Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 72-year-old woman was referred to our hospital for evaluation of leukocytosis revealed by a medical examination. Her physical examination demonstrated no splenomegaly and no palpable lymph nodes. Her white cell count was 10,900/microl with atypical lymphocytosis (84.5%). Her hemoglobin concentration was 10.4 g/dl, and platelet count 151,000/microl. On peripheral blood smears, the atypical lymphocytes had a hairy cell-like appearance, and phase-contrast microscopic and transmission electron microscopic findings revealed the lymphocytes had many long surface microvilli. Flowcytometric analysis of peripheral blood lymphocytes identified expanded B-lymphocytes as having the IgG+, CD5- CD10- CD11c+ CD19+ CD20+ CD23- CD25- and CD103- cell surface phenotype. Serum electrophoresis disclosed polyclonal elevation of IgG and IgM (2620 mg/dl and 840 mg/dl, respectively). No light-chain restriction and a polyclonal VH gene rearrangement pattern indicated the polyclonal proliferation of B cells. The patient was a nonsmoker and had HLA-DR4, as in previous reports which have suggested an association between hairy B-cell lymphoproliferative disorder (HBLD) and HLA-DR4. No chromosome 3 abnormality was observed. These findings were consistent with the characteristics of HBLD, but differed in some respects from those of persistent polyclonal B-cell lymphocytosis (PPBL). Therefore, we diagnosed this patient as having HBLD.
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PMID:[Polyclonal B-cell lymphocytosis with hairy cell appearance: hairy B-cell lymphoproliferative disorder]. 1786 2

Hairy cell leukemia (HCL) is an indolent B-cell lymphoproliferative disease, characterized by splenomegaly and pancitopenia related to this. The lymphocytes present characteristic citoplasmatic projections and are positive for tartrate-resistant acid phosphatase (TRAP). Immunophenotyping is necessary to identify the co expression of CD103, CD25, CD11c associated with a typical B-cell clonally pattern and to make a differential diagnosis from other indolent malignancies. Despite the indolent clinical course, treatment is required to resolve symptoms related to splenomegaly and to reduce the incidence of severe infections that are the major complications and a common cause of death. In the past the treatment was only able to resolve the symptoms. In the revised literature, purine analog have been identified as the treatment of choice for this disease. Cladribrine (2-CdA) is able to induce more than 80% of complete remission and is also effective in relapsed patients. Rituximab after 2-CdA treatment can obtain a molecular response in most cases. The introduction of purine analog, and recently of Rituximab, in association with conventional chemotherapy can modify the clinical course of the disease with low toxicities.
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PMID:Hairy Cell Leukemia. 1792 10

A 78-year-old woman was admitted to our hospital because for pancytopenia and splenomegaly. The bone marrow examination revealed hairy cells in 11.6% of all nucleated bone marrow cells. Hairy cells were positive for tartaricresistance acid phosphatase (TRAP) staining, CD2, CD11c, CD19, CD20, sIgD, CD25, CD103 and k chain. In addition, abdominal enhanced computed tomography (CT) demonstrated splenomegaly and multiple nodular early stains in the spleen. She was diagnosed as having typical hairy cell leukemia (HCL). The patient was treated with cladribine infused continuously for 7 days at a dose of 0.09 mg/kg/day, which induced partial remission without severe adverse effects. Purine analogs such as cladribine and pentostatine are considered first-line agents for patients with HCL. Treatment with cladribine achieved a high overall response rate for patients with HCL and was safe even in elderly patients like ours. It is necessary to observe carefully the complications of severe infections, second malignancies and relapse of HCL after treatment with cladribine.
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PMID:[Successful use of cladribine in the treatment of an elderly woman with typical hairy cell leukemia]. 1803 31

