Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juvenile chronic myelogenous leukemia (JCML) is a rare pediatric malignancy characterized by marked hepatosplenomegaly, leukocytosis with prominent monocytosis, elevated fetal hemoglobin, no Philadelphia chromosome, and generally a poor prognosis. In vitro, JCML peripheral blood granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) demonstrate the unique characteristic of "spontaneous" proliferation at very low cell densities in the absence of exogenous growth factors. The "spontaneous" CFU-GM proliferation can be abolished by prior adherent cell (monocyte) depletion, suggesting a paracrine mode of cellular proliferation. Although previous studies using a [3H]thymidine ([3H]TdR) incorporation assay suggested an important role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in JCML, many non-growth factor-related reasons for [3H]TdR incorporation and the relatively low level of inhibition of [3H]TdR uptake left those conclusions open to question. Therefore, we performed clonal CFU-GM assays, which more specifically reflect cytokine effects on CFU-GM, using JCML peripheral blood mononuclear cells (PBMNC) and neutralizing antibodies against GM-CSF, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating (M-CSF), interleukin 3 (IL-3), interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), interleukin 4 (IL-4), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma). Cultures containing anti-GM-CSF alone inhibited "spontaneous" JCML CFU-GM by 87% +/- 9% (mean +/- standard error of the mean [SEM]). No other anti-cytokine antibody produced a significant inhibition of CFU-GM growth. Various combinations of antibodies, excluding anti-GM-CSF, failed to demonstrate any synergistic inhibitory effects upon CFU-GM. Because this apparent paracrine cellular stimulation could be due to excessive cytokine production, by monocytes or other accessory cells, we examined cytokine levels in conditioned media from various JCML cell populations using enzyme-linked immunosorbent assays (ELISAs). Monocytes from only a minority of JCML patients produced higher than normal quantities of GM-CSF, G-CSF, IL-1 beta, IL-6, and/or TNF alpha, but no obvious pattern could be discerned. Further, only 7 of 15 JCML monocyte-conditioned media (MCM) had elevated GM-CSF, and 6 of 15 JCML patients had normal levels of all nine cytokines tested. The monocyte depletion experiments and the inhibition experiments with anti-cytokine antibodies taken together demonstrate clearly that the "spontaneous" growth of JCML CFU-GM in vitro critically depends on at least one monocyte-derived growth factor, GM-CSF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of monocyte-derived hemopoietic growth factors in the regulation of myeloproliferation in juvenile chronic myelogenous leukemia. 191 2

A patient with chronic myeloproliferative disorder (CMPD) developed Sweet's syndrome during granulocyte colony-stimulating factor (G-CSF) therapy. A 61-year-old man with essential thrombocythemia was treated with busulfan intermittently since April, 1991. In February, 1993, hepatosplenomegaly with leukoerythroblastosis arose and a diagnosis of myelofibrosis with extramedullary hematopoiesis in the spleen was established. For alleviation of left hypochondralgia due to splenomegaly, he received splenic irradiation in September, 1993. Soon after the irradiation, his peripheral blood revealed pancytopenia and then administration of rhG-CSF was begun on the 9th of October, 1993. One week after G-CSF therapy, he became feverish and painful eruptions on the face and the upper extremities appeared and enlarged. Skin biopsy resulted in a diagnosis of Sweet's syndrome. Treatment with oral prednisone, 30 mg daily, was begun, and rapid and significant improvement of the skin lesions was obtained. The pathogenesis of Sweet's syndrome remains obscure, but careful follow up is necessary for patients during G-CSF therapy with respect to development of Sweet's syndrome.
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PMID:[Sweet's syndrome in a patient with chronic myeloproliferative disorder during recombinant human granulocyte colony stimulating factor therapy]. 754 Feb 25

A 20-year-old Japanese man developed generalized, subcutaneous, painless nodules, fever, abnormal liver function, serosal effusions, hepatosplenomegaly, lymphadenopathy and anemia. Skin biopsies revealed lobular panniculitis with a morphologically benign histiocytic infiltration and prominent phagocytosis. Atypical T lymphocytes were also present in the skin and liver. The diagnosis given was aggressive cytophagic histiocytic panniculitis (CHP) or aggressive subcutaneous panniculitic T cell lymphoma (SPTCL). He received cyclophosphamide, doxorubicin, and vincristine on day 1, prednisolone on days 1-5, and etoposide on days 1, 3 and 5 (CHOP-E), with the support of granulocyte colony-stimulating factor. This regimen was repeated every 2 weeks and complete clinical remission (CCR) was attained after three cycles of CHOP-E. As the clinical course of aggressive CHP is recurrent and often fatal, he was given high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT), after five cycles of CHOP-E. He has remained in CCR for 12 months after APBSCT. High-dose chemotherapy followed by APBSCT is considered to be one of the most beneficial therapies for patients with aggressive CHP and aggressive phase SPTCL.
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PMID:Effective high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis. 924 23

