Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myeloperoxidase is a component of the microbicidal network of polymorphonuclear leukocytes. The enzyme is a tetramer consisting of two heavy and two light subunits. A large proportion of humans demonstrate genetic deficiencies in the production of myeloperoxidase. As a first step in analyzing these deficiencies in more detail, we have isolated cDNA clones for myeloperoxidase from an expression library of the HL-60 human promyelocytic leukemia cell line. Two overlapping plasmids (pMP02 and pMP062) were identified as myeloperoxidase cDNA clones based on the detection with myeloperoxidase antiserum of 70 kDa protein expressed in pMP02-containing bacteria and a 75 kDa polypeptide produced by hybridization selection and translation using pMP062 and HL-60 RNA. Formal identification of the clones was made by matching the predicted amino acid sequences with the amino terminal sequences of the heavy and light subunits. Both subunits are encoded by one mRNA in the following order: pre-pro-sequences--light subunit--heavy subunit. The molecular weight of the predicted primary translation product is 83.7 kDa. Northern blots reveal two size classes of hybridizing RNAs (approximately 3.0-3.3 and 3.5-4.0 kilobases) whose expression is restricted to cells of the granulocytic lineage and parallels the changes in enzymatic activity observed during differentiation.
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PMID:Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species. 303 85

The observation that myeloperoxidase precursor and larger intermediate (Mr 91,000 and 81,000, respectively) were extracted in the presence of detergent from isolated granule fractions of human promyelocytic leukemia HL-60 cells under mildly acidic conditions was investigated. In contrast, under conditions of neutral pH, only the Mr 74,000 intermediate and mature species were extracted. Extraction of the Mr 91,000 and 81,000 forms was also enhanced in the presence of EDTA. Kinetic studies of the processing of the different myeloperoxidase species confirmed the intermediate nature of the Mr 81,000 and 74,000 forms. Support for a role of an acidic intracellular compartment was obtained through evidence that the acid-extractable precursor and intermediates accumulated in HL-60 cells which had been treated with 1 microM monensin. Under these conditions, the production of mature heavy (Mr 63,000) and light (Mr 13,500) subunits of myeloperoxidase was consistently inhibited by greater than 40% over a 16-h period. The effects of monensin on processing of myeloperoxidase were completely reversed if monensin was removed during this 16-h period. These data support the idea that an acidic compartment may be involved in the transport of myeloperoxidase precursors to azurophil granules and/or their processing to a smaller intermediate form (Mr 74,000) of the enzyme.
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PMID:Evidence for the involvement of an acidic compartment in the processing of myeloperoxidase in human promyelocytic leukemia HL-60 cells. 303 7

Male ACI/N rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water, and in conjunction with histological examination, the changes of the expressed cytochrome P-450 components in the urothelium and other tissues (liver, kidney, esophagus, intestines) were examined by means of immunohistochemistry. Frozen tissue sections were prepared and immunostained with anti-rat cytochrome P-450 monoclonal antibodies and an avidin-biotin-peroxidase complex. Monoclonal antibodies used were APH-3 and APH-8 raised against a high-spin form of cytochrome P-448, APL-1 and APL-2 against a low-spin form of cytochrome P-448, and APF-3 against cytochrome P-450. BBN-induced qualitative and quantitative changes of cytochrome P-450 components recognized by these monoclonal antibodies were not observed in tissues other than the bladder. Untreated rat bladder epithelium was not stained with any of these 5 monoclonal antibodies. The treatment with BBN for more than 3 weeks, however, resulted in the expression of cytochrome P-450 component(s) recognized by APH-8 antibody. This cytochrome P-450 component increased with the advance of carcinogenic changes in the urothelium. The component reactive with AHP-8 was also detected in the cancer tissues of transplantation lines of rat bladder cancers. In contrast, the cytochrome P-450 components recognized by APL-1, APL-2 or APF-3 were undetectable or present at low levels throughout the BBN carcinogenesis. These results suggest that a certain cytochrome P-450 component(s), probably a high-spin form of cytochrome P-448, is selectively induced in urothelium in association with neoplastic bladder lesion.
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PMID:Altered expression of immunohistochemically detected cytochrome P-450 component(s) in nitrosamine-induced rat urinary bladder lesion. 311 31