Tago, F., Tsukimoto, M., Nakatsukasa, H. and Kojima. S. Repeated 0.5 Gy Gamma Irradiation Attenuates Autoimmune Disease in MRL-lpr/lpr Mice with Suppression of CD3(+)CD4(-)CD8(-)B220(+) T-Cell Proliferation and with Up-regulation of CD4(+)CD25(+)Foxp3(+) Regulatory T Cells. Radiat. Res. 169, 59-66 (2008). MRL-lpr/lpr mice are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MRL-lpr/lpr mice by repeated gamma irradiation (0.5 Gy each time). In this study, we investigated the mechanisms of this attenuation by measuring the weight of the spleen and the population of highly activated CD3(+)CD4(-)CD8(-)B220(+) T cells, which are characteristically involved in autoimmune pathology in these mice. Splenomegaly and an increase in the percentage of CD3(+)CD4(-)CD8(-)B220(+) T cells, which occur with aging in nonirradiated mice, were suppressed in irradiated mice. The high proliferation rate of CD3(+)CD4(-)CD8(-)B220(+) T cells was suppressed in the irradiated animals. The production of autoantibodies and the level of IL6, which activates B cells, were also lowered by radiation exposure. These results indicate that progression of pathology is suppressed by repeated 0.5-Gy gamma irradiation. To uncover the mechanism of the immune suppression, we measured the regulatory T cells, which suppress activated T cells and excessive autoimmune responses. We found that regulatory T cells were significantly increased in irradiated mice. We therefore conclude that repeated 0.5-Gy gamma irradiation suppresses the proliferation rate of CD3(+)CD4(-)CD8(-)B220(+) T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.
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PMID:Repeated 0.5-Gy gamma irradiation attenuates autoimmune disease in MRL-lpr/lpr mice with suppression of CD3+CD4-CD8-B220+ T-cell proliferation and with up-regulation of CD4+CD25+Foxp3+ regulatory T cells. 1815 52

A 72-year-old Japanese man presented with 43.1 x 10(9)/l hairy cells and apparent splenomegaly. The leukemia cells had unevenly distributed microvilli and round nuclei with dense chromatin and one or two clear nucleoli, lacked CD25 expression and were negative for tartrate-resistant acid phosphatase. The case was diagnosed as hairy cell leukemia variant (HCLv) and proved refractory to various chemotherapies, including cladribine, pentostatin, interferon-alpha, CHOP and rituximab. Because of the CD52 expression, we treated the patient with alemtuzumab. Pretreatment with 22.5 Gy to the spleen reduced the spleen size from 12 to 4 cm below the left costal margin, and the number of circulating leukemic cells decreased from 229.0 to 63.6 x 10(9)/l. Subsequent administration of 24.0 mg of alemtuzumab eliminated leukemic cells in the peripheral blood on day 12, and the spleen was not palpable after the administration of 54.0 mg of alemtuzumab. In vitro treatment with alemtuzumab confirmed the cytotoxic effect against the patient's leukemic cells in the presence of complement. This is the first report showing clinical effectiveness of splenic irradiation and alemtuzumab against refractory HCLv.
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PMID:Effective treatment of a refractory hairy cell leukemia variant with splenic pre-irradiation and alemtuzumab. 1825 14

Hairy cell leukemia is an indolent B-cell non-Hodgkin's lymphoma with a characteristic presentation of pancytopenia, splenomegaly, and circulating hairy cells. An immunophenotypic pattern of CD11c, CD25, and CD103 expression. TRAP staining, reticulin deposition, and morphology of bone marrow and circulating cells help establish the diagnosis. Although up to 10% of patients might not require systemic treatment, for the vast majority effective treatments are available with the purine-nucleoside analogues cladribine and pentostatin. Cladribine is considered the drug of choice in the first-line setting due to the very high complete remission rate and prolonged duration of response following a single 7-day infusion. Cladribine and pentostatin both have unique but different mechanisms of action, with a lack of cross-resistance between them, which might be exploited in the relapsed or refractory disease setting. Therapy for relapsed and refractory patients also includes novel biologic agents as well as splenectomy. Despite the effective treatment options, the prospect of cure remains elusive due to the frequent presence of MRD even in complete responders. Future studies employing combination therapies targeting the eradication of MRD will hopefully improve relapse-free survivals as well as overall survival, and might even offer the prospect of cure.
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PMID:Hairy cell leukemia. 1828 87

Suppression of tumor-specific T cell sensitization is a predominant mechanism of tumor escape. To identify tumor-induced suppressor cells, we transferred spleen cells from mice bearing progressive MCA205 sarcoma into sublethally irradiated mice. These mice were then inoculated subdermally with tumor cells to stimulate T cell response in the tumor-draining lymph-node (TDLN). Tumor progression induced splenomegaly with a dramatic increase (22.1%) in CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) compared with 2.6% of that in normal mice. Analyses of therapeutic effects by the adoptive immunotherapy revealed that the transfer of spleen cells from tumor-bearing mice severely inhibited the generation of tumor-immune T cells in the TDLN. We further identified MDSC to be the dominant suppressor cells. However, cells of identical phenotype from normal spleens lacked the suppressive effects. The suppression was independent of CD4(+)CD25(+) regulatory T cells. Intracellular IFN-gamma staining revealed that the transfer of MDSC resulted in a decrease in numbers of tumor-specific CD4(+) and CD8(+) T cells. Transfer of MDSC from MCA207 tumor-bearing mice also suppressed the MCA205 immune response indicating a lack of immunologic specificity. Further analyses demonstrated that MDSC inhibited T cell activation that was triggered either by anti-CD3 mAb or by tumor cells. However, MDSC did not suppress the function of immune T cells in vivo at the effector phase. Our data provide the first evidence that the systemic transfer of MDSC inhibited and interfered with the sensitization of tumor-specific T cell responses in the TDLN.
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PMID:Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. 1871 1

