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)

Hematological effects of tilorone, an interferon inducer, on the hematopoietic cell system of normal CBA/Ca mice and on the development of Friend virus (FV-P)-induced polycythemia in DBA/2 mice were studied. In normal mice 80 mg/kg IP had a marked depressive effect on pluripotent (CFU-s), granuloid committed (CFU-C), and erythroid committed (CFU-E) stem cells with regeneration between days 5 and 12. In bone marrow smears only lymphopenia was detected. Treatment of mice before FV-P infection caused a slight retardation in the development of the splenomegaly and the transformation of bone marrow cells to Ep independence. Repeated treatment after FV-P infection also reduced the increase in spleen weight and the development of reticulocytosis, but the Ep independence of bone marrow and spleen cells was not influenced. In vitro exposure of normal cells and cells from FV-P-infected animals to the drug showed the same sensitivity of colony growth in normal as well as in Ep-independent CFU-E. The action of the drug on Friend leukemia is at least in part considered a toxic effect on the hematopoietic stem cell system.
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PMID:Effects of tilorone on hemopoietic stem cells and on the development of Friend leukemia. 746 Jan 94

The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with HCL diagnosed over 25 years. We analysed this large series of patients with the aim of providing an evaluation of changes in clinical presentation, impact of initial therapy and modifications in prognostic factors over the period of two decades. Over time, a progressive down-staging of the disease at the onset, along with a reduction of patients with severe anemia and marked splenomegaly, has been observed. A second malignancy was found in 3.7% of patients, mostly detected several years after the onset of HCL. A striking improvement of survival rates has been observed, from 58.9% survival at five years for patients diagnosed before 1985 to 87.5% at five years for patients diagnosed after 1985 (p < 0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas after 1985, clinical stage and the number of leukocytes correlated better with patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy, steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9% (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our findings suggest that IFN has improved the prognosis of HCL, and that it must be considered a good initial treatment for patients with HCL.
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PMID:Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia. 751 10

In 1985, Cancer and Leukemia Group B initiated a multi-institutional study to define the role of interferon alpha in therapy of previously untreated active hairy cell leukemia (HCL). This is a long-term follow-up report of the study. Fifty-five evaluable patients were treated with recombinant interferon-2b 2 million units/m2 subcutaneously three times a week for 1 year. Treatment was well tolerated; toxicity mainly consisted of flu-like syndrome and pancytopenia, both of a transient nature. Seventy-three percent of patients had objective beneficial responses with 8.3 months median time to achieve at least a partial response (PR). After 1 year of therapy, the patients have been observed for a median of 5 years. There was a continual trend towards relapse throughout this period but 28% have remained in remission beyond 6 years. Forty-six patients (83%) are alive at 6 years. Among the 40 patients who achieved at least a PR, there were 28 with splenomegaly at the beginning of study: the spleen size was reduced in all with interferon alpha therapy and none required splenectomy. This study confirms the results of other investigators, and demonstrates that recombinant alpha interferon-2b is an effective agent for treatment of hairy cell leukemia.
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PMID:Recombinant alpha-2b-interferon in therapy of previously untreated hairy cell leukemia: long-term follow-up results of study by Cancer and Leukemia Group B. 763 Jan 81

The effectiveness of domestic alpha 2-interferon preparation reaferon was studied in vivo and in vitro for eradication of pathological hemopoietic clone in chronic myeloid leukemia. Reaferon administration for 1-30 months produced cytogenetic remission in 7%, hematological remission in 21%, partial hematological remission in 36% of the patients. Reaferon is indicated in chronic myeloid leukemia without splenomegaly. In the disease progression reaferon is uneffective. Mechanism of reaferon therapeutic action comprises three components: a direct antiproliferative effect on hemopoietic precursor cells, activation of cellular immunity, an effect on stem cell microenvironment.
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PMID:[Experience with the use of reaferon (alfa 2-interferon) for treating patients with chronic myeloleukemia]. 766 86

Interleukin (IL)-12 synergizes with other cytokines to stimulate the proliferation and differentiation of early hematopoietic progenitors in vitro. However, in vivo administration of IL-12 decreases peripheral blood counts and bone marrow hematopoiesis. Here, we used interferon (IFN) gamma receptor-deficient (IFN gamma R-/-) mice to investigate whether the in vivo inhibition of hematopoiesis by IL-12 is indirectly mediated by IL-12-induced IFN-gamma. IL-12 administered for 4 d (1 microgram/mouse per day) resulted in lower peripheral blood counts and a 2-fold decrease in bone marrow cellularity in wild-type mice, but not in IFN gamma R-/- mice. Bone marrow hematopoietic progenitors were decreased after IL-12 treatment in wild-type mice, but rather increased in IFN gamma R-/- mice. Splenic cellularity was 2.3-fold higher after IL-12 administration in wild-type mice, largely due to natural killer (NK) cell and macrophage infiltration together with some extramedullary hematopoiesis. In IFN gamma R-/- mice, spleen cellularity was less increased, there were fewer infiltrating NK cells, but a strong extramedullary hematopoiesis. Thus, alterations mediated by IL-12-induced IFN-gamma include reduction in bone marrow cellularity and hematopoietic progenitors, as well as pronounced splenomegaly, largely caused by NK cell infiltration. In the absence of IFN-gamma signaling, IL-12 promotes hematopoiesis, consistent with its in vitro activities.
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PMID:The stimulatory effects of interleukin (IL)-12 on hematopoiesis are antagonized by IL-12-induced interferon gamma in vivo. 772 64

