Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.
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PMID:In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. 195 74

A 55-year-old woman was first seen in October 1986, because of splenomegaly, moderate anemia and leukocytosis. The hemoglobin was 8.8 g/dl, platelet count 24.4 X 10(4)/microliters, and the white cell count 23,800/microliters with 73% atypical lymphoid cells. The bone marrow nucleated cell count was 99,000/microliters with 36% lymphoid cells. These atypical lymphoid cells showed hairy appearance under phase-contrast microscopy, and were positive for tartrate-resistant acid phosphatase. These cells showed the surface phenotype of CD10, CD19, CD20, Leu M5, HCM, and IgG K. Biochemical data revealed marked polyclonal hypergammagloburinemia (PHG) of IgG type (IgG 8756 mg/dl). To elucidate the mechanism of the PHG, we investigated whether hairy cells produce interleukin 6 (IL-6) and express IL-6 receptor. The culture supernatant of these hairy cells increased 3H-thymidine uptake of a IL-6 dependent hybridoma clone (MH60) in a dose-dependent manner. These cells were stained with anti-IL-6 antibody using immuno-cytochemical technique. Our results suggested that these hairy cells produce and secrete IL-6. Immunocytochemical staining with anti IL-6 receptor antibody and the binding assay with 125I-labelled recombinant IL-6 revealed that these cells express little or no receptors for IL-6. It was therefore suggested that IL-6 produced by hairy cells in this case is not an autocrine growth factor for these cells but may play a role in development of PHG by stimulating normal B lymphocytes to produce an excessive amount of immunoglobulin.
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PMID:[Production and secretion of BSF2/IL6 in a case of hairy cell leukemia with polyclonal hypergammaglobulinemia]. 238 10

Four cases of idiopathic acute tubulointerstitial nephritis (TIN) associated with uveitis (so-called TINU syndrome) were experienced between 1986 and 1990. Patients' ages ranged from 14 to 42 years old and three were female and one was male. All cases showed general symptoms, such as general malaise, anorexia and weight loss. All patients had initially TIN and became ill uveitis four to eight months after the onset of TIN. All cases had mild proteinuria, mild anemia, the lower serum levels of potassium, hyper gamma-globulinemia and the reduced glomerular filtration rate with the increased beta 2-microglobulin in urine and serum. All renal biopsies specimens showed mild edema and diffuse infiltration of inflammatory mononuclear cells in the interstitium without any glomerular or vascular abnormalities. Furthermore, numerous CD4 positive cells, CD8 positive cells and CD11c positive cells were seen in the interstitium. Of four patients, three cases were treated with both oral administration and eye drop of prednisolone (PSL), another one case was therapied with eye drop PSL only. In all cases TIN had good prognosis, but two patients had recurrences of uveitis. All patients underwent tissue typing for HLA-A, B, C and DR antigens. Three patients had identical HLA-Cw3 and all four cases revealed identical HLA-A24(9). These results suggest that immunological mechanism, especially cell-mediated, and HLA system may play an important role in the occurrence of TINU syndrome.
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PMID:[HLA tissue types in patients with acute tubulointerstitial nephritis accompanying uveitis]. 837 85

Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.
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PMID:Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation. 919 Oct 1

Hairy cell leukemia-variant (HCL-V) is an extremely rare chronic B-cell lymphoproliferative disorder clinically and morphologically distinct from classic hairy cell leukemia (HCL). HCL-V is thought to represent a hybrid between prolymphocytic leukemia and HCL, the nucleus more closely resembling a prolymphocyte and the cytoplasm a hairy cell. The clinical course of HCL-V is aggressive with short survivals. Since single courses of cladribine have profound activity in HCL, inducing durable complete responses in 91% of patients, we administered cladribine to 4 patients with HCL-V over a 7-year period. During this time interval 357 patients with classic HCL received cladribine at Scripps Clinic. Each patient received cladribine at 0.1 mg/kg per day by continuous intravenous infusion for 7 days, repeated at 28-day intervals depending on response status. The 4 patients ranged in age from 28 to 70. Two presented with B-symptoms, 1 had peripheral adenopathy, and all 4 displayed massive splenomegaly. Peripheral blood counts were notable for lymphocytosis associated with mild anemia and thrombocytopenia. Only 1 of the 4 patients had received prior treatment. Peripheral blood immunophenotypic analysis revealed monoclonal B cells with expression of CD11c in 3 patients, lack of CD25 expression in 3 patients and expression of CD103 in all but 1 patient. The number of cladribine courses administered ranged from two to five. Of these 4 patients, 1 (25%) achieved a complete response and 2 (50%) partial responses, for an overall response rate of 75%. Three patients underwent splenectomy after cladribine. Cladribine is an active agent in HCL-V albeit with a lower response rate than in classic HCL. The role of other treatment modalities, such as splenectomy, interferon-alpha, and 2'-deoxycoformycin, alone or in combination with cladribine awaits further evaluation.
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PMID:Treatment of hairy cell leukemia-variant with cladribine. 1070 59