Ten cases in which leukemic cells contained numerous cytoplasmic granules were examined by using a panel of cytochemical reactions. The diagnoses in the 10 cases were mast cell leukemia, chronic basophilic leukemia, and acute myeloid leukemia with basophilic differentiation in one case each, acute promyelocytic leukemia in two cases, acute megakaryoblastic leukemia in two cases, and blastic hairy cell leukemia in three cases. The cytochemical panel consisted of peroxidase, toluidine blue, chloroacetate esterase, aminocaproate esterase, tartrate-resistant acid phosphatase, and immunoalkaline phosphatase for platelet/megakaryocyte-specific antigen. The unusual cytologic features of leukemic cells in cases similar to our 10 cases have caused considerable diagnostic difficulties. In our 10 cases, however, the effective use of cytochemical studies helped to achieve accurate identification of the various types of leukemic cells. We conclude that the intelligent application of cytochemical techniques continues to be useful for the accurate cytodiagnosis of hematopoietic neoplasms.
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PMID:Cytochemical characterization of leukemic cells with numerous cytoplasmic granules. 311 18

We used somatic-cell hybrids, containing as their only human genetic contribution part or all of chromosome 17, as donors for chromosome-mediated gene transfer. A total of 54 independent transfectant clones were isolated and analyzed by use of probes or isoenzymes for greater than 20 loci located on chromosome 17. By combining the data from this chromosome-mediated gene transfer transfectant panel, conventional somatic-cell hybrids containing well-defined breaks on chromosome 17, and in situ hybridization, we propose the following order for these loci: pter-(TP53-RNP2-D17S1)-(MYH2-MYH1)-D17Z 1-CRYB1-(ERBA1-GCSF-NGL)-acute promyelocytic leukemia breakpoint-RNU2-HOX2-(NGFR-COLIAI-MPO)-GAA-UM PH-GHC-TK1-GALK-qter. Using chromosome-mediated gene transfer, we have also regionally localized the random probes D17S6 to D17S19 on chromosome 17.
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PMID:Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer. 318 46

Leukemic cells of 43 patients with acute promyelocytic leukemia (M3) were investigated morphologically and cytochemically to determine the percentage of aberrant enzymes and whether or not the presence impacts on the clinical outcome. Twelve patients (27.9%) showed alpha-naphthyl acetate esterase (ANAE) activity in their leukemic cells, and two of these cases revealed remarkably low myeloperoxidase (MPO) positivity, a pattern seen in monocytic precursors. However, further cytochemical evidence for this monocytic feature, the inhibition of naphthol AS-D acetate esterase (NASDA) activity with sodium fluoride (NASDA-F), was found in only five of these nine patients. In 31 cases (72.1%), there was minimal ANAE activity. Of interest, two of these were devoid of naphthol AS-D chloroacetate esterase (CAE), which is prominently displayed in neutrophilic granulocytes, even though these leukemic cells were 100% intensely positive for MPO activity. Between the two groups with and without ANAE activity, there were no remarkable differences in the distribution of sex and age, hematological findings, and rates of complete response. Our study has confirmed the cytochemical heterogeneity of M3 with no obvious relationship between this heterogeneity and early therapeutic outcome.
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PMID:Nonspecific esterase of acute promyelocytic leukemia (M3). 318 10

Terminal cell differentiation usually results in an irreversible arrest in the G1 phase of the cell cycle and loss of cell renewal ability. Human promyelocytic leukemia HL-60 cells induced with 12-o-tetradecanoylphorbol-13-acetate (TPA) differentiate into monocytes/macrophages and accumulate in G1. We determined the effect of TPA on the growth kinetics of a human leukemia cell line (KOPM-28), which developed several of the characteristics of megakaryocytes in response to TPA, such as the surface antigen complex IIb/IIIa, platelet peroxidase and polyploidy. Cell growth was immediately and completely inhibited by TPA. Flow cytometric analysis of cellular DNA content revealed a gradual decrease in cells in G1 and an accumulation of cells in G2. These data suggest that TPA prolonged G1 and rapidly arrested the cells in G2. Synchronized cells were utilized to further analyze the rapid G2 arrest. Cells arrested with aphidicolin at the G1/S interphase were released, and the effects of TPA (added at different intervals) on cell cycle progression were examined 14 h after release. The results showed that TPA added at the end of the S phase, as well as at the G1/S interphase incompletely but distinctly arrested cells in G2. Moreover, G2 arrest was observed when TPA was added to cells released from a colcemid-induced G2/M block, suggesting that cells already in G2 were inhibited by TPA from moving through M to G1. Since some cells became multi-nucleated in the course of incubation with TPA, this G2 accumulation may have resulted at least in part from a prolongation of the phase or a transient G2 block. These changes in cell cycle progression induced by TPA may be characteristic of and/or related to megakaryocytic differentiation of hemopoietic precursor cells.
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PMID:Alteration of cell cycle progression in human leukemia cell line (KOPM-28) induced by 12-o-tetradecanoylphorbol-13-acetate. 339 93

