Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel human leukaemic cell line, designated CTS, was established from the peripheral blood of a 13-year-old girl suffering from acute myeloblastic leukaemia (AML) in relapse. CTS cells expressed CD7, CD13, CD33, CD34 and HLA-DR antigens, and showed ultrastructural myeloperoxidase activity. In addition, CTS cells showed DNA rearrangements of the immunoglobulin heavy chain gene and the light kappa chain gene, and deletions of the T-cell receptor delta 1 gene. Cytogenetic analysis revealed a human female diploid karyotype with a t(6;11)(q27;q23) chromosomal translocation. Molecular studies demonstrated a DNA rearrangement of the MLL gene, the expression of a truncated 11.0 kb MLL mRNA and the detection of the MLL/AF-6 fusion transcript in CTS cells. To our knowledge, this cell line is the first report of a human leukaemic cell line with a t(6;11) chromosomal translocation. CTS cells showed no significant proliferative response to the cytokines, IL-2, IL-3, IL-6, IL-11, GM-CSF, G-CSF, EPO, SCF, but were induced to differentiate to the T-cell, B-cell, erythroid or megakaryocytic lineage in the presence of particular cytokines. This CTS cell line may provide a useful tool in the study of the oncogenesis of mixed lineage leukaemia with 11q23 abnormalities and for the analysis of growth and differentiation of pluripotent stem cells.
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PMID:A novel human leukaemic cell line, CTS, has a t(6;11) chromosomal translocation and characteristics of pluripotent stem cells. 890 86

Inflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 micrograms/kg. rhG-CSF caused a time- and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B4 (LTB4) and thromboxane B2 (TXB2) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB4: both P < 0.01; TXB2: both P < 0.01. Prostaglandin E2 (PGE2) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE2 was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.
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PMID:Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis. 897 23

Any influence of G-CSF on eosinophils is mostly negative, although reports which have studied this relationship are few with varied results. The aim of this study was to investigate the influence of G-CSF administration to healthy subjects on eosinophils in peripheral blood. Blood eosinophil counts, serum levels of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil protein X (EPX), as well as cell morphology were studied. 14 healthy volunteers received 7.5 microg (n = 8) or 10 microg/kg body weight (n = 6) G-CSF daily for six consecutive days. ECP and EPX were assessed by specific RIAs and EPO by a specific FEIA. Cell morphology was examined by electron microscopy. During G-CSF administration, eosinophil counts increased from 0.22 +/- 0.04 x 10(9)/l to 0.61 +/- 0.098 x 10(9)/l (P = 0.001), serum ECP from 12.39 +/- 2.45 microg/l to 61.82 +/- 7.38 microg/l (P = 0.0014), serum EPX from 28.05 +/- 4.54 microg/l to 87.86 +/- 9.84 microg/l (P = 0.002) and serum EPO from 8.89 +/- 2.2 microg/l to 19.98 +/- 5.1 microg/l (P = 0.003). All variables returned gradually to initial values after discontinuation of G-CSF. Distinct changes in the morphology of secondary granules were observed 24 h after G-CSF administration. The granules became irregular and their matrix less electron dense. We conclude that administration of G-CSF to healthy humans increases the number of circulating eosinophils and affects the mobilization of eosinophil granule proteins.
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PMID:Administration of G-CSF to healthy subjects: the effects on eosinophil counts and mobilization of eosinophil granule proteins. 902 10

1. The aim of our study was to investigate the effects of recombinant human granulocyte-colony stimulating factor in a rat model of splanchnic ischaemia-reperfusion injury. 2. Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock. SAO shock). Sham operated animals were used as controls. Survival rate, serum tumour necrosis factor-alpha (TNF-alpha), neutrophil count, bone marrow myeloid precursor cells, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation), mean arterial blood pressure and the responsiveness of aortic rings to phenylephrine (PE, 1 nM-10 microM) were studied. 3. SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), increased serum levels of TNF-alpha (201 +/- 10 u ml-1; sham shocked rats = undetectable), neutropenia, enhanced MPO activity in the ileum (0.11 +/- 0.06 u x 10(-3) g-1 tissue; sham shocked rats = 0.02 +/- 0.001 u x 10(-3) g-1 tissue) and in the lung (1.5 +/- 0.2 u x 10(-3) g-1 tissue; sham shocked rats = 0.19 +/- 0.05 u x 10(-3) g-1 tissue) and unchanged bone marrow myeloid precursor cells. Furthermore aortic rings from shocked rats showed a marked hyporeactivity to PE. 4. Administration of recombinant human granulocyte colony stimulating factor (rh G-CSF; 5, 10 and 20 micrograms kg-1 5 min following the release of occlusion) increased in a dose-dependent manner survival rate (90% at 4 h of reperfusion with the dose of 20 u x 10(-3) g kg-1), reduced serum TNF-alpha (13 +/- 5 u ml-1) and MPO activity in the ileum (0.065 +/- 0.002 u x 10(-3) g-1 tissue) and in the lung (0.7 +/- 0.03 microgram kg-1 tissue), improved neutropenia and mean arterial blood pressure but did not modify bone marrow myeloid progenitor cells. Furthermore rh G-CSF, either in vivo or in vitro (200 nM for 1 h in the organ bath), restored to control values the hyporeactivity to PE. Finally rh G-CSF potently inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. 5. Our results suggest that rh G-CSF protects against splanchnic ischaemia reperfusion injury by a mechanism(s) that does not depend upon its haematopoietic effects.
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PMID:The effects of recombinant human granulocyte-colony stimulating factor on vascular dysfunction and splanchnic ischaemia-reperfusion injury. 911 28

