TCR gamma delta- CD4-CD8+CD25+ (TCR0) lymphocytes. Donor cells encountered in the spleen prevalently exhibit a TCR alpha beta+CD4+CD8-CD25+ phenotype and proliferate in vivo. The data demonstrate that nonspecific host and potentially specific donor-derived cellular elements contribute to splenomegaly.
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PMID:T-lymphocyte subsets in the embryonic spleen undergoing a graft-versus-host reaction. 182 95

A case of acute adult T-cell leukemia-lymphoma (ATLL) was observed in northeast Italy, presenting with fever, lymphadenomegaly, splenomegaly, hypercalcemia and renal failure. Leukaemic cells were morphologically typical, expressed a T-cell CD4+ phenotype, did not display any helper functions, and grew in vitro under supply of exogenous interleukin-2. Antibodies to human T-cell lymphotropic virus (HTLV-I) were found in the serum, and the virus was isolated from leukaemic cells. The family members who could be tested were seronegative. The patient had never travelled outside Italy, had never received blood transfusions and did not belong to any known categories at risk of viral disease transmission. Present knowledge of the epidemiology of HTLV-I infection warns that other cases of HTLV-I induced disease are expected to occur outside already recognised endemic areas. This case suggests that untraceable, presumably short-term exposures can also account for HTLV-I transmission.
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PMID:HTLV-I positive adult T-cell leukaemia-lymphoma: report of a typical case from Italy. 198 Apr 80

Three lines of transgenic mice carrying the human T-cell lymphotropic virus type 1 tax gene have previously been reported to develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1329, 1987). Tumors from these mice and tumor cell lines derived from them expressed high levels of tax RNA and protein. They also expressed high levels of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene as measured by proliferative responses of FD-CP1 target cells using conditioned media from tumor cells and by Northern (RNA) blot analysis of RNA from tumors and tumor cell lines. Although other tissues, such as salivary glands and muscles, in the transgenic mice also expressed high levels of tax, they did not express the gene for GM-CSF. This indicates that tissue-specific cellular factors, in addition to tax, are required for GM-CSF gene expression. Systemic effects of excessive GM-CSF production were demonstrated by infiltration of polymorphonuclear leukocytes into tumor tissues which are not necrotic, by peripheral granulocytosis, and by splenomegaly resulting from myeloid hyperplasia. The interleukin-2 (IL-2) receptor was also found to be expressed by the tumors and tumor cell lines as measured by IL-2-binding and cross-linking studies. This is the first demonstration that the IL-2 receptor can be activated by tax in a nonlymphoid cell type. These in vivo findings are consistent with other reports which have demonstrated in vitro cis-regulatory elements within the 5'-flanking regions of the genes for GM-CSF and the IL-2 receptor which are responsive to trans activation by the tax gene.
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PMID:trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. 268 63

T-cell chronic lymphocytic leukemia (T-CLL) accounts for about 2% of the various types of CLL and can be subtyped into helper/inducer (h/i) and cytotoxic/suppressor (c/s) cell membrane phenotypes. Seven patients with CLL were shown to have T-CLL with a h/i cell membrane phenotype; four with monoclonal antibody reagents and three by demonstration of the E-rosette receptor and focal acid alpha naphthyl acetate esterase activity. The clinical courses, treatment responses, and laboratory findings of these seven patients were reviewed to determine the prognosis and unique clinicopathologic features of this subtype. Two patients presented with skin rashes, and five were diagnosed during evaluation for other medical problems. Initially, four patients had splenomegaly and two had lymphadenopathy, but none of the patients had hepatomegaly. Morphologic examination revealed uniform, small lymphocytes in three patients, and the lymphocytes had nuclear indentations in four patients. Sera from the three patients tested were negative for antibody to the human T-cell leukemia/lymphoma virus I. Peripheral blood mononuclear cells from one patient showed normal interleukin-2 production and lacked antibody-dependent cell-mediated cellular cytotoxicity and natural killer activity. Cytogenetic analysis was done on one patient, revealing an abnormal clone with several chromosomal abnormalities, including an X;14 translocation with a break point at 14q11. All patients required chemotherapy, and all died a median of 21 months from the time of diagnosis. The findings in these patients, in addition to those in 31 patients described in the literature, indicate that h/i T-CLL is associated with a poor prognosis and has distinct clinical and pathologic features that separate it from c/s T-CLL, adult T-cell leukemia/lymphoma, the cutaneous T-cell lymphomas, and B-CLL.
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PMID:T-cell chronic lymphocytic leukemia with a helper/inducer membrane phenotype: a distinct clinicopathologic subtype with a poor prognosis. 293 74