Bone marrow and/or peripheral blood cells from 12 patients with acute promyelocytic leukemia (APL) were cultured in soft agar or methylcellulose in the presence of 15% human placental conditioned medium as a source of colony stimulating factor. Buffy coat cells, taken from ten patients when APL was diagnosed, produced a growth pattern in soft agar that was characterized by a high incidence of small, relatively uniform clusters of promyelocytes, which, when stained in situ, reacted strongly with myeloperoxidase, Sudan black B and chloroacetate esterase. In six cases, the leukemic origin of the cluster forming cells was demonstrated by the presence of the t(15;17) in these cells. During periods of complete remission the small clusters were replaced by larger and more diverse aggregates which had a normal karyotype. At relapse the small cluster growth pattern returned. The growth pattern of small clusters is more commonly associated with APL than with other types of acute myeloid leukemia.
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PMID:A characteristic CFU-GM growth pattern in acute promyelocytic leukemia. 347 28

An IgG2a murine monoclonal antibody derived against human eosinophils was shown to immunoprecipitate the 78,000 dalton form of human eosinophil peroxidase (EPO). To confirm the specificity of the antibody, we used a glucose-oxidase avidin biotin procedure to immunostain 32 human cell lines and tissues. An eosinophilic subline of HL-60 promyelocytic leukemia was the only cell type other than eosinophils to be recognized by the antibody. Because previous reports have described occult eosinophilic degranulation in tissues with a variety of pathological conditions, we immunostained cryostat sections of four consecutive lymph node biopsies of nodular sclerosis Hodgkin's disease with the monoclonal antibody. Our objective was to characterize by immunohistology the eosinophilic infiltration in a lymphoma that frequently contains substantial numbers of eosinophils. In all four cases of nodular sclerosis Hodgkin's disease, there was striking and extensive deposition of EPO in a dendritic pattern throughout the connective tissue and collagen bands. The extent of deposition of EPO in the bands far exceeded the degree of infiltration by intact eosinophils, as determined by examination of routinely stained tissue sections. A similar dendritic pattern was not observed in any of six benign lymph nodes that were immunostained for EPO. We conclude that the monoclonal antibody described in this report is specific for EPO and that eosinophils extensively degranulate and release EPO in the bands of nodular sclerosis Hodgkin's disease. Moreover, the degree of eosinophilic infiltration in this disorder cannot be assessed solely on the basis of intact eosinophils.
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PMID:Eosinophil peroxidase is detectable with a monoclonal antibody in collagen bands of nodular sclerosis Hodgkin's disease. 355 Feb 88

The rat monoclonal antibody CAMPATH-1 recognizes a hitherto undefined antigen present on virtually all normal lymphocytes and monocytes. Its reactivity with 105 samples of fresh leukaemic cells and 13 cell lines was measured by indirect fluorescence and peroxidase staining to define in more detail which stages of differentiation it recognizes. It was found to bind to cells from virtually all cases of lymphoid leukaemia (B cell CLL, T cell ALL, cALL and the few examples of HCL, PLL, Sezary syndrome and CGL in lymphoid blast crisis). The single case of cALL in relapse and four of six cases of null ALL were negative. Binding to non-lymphoid leukaemia cells (AML, AMML, AMoL, APL, AEL and CGL in blast crisis) was weaker or undetectable. Binding to established lymphoid cell lines was generally weak compared with fresh cells but some lines (MOLT4, DAUDI and X308) expressed adequate amounts of antigen to be lysed by CAMPATH-1 with human complement. Because CAMPATH-1 is very effective at killing lymphocytes in the presence of human complement, it has been used for removal of T cells in allogeneic transplants. The present results suggest that it might also have a role in purging bone marrow of leukaemia cells prior to autologous transplantation for acute lymphocytic leukaemia.
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PMID:Reactivity of rat monoclonal antibody CAMPATH-1 with human leukaemia cells and its possible application for autologous bone marrow transplantation. 389 Sep 29


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