Bone marrow is a major granulopoietic organ whose hematopoietic microenvironment is comprised of stromal cells. In the present work, we examined the regulation of in vitro granulopoiesis with an established line of bone marrow stromal cells. In coculture of the progenitor cells on the particular stromal cell lines from bone marrow, large granulocyte (G) colonies consisting of over 200 cells were formed without G-CSF for 5 days. Stromal cells supported development of Gr-1 (granulocyte specific surface marker)-negative progenitors into Gr-1 and myeloperoxidase positive granulocytes. Seventy percent of the large G-colonies were formed on the stromal layers even in the presence of anti-G-CSF antibody, which indicates the G-CSF independent pathway of granulopoiesis. Inhibition of the large G-colony formation by the addition of anti-adhesion molecules, such as very late activation antigen-4 (VLA-4) and CD31 (PECAM-1), suggested the role of cell-to-cell adhesion in stroma-supported granulopoiesis.
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PMID:Selective stimulation of granulopoiesis in vitro by established bone marrow stromal cells. 924 99

CBF beta-SMMHC is expressed from the inv(16) chromosome in M4Eo AML. Mice lacking CBF subunits or expressing the CBF beta-SMMHC or AML1-ETO oncoproteins failed to develop definitive hematopoiesis. To investigate these effects on hematopoiesis, we expressed CBF beta-SMMHC from the metallothionein promoter, in both 32D cl3 myeloid cells and Ba/F3 B-lymphoid cells. Addition of zinc increased CBF beta-SMMHC levels more than tenfold, with higher levels evident in Ba/F3 lines. Levels obtained in 32D cl3 cells were similar to those of endogenous CBF beta. Indirect immunofluorescence revealed zinc-inducible speckled, nuclear staining in Ba/F3 cells and diffuse nuclear staining in 32D cl3 cells. CBF beta-SMMHC reduced endogenous CBF DNA-binding fivefold in both cell types, increased cell generation time 1.9-fold, on average, in 32D cl3 cells and 1.5-fold in Ba/ F3 cells and decreased tritiated thymidine incorporation into DNA correspondingly. CBF beta-SMMHC increased the proportion of cells in G1 1.7-fold, on average, in 32D cl3 and Ba/F3 cells, and decreased the proportion of cells in S phase by a similar degree. CBF beta-SMMHC induced a marked increase in hypophosphorylated Rb, but did not alter IL-3 Receptor alpha or beta subunit levels. Neither apoptosis nor 32D differentiation was induced by zinc in IL-3 in these lines. Induction of CBF beta-SMMHC in 32D cl3 cells did not inhibit their differentiation to neutrophils or their expression of myeloperoxidase mRNA in G-CSF, and did not produce an eosinophilic phenotype. Additional, proliferative genetic changes in M4eo AMLs might potentiate inhibition of differentiation by CBF beta-SMMHC by allowing its increased expression.
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PMID:CBF beta-SMMHC, expressed in M4Eo AML, reduced CBF DNA-binding and inhibited the G1 to S cell cycle transition at the restriction point in myeloid and lymphoid cells. 931

PU.1 is a unique regulatory protein required for the generation of both the innate and the adaptive immune system. It functions exclusively in a cell-intrinsic manner to control the development of granulocytes, macrophages, and B and T lymphocytes. We demonstrate that mutation of the PU.1 gene causes a severe reduction in myeloid (granulocyte/macrophage) progenitors. PU.1 -/- myeloid progenitors can proliferate in vitro in response to the multilineage cytokines interleukin-3 (IL-3), IL-6 and stem cell factor but are unresponsive to the myeloid-specific cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF and M-CSF. The failure of PU.1 -/- progenitors to respond to G-CSF is bypassed by transient signaling with IL-3. In the presence of IL-3 and G-CSF, PU.1 -/- progenitors can differentiate into granulocytic precursors containing myeloperoxidase-positive granules. Thus PU.1 is not essential for specification of granulocytic precursors, but is required for their further differentiation. The failure of PU.1 -/- progenitors to respond to M-CSF is due to lack of c-fms gene transcription. Transduction of c-fms into PU.1 -/- myeloid progenitors bypasses the block to M-CSF-dependent proliferation but does not induce detectable macrophage differentiation. Therefore, PU. 1 appears to be essential for specification of monocytic precursors. Importantly, retroviral transduction of PU.1 into mutant progenitors restores responsiveness to myeloid-specific cytokines and development of mature granulocytes and macrophages. Thus PU.1 controls myelopoiesis by regulating both proliferation and differentiation pathways.
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PMID:PU.1 regulates both cytokine-dependent proliferation and differentiation of granulocyte/macrophage progenitors. 968 12