We report an unusual case of hairy cell leukemia (HCL) in a 55-year-old male who presented with fatigue, increased bruising, leukocytosis, anemia, thrombocytopenia and moderate splenomegaly without lymphadenopathy. Microscopically, a monomorphic population of small to medium-sized lymphoid cells with bean-shaped nuclei, ground glass chromatin and fine cytoplasmic projections was identified in the peripheral blood and bone marrow. Flow cytometric immunophenotyping demonstrated a monoclonal population of mature B cells with coexpression of CD25, CD11c and CD103. The clonal B-cells all exhibited homogenous expression of CD20 and uniform light scatter characteristics. However, CD103 expression was present in only half of the clonal B-cells. Flow cytometric cell cycle analysis using DRAQ5 DNA dye in intact live cells showed that both the CD103-positive and CD103-negative cell subsets exhibited a low S-phase fraction with no significant difference between the two subpopulations. Clinical remission was achieved by treatment with 2-chlorodeoxyadenosine. Variant and atypical cases of HCL have been described with varying intensity of CD11c, loss of CD25, aberrant expression of CD10, and lack of CD103 expression. However, the lack of CD103 in only a subset of the malignant cells in our case is an immunophenotypic aberrance that, to our knowledge, has not been previously reported.
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PMID:Hairy cell leukemia with unusual loss of CD103 in a subset of the neoplastic population: immunophenotypic and cell cycle analysis by flow cytometry. 1878 8

Hemophagocytic lymphohistiocytosis is a rare condition characterized by highly stimulated but inactive immune response. The disease may be inherited or acquired due to infections, collagen vascular diseases and malignancies. The pathological hallmark of the syndrome is aggressive proliferation of macrophages and histiocytes. Decreased NK cell activity results in increased T cell activation resulting production of large quantities of interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha) and granulocyte macrophage colony stimulating factor (GM-CSF). This causes sustained macrophage activation and tissue infiltration as well as production of interleukin 1 (IL1) and interleukin 6 (IL6).The resulting inflammatory reaction causes extensive damage and associated symptoms. Patients with HLH commonly present with high fever, anemia and splenomegaly. Minimal diagnostic parameters are a complete hemogram, liver function test, serum triglycerides and ferritin, coagulation profile including fibrinogen and bone marrow aspiration. Two highly sensitive diagnostic marker are an increased plasma concentration of the alpha chain of soluble IL2 receptor (CD25) and impaired NK cell activity. Hyperinflammation can be treated with steroid, Cyclosporine prevents T lymphocytes and immunoglobulin infusion helps to control the infection. Etoposide may be life saving specially in case of HLH with Ebstein Barr Viruses infection. The Histiocyte Society in 1994 developed a common treatment protocol (HLH-94). In January 2004 a revised HLH treatment protocol was opened entitled HLH-2004, which is based on HLH-94 with minor modifications. There is a high remission rate on the HLH-94 and HLH-2004 treatment protocols.
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PMID:Hemophagoctic lymphohistiocytosis--recent concept. 1882 26

Certain viral nucleic acids aggravate autoimmunity through nucleic acid-specific TLR. Viral 5'-triphosphate RNA (3P-RNA) and double-stranded non-CpG DNA induce antiviral immunity via TLR-independent pathways but their role in autoimmunity is unknown. Transient exposure of 16-wk-old MRL(lpr/lpr) mice to 3P-RNA aggravated lupus nephritis by increasing IFN signaling and decreasing CD4(+)CD25(+) T cells. By contrast, transient exposure to non-CpG DNA exacerbate lupus nephritis in association with splenomegaly, lymphoproliferation, hypergammaglobulinaemia and increased B220(+)CD138(+) plasma cells. Both, 3P-RNA and non-CpG DNA increased glomerular complement factor C3c deposits but both nucleic acid formats were less potent in aggravating renal pathology as compared with CpG DNA. 3P-RNA and non-CpG DNA also localized to the glomerular mesangial cells and activated cultured mesangial cells to produce IL-6. We conclude, 3P-RNA or non-CpG DNA both trigger autoimmune disease in MRL(lpr/lpr) mice by specifically activating adaptive immunity but similarly enhance inflammation on the tissue level.
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PMID:Viral 5'-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses. 1900 28


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