Although isolated intraepithelial lymphocytes (IEL) have been shown to have specific and non-specific cytolytic functions, their ability to proliferate in response to T-cell mitogens or alloantigens is controversial. Here we show that IEL from mouse small intestine do not respond to mitogens such as concanavalin A and phytohaemagglutinin A or in mixed lymphocyte reactions unless an accessory spleen cell is also present. Adherent spleen cells possess the most potent helper function, but a dividing accessory cell may also be required. Supernatants from stimulated lymphocytes also assist IEL to proliferate in vitro, particularly in the presence of adherent accessory cells. IEL could not mediate lethal graft-versus-host disease in irradiated hosts, but could produce popliteal lymph node hypertrophy or splenomegaly in unirradiated hosts. Thus, IEL have the potential for proliferative activities characteristic of T cells, but they require accessory cells and/or factors such as interleukin-2 for their function in vitro and in vivo.
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PMID:Functional characteristics of intraepithelial lymphocytes from mouse small intestine. II. In vivo and in vitro responses of intraepithelial lymphocytes to mitogenic and allogeneic stimuli. 294 64

Recombinant interleukin-2 (rIL-2) is a biologic response modifier that is capable of enhancing or restoring the cytolytic capacity of large granular lymphocytes (LGL). We utilized this biologic response modifier in the treatment of B-chronic lymphocytic leukemia (B-CLL), a disease frequently characterized by deficient or absent natural killer activity. B-CLL (n = 12) patients previously refractory to chemotherapy or with progressive disease post cessation of chemotherapy were eligible. rIL-2 was given as i.v. infusion (2 x 10(6) units/m2) over 2 h 5 times per week for 3 weeks as induction. Responding patients were placed on maintenance therapy. Although there were no complete or partial responses (by ECOG criteria) there was clear evidence of tumor reduction. Seven of 10 evaluable patients had a reduction of the peripheral blood B cell clone, 3 had node reduction and 2 had reduction in their splenomegaly. All patients experienced mild to moderate toxicity and 1 patient died while on induction therapy. Three B-CLL patients following induction rIL-2 treatment were placed back on chemotherapy because of progressive disease. Interestingly, these 2 B-CLL patients achieved extremely rapid and complete responses to chemotherapy which had previously been ineffective. These data suggest a possible role for rIL-2 in treatment of B-CLL.
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PMID:Evidence for tumor reduction in refractory or relapsed B-CLL patients with infusional interleukin-2. 326 9

Two cases of large cell lymphoma, B-cell type, primarily involving the red pulp of the spleen rather than the white pulp are described. A number of unusual features suggest that this may be a lymphoma originating from a distinct splenic B-cell lymphocyte whose origin may be the marginal zone of the spleen or the splenic cords. The patients presented with splenomegaly, cytopenias, and no peripheral lymphadenopathy. The gross appearance of the spleens was beefy red without tumor nodules. The tumor cells were primarily in the splenic cords and surrounding residual normal white pulp. There was a minimal hemic phase. The tumor cells had abundant cytoplasm, surface IgM, IgD, kappa, and FC receptors, tartrate-resistant acid phosphatase, but no alkaline phosphatase or interleukin-2 receptors. They had a similar DNA aneuploidy. The most unusual feature was that tumor cells in both cases had phagocytic properties. These lymphomas may be clinically more indolent than their follicular center counterparts.
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PMID:B lymphocytic lymphoma (large cell) of possible splenic marginal zone origin presenting with prominent splenomegaly and unusual cordal red pulp distribution. 329 36

The effect of parenteral administration of prostaglandins, 15-(s)-15-methyl PGE1 (M-PGE) and PGF2 alpha (PGF) on the pathophysiologic manifestations of active murine Schistosoma mansoni infection was examined. Both M-PGE and PGF resulted in a nearly 50% suppression of granuloma size following a 7-day course of treatment. M-PGE and PGF appeared to act by different mechanisms. The former caused a broad-spectrum immunosuppression manifested as reduced splenomegaly, B-cell proliferation, and antigen-specific interleukin-2 (IL-2) production as well as decreased granuloma macrophage Ia antigen expression, superoxide anion (O2-) production, and interleukin-1 (IL-1) production. In contrast, PGF did not ameliorate splenomegaly, but caused increases in splenic asialo-GM1 (natural killer cells) and L3T4 (helper) positive T cells. Prostaglandin F also reduced IL-2 production, but to a lesser extent that M-PGE. Although PGF caused reduced granuloma macrophage Ia expression and O2- production, it did not suppress IL-1 production. Overall, these data show that PGs can significantly modulate immunopathologic events in chronic granulomatous disease states.
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PMID:Modulation of murine schistosomiasis by exogenously administered prostaglandins. 349 Jul 91


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