Three patients with chronic myeloid leukemia (CML) in blastic transformation were treated with G-CSF plus middle dose cytosine arabinoside (Ara-C). G-CSF was administered (150 mg, s.c. or 300 mg, d.i.v./day) 24 hr prior to Ara-C (2-3 g/body, 6 hour d.i.v. for 2-5 days) and continued until the peripheral neutrophil count rose above 1,000/microlitre. As a supplement, VP-16 (80 mg/m2, for 2 days) was administered as warranted to control the growth of blastic cells. All 3 patients survived for more than 12 months with a favorable performance status. Normal karyotypes were detected in 2 of the patients after chemotherapy. One of those patients in paticular demonstrated normal bone marrow findings with the almost complete disappearance of the Ph-positive clone. In vitro cultures of peroxidase-negative CML blastic cells revealed that G-CSF stimulated the induction of blastic cells into the cell cycle and that blastic cell apoptosis was more pronounced in cells cultured with G-CSF plus Ara-C than with G-CSF or Ara-C alone. G-CSF plus middle dose Ara-C therapy appears to be a strong candidate for the treatment of CML in blastic transformation with a poor prognosis.
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PMID:[Induction of Ph-negative normal clone and long-term survival by combined treatment with G-CSF plus middle dose cytosine arabinoside for patients with chronic myeloid leukemia in blastic transformation]. 1002 46

We sought to define the time of first-appearance of neutrophils within the developing human bone marrow cavity, and to compare this with the time of appearance of G-CSF and its receptor (G-CSF-R) at that site. We hypothesized that the onset of G-CSF production is an initiation signal for neutrophil production within the marrow cavity, and that therefore G-CSF mRNA and G-CSF protein in the marrow cavity would immediately precede the first-appearance of neutrophils. To test this, we determined the time of first-appearance of neutrophils in the clavicular marrow space using a monoclonal antibody against myeloperoxidase (MPOAb), and then validated these findings by flow cytometric analyses, for neutrophil cell-surface markers, of cells flushed from the marrow cavity. After thus defining the time of first-appearance of neutrophils, specific mRNA transcripts for G-CSF and G-CSF-R were sought from clavicles of varying gestational ages, using RT-PCR, and the presence of these proteins in the clavicles were sought using immunohistochemistry. We observed that; (1) MPO+ cells first appeared in the clavicular marrow cavity between the 10 to 11th weeks post-conception, (2) Flow cytometric analyses confirmed that these MPO+ marrow cells included CD11b+, CD15+ neutrophils, (3) Transcripts for G-CSF and G-CSF-R, and the specific G-CSF and G-CSF-R proteins, were present in the clavicles by 6 weeks post-conception, 4 to 5 weeks before the first-appearance of neutrophils. Thus, neutrophils first appear in the human clavicular marrow at 10-11 weeks post-conception, and G-CSF and G-CSF-R are present in the developing bone rudiment preceding the appearance of neutrophils. It is unclear whether neutrophils arise in the marrow cavity in response to the onset of production of G-CSF or to other initiation signals.
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PMID:The first-appearance of neutrophils in the human fetal bone marrow cavity. 1019 6

We report the first Japanese case of acute promyelocytic leukemia with t(11;17)(q23;q21) and CD56. A 41-year-old man with schizophrenia was hospitalized because of the appearance of blasts with Auer bodies in his peripheral blood. A bone marrow smear showed an abundance of abnormal cells with scanty azurophile granules in the cytoplasm and somewhat lobulated nuclei. Because the abnormal cells demonstrated strongly positive peroxidase reactivity with a few faggot bodies, the patient was given a diagnosis of acute promyelocytic leukemia (M3v according to the FAB classification). However, chromosome analysis revealed t(11;17)(23; q21). All-trans retinoic acid (ATRA) was not effective. Mitoxantrone was more effective than daunorubicin, and resulted in a complete remission with a normal karyotype. About 9 months later, the patient suffered a relapse. Surface marker analysis demonstrated blasts that were positive for CD56, CD13, and CD33. MEC (mitoxantrone, etoposide, cytarabine) therapy was ineffective. Although ATRA was administered at a dose of 80 mg/day for more than 2 months, the number of myelocytes and promyelocytes increased Finally CAG (cytarabine, aclarubicin, G-CSF) therapy was initiated, but the patient died due to intracranial invasion and hemorrhage accompanied by disseminated intravascular coagulation.
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PMID:[Acute promyelocytic leukemia with t(11;17)(q23;q21)]. 1019 5


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