Clinical, hematologic, and immunophenotypic data were studied in 25 dogs with large granular lymphocyte (LGL) lymphocytosis. Primarily large-breed dogs were affected, with an average age at initial diagnosis of 10 years (range 5-14 years). All dogs had persistent (>4 months) LGL lymphocytosis except for three that were euthanized with aggressive disease. Splenomegaly was reported in 12 of 20 dogs in which splenic size was evaluated. The clinical course was heterogeneous and dogs were divided into four groups based on similar clinical and hematologic findings: acute leukemia (3/25), persistent lymphocytosis with anemia (12/25), persistent lymphocytosis without anemia (8/25), and reactive lymphocytosis (2/25). Immunophenotypes varied within groups but were homogeneous among cells from the same patient except in the two dogs classified as reactive LGL lymphocytosis. Analysis of T-cell receptor (TCR) usage identified three main LGL lineages. TCRalphabeta was expressed in 15/25 (60%) cases. TCRgammadelta was expressed in 8/25 (32%) cases, and 2/25 (8%) cases were CD3-, compatible with NK cells. beta2 integrin expression was distinctive. CD11a was consistently expressed, while CD11b was absent. CD11c was expressed only weakly in 16/25 (64%) cases. The leukointegrin alphadbeta2 was highly prevalent on all LGL lineages, being expressed in 23/25 (92%) cases. Prominent involvement of the spleen, relative sparing of bone marrow, an unexpectedly large proportion of gammadelta T-cell LGLs, and the distinctive beta2 integrin expression pattern on diverse lineages of LGLs suggest the disease arises from unique populations of lymphocytes that preferentially localize in the splenic red pulp.
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PMID:Clinical, hematologic, and immunophenotypic characterization of canine large granular lymphocytosis. 1110 53

Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder comprising approximately 2 to 3% of all adult leukemias in the United States. Hairy cells are clonal expansions of mature, activated B-cells. They co-express CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal immunoglobulin gene rearrangements and express monoclonal surface immunoglobulin of either IgG or multiple heavy-chain isotypes. Treatment of hairy cell leukemia should be considered for symptomatic patients. It is indicated in patients with significant neutropenia, anemia, thrombocytopenia, symptomatic splenomegaly, constitutional symptoms due to hairy cell leukemia, or recurrent serious infections. Many treatments exist, including cladribine, pentostatin, interferon-alpha, splenectomy, rituximab (mabthera), and BL-22 immunotoxin.
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PMID:Hairy cell leukemia: an update. 1279 30

We present a 75-year-old man who was admitted to our hospital because of splenomegaly, transfusion-dependent anemia and thrombocytopenia. The diagnosis of idiopathic myelofibrosis was suggested by the bone marrow trephine biopsy, which was hypocellular with myelofibrosis. Thalidomide was started at a daily dose of 100 mg/d and increased to 400 mg/d. Within 12 weeks, thrombocytes increased to 100.000/microl, hemoglobin normalized, lasting for about 11 months. Then, thalidomide had to be discontinued because of mild polyneuropathy. A second bone marrow biopsy showed fibrosis as well as a diffuse infiltration of the bone marrow (80%) by lymphocytes with expression of CD11c, CD19, CD20, CD103. Tartrate resistant acid phosphatase test (TRAP) was also positive. Hairy cell leukemia was diagnosed and he was administered 2-chlorodeoxyadenosine (2-CDA) achieving a complete remission.
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PMID:Hairy cell leukemia (HCL) with extensive myelofibrosis responds to thalidomide. 1597 49

T-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRalphabeta. Much less is known about the characteristics and pathogenesis of TCRgammadelta+ cases. We evaluated 44 patients with clonal TCRgammadelta+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRgammadelta+ T-LGL leukemia patients had similar clinical presentations as TCRalphabeta+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias - neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) - and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vgamma9/Vdelta2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vdelta1, reflecting the TCR-spectrum of normal TCRgammadelta+ T-cells in adult PB. Identification of the well-defined post-thymic Vdelta2-Jdelta1 selection determinant in all evaluable Vgamma9+/Vdelta2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRgammadelta+ T-LGL leukemia patients.
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PMID:TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRgammadelta+ T-cells. 1643 45

Histiocytic disorders of dogs include histiocytoma, localized histiocytic sarcoma (HS), disseminated HS (malignant histocytosis), and the reactive histiocytoses: cutaneous and systemic. A common element to these diseases is proliferation of dendritic cells (DC) of either Langerhans cell (epithelial DC) or interstitial DC lineage. In this report, 17 dogs with hemophagocytic HS are described. Breeds affected included Bernese Mountain Dog (6), Golden Retriever (4), Rottweiler (3), Labrador Retriever (2), a mixed-breed dog, and a Schnauzer, which were from 2.5 to 13 years old. The dogs presented with Coombs negative responsive anemia in 16/17 dogs (94%), thrombocytopenia in 15/17 dogs (88%), hypoalbuminemia in 16/17 dogs (94%), and hypocholesterolemia in 11/16 dogs (69%). All dogs died or were euthanized. The clinical course ranged from 2 to 32 weeks (mean 7.1 weeks). Diffuse splenomegaly with ill-defined masses was consistently present. Microscopic lesions were prevalent in spleen, liver, lung, and bone marrow. Metastasis occurred by insidious intravascular invasion with minimal mass formation. Histiocytes were markedly erythrophagocytic and accompanied by foci of extramedullary hemopoiesis. Cytologically, the histiocytes varied from well differentiated to atypical, with atypia more prevalent in spleen than bone marrow. These tumors arose from splenic red pulp and bone marrow macrophages, which expressed major histocompatibility complex class II and the beta2 integrin, CD11d. They had low and/or inconsistent expression of CD1 and CD11c, which are dominantly expressed by canine nonhemophagocytic HS of DC origin. Canine histiocytic proliferative diseases now encompass proliferation of all members of the myeloid histiocytic lineage: Langerhans cells, interstitial DC, and macrophages.
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PMID:Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+ macrophages. 1696 40


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