We report on an 83-year-old male with chronic neutrophilic leukemia (CNL) associated initially with IgM monoclonal gammopathy and later with B cell chronic lymphocytic leukemia (CLL), in which the clone differed from that of the preceding monoclonal gammopathy. At initial presentation, the patient had hepatosplenomegaly, leukocytosis (29100 x 10(6)/l) with an increase of mature neutrophils (83%), 20q- chromosomal abnormality, an increased leukocyte alkaline phosphatase score, elevated serum levels of vitamin B12 and uric acid, a low serum level of granulocyte colony-stimulating factor, and high serum IgM (1015 mg/dl: lambda type M protein). Thereafter, lymphocytosis developed gradually. Three years after the initial presentation, the patient had no serum M protein, but showed evidence of leukocytosis (36600 x 10(6)/l) with 20q- chromosomal abnormality and an increase of mature neutrophils (51%) and small lymphocytes (43.5%), CD5+/19+/20+/HLA-DR+ and surface membrane IgM+/D+/kappa+. Gene rearrangements of the immunoglobulin heavy and kappa light chains were also present. To our knowledge, this is the first reported case of CNL associated with CLL.
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PMID:Chronic neutrophilic leukemia associated with chronic lymphocytic leukemia. 971 72

A 6-year-old boy developed hemophagocytic syndrome during the recurrent course of Kawasaki disease. Despite the appropriate treatment modalities for Kawasaki disease, he developed pancytopenia, marked hepatosplenomegaly, high-grade fever, hyperferritinemia, hypertriglyceremia, and evidence of hemophagocytosis in the liver biopsy. Although the course was stormy, he responded well to a combination therapy of corticosteroids, etoposide VP16, and granulocyte colony-stimulating factor G-CSF. The clinical course and the treatment given were compared with the previous reported cases.
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PMID:Hemophagocytosis complicating Kawasaki disease. 1084 31

The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.
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PMID:Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG-CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is related to stage of infection. 1095 Apr 51

We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.
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PMID:Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage. 1127 13

Glycogen storage disease (GSD) is a rare autosomal-recessive disorder characterized by hypoglycemia, hepatosplenomegaly, seizures, and failure to thrive in infants. Neutropenia and/or neutrophil dysfunction develops in GSD1b, but not in other types. GSD1b results from a deficiency of the glucose-6-phosphate translocase enzyme and the genetic defect maps to chromosome 11q23. Patients with GSD1b are susceptible to recurrent bacterial infections, commonly involving the perirectal area, ears, skin, and urinary tract, although life-threatening infections, such as septicemia, pneumonia, and meningitis occur less frequently. Although the exact mechanism of neutropenia in patients with GSD1b is not known, treatment with recombinant human granulocyte colony-stimulating factor (G-CSF) has reduced the incidence of infections and has improved the quality of life of these patients. Defects in neutrophil chemotaxis and intracellular bacterial killing have been described and appear to be corrected by the use of G-CSF. To date, no cases of myelodysplasia or acute myeloid leukemia have been observed in patients with GSD1b treated with G-CSF. A significant complication of cytokine therapy is the development of hypersplenism, requiring either a reduction in the dosage of G-CSF or splenectomy.
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PMID:Glycogen storage disease. 1195 92

A 42-year-old woman was diagnosed with myelodysplastic syndrome with fibrosis that developed bilaterally, cervical lymphadenopathy and cutaneous infiltration by trilineage extramedullary hematopoiesis after granulocyte colony-stimulating factor therapy because of severe neutropenia. Hepatosplenomegaly was not observed during her follow-up. Extramedullary hematopoiesis disappeared after growth factor therapy was stopped. Although the neutropenia was alleviated by growth factor administration, the appearance of an unusual involvement of extramedullary hematopoiesis should be kept in mind.
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PMID:Unusual extramedullary hematopoiesis in a patient receiving granulocyte colony-stimulating factor. 1701 39

We diagnosed an 86-year-old woman with chronic neutrophilic leukemia (CNL) because she showed sustained leukocytosis dominated by mature neutrophils, hepatosplenomegaly, high neutrophilic alkaline phosphatase score, absence of the Ph chromosome, low serum level of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and no evidence of leukemoid reaction. We found that the extent of stimulation of her neutrophil functions by G-CSF and GM-CSF was greatly reduced compared to healthy donars neutrophils. We showed that CNL neutrophils have intact expression of granulocyte colony-stimulating factor receptor (G-CSFR) and granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR). This suggests that failure of enhancement by G-CSF and GM-CSF in CNL neutrophil functions might be due to disturbances in the intracellular domains of G-CSFR and GM-CSFR, regardless of external cytokine stimulation. However, the patient's neutrophils did not show any mutations in the G-CSFR and GM-CSFR intracellular critical regions. We also showed that stat3 and mitogen-activated protein kinase activation by G-CSF or GM-CSF in the patient's neutrophils were significantly lower than those in healthy donor neutrophils. These results suggest that deficiency of CNL neutrophil function might be due to insufficiency of some inflammatory cytokine-specific signaling. Hence, we are the first to show that CNL neutrophils have partially insufficiency in some cytokine-specific signaling. Further studies are needed to elucidate the signal transduction pathways relating to functional defects in CNL neutrophils.
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PMID:Neutrophil function and cytokine-specific signaling in chronic neutrophilic leukemia. 1824 Dec 14


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