Mouse AIDS (MAIDS) develops in mice infected with a mixture of replication-competent ecotropic and mink lung cell focus-inducing murine leukemia viruses and an etiologic replication-defective virus. Helper viruses are not required for induction of MAIDS, but the time course of disease is accelerated in their presence. To understand the possible contributions of ectropic murine leukemia viruses to MAIDS pathogenesis, we biologically cloned a series of viruses from the MAIDS-inducing LP-BM5 virus mixture. These viruses were examined for replication in tissues of infected mice and for effects on the immune system. All virus stocks replicated efficiently in mice. Infected animals showed slight lymphadenopathy and splenomegaly due primarily to B-cell proliferation associated with differentiation to immunoglobulin secretion resulting in twofold increases in serum immunoglobulin M levels; however, B-cell responses to helper T-cell-independent antigens were increased rather than decreased as in MAIDS. Analyses of CD8+ T-cell function showed that cytotoxic T-lymphocyte responses to alloantigens were comparable in control and infected mice. Finally, we showed that infection resulted in enhanced expression of transcripts for interleukin-10, interleukin-4, and gamma interferon. These cytokines can all contribute to B-cell activation and may promote the expansion of a target cell population for the MAIDS defective virus.
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PMID:Effects of exogenous, nonleukemogenic, ecotropic murine leukemia virus infections on the immune systems of adult C57BL/6 mice. 776 77

We report here two cases of a previously undescribed myeloproliferative disorder. Both were young adult males who presented with generalized lymphadenopathy, splenomegaly, leukocytosis, polycythemia, and persistent thrombocytopenia. The leukocyte alkaline phosphatase (LAP) score was low in both cases, and the bone marrow was hypercellular without dysplasia or fibrosis, but lacked the Philadelphia chromosome, BCR gene rearrangement, or other karyotypic abnormalities. The clinical course was indolent in each case. One patient died from an unusual "blast crisis" after 12 years, while the second patient remains in a complete hematologic remission on hydroxyurea and alpha interferon 4 years from diagnosis. Interestingly, changes in therapy in this patient have consistently resulted in precise and concerted fluctuations in his blood counts, with the red and white cells cycling together and the platelets and mean corpuscular volume (MCV) changing concomitantly but in the opposite direction. This unique myeloproliferative disorder is distinguishable from all previously described forms of chronic myeloid leukemia and other myeloproliferative syndromes.
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PMID:A new myeloproliferative syndrome. 786 27

Protective immunity against Brucella abortus is mediated by acquired cellular resistance, with gamma interferon (IFN-gamma)-producing T cells playing a key role. Interleukin-12 (IL-12) is a cytokine that has a profound effect on the induction of IFN-gamma-producing Th1 and NK cells. Here we report that depletion of endogenous IL-12 before infection of mice significantly exacerbated brucella infection. IL-12-depleted mice also had reduced splenomegaly resulting from infection and showed a decrease in percentage and absolute numbers of macrophages compared with those in control infected mice. Furthermore, spleen cells from IL-12-depleted mice had a reduced ability to produce nitrite, a product of activated macrophages. This could be the result of the low production of IFN-gamma by splenic T cells observed in the IL-12-depleted mice. The mechanism whereby IL-12 controls antibacterial resistance is discussed.
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PMID:Endogenous interleukin-12 is involved in resistance to Brucella abortus infection. 789 Mar 99

Hairy cell leukemia is a rare chronic B-lymphocyte malignancy characterized by pancytopenia, splenomegaly, immunological abnormalities and morphologically typical neoplastic mononuclear cells in blood and bone marrow. Until recently the disorder was treated with splenectomia and/or alpha-interferon. Intravenous infusion of 2-chloro-deoxy-adenosine (2-CdA) is a new and efficacious treatment principle making hairy cell leukemia a potentially curable disease. A Nordic cooperative study is currently examining the effects of 2-CdA given subcutaneously for seven days. 19 Norwegian patients are included so far, with encouraging results. The long-term effect of 2-CdA is not yet known. The high remission frequency, the short duration of the treatment and the few side effects make this drug a natural first choice in treating hairy cell leukemia.
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PMID:[Progress in the treatment of hairy cell leukemia. Subcutaneous administration of 2-chloro-deoxy-adenosine for 7 days]. 791 11

Hairy cell leukaemia is a rare chronic lymphoproliferative disease, characterized by splenomegaly, pancytopenia and recurrent infection. The characteristic 'hairy cells', present in the peripheral blood and bone marrow, are the hallmark of this leukaemia. The disease has a chronic, progressive course, and the majority of patients afflicted by it require therapy. The most common reason to initiate treatment is neutropenia with or without associated infectious complications, or the development of severe thrombocytopenia. Therapeutic options in hairy cell leukaemia include splenectomy, interferon administration, or the use of chemotherapeutic agents such as pentostatin (2'-deoxycoformycin) and 2-chlorodeoxyadenosine. Splenectomy is still indicated in the treatment of young patients with significant splenomegaly and only minimal bone marrow involvement. Interferon treatment induces remission in approximately 90% of patients with hairy cell leukaemia, but complete remission is obtained in only 5-10%. The development of antibodies against interferon was initially considered a major problem, but longer follow-up of patients who developed antibodies has shown that it is transient and does not have a significant impact on the overall response to treatment. Pentostatin induces complete remission in 60-70% of patients and partial remission in 20-40%. 2-Chlorodeoxyadenosine is a very promising drug in the treatment of this rare leukaemia, inducing long-lasting complete remission in approximately 80% of patients. While interferon does not cure the disease, it is possible that a subset of patients treated with pentostatin or 2-chlorodeoxyadenosine are cured. Longer follow-up of these patients will determine whether this is true.
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PMID:Hairy cell leukaemia. 791 37


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